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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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March 19, 2014

Another Whack at the Stem Shortage Myth

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Posted by Derek

Over at The Atlantic, Michael Teitelbaum has another crack at demolishing the "STEM shortage" myth. Looking over actual employment data, he finds:

All have concluded that U.S. higher education produces far more science and engineering graduates annually than there are S&E job openings—the only disagreement is whether it is 100 percent or 200 percent more. Were there to be a genuine shortage at present, there would be evidence of employers raising wage offers to attract the scientists and engineers they want. But the evidence points in the other direction: Most studies report that real wages in many—but not all—science and engineering occupations have been flat or slow-growing, and unemployment as high or higher than in many comparably-skilled occupations.

Right on all counts. I have taken many, many cracks at this subject myself. Heck, I've even said so in pieces at The Atlantic's own web site. But the "critical shortage of scientists and engineers" idea just refuses to go back into its hole, no matter how many times it's hit on the head. In this article, Teitelbaum doesn't go into the reasons for this, but he's been clear about it in recent appearances:

So from where does the STEM hype stem? According to Teitelbaum — who has written a book on the subject, due out in March, titled “Falling Behind?: Boom, Bust and the Global Race for Scientific Talent” — some of it comes from the country’s longtime cycle of waxing and waning interest in science; attention seems to focus on science every 10 to 15 years before slacking off.

The only forces pushing the idea of STEM doom, he said, are those that have something to gain from it. Mostly those are STEM employers — the tech industry, for example — that want to pack the labor force with people to suppress wages, he said, as well as lobby for looser immigration laws so that they can bring in less expensive overseas workers. Joining the chorus are universities that want more funding for science programs, as well as immigration lawyers who see the potential for handling large numbers of work visas.

Those are, I'm sad to say, pretty much the same conclusions I've come to. I don't like sounding like a 1920s IWW organizer or something - it goes very much against my usual tendencies. And I continue to think that unionism in the sciences would be a bad idea. But drumming up cheap labor by pretending that there's a shortage of it is a bad idea, too.

As mentioned above, Teitelbaum has a book out on this subject - here it is. Next time you run across someone going on about scientist shortages, hit them over the head with it.

Comments (42) + TrackBacks (0) | Category: Business and Markets | Current Events

March 18, 2014

Jailhouse Secrets They Don't Want You to Know About!

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Posted by Derek

As I had hoped last year, scam artist Kevin Trudeau is indeed heading off for a ten-year sentence. I have searched, without success, for a photo of him wearing an orange jumpsuit and being bundled into a windowless prison van, but we'll just have to use our imaginations for that. Not to worry - a good steam cleaning, and the vehicle will be surely be fit to transport honest burglers again.

Trudeau had been convicted of criminal contempt, for egregiously violating earlier court orders to stop ripping people off through his all-natural-cures informercial empire. Past entries here have detailed what the man is like, and if you know anything about chemistry or biology, twenty seconds of listening to any of his pitches has usually been enough to make you bury your head in your hands. But there are untold millions of people out there who know nothing about either subject, and are willing to listen when someone spins them tales of wonderful medicines and cures that the great shadowy "They" don't want anyone to know about. Trudeau cynically raked in the cash by appealing to ignorance and promoting suspicion. With any luck, we shall not see his like again. But I'm afraid we will.

Comments (14) + TrackBacks (0) | Category: Current Events | Snake Oil

January 30, 2014

The West Virginia Formaldehyde Claim Is Nonsense

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Posted by Derek

This morning I heard reports of formaldehyde being found in Charleston, West Virginia water samples as a result of the recent chemical spill there. My first thought, as a chemist, was "You know, that doesn't make any sense". A closer look confirmed that view, and led me to even more dubious things about this news story. Read on - there's some chemistry for a few paragraphs, and then near the end we get to the eyebrow-raising stuff.
4-MCHM.png
The compound that spilled was (4-methylcyclohexane)methanol, abbreviated as 4-MCHM. That's its structure over there.

For the nonchemists in the audience, here's a chance to show how chemical nomenclature works. Those lines represent bonds between atoms, and if the atom isn't labeled with its own letter, it's a carbon (this compound has one one labeled atom, that O for oxygen). These sorts of carbons take four bonds each, and that means that there are a number of hydrogens bonded to them that aren't shown. You'd add one, two, or three hydrogens as needed to each to take each one up to four bonds.

The six-membered ring in the middle is "cyclohexane" in organic chemistry lingo. You'll note two things coming off it, at opposite ends of the ring. The small branch is a methyl group (one carbon), and the other one is a methyl group subsituted with an alcohol (OH). The one-carbon alcohol compound (CH3OH) is methanol, and the rules of chemical naming say that the "methanol-like" part of this structure takes priority, so it's named as a methanol molecule with a ring stuck to its carbon. And that ring has another methyl group, which means that its position needs to be specified. The ring carbon that has the "methanol" gets numbered as #1 (priority again), so the one with the methyl group, counting over, is #4. So this compound's full name is (4-methylcyclohexane)methanol.

I went into that naming detail because it turns out to be important. This spill, needless to say, was a terrible thing that never should have happened. Dumping a huge load of industrial solvent into a river is a crime in both the legal and moral senses of the word. Early indications are that negligence had a role in the accident, which I can easily believe, and if so, I hope that those responsible are prosecuted, both for justice to be served and as a warning to others. Handling industrial chemicals involves a great deal of responsibility, and as a working chemist it pisses me off to see people doing it so poorly. But this accident, like any news story involving any sort of chemistry, also manages to show how little anyone outside the field understands anything about chemicals at all.

I say that because among the many lawsuits being filed, there are some that show (thanks, Chemjobber!) that the lawyers appear to believe that the chemical spill was a mixture of 4-methylcyclohexane and methanol. Not so. This is a misreading of the name, a mistake that a non-chemist might make because the rest of the English language doesn't usually build up nouns the way organic chemistry does. Chemical nomenclature is way too logical and cut-and-dried to be anything like a natural language; you really can draw a complex compound's structure just by reading its name closely enough. This error is a little like deciding that a hairdryer must be a device made partly out of hair.

I'm not exaggerating. The court filing, by the law firm of Thompson and Barney, says explicitly:

30. The combination chemical 4-MCHM is artificially created by combining methylclyclohexane (sic) with methanol.

31. Two component parts of 4-MCHM are methylcyclohexane and methanol which are both known dangerous and toxic chemicals that can cause latent dread disease such as cancer.

Sure thing, guys, just like the two component parts of dogwood trees are dogs and wood. Chemically, this makes no sense whatsoever. Now, it's reasonable to ask if 4-MCHM can chemically degrade to methanol and 4-methylcyclohexane. Without going into too much detail, the answer is "No". You don't get to break carbon-carbon bonds that way, not without a lot of energy. If you ran the chemical (at high temperature) through some sort of catalytic cracking reactor at an oil refinery, you might be able to get something like that to happen (although I'd expect other things as well, probably all at the same time), but otherwise, no. For the same sorts of reasons, you're not going to be able to get formaldehyde out of this compound, either, not without similar conditions. Air and sunlight and water aren't going to do it, and if bacteria and fungi metabolize it, I'd expect things like (4-methylcyclohexane)carboxaldehyde and (4-methylcyclohexane)carboxylic acid, among others. I would not expect them to break off that single-carbon alcohol as formaldehyde.
MeOH%20rxn.png
So where does all this talk of formaldehyde come from? Well, one way that formaldehyde shows up is from oxidation of methanol, as shown in that reaction (this time I've drawn in all the hydrogens). This is, in fact, one of the reasons that methanol is toxic. In the body, it gets oxidized to formaldehyde, and that gets oxidized right away to formic acid, which shuts down an important enzyme. Exposure to formaldehyde itself is a different problem. It's so reactive that most cancers associated with exposure to it are in the upper respiratory tract; it doesn't get any further.

As that methanol oxidation reaction pathway shows, the body actually has ways of dealing with formaldehyde exposure, up to a point. In fact, it's found at low levels (around 20 to 30 nanograms/milliliter) in things like tomatoes and oranges, so we can assume that these exposure levels are easily handled. I am not aware of any environmental regulations on human exposure to orange juice or freshly cut tomatoes. So how much formaldehyde did Dr. Scott Simonton find in his Charleston water sample? Just over 30 nanograms per milliliter. Slightly above the tomato-juice level (27 ng/mL). For reference, the lowest amount that can be detected is about 6 ng/mL. Update: and the amount of formaldehyde in normal human blood is about 1 microgram/mL, which is over thirty times the levels that Simonton says he found in his water samples. This is produced by normal human metabolism (enzymatic removal of methyl groups and other reactions). Everyone has it. And another update: the amount of formaldehyde in normal human saliva can easily be one thousand times that in Simonton's water samples, especially in people who smoke or have cavities. If you went thousands of miles away from this chemical spill, found an untouched wilderness and had one of its natives spit in a collection vial, you'd find a higher concentration of formaldehyde.

But Simonton is a West Virginia water quality official, is he not? Well, not in this capacity. As this story shows, he is being paid in this matter by the law firm of Thompson and Barney to do water analysis. Yes, that's the same law firm that thinks that 4-MCHM is a mixture with methanol in it. And the water sample that he obtained was from the Vandalia Grille in Charleston, the owners of which are defendants in that Thompson and Barney lawsuit that Chemjobber found.

So let me state my opinion: this is a load of crap. The amounts of formaldehyde that Dr. Simonton states he found are within the range of ozonated drinking water as it is, and just above those of fresh tomato juice. These are levels that have never been shown to be harmful in humans. His statements about cancer and other harm coming to West Virginia residents seem to me to be irresponsible fear-mongering. The sort of irresponsible fear-mongering that someone might do if they're being paid by lawyers who don't understand any chemistry and are interested in whipping up as much panic as they can. Just my freely offered opinions. Do your own research and see what you think.

Update: I see that actual West Virginia public health officials agree.

Another update: I've had people point out that the mixture that spilled may have contained up to 1% methanol. But see this comment for why this probably doesn't have any bearing on the formaldehyde issue. Update, Jan 31: Here's the MSDS for the "crude MHCM" that was spilled. The other main constituent (4-methoxymethylcyclohexane)methanol is also unlikely to produce formaldehyde, for the same reasons given above. The fact remains that the levels reported (and sensationalized) by Dr. Simonton are negligible by any standard.

Comments (112) + TrackBacks (0) | Category: Chemical News | Current Events | Press Coverage | Toxicology

July 18, 2013

China's GlaxoSmithKline Crackdown

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Posted by Derek

Keeping up with the GlaxoSmithKline/China story has been hard - every day or two there's a new twist. But here's what's going on so far:

Four GSK executives have been arrested on charges of bribery. Hospitals, doctors, officials of all kinds - the accusations are the the GSK people jacked up prices and sales figures by greasing people everywhere they thought necessary. Report have it that travel agencies (to inflate the costs of meetings and trips as a form of payment), high-priced consultation deals, and good ol' sexual favors were involved. In addition to the four executives who've been arrested, China has told GSK's financial director for that unit that he's not allowed to leave the country.

A mess indeed, and pretty much the last thing that GSK was in the market for, I'll bet. I am, sadly, not amazed at the idea of large organized bribery in the Chinese market. Nor, I'm sure, are the Chinese authorities. The country has a well-publicized problem with corruption, with high-level officials regularly being removed from their positions amid accusations of all sorts of malfeasance. Even if you mark some of that up to political maneuvering and score-settling (which I'm sure are factors, too), the country's current system of authoritarian capitalism is an invitation to such behavior on every level. Every country in the world has this sort of thing to some degree - who you know, who you're related to, who owes you favors, who you've paid off - but the combination of China's one-party system and its huge business boom of the last decades combine to make it a particular problem there.

It also combines to breed conspiracy theories. You might wonder if GSK is in trouble because their behavior was particularly noticeable or on a large scale, of if there's some other reason that we're not seeing. It's impossible to say, and not very fruitful to speculate on, but it's not a line of thought that can be dismissed easily, either. Perhaps the idea was pour encourager les autres. This article is along those lines:

A Chinese bribery investigation into British drugmaker GlaxoSmithKline (GSK.L) has sent tremors through multinational pharmaceutical firms in China, prompting at least one to review how they do business in the country.

Experts said foreign companies across the spectrum were watching closely to see what happened to GSK and its four detained Chinese executives given bribery and business go hand-in-hand in the world's second biggest economy. . .

Pharmaceutical companies are at the mercy of Chinese regulators in getting products licensed for import or manufacture in China, or to get them listed on the national drug registry. They typically rely on hired distributors to get their drugs to market and into hospitals. . .

. . .According to sources with knowledge of the industry, China's sophisticated and thriving market for fake documents also allows local employees to provide forged paperwork to more senior or global managers.

Efforts made by drug firms at compliance training can even backfire, as some employees learn how to avoid detection.

That Reuters piece also mentions speculation that the Chinese government is leaning hard on drug companies for better pricing, as it faces mounting health care costs, and you can't rule that one out, either. That's the problem - you can't rule much of anything out at all.

Comments (23) + TrackBacks (0) | Category: Current Events | The Dark Side

June 21, 2013

Eight Toxic Foods: A Little Chemical Education

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Posted by Derek

Update: You'll notice in this post that I refer to some sites that the original BuzzFeed article I'm complaining out sends people to, often pointing out that these didn't actually support the wilder claims it's making. Well, the folks at BuzzFeed have dealt with this by taking down the links (!) The article now says: "Some studies linked in the original version of this article were concerning unrelated issues. They have been replaced with information directly from the book Rich Food, Poor Food". But as you'll see below, the studies weren't unrelated at all. So when you read about links to the American Cancer Association or NPR, well, all I can say is that they used to be there, until someone apparently realized how embarrassing they were.

Many people who read this blog are chemists. Those who aren't often come from other branch of the sciences, and if they don't, it's safe to say that they're at least interested in science (or they probably don't hang around very long!) It's difficult, if you live and work in this sort of environment, to keep in mind what people are willing to believe about chemistry.

But that's what we have the internet for. Many science-oriented bloggers have taken on what's been called "chemophobia", and they've done some great work tearing into some some really uninformed stuff out there. But nonsense does not obey any conservation law. It keeps on coming. It's always been in long supply, and it looks like it always will be.

That doesn't mean that we just have to sit back and let it wash over us, though. I've been sent this link in the last few days, a popular item on BuzzFeed with the BuzzFeedy headline of "Eight Foods That We Eat in The US That Are Banned in Other Countries". When I saw that title, I found it unpromising. In a world that eats everything that can't get away fast enough, what possible foods could we have all to ourselves here in the States? A quick glance was enough: we're not talking about foods here - we're talking about (brace yourselves) chemicals.

This piece really is an education. Not about food, or about chemistry - on the contrary, reading it for those purposes will make you noticeably less intelligent than you were before, and consider that a fair warning. The educational part is in the "What a fool believes" category. Make no mistake: on the evidence of this article, its author is indeed a fool, and has apparently never yet met a claim about chemicals or nutrition that was too idiotic to swallow. If BuzzFeed's statistics are to be believed (good question, there), a million views have already accumulated to this crap. Someone who knows some chemistry needs to make a start at pointing out the serial stupidities in it, and this time, I'm going to answer the call. So here goes, in order.

Number One: Artificial Dyes. Here's what the article has to say about 'em:

Artificial dyes are made from chemicals derived from PETROLEUM, which is also used to make gasoline, diesel fuel, asphalt, and TAR! Artificial dyes have been linked to brain cancer, nerve-cell deterioration, and hyperactivity, just to name a few.

Emphasis is in the original, of course. How could it not lapse into all-caps? In the pre-internet days, this sort of thing was written in green ink all around the margins of crumpled shutoff notices from the power company, but these days we have to make do with HTML. Let's take this one a sentence at a time.

It is true, in fact, that many artificial dyes are made from chemicals derived from petroleum. That, folks, is because everything (edible or not) is made out of chemicals, and an awful lot of man-made chemicals are derived from petroleum. It's one of the major chemical feedstocks of the world. So why stop at artificial dyes? The ink on the flyer from the natural-foods co-op is made from chemicals derived from petroleum. The wax coating the paper wrapped around that really good croissant at that little bakery you know about is derived from petroleum.

Now, it's true that more things you don't eat can be traced back to petroleum feedstocks than can things you do eat. That's because it's almost always cheaper to grow stuff than to synthesize it. Synthesized compounds, when they're used in food, are often things that are effective in small amounts, because they're so expensive. And so it is with artificial dyes - well, outside of red velvet cake, I guess. People see the bright colors in cake icing and sugary cereals and figure that the stuff must be glopped on like paint, but paint doesn't have very much dye or pigment in it, either (watch them mix it up down at the hardware store sometime).

And as for artificial colors causing "brain cancer, nerve-cell deterioration, and hyperactivity", well, these assertions range from "unproven" all the way down to "bullshit". Hyperactivity sensitivities to food dyes are an active area of research, but after decades of work, the situation is still unclear. And brain cancer? This seems to go back to studies in the 1980s with Blue #2, where rats were fed the dye over a long period in much larger concentrations (up to 2% of their total food intake) than even the most dedicated junk-food eater could encounter. Gliomas were seen in the male rats, but with no dose-response, and at levels consistent with historical controls in the particular rat strain. No one has ever been able to find any real-world connection. Note that glioma rates increased in the 1970s and 1980s as diagnostic imaging improved, but have fallen steadily since then. The age-adjusted incidence rates of almost all forms of cancer are falling, by the way, not that you'd know that from most of the coverage on the subject.

Number Two: Olestra

This, of course, is Proctor & Gamble's attempted non-calorific fat substitute. I'm not going to spend much time on this, because little or nothing is actually made with it any more. Olestra was a major flop for P&G; the only things (as far as I can tell) that still contain it are some fat-free potato chips. It does indeed interfere with the absorption of fat-soluble vitamins, but potato chips are not a very good source of vitamins to start with. And vitamin absorption can be messed with by all kinds of things, including other vitamins (folic acid supplements can interfere with B12 absorption, just to pick one). But I can agree with the plan of not eating the stuff: I think that if you're going to eat potato chips, eat a reasonable amount of the real ones.

Number Three: Brominated Vegetable Oil. Here's the article's take on it:

Bromine is a chemical used to stop CARPETS FROM CATCHING ON FIRE, so you can see why drinking it may not be the best idea. BVO is linked to major organ system damage, birth defects, growth problems, schizophrenia, and hearing loss.

Again with the caps. Now, if the author had known any chemistry, this would have looked a lot more impressive. Bromine isn't just used to keep carpets from catching on fire - bromine is a hideously toxic substance that will scar you with permanent chemical burns and whose vapors will destroy your lungs. Drinking bromine is not just a bad idea; drinking bromine is guaranteed agonizing death. There, see what a little knowledge will do for you?

But you know something? You can say the same thing for chlorine. After all, it's right next to bromine in the same column of the periodic table. And its use in World War I as a battlefield gas should be testimony enough. (They tried bromine, too, never fear). But chlorine is also the major part, by weight, of table salt. So which is it? Toxic death gas or universal table seasoning?

Knowledge again. It's both. Elemental chlorine (and elemental bromine) are very different things than their ions (chloride and bromide), and both of those are very different things again when either one is bonded to a carbon atom. That's chemistry for you in a nutshell, knowing these differences and understanding why they happen and how to use them.

Now that we've detoured around that mess, on to brominated vegetable oil. It's found in citrus-flavored sodas and sports drinks, at about 8 parts per million. The BuzzFeed article claims that it's linked to "major organ system damage, birth defects, growth problems, schizophrenia, and hearing loss", and sends readers to this WebMD article. But if you go there, you'll find that the only medical problems known from BVO come from two cases of people who had been consuming, over a long period, 4 to 8 liters of BVO-containing soda per day, and did indeed have reactions to all the excess bromine-containing compounds in their system. At 8 ppm, it's not easy to get to that point, but a determined lunatic will overcome such obstacles. Overall, drinking several liters of Mountain Dew per day is probably a bad idea, and not just because of the BVO content.

Number Four: Potassium Bromate. The article helpfully tells us this is "Derived from the same harmful chemical as brominated vegetable oil". But here we are again: bromate is different from bromide is different than bromine, and so on. If we're going to play the "made from the same atoms" game, well, strychnine and heroin are derived from the same harmful chemicals as the essential amino acids and B vitamins. Those harmful chemicals, in case you're wondering, are carbon, hydrogen, oxygen, and nitrogen. And to get into the BuzzFeed spirit of the thing, maybe I should mention that carbon is found in every single poisonous plant on earth, hydrogen is the harmful chemical that blew up the Hindenburg, oxygen is responsible for every death by fire around the world, and nitrogen will asphyxiate you if you try to breathe it (and is a key component of all military explosives). There, that wasn't hard - as Samuel Johnson said, a man might write such stuff forever, if only he would give over his mind to it.

Now, back to potassium bromate. The article says, "Only problem is, it’s linked to kidney damage, cancer, and nervous system damage". And you'll probably fall over when I say this, but that statement is largely correct. Sort of. But let's look at "linked to", because that's an important phrase here.

Potassium bromate was found (in a two-year rat study) to have a variety of bad effects. This occurred at the two highest doses, and the lowest observed adverse effect level (LOAEL) was 6.1 mg of bromate per kilo body weight per day. It's worth noting that a study in male mice took them up to nearly ten times that amount, though, with little or no effect, which gives you some idea of how hard it is to be a toxicologist. Whether humans are more like mice or more like rats in this situation is unknown.

I'm not going to do the whole allometric scaling thing here, because no matter how you do it, the numbers come out crazy. Bromate is used in some (but not all) bread flour at 15 to 30 parts per million, and if the bread is actually baked properly, there's none left in the finished product. But for illustration, let's have someone eating uncooked bread dough at the highest level, just to get the full bromate experience. A 75-kilo human (and many of us are more than that) would have to take in 457 mg of bromate per day to get to the first adverse level seen in rats, which would be. . .15 kilos (about 33 pounds) of bread dough per day, a level I can safely say is unlikely to be reached. Hell, eating 33 pounds of anything isn't going to work out, much as my fourteen-year-old son tries to prove me wrong. You'd need to keep that up for decades, too, since that two year study represents a significant amount of a rat's lifespan.

Number Five: Azodicarbonamide. This is another bread flour additive. According to the article, "Used to bleach both flour and FOAMED PLASTIC (yoga mats and the soles of sneakers), azodicarbonamide has been known to induce asthma".

Let's clear this one up quickly: azodicarbonamide is indeed used in bread dough, and allowed up the 45 parts per million. It is not stable to heat, though, and it falls apart quickly to another compound, biurea, on baking. It not used to "bleach foamed plastic", though. Actually, in higher concentrations, it's used to foam foamed plastics. I realize that this doesn't sound much better, but the conditions inside hot plastic, you will be glad to hear, are quite different from those inside warm bread dough. In that environment, azodicarbonamide doesn't react to make birurea - it turns into several gaseous products, which are what blow up the bubbles of the foam. This is not its purpose in bread dough - that's carbon dioxide from the yeast (or baking powder) that's doing the inflating there, and 45 parts per million would not inflate much of anything.

How about the asthma, though? If you look at the toxicology of azodicarbonamide, you find that "Azodicarbonamide is of low acute toxicity, but repeated or prolonged contact may cause asthma and skin sensitization." That, one should note, is for the pure chemical, not 45 parts per million in uncooked flour (much less zero parts per million in the final product). If you're handling drums of the stuff at the plastics plant, you should be wearing protective gear. If you're eating a roll, no.

Number Six: BHA and BHT. We're on the home stretch now, and this one is a two-fer. BHA and BHT are butylated hydroxyanisole and butylate hydroxytoluene, and according to the article, they are "known to cause cancer in rats. And we’re next!"

Well, of course we are! Whatever you say! But the cancer is taking its time. These compounds have been added to cereals, etc., for decades now, while the incidence rates of cancer have been going down. And what BuzzFeed doesn't mention is that while some studies have shown an increase in cancer in rodent models with these compounds, others have shown a measurable decrease. Both of these compounds are efficient free radical scavengers, and have actually been used in animal studies that attempt to unravel the effects of free radicals on aging and metabolism. Animal studies notwithstanding, attempts to correlate human exposure to these compounds with any types of cancer have always come up negative. Contrary to what the BuzzFeed article says, by the way, BHT is indeed approved by the EU.

Weirdly, you can buy BHT in some health food stores, where anti-aging and anti-viral claims are made for it. How does a health food store sell butylated hydroxytoluene with a straight face? Well, it's also known to be produced by plankton, so you can always refer to it as a natural product, if that makes you feel better. That doesn't do much for me - as an organic chemist, I know that the compounds found in plankton range from essential components of the human diet all the way down to some of the most toxic molecules found in nature.

Number Seven: Synthetic Growth Hormones. These are the ones given to cattle, not the ones athletes give to themselves. The article says that they can "give humans breast, colon, and prostate cancer", which, given what's actually known about these substances, is a wildly irresponsible claim.

The article sends you to a perfectly reasonable site at the American Cancer Society, which is the sort of link that might make a BuzzFeed reader think that it must then be about, well, what kinds of cancer these things give you. But have a look. What you find is (first off) this is not an issue for eating beef. Bovine growth hormone (BGH) is given to dairy cattle to increase milk production. OK, so what about drinking milk?

Here you go: for one, BGH levels in the milk of treated cows are not higher than in untreated ones. Secondly, BGH is not active as a growth hormone in humans - it's selective for the cow receptor, not the human one. The controversy in this area comes from the way that growth hormone treatment in cows tends to increase levels of another hormone, IGF-1, in the milk. That increase still seems to be within the natural range of variability for IGF-1 in regular cows, but there is a slight change.

The links between IGF-1 and cancer have indeed been the subject of a lot of work. Higher levels of circulating IGF-1 in the bloodstream have (in some studies) been linked to increased risk of cancer, but I should add that other studies have failed to find this effect, so it's still unclear what's going on. I can also add, from my own experiences in drug discovery, that all of the multiple attempts to treat cancer by blocking IGF-1 signaling have been complete failures, and that might also cause one to question the overall linkage a bit.

But does drinking milk from BGH-treated cows increase the levels of circulating IGF-1 at all? No head-to-head study has been run, but adults who drink milk in general seem to have slightly higher levels. The same effect, though, was seen in people who drink soymilk, which (needless to say) does not have recombinant cow hormones in it. No one knows to what extent ingested IGF-1 might be absorbed into the bloodstream - you'd expect it to be digested like any other protein, but exceptions are known.

But look at the numbers. According to that ACA web summary, even if the protein were not degraded at all, and if it were completely absorbed (both of which are extremely unrealistic top-of-the-range assumptions), and even if the person drinking it were an infant, and taking in 1.6 quarts a day of BGH-derived cow milk with the maximum elevated levels of IGF-1 that have been seen, the milk would still contribute less than 1% of the IGF-1 in the bloodstream compared to what's being made in the human body naturally.

Number Eight, Arsenic. Arsenic? It seems like an unlikely food additive, but the article says "Used as chicken feed to make meat appear pinker and fresher, arsenic is POISON, which will kill you if you ingest enough."

Ay. I think that first off, we should make clear that arsenic is not "used as chicken feed". That brings to mind someone pitching powdered arsenic out for the hens, and that's not part of any long-term chicken-farming plan. If you go to the very NPR link that the BuzzFeed article offers, you find that a compound called roxarsone is added to chicken feed to keep down Coccidia parasites in the gut. It is not just added for some cosmetic reason, as the silly wording above would have you believe.

In 2011, a study found that chicken meat with detectable levels of roxarsone had 2.3 parts per billion (note the "b") of inorganic arsenic, which is the kind that is truly toxic. Chicken meat with no detectable roxarsone had 0.8 ppb inorganic arsenic, threefold less, and the correlation seems to be real. (Half of the factory-raised chickens sampled had detectable roxarsone, by the way). This led to the compound being (voluntarily) withdrawn from the market, under the assumption that this is an avoidable exposure to arsenic that could be eliminated.

And so it is. There are other (non-arsenic) compounds that can be given to keep parasite infestations down in poultry, although they're not as effective, and they'll probably show up on the next edition of lists like this one. But let's get things on scale: it's worth comparing these arsenic levels to those found in other foods. White rice, for example comes in at about 100 parts per billion of inorganic arsenic (and brown rice at 170 ppb). These, by the way, are all-natural arsenic levels, produced by the plant's own uptake from the soil. But even those amounts are not expected to pose a human health risk (says both the FDA and Canadian authorities), so the fifty-fold lower concentrations in chicken would, one thinks, be even less to worry about. If you're having chicken and rice and you want to worry about arsenic, worry about the rice.

This brings me to the grand wrap-up, and some of the language in that last item is a good starting point for it. I'm talking about the "POISON, which will kill you if you ingest enough" part. This whole article is soaking in several assumptions about food, about chemistry, and about toxicology, and that's one of the big ones. In my experience, people who write things like this have divided the world into two categories: wholesome, natural, healthy stuff and toxic chemical poisons. But this is grievously simple-minded. As I've emphasized in passing above, there are plenty of natural substances, made by healthy creatures in beautiful, unpolluted environments, that will nonetheless kill you in agony. Plants, fungi, bacteria, and animals produce poisons, wide varieties of intricate poisons, and they're not doing it for fun.

And on the other side of the imaginary fence, there are plenty of man-made substances that really won't do much of anything to people at all. You cannot assume anything about the effects of a chemical compound based on whether it came from a lovely rainforest orchid or out of a crusty Erlenmeyer flask. The world is not set up that way. Here's a corollary to this: if I isolate a beneficial chemical compound from some natural source (vitamin C from oranges, for example, although sauerkraut would be a good source, too), that molecule is identical to a copy of it I make in my lab. There is no essence, no vital spirit. A compound is what it is, no matter where it came from.

Another assumption that seems common to this mindset is that when something is poisonous at some concentration, it is therefore poisonous at all concentrations. It has some poisonous character to it that cannot be expunged nor diluted. This, though, is more often false than true. Paracelsus was right: the dose makes the poison. You can illustrate that in both directions: a beneficial substance, taken to excess, can kill you. A poisonous one, taken in very small amounts, can be harmless. And you have cases like selenium, which is simultaneously an essential trace element in the human diet and an inarguable poison. It depends on the dose.

Finally, I want to return to something I was saying way back at the beginning of this piece. The author of the BuzzFeed article knows painfully little about chemistry and biology. But that apparently wasn't a barrier: righteous conviction (and the worldview mentioned in the above three paragraphs) are enough, right? Wrong. Ten minutes of unbiased reading would have served to poke holes all through most of the article's main points. I've spent more than ten minutes (as you can probably tell), and there's hardly one stone left standing on another. As a scientist, I find sloppiness at this level not only stupid, not only time-wasting, but downright offensive. Couldn't anyone be bothered to look anything up? There are facts in this world, you know. Learn a few.

Comments (382) + TrackBacks (0) | Category: Current Events | Snake Oil | Toxicology

June 19, 2013

The Drug Industry and the Obama Administration

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Posted by Derek

Over at Forbes, John Osborne adds some details to what has been apparent for some time now: the drug industry seems to have no particular friends inside the Obama administration:

Earlier this year I listened as a recently departed Obama administration official held forth on the industry and its rather desultory reputation. . .the substance of the remarks, and the apparent candor with which they were delivered, remain fresh in my mind, not least because of the important policy implications that the comments reflect.

. . .In part, there’s a lingering misimpression as to how new medicines are developed. While the NIH and its university research grantees make extraordinary discoveries, it is left to for-profit pharmaceutical and biotechnology companies to conduct the necessary large scale clinical studies and obtain regulatory approval prior to commercialization. Compare the respective annual spending totals: the NIH budget is around $30 billion, and the industry spends nearly double that amount. While the administration has great affection for universities, non-profit patient groups and government researchers (and it was admirably critical of the sequester’s meat cleaver impact on government sponsored research programs), it does not credit the essential role of industry in bringing discoveries from the bench to the bedside.

Terrific. I have to keep reminding myself how puzzled I was when I first came across the "NIH and universities discover all the drugs" mindset, but repeated exposures to it over the last few years have bred antibodies. If anyone from the administration would like to hear what someone who is not a lobbyist, not a CEO, not running for office, and has actually done this sort of work has to say about the topic, well, there are plenty of posts on this blog to refer to (and the comments sections to them are quite lively, too). In fact, I think I'll go ahead and link to a whole lineup of them - that way, when the topic comes up again, and it will, I can just send everyone here:

August 2012: A Quick Tour Through Drug Development Reality
May 2011: Maybe It Really Is That Hard?
March 2011: The NIH Goes For the Gusto
Feb 2011: The NIH's New Drug Discovery Center: Heading Into the Swamp?
Nov 2010: Where Drugs Come From: The Numbers
August 2009: Just Give It to NIH
August 2009: Wasted Money, Wasted Time?
July 2009: Where Drugs Come From, and How. Once More, With A Roll of the Eyes
May 2009: The NIH Takes the Plunge
Sep 2007: Drugs From Where?
November 2005: University of Drug Discovery?
October 2005: The Great Divide
September 2004: The NIH in the Clinic
September 2004: One More On Basic Research and the Clinic
September 2004: A Real-World Can O' Worms
September 2004: How Much Basic Research?
September 2004: How It Really Works

There we go - hours of reading, and all in the service of adding some reality to what is often a discussion full of unicorn burgers. Back to Osborne's piece, though - he goes on to make the point that one of the other sources of trouble with the administration is that the drug industry has continued to be profitable during the economic downturn, which apparently has engendered some suspicion.

And now for some 100-proof politics. The last of Osborne's contentions is that the administration (and many legislators as well) see the Medicare Part D prescription drug benefit as a huge windfall for the industry, and one that should be rolled back via a rebate program, setting prices back to what gets paid out under the Medicaid program instead. Ah, but opinions differ on this:

It’s useful to recall that former Louisiana Congressman and then PhRMA head Billy Tauzin negotiated with the White House in 2009 on behalf of the industry over this very question. Under the resulting deal, the industry agreed to support passage of the ACA and to make certain payments in the form of rebates and fees that amounted to approximately $80 billion over ten years; in exchange the administration agreed to resist those in Congress who pressed for more concessions from the drug companies or wanted to impose government price setting. . .

Tauzin's role, and the deal that he helped cut, have not been without controversy. I've always been worried about deals like this being subject to re-negotiations whenever it seems convenient, and those worries are not irrational, either:

. . .The White House believes that the industry would willingly (graciously? enthusiastically?) accept a new Part D outpatient drug rebate. Wow. The former official noted that the Simpson-Bowles deficit reduction panel recommended it, and its report was favorably endorsed by no less than House Speaker Boehner. Apparently, it is inconceivable to the White House that Boehner’s endorsement of the Simpson-Bowles platform would have occurred without the industry’s approval. Wow, again. That may be a perfectly logical assumption, but the other industry representatives within earshot never imagined that they had endorsed any such thing. No, it’s clear they have been under the (naïve) impression that the aforementioned $80 billion “contribution” was a very substantial sum in support of patients and the government treasury – and offered in a spirit of cooperation in recognition of the prospective benefits to industry of the expanded coverage that lies at the heart of Obamacare. With that said, the realization that this may be just the first of several installment payments left my colleagues in stunned silence; some mouths were visibly agape.

This topic came up late last year around here as well. And it'll come up again.

Comments (37) + TrackBacks (0) | Category: Academia (vs. Industry) | Current Events | Drug Development | Regulatory Affairs

June 14, 2013

Making Changes Inside Merck's R&D

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Posted by Derek

I've heard from more than one source that Roger Perlmutter has been shaking things up this week at Merck. Since he only took over R&D in March, that's a pretty short lag time - if these reports are accurate, he clearly has some strong opinions and is ready to act on them. From what I've been hearing, bench-level people aren't being affected. It's all in the managerial levels. Anyone with more knowledge and a willingness to share it is welcome to do so in the comments. . .

Comments (115) + TrackBacks (0) | Category: Current Events

One. . .Million. . .Pounds (For a New Antibiotic?)

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Posted by Derek

Via Stuart Cantrill on Twitter, I see that UK Prime Minister David Cameron is prepared to announce a prize for anyone who can "identify and solve the biggest problem of our time". He's leaving that open, and his examples are apparently ". . .the next penicillin, aeroplane or world wide web".

I like the idea of prizes for research and invention. The thing is, the person who invents the next airplane or World Wide Web will probably do pretty well off it through the normal mechanisms. And it's worth thinking about the very, very different pathways these three inventions took, both in their discovery and their development. While thinking about that, keep in mind the difference between those two.

The Wright's first powered airplane, a huge step in human technology, was good for carrying one person (lying prone) for a few hundred yards in a good wind. Tim Berners-Lee's first Web page, another huge step, was a brief bit of code on one server at CERN, and mostly told people about itself. Penicillin, in its early days, was famously so rare that the urine of the earliest patients was collected and extracted in order not to waste any of the excreted drug. And even that was a long way from Fleming's keen-eyed discovery of the mold's antibacterial activity. A more vivid example than penicillin of the need for huge amounts of development from an early discovery is hard to find.

And how does one assign credit to the winner? Many (most) of these discoveries take a lot of people to realize them - certainly, by the time it's clear that they're great discoveries. Alexander Fleming (very properly) gets a lot of credit for the initial discovery of penicillin, but if the world had depended on him for its supply, it would have been very much out of luck. He had a very hard time getting anything going for nearly ten years after the initial discovery, and not for lack of trying. The phrase "Without Fleming, no Chain; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin" properly assigns credit to a lot of scientists that most people have never heard of.

Those are all points worth thinking about, if you're thinking about Cameron's prize, or if you're David Cameron. But that's not all. Here's the real kicker: he's offering one million pounds for it ($1.56 million as of this morning). This is delusional. The number of great discoveries that can be achieved for that sort of money is, I hate to say, rather small these days. A theoretical result in math or physics might certainly be accomplished in that range, but reducing it to practice is something else entirely. I can speak to the "next penicillin" part of the example, and I can say (without fear of contradiction from anyone who knows the tiniest bit about the subject) that a million pounds could not, under any circumstances, tell you if you had the next penicillin. That's off by a factor of a hundred, if you just want to take something as far as a solid start.

There's another problem with this amount: in general, anything that's worth that much is actually worth a lot more; there's no such thing as a great, world-altering discovery that's worth only a million pounds. I fear that this will be an ornament around the neck of whoever wins it, and little more. If Cameron's committee wants to really offer a prize in line with the worth of such a discovery, they should crank things up to a few hundred million pounds - at least - and see what happens. As it stands, the current idea is like me offering a twenty-dollar bill to anyone who brings me a bar of gold.

Comments (28) + TrackBacks (0) | Category: Current Events | Drug Industry History | Infectious Diseases | Who Discovers and Why

May 21, 2013

Promoting STEM Education, Foolishly

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Posted by Derek

Here's a man who says what he thinks about getting students into STEM careers:

The United States spent more than US$3 billion last year across 209 federal programmes intended to lure young people into careers in science, technology, engineering and mathematics (STEM). The money goes on a plethora of schemes at school, undergraduate and postgraduate levels, all aimed at promoting science and technology, and raising standards of science education.

In a report published on 10 April, Congress’s Government Accountability Office (GAO) asked a few pointed questions about why so many potentially overlapping programmes coexist. The same day, the 2014 budget proposal of President Barack Obama’s administration suggested consolidating the programmes, but increasing funding.

What no one asked was whether these many activities actually benefit science and engineering, or society as a whole. My answer to both questions is an emphatic ‘no’.

And I think he's right about that. Whipping and driving people into science careers doesn't seem like a very good way to produce good scientists. In fact, it seems like an excellent way to produce a larger cohort of indifferent ones, which is exactly what we don't need. Or does that depend on the definition of "we"?

The dynamic at work here isn’t complicated. By cajoling more children to enter science and engineering — as the United Kingdom also does by rigging university-funding rules to provide more support for STEM than other subjects — the state increases STEM student numbers, floods the market with STEM graduates, reduces competition for their services and cuts their wages. And that suits the keenest proponents of STEM education programmes — industrial employers and their legion of lobbyists — absolutely fine.

And that takes us back to the subject of these two posts, on the oft-heard complaints of employers that they just can't seem to find qualified people any more. To which add, all too often, ". . .not at the salaries we'd prefer to pay them, anyway". Colin Macilwain, the author of this Nature piece I'm quoting from, seems to agree:

But the main backing for government intervention in STEM education has come from the business lobby. If I had a dollar for every time I’ve heard a businessman stand up and bemoan the alleged failure of the education system to produce the science and technology ‘skills’ that his company requires, I’d be a very rich man.

I have always struggled to recognize the picture these detractors paint. I find most recent science graduates to be positively bursting with both technical knowledge and enthusiasm.

If business people want to harness that enthusiasm, all they have to do is put their hands in their pockets and pay and train newly graduated scientists and engineers properly. It is much easier, of course, for the US National Association of Manufacturers and the British Confederation of British Industry to keep bleating that the state-run school- and university-education systems are ‘failing’.

This position, which was not my original one on this issue, is not universally loved. (The standard take on this issue, by contrast, has the advantage of both flattering and advancing the interests of employers and educators alike, and it's thus very politically attractive). I don't even have much affection for my own position on this, even though I've come to think it's accurate. As I've said before, it does feel odd for me, as a scientist, as someone who values education greatly, and as someone who's broadly pro-immigration, to be making these points. But there they are.

Update: be sure to check the comments section if this topic interests you - there are a number of good ones coming in, from several sides of this issue.

Comments (76) + TrackBacks (0) | Category: Business and Markets | Current Events

April 29, 2013

Just Work on the Winners

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Posted by Derek

That Lamar Smith proposal I wrote about earlier this morning can be summarized as "Why don't you people just work on the good stuff?" And I thought it might be a good time to link back to a personal experience I had with just that worldview. As you'll see from that story, all they wanted was for us to meet the goals that we put down on our research goals forms. I was told, face to face, that the idea was that this would make us put our efforts into the projects that were most likely to succeed. Who could object to that? Right?

But since we here in the drug industry are so focused on making money, y'know, you'd think that we would have even more incentives to make sure that we're only working on the things that are likely to pay off. And we can't do it. Committees vet proposals, managers look over progress reports, presentations are reviewed and data are sifted, all to that end, because picking the wrong project can sink you good and proper, while picking the right one can keep you going for years to come. But we fail all the time. A good 90% of the projects that make it into the clinic never make it out the other end, and the attrition even before getting into man is fierce indeed. We back the wrong horses for the best reasons available, and sometimes we back the right ones for reasons that end up evaporating along the way. This is the best we can do, the state of the art, and it's not very good at all.

And that's in applied research, with definite targets and endpoints in mind the whole way through. Now picture what it's like in the basic research end of things, which is where a lot of NSF and NIH money is (and should be) going. It is simply not possible to say where a lot of these things are going, and which ones will bear fruit. If you require everyone to sign forms saying that Yes, This Project Has Immediate Economic and National Security Impact, then the best you can hope for is to make everyone lie to you.

Update: a terrific point from the comments section: "(This) argument was often made when firms were reducing costs by shutting down particular pieces of R&D. The general idea was that the firm would stop doing the things that were unlikely to work, and focus more on the things that would work, and hence improve financial returns on R&D. This argument is implausible because successful R&D is wildly profitable. Financial returns are only dragged down by the things that don't work. Therefore, any company that could REALLY distinguish with any precision between winners and losers on a prospective basis should double or triple its R&D investment, and not cut it."

Comments (13) + TrackBacks (0) | Category: Current Events | Who Discovers and Why

A Dumb Proposal for the NSF

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Posted by Derek

This is a bad idea: Representative Lamar Smith (R-TX) is circulating a draft of a bill to change the way the National Science Foundation reviews grant applications. Science magazine obtained a copy of the current version, and it would require the NSF to certify that all research it funds is:

1) "…in the interests of the United States to advance the national health, prosperity, or welfare, and to secure the national defense by promoting the progress of science;

2) "… the finest quality, is groundbreaking, and answers questions or solves problems that are of utmost importance to society at large; and

3) "…not duplicative of other research projects being funded by the Foundation or other Federal science agencies."

If we could fund things this way, we would be living in a different world entirely. Research, though, does not and cannot follow these guidelines. A lot of stuff gets looked into that doesn't work out, and a lot of things that do work out don't look like they're ever going to be of much use for anything. We are not smart enough to put bets down on only the really important stuff up front - and by "we", I mean the entire scientific community, and the director of the NSF, and even Representative Lamar Smith.

Useless and even bizarre things get funded under the current system, of that I have no doubt. But telling everyone that all research has to be certified as good for something is silly grandstanding. What will happen is that people will rewrite their grant applications in order to make them look attractive under whatever rules apply - which, naturally, is how it's always worked. So I'm not saying that Rep. Smith's proposal would Destroy Science in America. That would take a lot more work. No, what I'm saying is that Rep. Smith's view of the world is flawed. He seems to believe that legislation of this sort is the answer to large, difficult problems (witness his work on the Stop Online Piracy Act). As such, he would seem to be exactly the sort of person that I wish could be barred from serving as an elected official.

If I were Lamar Smith, I would probably be thinking of a bill that I could introduce to that effect (the Stop Overreaching Legislators Act?) But I'm not the sort of person who thinks that the world can be fixed up by passing the right laws and signing the right papers. I'm more in line with Mark Twain, when he said that no one's life, liberty, or property was safe while the legislature was in session.

Note: more thoughts added here, later in the day

Comments (25) + TrackBacks (0) | Category: Current Events

April 16, 2013

A Bombing

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Posted by Derek

I'm still trying to figure out if anyone I know personally was injured during yesterday's bombing of the Boston Marathon. So far, it's just been a couple of close calls. As it happened, I was out of town yesterday, and only saw the news in the early evening.

What sort of explosive chemistry was used might provide some clues about the people who did this - different groups have different ideas about what makes the best catastrophe. What sort of thinking allows a human being to go ahead with an act like this - bombing a festive crowd of innocent spectators and families on a spring afternoon - is beyond my comprehension, though.

I'll be traveling today, so I probably won't have another post up. My condolences to everyone affected by this act, and for those who perpetrated it, honi soit qui mal y pense, in the sense of "Evil to those who think evil".

Comments (38) + TrackBacks (0) | Category: Current Events

January 22, 2013

Pick Your Stench

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Posted by Derek

OK, folks, time to choose: would you rather be downwind of an industrial-scale spill of butyl mercaptan (which started in Rouen and is already being smelled in London), or. . .would you rather deal with a twenty-seven tons of burning goat cheese in Norway?

Tough call. I think, though, that I might go with the devil I know, which means the mercaptan. I've never encountered a Goat Cheese Inferno, and I live in fear of discovering even more revolting odors than I've already experienced. Good luck to the Norwegians, I say.

Update: for the curious, natural gas odorant mixes are usually t-butylthiol and isopropyl thiol, with perhaps some other lovelies (dimethyl sulfide) thrown in for that special je ne sais quoi. Although across northern France today, I'll bet they can tell you quoi for sure at the moment.

Comments (35) + TrackBacks (0) | Category: Current Events

January 4, 2013

Anti-GMO. Until This Week.

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Posted by Derek

I wanted to take a moment to highlight this speech, given recently by environmentalist and anti-genetically modified organism activist Mark Lynas.

Let's make that former anti-GMO activist. As the speech makes clear, he's had a completely change of heart:

I want to start with some apologies. For the record, here and upfront, I apologise for having spent several years ripping up GM crops. I am also sorry that I helped to start the anti-GM movement back in the mid 1990s, and that I thereby assisted in demonising an important technological option which can be used to benefit the environment.

As an environmentalist, and someone who believes that everyone in this world has a right to a healthy and nutritious diet of their choosing, I could not have chosen a more counter-productive path. I now regret it completely.

. . .(This was) explicitly an anti-science movement. We employed a lot of imagery about scientists in their labs cackling demonically as they tinkered with the very building blocks of life. Hence the Frankenstein food tag – this absolutely was about deep-seated fears of scientific powers being used secretly for unnatural ends. What we didn’t realise at the time was that the real Frankenstein’s monster was not GM technology, but our reaction against it. . .

. . .desperately-needed agricultural innovation is being strangled by a suffocating avalanche of regulations which are not based on any rational scientific assessment of risk. The risk today is not that anyone will be harmed by GM food, but that millions will be harmed by not having enough food, because a vocal minority of people in rich countries want their meals to be what they consider natural.

As this post and this one make clear, I agree with this point of view wholeheartedly. I'm very glad to see this change of heart, and I hope that Lynas is able to get more people to thinking about this issue. He should be ready for a rough ride, though. . .

Update: well, not quite just this week. Lynas' recent book The God Species, which is referred to in the speech, marks his public break with his former views. He's also recently come to the defense of nuclear power - a view I also support - and this interview gives some of the reactions he's had so far to these turnabouts.

Comments (51) + TrackBacks (0) | Category: Current Events | General Scientific News

December 21, 2012

C&E News Covers the Apocalypse

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Posted by Derek

Hey, it's not midnight yet in Guatemala. Well, OK, it's not C&E News, it's Chemjobber, but it should have been C&E News. . .

Comments (3) + TrackBacks (0) | Category: Current Events

December 5, 2012

Chemical Warfare in Syria?

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Posted by Derek

It's a grim topic, but I see that there are worries that the Syrian government, or what's left of it, is being warned not to use its stockpiles of chemical weapons. Back in the early days of the blog, I did a series on the chemistry of these things, and they can be found by scrolling down to the bottom of this page.

As I said at the time, "I'm prepared to argue that against a competent and prepared opponent, the known chemical weapons are essentially useless. The historical record seems to bear this out. Look at the uses of mustard gas since World War I. Morocco in the 1920s, Ethiopian villages in the 1930s, Yemen in the 1960s - a motley assortment of atrocities against people who couldn't retaliate." The uses of nerve gas are a similarly horrible roll call, mainly (and infamously) in Northern Iraq, by the Saddam Hussein government against its Kurdish population. Let's hope that no one is going to add another entry to that list.

Comments (16) + TrackBacks (0) | Category: Chem/Bio Warfare | Current Events

November 29, 2012

There Go the Lights

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Posted by Derek

An awful lot of people are using an awful lot of bad language in Cambridge, MA right now. At about 4:25 PM (EST), the power flickered and went out in a large swath of East Cambridge, out to somewhere near Harvard Square. That takes out MIT and more technology-based companies than you'd care to count, so everyone is getting the chance to find out how their backup power supplies work (or don't), and how their expensive, finicky equipment takes to having the current lurch around.

I was in my office when things browned down and went out, and it soon became clear that the whole area had gone dark. Public transit was working (when I got on it, anyway), and my commute home is the same as always (for better or worse!), but that won't be the case for people depending on spotty streetlights and the like. Not to mention the various homeward-bound folks who are presumably sitting, none too happily, in elevators right now.

Servers, NMR machines, LC/MS units, -80 degree freezers, lab fridges, automation of all sorts are to be found in heaps in that part of town; it's probably got one of the densest concentrations of such equipment anywhere. Getting it all running again will not be enjoyable.

Comments (32) + TrackBacks (0) | Category: Current Events

November 14, 2012

Budgets and Revenues

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Posted by Derek

Note: politics ahead. This will not be a regular feature around here, but when events warrant, it'll rear its scaly head.

BioCentury has an interesting piece this week on the growing budget impasse and its implications for both academic and industrial biomedical research. It's already widely known that the so-called "Fiscal Cliff", the budget sequestration process that will trigger if no better deal is reached, will perforce come after funding for both the NIH and the FDA. It's always tricky to figure out the impact of such spending cuts, due to the well-known "Washington Monument" tactic. (That refers to the way that if you try to cut the budget for, say, the Park Service, the first thing they'll do is close the Washington Monument. After all, you are having to save money, right? And if you can do it in a way that causes the most outrage and inconvenience, thus increasing the chance that your budget will be restored, well, why wouldn't you?)

So that means that I don't necessarily believe all the predictions for what sequestration would do to any given agency's budget. But there's no doubt that it would have a powerful effect. At the very least, current plans for increased services or expanded programs would immediately go into the freezer, and there would be layoffs and program cancellations on top of that. New NIH grants would surely be hit, and the approval process at the FDA would slow down. Budget sequestration would not mean The End of Science in America, but we'd feel it, all right.

The flip side of budget-cutting is raising revenue. And for that, we can (among many other places) turn back to the deals made with PhRMA when the Affordable Care Act (aka "Obamacare") was passed. Says BioCentury:

Many of the deficit reduction playbooks Congress and the White House will consult include recommendations to suck money out of the pharmaceutical industry. These include a number of proposals that were taken off the table in the PhRMA deal to support the Affordable Care Act.

Near the top of the list: Imposing rebates on drugs purchased under Medicare Part D by so-called “dual-eligibles,” individuals who are eligible for both Medicare and Medicaid.

The Obama administration’s proposed fiscal 2013 budget projected $135 billion in revenues over a decade from dual-eligibles rebates. The idea, which is anathema to PhRMA, was also endorsed by the National Commission on Fiscal Responsibility and Reform chaired by Alan Simpson, a former Republican senator from Wyoming, and Erskine Bowles, President Clinton’s chief of staff.

The White House is also likely to continue to press for reducing the exclusivity period for biologics to seven years from the 12 years established when Congress created a biosimilars pathway in the Affordable Care Act.

Some readers may recall that I predicted something like this. There's a quote from the head of a health-care consulting firm, who says that "Everything that was taken off the table is back", and I can't say that I'm surprised. The twelve-year exclusivity idea had already been on the block to be chopped; I assume that one way or another, it's a goner.

Here's another provision of the Affordable Care Act that could affect the pharma industry. Starting in 2014, health insurance plans will have a defined "minimum level of coverage", which will be determined state-by-state. Late last year, the Department of Health and Human Services said that it plans to require that "essential" will mean one drug in each therapeutic class, with that one drug to be determined by some process I can only imagine. That idea hasn't been popular, with either drug companies or patients, and one might expect to see it altered. But not without a huge amount of wrangling, that's for sure.

Comments (12) + TrackBacks (0) | Category: Business and Markets | Current Events | Regulatory Affairs

November 6, 2012

Time For An Election Post

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Posted by Derek

Well, every other web site in the US will be going on about the election today, and with good reason. So I'll put up a quick post of my own, because I'll be glued to the returns tonight myself. Along the way, I've been teaching my children how to interpret them, which makes them, I'd say, among the few local middle-schoolers who know that Florida has two different poll closing time (the panhandle's on CST), to wait for Pennsylvania because Philadelphia's ballots always seem to drag in last, and that on a country-by-county basis, Ohio looks like something that Dr. Frankenstein assembled on his day off. My father was an election commissioner when I was growing up back in Arkansas, and it left a mark. I've found, though, that a background in the Arkansas politics of that era has served me well, not least in making me difficult to shock when it comes to the behavior of politicians during (and after) elections.

So what do I think is going to happen? Well, I'm used to seeing raw biological assay data, so when I see people giving probabilities of political victory with figures to the right of the decimal place, I just smile. All I'll say is that I think it's going to be a close call for whoever wins, and that anyone (on either side) who's confident it won't be needs to get out more. Were I a betting man (perish the thought), I'd put some money down on a Romney upset, because I think you could get some good odds, thanks to Nate Silver. But we'll see - tonight, or in the morning, or (God help us all) even later than that.

Comments (54) + TrackBacks (0) | Category: Current Events

November 1, 2012

Lab Animals Wiped Out in Hurricane Sandy

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Posted by Derek

When I mentioned the people working in the research animal facilities before Hurricane Sandy, I had no idea that this was going to happen: thousands of genetically engineered and/or specially bred rodents were lost from an NYU facility due to flooding. The Fishell lab appears to have lost its entire stock of 2,500 mice, representing 10 years of work. Very bad news indeed for the people whose careers were depending on these.

Comments (34) + TrackBacks (0) | Category: Animal Testing | Current Events

October 9, 2012

Way Too Much Hydrofluoric Acid

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Posted by Derek

Eight tons of hydrofluoric acid released? This industrial accident in South Korea sounds horrific. I'm surprised that only 3,000 people were injured, given the population density there. And declaring it a "special disaster zone" seems appropriate, because believe me, that's a special disaster.

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September 25, 2012

A Russian Chemist in Jail

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Posted by Derek

There's a bizarre case in Russia involving chemist Olga Zelenina:

Zelenina heads a laboratory at the Penza Agricultural Institute, some 600 kilometres southeast of Moscow, one of the best-equipped chemical-analysis labs in Russia. She is a specialist in the biology of hemp and poppy, and is a sought-after expert in legal cases involving narcotics produced from these plants.

In September 2011, the defence attorneys of Sergey Shilov, a Russian businessman under investigation by the Russian Federal Drug Control Service (FDCS), asked her to provide an expert opinion on the amount of opiates that could possibly be extracted from 42 metric tonnes of food poppy seeds that Shilov had imported from Spain in 2010. . .

. . .On the basis of gas-chromatography and mass-spectrometry measurements of samples analysed in her lab, Zelenina calculated the overall morphine and codeine content in the poppy-seed consignment in question to be 0.00069% and 0.00049%, respectively. In such low concentrations, opiates can only be identified or extracted in well-equipped analytical chemistry labs, she wrote.

“This opinion apparently failed to satisfy the prosecutors,” says Irina Levontina, a linguist at the Russian Language Institute in Moscow, who is frequently heard as an expert in libel and drug lawsuits. “It has become quite common for Russian prosecutors to accuse independent experts if they don’t like their opinions. It can be downright dangerous for experts to appear in court.”

Apparently so. She was arrested in August, for allegedly assisting drug trafficking, and ordered held until October 15, awaiting a still-unspecified trial date. C&E News reports that scientists in Moscow and elsewhere are signing petitions for her release and showing support for her in court hearings. But if the Russian government doesn't like you, what can avail? Perhaps bad publicity can help?

Update:Zelenina has been released from custody, pending her trial. It's a start, but she's still facing all sorts of penalties if convicted.

Comments (17) + TrackBacks (0) | Category: Current Events

June 28, 2012

PhRMA Waits For The Supreme Court

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Posted by Derek

There's no escaping politics and health care policy today. No matter what happens to the Affordable Care Act this morning (and no matter what you think of it either way), if you work in the drug industry, it's worth recalling that PhRMA (the big-company industry association) was very much in favor of the legislation. At least as it was finally passed, that is - there was a lot of quid-pro-quo-ing about drug reimportation and Medicare pricing, and agreement on those appears to have been PhRMA's price for supporting the bill. It was a deal that many objected to at the time, and in one of the few other times I've talked politics on this blog, I wondered if it was going to hold up even at that.

We know more of these details because of a set of e-mails and internal memos that show the group's agreement to advertise in favor of its passage, and to help senators and representatives who voted for it:

“As part of our agreement, PhRMA needs to undertake a very significant public campaign in order to support policies of mutual interest to the industry and the Administration,” according to a July 14, 2009, memo from the Pharmaceutical Research and Manufacturers of America. “We have included a significant amount for advertising to express appreciation for lawmakers’ positions on health care reform issues.”

The goal, the memo said, was to “create momentum for consensus health care reform, help it pass, and then acknowledge those senators and representatives who were instrumental in making it happen and who must remain vigilant during implementation.”

One of the vehicles for this was a coalition (involving PhRMA, the AMA, and others) called "Healthy Economy Now" (HEN), which appears to have been started by White House staffers. None of that is surprising or particularly unusual, but an unusual twist involves the White House's David Axelrod and his former advertising company AKPD. The company was still paying Axelrod at the time, and his son was working there, and it appears that they got a good part of the advertising business that PhRMA and the other funded:

A 2009 PhRMA memo also makes clear that AKPD had been chosen before PhRMA joined HEN. It's also clear that some contributors didn't like the conflict of interest. When, in July 2009, a media outlet prepared to report AKPD's hiring, a PhRMA participant said: "This is a big problem." Mr. Baldick advises: "just say, AKPD is not working for PhRMA." AKPD and another firm, GMMB, would handle $12 million in ad business from HEN and work for a successor 501(c)4.

Well, that's Washington, and no mistake. If you don't sit down at the table and cut a deal with these folks, this sort of thing happens to you. But no matter which way the Supreme Court goes this morning, or what parts of the bill might be struck down, it will affect the drug industry. From PhRMA's standpoint, the current legislation represents the fruits of a great deal of lobbying and arm-twisting (in both directions), a great deal of money, and a great deal of worry about future revenues. This work may be in danger of going partially or wholly for naught. We'll find out at 10 AM.

Comments (6) + TrackBacks (0) | Category: Current Events

April 3, 2012

Information Density

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Posted by Derek

This is a small thing, but nonetheless irritating, at least to me. Can anyone explain why some of the pharma-and-tech news sites (such as Xconomy and FiercePharma) have been redesigning their sites with lots of great, big, headline fonts set in plenty of roomy white space? First it was Gmail going to "you-don't-need-all-that" mode, which makes me wonder if this is some sort of foul trend. I may be an oddball, but I like information-dense pages, at least in a news site. All these newer versions look like the low-calorie versions, a bit of colorful stuff dabbed onto an oversized white plate. OK, /grumble for now. . .

Comments (24) + TrackBacks (0) | Category: Current Events

January 26, 2012

Science, A Zero-Sum World, and the State of the Union

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Posted by Derek

I always regret it when politics creeps into this blog. But I just finished reading this post over at The Economist's "Free Exchange" glog, and I can't resist linking to it. The author focuses on a few lines from the President's State of the Union speech, and gets rather agitated:

Later, the president added: "Don’t let other countries win the race for the future."

The context, innocuously enough, was in calling for greater support for American research and development efforts. But the language of this statement is either daft or ghastly, depending on how charitably one is willing to read it. Is Mr Obama so dense as to miss that when America invents things other countries benefit, and vice versa? If a German discovers a cure for cancer, shouldn't we be ecstatic about that, rather than angry? Indeed, shouldn't we be quite happy and interested in ensuring that Germans and Britons and Indians have the capability and opportunity to develop fantastic new technologies? In the more nefarious reading, Mr Obama seems to accept that only relative standing really matters. A sick, poor world in which America always triumphs is preferable in all cases to one in which America maybe doesn't "win" the race to discover every last little thing that's out there to be discovered. And hell, one has to ask again whether the easiest way to prevent other countries from winning the race for the future isn't simply to blow up their labs.

Look, I understand the forgiving interpretation of these remarks. Americans are motivated by competition and patriotism, and if that's the only way to rally the country behind fundamentally sound policies like subsidies for basic research, then that's the card you play. And, in practice, Mr Obama's reforms will probably not do much more than offset the crummy, mercantilist choices made by other governments elsewhere. . .

I don't see that that's an acceptable excuse. People who live outside of America are people just like Americans, and we should all rejoice in their rising prosperity, the more so when it occurs through additions to the stock of human knowledge that will benefit people everywhere. If an American president can't communicate that simple idea to his citizenry, out of fear that he'll be drummed out of office on a wave of nationalistic outrage, then he doesn't deserve to be president and his country doesn't deserve to win a damned thing. . .

I'm very far from a zero-sum person, myself. The world really has gotten wealthier, and if we have disagreements about how that wealth is distributed, fine - as long as we first realize that we're sharing a much, much, larger pile of it than we used to. Much of that wealth has come from human ingenuity, from science and technology, and on those days when I can get my experiments to work, I like to imagine that I'm adding a bit to the pile.

And yes, I think that this was just speechmaking. But if it reflects, as it might, "permanent tendencies of heart and mind", then I have to say, I don't much like it.

Back to science after this. No more politics until November, I hope, and maybe not even then.

Comments (33) + TrackBacks (0) | Category: Current Events

December 15, 2011

More on Chinese Pharma Espionage

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Posted by Derek

Well, a lot of comments have come in about the last post on Chinese industrial espionage - some temperate, some not. I wanted to fill out another post responding to some of these, so, in no particular order:

1. "Everyone does this all the time". Indeed. Espionage is a constant fact of international relations; the "gentlemen do not read each other's mail" comment was wildly out of sync with reality even in its own time. I don't mean to suggest that I'm shocked by the fact of Chinese intelligence-gathering, although its scope and thoroughness is impressive. But I think that everyone should be aware that it goes on - and that pointing out that it's going on is also a move in the same game. We're not hearing so much about this from the US government now for no reason; someone thinks that there's an advantage in making these accusations public in such detail.

2. "More to the point, the US does this too, and thus has no room to talk". This is merely a tu quoque argument, and as such doesn't address any underlying issues. Of course the US engages in espionage, and I hope that we're good at it. But for the most part, we're doing it for a different purpose than some of the Chinese activity that's been revealed. I tend to think that more of ours is national-security related, and less pure economics - more "How can we figure out what these guys are up to?" and less "How can we jump-start our aerospace industry?"

Now, one big reason for that is that the US is not as far behind anyone else in the world as China feels itself to be behind in some key industries. They have more to gain. I'm sure that China does plenty of national-security spying, but for a country whose economy is as export-driven as China's, economic reasons and national security reasons are even more tangled together than usual. And yes, other countries have done just this sort of thing in the past. See the story of how the British got rubber-tree seeds to plant in Malaysia. Or earlier, how they learned the details of tea production and got that going in India, and that's not even mentioning their strategy of smoothing out the trade imbalance with opium sales. We shouldn't allow ourselves, though, to think that this stuff is just for the history books.

3. "OK then, what's more, the US did just this kind of economic/industrial snooping back when it was an up-and-coming nation".. This is another tu quoque, but the facts are as stated. In the 19th century, the US was generally a backwater compared to the European powers, and we did indeed have a reputation as the Kings of Shoddy Unauthorized Knockoffs (even of our own inventions). Charles Dickens was enraged when he visited to find how many pirated versions of his works were for sale, and this tradition took a long time to die out. (See, for example, the saga of how Donald Wollheim unilaterally decided in the 1960s that Tolkein's publishers had not properly secured the US copyright for The Lord of the Rings).

But while we were at our peak as intellectual property buccaneers, we were not simultaneously considered both a world power and a huge financial market. China is not to the rest of the world as the US of the 1850s was. Our big exports were agricultural products; we did not have huge factories on which many of the world's largest corporations were depending. China, in catch-up mode though it may be, is not a technological backwater. It has nuclear weapons and a manned space program - mind you, both of those were developed partly through just the sort of short-cutting we're talking about.

4. OK, that means that every Chinese post-doc is a spy. Or a potential spy, right? Here's where I flip over to the other side. Now, there surely has been intelligence gathering by such routes. But it appears that a lot of work is being done from back home, by large groups associated with the People's Liberation Army and various Chinese intelligence agencies. And when you consider what a lot of postdocs end up working on, you can see that most of it isn't going to confer much of an advantage on anyone - what are they going to do, steal K. C. Nicolau's strategy for an 89-step synthesis? I think it would be a lot more useful for US institutions to spend their time hardening their security against wholesale data-scooping than giving their foreign postdocs the fish-eye. Most of them are just trying to make better lives for themselves.

So where does this leave us? I think that China's position is unique. They're an enormous country of huge economic and political importance. And their economy is a mixture that might be called "authoritarian capitalist", no matter what they call it themselves. So for a country like the US, they're simultaneously a vital trading partner, and a potential political adversary and rival. (And the US is the same thing to China, naturally). It's a tricky balance, and there are a lot of conflicts of interest.

We're seeing one in the drug industry. No major company can afford to ignore the Chinese market. The financial advantages of pharma outsourcing have been hard to ignore, too (leaving aside the question of its effectiveness, which varies). But no company can afford to ignore the possibility that Chinese industry (or the Chinese government itself) might rip them off. These things exist simultaneously, and it's very much worth the effort keeping both of them in mind.

Comments (57) + TrackBacks (0) | Category: Business and Markets | Current Events | The Dark Side

October 21, 2011

The Force of Cluelessness

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Posted by Derek

I would like to heartily recommend the policy outlined in this post: that anyone advocating some political, economic, or social proposal should first be required to write a short essay explaining what the hell it is, and thus demonstrating that they have some minimal idea of what they're talking about. We will never see such a thing in this world, but a man can dream.

In an open forum, there is generally a good correlation between the passion with which some idea is advanced and the ignorance of the person advocating it. The comments section of any blog - this one not excepted - will demonstrate this to anyone with doubts. (That's also why I support this worthwhile initiative), one of many proposed by its parent web site. Yeats had it right: "The best lack all conviction, while the worst / Are full of passionate intensity."

And so it has always been. In the purview of this blog, for example, no one in my experience ever offers the tentative conclusion that the drug companies might possibly be an evil conspiracy to poison the public. No, that view is delivered with powerful conviction, accompanied by an equally strong belief that anyone who thinks differently is either a moron or a bought-and-paid-for tool.

Correcting for ignorance, were it possible, would change the world. I recall this insight hitting me with some force about 25 years ago. I was watching TV coverage of the House debating a bill that would have provided aid to the Nicaraguan contras. A graphic came up on the screen of a public opinion poll on the issue - this many people thought we should give them money, this many didn't. But then a follow-up question was shown, where they asked the same sample who these contras were. And an alarming number of people answered either "don't know" or thought that they were part of the Nicaraguan government forces, which made me realize that no weight whatsoever should have been given to the answers to that earlier question. If you don't know who the contras are, in other words, why should anyone care what you think should be done about them?

Allow me to wander off topic a bit - anyone who wants can bail out at this point; the rest of this post will be idle political speculation. OK, that line of thought leads one to several interesting conclusions about voting. I've long thought very much like this. I think that strenuous efforts to get people to vote are misguided - if someone is not motivated enough to get out and vote in an election, then society is better off if they do, in fact, stay home. And I'm not advocated some sort of closed-off elite; the doors are always wide open. There are thousands upon thousands of ways for someone to become more informed about any issue or any candidate, and if a person does not avail themselves of any of them, they have (in my view) disqualified themselves from voting.

That, though, leads us back to Yeats and that passionate intensity problem. Doesn't this mean that a lot of strongly motivated voters will, in fact, be ignorant? My solution to that, which I've been advocating since I was about seventeen, is for all voting booths to have two doors. The inner one can be the usual curtain. The outer one, though, presents the prospective voter with a few questions on general political and social knowledge, randomly selected from a larger pool. How often is your state's governor elected - every two years, every four, every six? Which of these names is the name of your state's other senator, the one who's not up for re-election this time? Who writes budget bills, the House or the Senate? That sort of thing. But if you can't get a majority of these high-school-civics questions right, the outer door does not open, and you must go home. When I'm in a bad mood, I toy with the idea of rigging up some sort of trap door system as well, but that's harder to implement.

Oh, I'm just full of improving ideas. I'd also like to see "None of the above" be an option on all ballots. What if NOTA wins? Well, new election in sixty days, and none of the previous candidates can run. It's been pointed out to me that had this system actually been in force that we might be behind by several presidential elections by this point, but I'm still not convinced if that's a bug or a feature. And another reform that's often occurred to me would probably only be possible in a much smaller country than the US. I could imagine, though, getting everyone in such a state together and asking which of them really, really wanted to be President. Whoever raises their hand is disqualified. There really should be some way to weed out candidates whose life's burning ambition is to Be In Charge. I'm reading The Twelve Caesars by Suetonius and Gibbon's Decline and Fall these days, and you can't help but think that the Roman Empire ran things the exact opposite way: the people who climbed to the top were the ones who were willing to make it the organizing principle of their entire lives. The same goes for any autocracy.

And in fact, just to drag things back by force to the usual topics of this site, it often goes for large companies. Recall this stuff - Tiberius would have nodded and smiled. And you didn't want to see what made him smile.

Comments (68) + TrackBacks (0) | Category: Current Events

May 2, 2011

A Brief Note on Current Events

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Posted by Derek

John Donne's observation does not, it seems, hold for every case. I don't feel particularly diminished at all.

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March 21, 2011

A Radiation Chart to Clip and Save

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Posted by Derek

If any of you haven't seen it, here's a fine radiation-dose graphic from xkcd to help keep your Sieverts straight. And yes, it does have the banana-equivalent dose.

Comments (7) + TrackBacks (0) | Category: Current Events

March 16, 2011

Potassium Iodide Pills

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Posted by Derek

Well, the nuclear crisis in Japan seems to be causing a run on potassium iodide (KI), and not just in Japan. If news reports are to be believed, people in many other regions (such as the west coast of the US and Canada) are stocking up, and some of these people may have already started dosing themselves.

Don't do that. Don't do it, for several reasons. First, as the chemists and biologists in this site's readership can tell you, it's not like KI is some sort of broad-spectrum anti-radiation pill. It can protect people against the effects of radioactive iodine-131, which is a major fission product from uranium. It does that by basically swamping out the radioactive iodine a person might have been exposed to, keeping it from being taken up into the body. Iodine tends to localize in the thyroid gland, and that uptake and local concentration is the real problem. An unfolded newspaper will shield you just fine from the alpha particles that I-131 gives off, but not if it's giving them off from inside your thyroid. Correction: I-131 is a beta/gamma emitter - my apologies! The point about not wanting it in your thyroid, of course, stands. . .

And this is why potassium iodide won't do a thing to help with the other radioactive isotopes found in nuclear reactors. That includes both the uranium and/or plutonium fuel, as well as the fission products like strontium-90 and radioactive cesium. Strontium-90 is a real problem, since it tends to concentrate in the bones (and teeth), and it has a much longer half-life than I-131. Unfortunately, calcium is so ubiquitous in the body that it's not feasible to do that uptake-blocking trick the way you can with iodide. The only effective way to deal with strontium-90 is to not get exposed to it.

Another good reason not to take KI pills is that unless you're actually being exposed to radioactive iodine, it's not going to do any good at all, and can actually do you harm. Pregnant women and people with thyroid problems, especially, should not go around gulping potassium iodide. Nothing radioactive is reaching North America yet - there's the Pacific Ocean to dilute things out along the way - which makes it very likely that more people on this side are in the process of injuring themselves by taking large unnecessary doses of iodide. This is like watching people swerve their cars off the road into the trees because they've heard that there's an accident fifty miles ahead.

Now, if I were in Japan and downwind of the Fukushima reactors, I would indeed be taking potassium iodide pills, and doing so while getting the hell out of the area. (That last part, when feasible, is the absolute best protection against radioactive exposure). But here in North America, we're already the hell out of the area. The only time to take KI pills is when a plume of radioactive iodine is on the way, and that's not the case over here. We'll have plenty of notice if anything like that happens, believe me - any event that dumps enough radioactivity to make it to California will be very noticeable indeed. Let's hope we don't see anything of the kind - and in the meantime, spare a thought for those reactor technicians who are trying to keep such things from happening. Those people, I hope, will eventually have statues raised to them.

Comments (42) + TrackBacks (0) | Category: Current Events | Toxicology

March 15, 2011

Quick Japan Update

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Posted by Derek

Just a quick note that the Japanese chemist I mentioned a couple of days ago, my old colleague Masanori Yamaura, has reported in. He and his family made it through the quake (he reports that his labs are pretty well trashed, though), and they're now evacuating Iwaki City due to the nuclear plant problems up the coast. A bit of good news, at a time when there isn't a whole bunch of it around.

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Bias And How to Deal With It

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Posted by Derek

The coverage of the Japanese reactor situation reminds me of the coverage of many other technical issues when they overlap with serious breaking news stories. I wrote a little on this subject a few years ago, talking about the Merck/Vioxx business, but I wanted to expand on it.

I'm not going to rant on about the popular press not understanding this or that scientific or technical issue. There are more systemic problems with the way that news is reported, and in the way that we take it in. I'm not sure of what to do about them other than to be aware of them, but that's an important step right there.

The first of these is narrative bias. Reporters like to relay stories (and the rest of us like to hear stories) that have a progression. They have a beginning, a middle, and an end, the way our most popular novels and movies do. Something starts, something happens, something ends. Real life sometimes conforms to this template, but sometimes it doesn't. For example, some situations don't start, so much as they suddenly get noticed after they've been there all along. And some don't end, so much as they just stop having attention paid to them.

Another narrative-bias problem is the tendency to assign participants in any event to recognizable categories: good guys and bad guys, for starters. Moving to finer distinctions, there's Plucky Young X, Suffering Y, Salt-of-the-Earth Z, along with Untrustworthy Spokesman A, Obfuscating B, Crusading C, and the whole crowd. Mentally, we tend to assign people to such categories, especially if we don't know them personally, and it makes it easier for reporters, too. It's a team effort. The problem is, of course, that not everyone fits into a recognizable category, and many others overlap in ways that a simple narrative structure won't accommodate. Most real people are capable (more or less simultaneously) of great and venal actions, of heroism and cowardice, of altuism and selfishness.

Even when events are progressing in some sort of recognizable way, they're seldom doing that at the tempo that we'd like. This is the problem of temporal bias. They're especially unlikely to do that at the tempo that various news organizations would like. A cable news network would like to have something new to report every fifteen or twenty minutes; a newspaper would like something every day. But events happen when they happen, which means that in the absence of anything new to report or talk about, a tremendous amount of wind is generated to make it appear as if something is actually going on.

Our sense of history reinforces this bias. We compress and even out timelines. Look, say, at the start of World War II. Yep, Hitler invades Poland. Then he invades France. Dunkirk, Rotterdam, Battle of Britain, here we go. But there was a big gap in there, the so-called "Phoney War", where nothing much happened (at least, not compared to the way things started happening afterwards). We sort of edit that out, mentally, but it was a long period to the people living it at the time. A 24-hour news outlet would have had a rough time of it.

As an aside, a large, complex, and relatively well-documented event such as the Second World War (and the common knowledge that people have about it) furnishes all sorts of illustrations of the various forms of cognitive bias. Not so many people these days, unless they're history buffs, are aware of lacunae such as the Phoney War, out-of-the-spotlight actions such as the Battle of Madagascar, roads-not-taken such as the shipload of mustard gas that sank at Bari, or tragic mistakes such as the Cap Arcona incident. These and many other parts of the record have been sanded down or paved over, not by any conspiracy, but by natural human tendencies.

I find, getting back to the Japanese situation, that I'm getting more useful information from blogs and even the Wikipedia pages on the Fukushima incidents than I'm getting from primary news sources. Those tend to have jumbled timelines, unclear sourcing, and all sorts of overlap and garble. Reading the efforts of various other people who are trying to make sense of it all (and checking them against each other) is so far providing me with more useful information. My television is turned off.

Comments (31) + TrackBacks (0) | Category: Current Events

March 14, 2011

Japan

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Posted by Derek

Like everyone else, I spent the weekend following the events in Japan. A great many organic chemists have or have had Japanese colleagues; it's a field with a strong history in that country. I've heard from several people, but one of my former colleagues is still in the "unknown" category: Masanori Yamaura, of Iwaki Meisei University.

Iwaki, unfortunately, was hit pretty hard, and it's not that far away from the Fukushima reactor complex. So things are pretty chaotic up there, to say the least, and I'm sure that a great many people in the area remain unaccounted for.

As far as the reactors go, from what can be figured out at this distance it doesn't look like they're going to do anything Chernobylish - seawater and boric acid should forestall that. But the only reason you'd pump that mix into your reactor cores is if a meltdown is the only alternative; that's surely going to turn them into nothing but massive cleanup sites for many years to come. It's also going to take a mighty amount of generating capacity offline for good, which is another long-term problem. But for the moment, when the good news is that your primary containment vessels are still intact, then you know that you have a pretty full schedule.

I've often thought that if intelligent aliens looked over the planet's population centers, they'd ask us what the heck we thought we were doing when we developed Japan, coastal California, and a number of other areas. But here we are.

Update: many of you may have seen this link already. It's a clear-headed explanation of what seems to be going on (and going wrong) inside the Japanese reactors, with links to other useful sites. By the way, I agree with the comments that one of the other long-lasting bad effects of this crisis is the damage it will do to the idea of using nuclear power.

Comments (40) + TrackBacks (0) | Category: Current Events

February 22, 2011

Science and Revolution

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Posted by Derek

GIven everything that's happening across North Africa and the Middle East, I thought a quick geopolitical note might be in order. This is very far from being a world politics blog, but there is a connection to science.

Specifically, it's been notable for some time how under-performing these regions of the world are, scientifically. I last wrote about this topic here, with a link to this map. That's ten-year-old data, but the main changes would be shifts among the bigger players. From roughly the western border of India over to the Atlantic ocean, things haven't changed much - the only country in that swath that's made a serious R&D mark is Israel.

In some cases, that's perfectly understandable. No one expects a country at Afghanistan's level of development to have much of a research culture; they've got plenty of other priorities. But you hit some pretty gaudy GDP/per capita numbers when you cross the oil-rich regions, and that money has not been plowed into science and technology. That's in spite of the funding that Saudi Arabia, for one, has thrown into various King-This and Prince-That institutions. Maybe they're going for more applied training - I absolutely cannot recall seeing any notable research result out of the Saudi system. Examples welcomed in the comments, if there are any. And the other oil-rich states are even further out in the wilderness, scientifically. The UAE? Kuwait? You'd have to do some real digging to find much of anything, as far as I can tell. Science, research, and invention have just not been priorities for these places, and changing that isn't easy.

Then you hit countries like Egypt, which are in the broad and sad category of "countries that really should be doing better than they are". I'd put Iran on that list, too. Scientifically, nations in this category have some infrastructure, but it's usually not enough to produce anything noteworthy. Their expatriate scientists and engineers, though, have flourished. There's clearly a lot of talent going to waste inside these places. Algeria and Morocco, too? They don't look so bad, though, when opposed to the next category, the Syrias and Libyas of the world. There's some GDP in these places (although nowhere near as much as there could be), but scientifically, they're absolutely off the map.

So now we get to asking why this should be so. Some of it can be put down to development, as mentioned above, but even the countries in this region that are better developed still aren't making much of a mark. I realize that I may be coming across as culturally insensitive here, because I'm assuming that R&D is the sort of thing that any society with enough money and talent would choose to do. But I'm willing to defend that assumption. I think that these activities really are a key part of a modern economy, and provide a productive outlet for a lot of brainpower. Instead, we have countries that are too poor to even think about these things (Afghanistan), too occupied in keeping the boot pressed down (Syria), several that have decided to sit back and enjoy their money (the oil sheikdoms), and a few that would like to do this sort of thing but aren't getting so much out of their efforts, like Iran.

And that brings us to the volatile topic of religion. Most of the region we're talking about is Islamic, of course. And while it led the world for a good while in mathematics, astronomy, and other sciences, it's also been clear for a long time that it later adopted a different attitude towards homegrown advancements in science and engineering. And this could well have something to do with the religious character of society. The pursuit of secular knowledge can, in some religious environments, seem like at best a distraction from more important matters, and at worst an active source of evil and discord. The present-day countries have all sorts of varying amounts and styles of religious observance, but this is always going to be a factor to consider.

And now we have revolutions ongoing in a lot of these places, and you have to assume that there are more to come - if not right now, then eventually. My own interest in Iran leads me to think, for example, that the lid is going to come off there at some point - and the longer the wait is, the worse the boilover will be. The question that everyone has, though, is what will replace the former regimes, once the lids have blown off? I would like, naturally, to see an Egyptian Republic (for example) that has a chance to get its act together. But that's not going to be easy, to put it very mildly. There are a lot of problems to solve, and a shortage of people who've had to opportunity to try solving them under the former regime of the Big Boss Leader. I fear that the most likely result is the advent of a new boss - who may be wearing a uniform, or robes, or even a nice suit, but who has the same ideas in mind as the last guy. I very much hope I'm wrong about that. Doors are opening; let's hope that many of them don't just slam shut again.

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February 17, 2011

Health Care Reform and the Drug Industry: How Goes It?

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Posted by Derek

We haven't had enough controversy and arguing around here this week, have we? Let's talk politics for the morning, then. Here's a piece from a former VP for public affairs at Pfizer, arguing that PhRMA got thoroughly snookered during the health care reform bill. He's looking over the current budget proposal:

For biotech and pharmaceutical companies, the president’s budget repudiates one of the most important benefits of their “deal” with the White House: the ability to market biotech drugs without generic competition for twelve years. The president would reduce that period to seven years, precisely the position of the generics industry and a position that the pharmaceutical industry had fought aggressively before it decided to make a deal with the president.

I worried about this sort of thing at the time, in the last post in which I had the nerve to bring up this issue. (In fact, if you go back and read some of the dissenting comments to that post, the twelve-year exclusivity provision was listed as one of the main reasons the bill was a good idea for the industry). Even I didn't think my last paragraph would start coming true quite this quickly, though. (I'll note in passing that my worries about the "doc fix" were justified, too). And yes, it's true that the President's budget proposal is a political football, put onto this earth to be kicked around by all parties, and that nothing in it will necessarily turn into reality. But still - isn't that a rather short time to be about-facing on this provision? Less than a year?

There's an alternate explanation: that the twelve-year provision was never really in there at all. We just thought it was! No, that wasn't marketing exclusivity at all, but data exclusivity. Or not - was it a mix of the two? What sort of mix? All sorts of people are writing to the FDA these days, telling them what they think the law actually means. Not that the agency is legally bound to listen to a word of it.

Even without any backtracking on exclusivity, the article maintains that health care reform was a loser for the drug industry. The author goes on on to detail the various other costs of the bill as it was passed, and then gets to the biggest structural problem:

While the healthy part of the pharmaceutical market will be pounded, the government-run segment of the market, Medicaid, will be expanded by 16 million patients. Medicaid has the worst pricing structure and the worst track record in paying for innovations of any sector in the United States market. Like government health-care systems around the world, Medicaid must be dragged to pay for medical advances. Unlike employers and seniors in Part D, Medicaid patients cannot vote with their feet if their health plan does not provide the new medicines they want. The incentives in Medicaid all run against paying for pharmaceutical innovations.

So, Obamacare significantly expands the worst sectors of the pharmaceutical market while degrading the best.

Well, fine, you may say, this are quotes from an opinion piece at National Review, and what else would you expect but that they're opposed to the bill over there? But these issues would be worth thinking about even if they were squawked out by flocks of crows. I really do worry that the drug industry made a serious mistake by agreeing to the health care reform bill - not only agreeing to it, mind you, but committing large amounts of money to beating the drum for it and seeing that it got passed. And that means that PhRMA made a serious mistake by putting Billy Tauzin in charge of that effort. Perhaps a backslapping deal-maker wasn't what was needed?

Okay, that gets politics out of my system for a bit. The whole health care reform bill is going to end up in the Supreme Court anyway, on commerce-clause grounds, so arguing about specific language may turn out to be a waste of time. But while I'm in the mood, though, I'll close with (what else?) a quote from Barry Goldwater. A government that's big enough to give you everything you want, he used to say, is big enough to take it all away. . .

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January 28, 2011

And a Quick Political Note

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Posted by Derek

One of the authors (Mostafa Fekry) of the paper mentioned in my last post is at Cairo University. Which means that things must be rather uncertain for him right now, as it is for everyone in Egypt.

Readers will recall the mentions here of the 2009 unrest in Iran (behind-the-scenes note: my wife is Iranian), and this seems to have moved rapidly to an even more extreme stage. I have to say, I don't mind seeing autocrats and dictators (and their security forces) chased through the streets. I do wonder, though, what might replace them (which speculation seems to be helping tank the stock market today). Let's hope for the best.

I advised readers during the most recent Iran unrest (there will be more, I'm sure) to pitch in by helping to run Tor relays. This time, though, since the Egyptian government seems to have pulled the internet plug completely out of the wall, in what must (economically and socially) be a shower of plaster fragments, that may not do as much good. But events are young.

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October 27, 2010

Lethal Injection: A Case For the FDA?

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Posted by Derek

I had trouble believing this headine today, but it's a real one. A convicted murderer was set to be executed in Arizona, but there's apparently been a shortage of sodium thiopental, which (I have to say) I didn't know was the preferred drug for this use. The Arizona authorities imported some from Great Britain, whereupon the convicted man's lawyers got a stay of execution, on the grounds that this particular material had not been FDA-approved.

Well, that's a new one. The idea that a drug being used to kill someone has to be properly evaluated for safety and efficacy is not one that would have occurred to me, but then, I'm not a lawyer. Thiopental, I should add, is not exactly an experimental drug. It's a short-acting barbituate that's been around forever as an anaesthetic. It has one supplier in the US, but can be sourced, no doubt, from many others around the world. And thus this Arizona case. I notice that many of the news stories refer to use of a "non-approved drug", but that should be more properly stated as a non-approved supplier of a drug that's been around forever, and (moreover) used a great number of times in executions and euthanasia.

This argument held things up, briefly, but the Supreme Court last night tossed that one out 5 to 4, and the prisoner involved (I've no desire to use his name) was executed. Readers from countries without the death penalty may well find this whole situation grotesque - well, you can be sure that many people inside the US do as well. My biggest problem, though, is that the prisoner involved committed his crime in 1989 and is only now paying this price for it.

Update: Here's the Supreme Court order in this case (PDF). The interesting passages:

. . .There is no evidence in the record to suggest that the drug obtained from a foreign source is unsafe. The district court granted the restraining order because it was left to speculate as to the risk of harm. . .But speculation cannot substitute for evidence that the use of the drug is “‘sure or very likely to cause serious illness and needless suffering.’” . . .There was no showing that the drug was unlawfully obtained, nor was there an offer of proof to that effect.

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May 24, 2010

Martin Gardner, RIP

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Posted by Derek

I note with sadness that Martin Gardner died this weekend at the age of 95.. Many will know him from his longtime "Mathematical Games" column in Scientific American (where I first encountered him while I was growing up in the 1970s). In recent years, he devoted a lot of time to speaking up for skeptical causes and against all sorts of quackery, a cause I respect very much (although I sometimes wonder how much good it does).

A good overview of his work is found in The Night Is Large: Collected Essays, 1938-1995, and there are many, many other collections of his work out there. He'll be missed.

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May 20, 2010

Floyd Landis: The Isotopes Weren't Lying, After All

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Posted by Derek

This post from 2006 on the science behind Floyd Landis's suspicious steroid blood tests set my blog record for comments - the debate went on and on about Landis, about the lab that reported the results, about how the samples were handled, etc.

Well, Landis has now admitted using performance-enhancing drugs for most of his career. Widely, expensively, and thoroughly did he use them. The blood test was correct. Carbon isotopes don't lie.

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April 26, 2010

Report from C&E News

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Posted by Derek

Well, the first thing I can tell everyone is that I think the entire editorial staff at Chemical and Engineering News read every comment to this post. And that includes the nasty ones, for sure. The readership around here is a self-selected lot, and the commentors even more so, but the quick volume of responses got a lot of attention.

I noticed a lot of discussion around the "Do we really need more chemists?" theme. Readers will be interested to know that many people at the magazine share their uneasiness with some of the never-ending "scientist shortage" talk. The ACS's own figures (which many here seem to feel are too low) nevertheless show the highest unemployment rates among chemists they've ever shown.

Outside of the issues that came up here on the site, one of the things I suggested was more focus on smaller companies - both in terms of plain science/business news, but also with reference to where they come from. My point was that chemists reading C&E News see all sorts of items about various companies, but it's as if they've condensed out of the air. If there really is any sort of economic recovery coming on, I think that one of the best chances to lower our profession's jobless rate is through startup formation, and I told the people at the magazine that they should keep this in mind.

I wasn't in the discussion groups that touched on another theme that came up here in the comments, the long-running "Women in Chemistry" articles. And it's probably a good thing - I tend to be pretty much an eye-roller when it comes to corporate diversity programs, but I get the feeling that no one at the ACS (or its publications) feels safe doing so much as that, even if they were so inclined. For the record, I have no problem at all, of course, with women in chemistry, or anyone else in chemistry - it's just the let's-all-join-hands march-of-progress stuff that can get tedious. The people whose march through the ranks I most want to promote are the people who are good at it, whoever that might turn out to be.

One thing I found interesting is that the writers, although almost all of them have chemistry training, seem to feel apart from the actual business of chemistry. That's understandable, I suppose, because their profession is really journalism. I told them that not being a journalist made writing a blog a lot easier. . .

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April 20, 2010

Bits And Pieces

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Posted by Derek

Still traveling, so not much time to update things. Here are a couple of interesting links, though:

Adam Feuerstein's take on the Rexahn clinical data (which I spoke about here). He's not all that impressed, either, to put it delicately.

Big Pharma bonds getting downgraded - orrg. Smaller companies tend to raise more money with equity, but debt financing gets more and more important as time goes on, so this isn't a good sign.

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March 22, 2010

Sir James Black, 1924-2010

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Posted by Derek

One of the giants of medicinal chemistry has died today at the age of 85 - Sir James Black, who pioneered beta-adrenoceptor antagonists and many other areas in drug discovery. Keep in mind that earlier in his career, many people thought of the concept of a "receptor" as an abstract placeholder, not necessarily something with any physical meaning. We've come a long way since then, and his work is one of the big reasons why.

He was part of the "pure medicinal chemistry" Nobel Prize award of 1988, along with George Hitchings and Gertrude Elion. There's a good interview with him at that Nobel site, and here's a tribute to him on YouTube.

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The Health Care Bill: A Therapeutic Rant

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Posted by Derek

Since I've written occasionally about the current health care reform efforts here, I feel as if I should say something now that a bill has passed the House. To be honest, though, I'm having a bit of trouble getting my thoughts in order, although I do feel the need to vent. Readers who aren't in the mood for my political opinions can skip this one.

Here goes: first off, it's rather hard for me to get past my anger at being told (repeatedly, by both the President and members of Congress) that this bill will "bend the cost curve" and on top of that, actually reduce the deficit. This is, in this case, such a transparent lie that it indicates actual contempt for their audience on the part of those repeating it. We can start with history and general principles: I have yet to hear of a state or federal health care system in this country that has not ended up costing hugely more than it was ever slated to.

I can get more specific in this case, though, since the entire bill was carefully structured to show a spurious deficit reduction (in order for it to be pushed through the budget reconciliation process, without which it could not have passed at all). Costs are pushed out past the Congressional Budget Office's ten-year time horizon, offloaded onto the states (whose Attorneys-General are now frantically trying to figure out what to do), or just blatantly left out. In the last category is the "doc fix", the adjustment to Medicare reimbursement rates that had to be dropped from the current bill in order to hocus the CBO numbers. The firm understanding between the interested parties is that the House will quietly pass that in the near future when not so many people are paying attention, and damn the numbers anyway. As I said above, "contempt" is the word that keeps coming to mind.

To my mind, this bill will indeed manage to provide health insurance to a portion of those now uninsured, but at a ferocious cost. And to that point, I was unhappy with the amount of money the Bush administration spent, but had I only known what was coming, I would have enjoyed the fiscal restraint while I could. I believe that we're spending entirely too much money that we don't have, and not getting that much in return for it (other than lots of warm, heartfelt favors to friendly constituencies that can be expected to support the current administration).

And here's my last point: my own industry's trade association, PhRMA, believes itself to be in that last category. Whether you felt like it or not, if you work in the drug industry, you spent a lot of money to help get this bill passed. I haven't heard the details of the quid pro quo deals for our business, but no doubt there are some nice ones hidden in the recesses of the bill (or just outside it, like the doc fix). My worry, though, is that dealing with the government on this level is like dealing with a hungry bear. Sooner than we think, the costs of this bill will kick in. At that point, I predict that we will find ourselves in yet another Health Care Crisis, having failed to bend any cost curves whatsoever. Then the bear will turn its head to us again, but this time, with a new look in its eyes.

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March 17, 2010

Theft at Eli Lilly

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Posted by Derek

$75 million dollars worth of antipsychotics - that's a lot of pills, and I'm not surprised to see that the thieves used a tractor-trailer to haul everything off. You'd have to assume that there's a well-worked-out pathway to unload all of these things, and that no one's going to go to all this trouble on "spec".

Glad to see that my industry's products are so much in demand. . .

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February 16, 2010

Pharma and the Health Care Bill: Value For the Money?

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Posted by Derek

I hesitate to open up the whole topic of health care reform again. (For the record, I think that the bills, in their current forms, are dead). But one thing that struck me was how early the pharma industry trade group PhRMA got involved in the negotiations, and the sort of deal that they struck.

I note that Billy Tauzin, head of the organization at the time, seems to have been instrumental in those negotiations, and that he has now left his position. You can read this account of the whole affair, courtesy of the Sunlight Foundation, and decide to what extent those two statements are related. I also note that, if that article is accurate, at least $100 million dollars was spent by the trade group in the process.

I get emails from people at PhRMA once in a while. I'm expecting the next one by this afternoon. . .

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February 11, 2010

Sanofi-Aventis Cuts Back

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Posted by Derek

The company says that it cut 7% out of the R&D budget last year, and looks to keep on this same path this year. And that goes for merger and acquisition activity, although they seem to be staying away from the Great Big Deals. Here's a statement from their CEO in a recent interview:

“The best predictor of what we’ll do in 2010 is what we’ve done in 2009,” Viehbacher said in an interview in Paris. “When you do smaller to mid-sized deals, it is easier to search, complete a deal, and then hand it over to your line management and move on to the next deal. It’s when you do a big deal that the whole company gets bogged down in deciding whose e-mail system you’re going to use or where headquarters are going to be.”

All of this brings up a question. I've been hearing talk (which I haven't been able to verify) of re-orgs and layoffs in their US research sites recently. Anyone have any details?

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February 4, 2010

Here's a Business Plan For You

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Posted by Derek

On another front, we now have an ex-BMS associate scientist who's apparently been arrested for stealing company materials in preparation for starting his own company back in India. I presume he was planning to get into the advanced pharmaceutical intermediates business (or perhaps the biotech end of it), using as much proprietary information as he could download in order to get a quick leg up. The company's security folks seem to have flagged him over the Christmas break, and he's since been spending time with the FBI. . .

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GSK Day

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Posted by Derek

I'll start a post here so those with details on today's GlaxoSmithKline news can leave comments. I assume we'll be hearing from the UK folks shortly, and the US more in the middle of the day. I also wonder if these announcements will be like the AstraZeneca one earlier - that is, cuts to be staged over a longer period. Those are a mixed bag. They keep people employed longer (and give them some hope that there may be a place to go by the time their position gets cut), but it also spreads Morale-B-Gone dust over a place for an extended time.

Good luck to all concerned.

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January 28, 2010

A Scorched-Earth Policy at Wyeth's Princeton Site?

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Posted by Derek

This information comes to me secondhand, so I'm not sure how accurate it is. I hope it turns out not to be true. A correspondent writes to me that he's spoken this week to someone who had recently been at the former Wyeth site in Princeton, which is in the process of shutting down. The usual practice is for industrial research sites to make surplus equipment available to academic labs and the like, but the report is that this isn't happening in this case.

Instead, glassware is just being broken and tossed, along with a lot of other equipment, and the entire chemical reagent collection is supposedly going to be carted off by a waste disposal firm for incineration. That must be the commercially available stuff on the shelves - sometimes it's not worth the paperwork and trouble to send those on somewhere else, but sometimes it is. But the glassware and equipment definitely shouldn't be going to waste, but from the sound of this report, that's just what's happening.

Can anyone add details to this? Are the people closing down that site really just heaving everything into dumpsters?

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December 22, 2009

GE Healthcare's Idiotic Libel Suit

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Posted by Derek

Courtesy of Pharmalot (and my mail!), I note this alarming story from London. GE Healthcare makes a medical NMR contrast agent, a gadolinium complex marketed under the name of Omniscan. (They picked it up when they bought Amersham a few years ago). Henrik Thomsen, a Danish physician had noted what may be an association with its use and a serious kidney condition, nephrogenic systemic fibrosis, and he gave a short presentation on his findings two years ago at a conference in Oxford.

For which GE is suing him. For libel. Update: the documents of the case can be found here. They claim that his conference presentation was defamatory, and continue to insist on damages even though regulatory authorities in both the UK and in the rest of Europe have reviewed the evidence and issued warnings about Omniscan's use in patients with kidney trouble. Over here in the US, the FDA had issued general advisories about contrast agents, but an advisory panel recently recommended that Omniscan (and other chemically related gadolinium complexes) be singled out for special warnings. From what I can see, Thomsen should win his case - I hope he does, and I hope that he gets compensatory damages from GE for wasting his time when he could have been helping patients.

And this isn't the only case going on there right now. Author Simon Singh is being sued by the British Chiropractic Association for claiming in a published article that chiropractic claims of being able to treat things like asthma as "bogus". Good for him! But he's still in court, and the end is not in sight.

This whole business is partly a function of the way that GE and the chiropractors have chosen to conduct business, but largely one of England's libel laws. The way things are set up over there, the person who brings suit starts out with a decided edge, and over the years plenty of people have taken advantage of the tilted field. There's yet another movement underway to change the laws, but I can recall others that apparently have come to little. Let's hope this one succeeds, because I honestly can't think of a worse venue to settle a scientific dispute than a libel suit (especially one being tried in London).

So, General Electric: is it now your company policy to sue people over scientific presentations that you don't like? Anyone care to go on record with that one?

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December 7, 2009

Once You Have Paid Him the Danegeld. . .

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Posted by Derek

. . .you never get rid of the Dane. (The rest of the poem, if you haven't come across it.)

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December 1, 2009

Climategate and Scientific Conduct

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Posted by Derek

Everyone has heard about the "Climategate" scandal by now. Someone leaked hundreds of megabytes of information from the University of East Anglia's Climatic Research Unit, and the material (which appears to be authentic) is most interesting. I'm not actually going to comment on the climate-change aspect of all this, though. I have my own opinions, and God knows everyone else has one, too, but what I feel needs to be looked at is the scientific conduct. I'm no climatologist, but I am an experienced working scientist - so, is there a problem here?

I'll give you the short answer: yes. I have to say that there appears to be several, as shown by many troubling features in the documents that have come out. The first one is the apparent attempts to evade the UK's Freedom of Information Act. I don't see how these messages can be interpreted in any other way as an attempt to break the law, and I don't see how they can be defended:

Can you delete any emails you may have had with Keith re AR4?
Keith will do likewise. He's not in at the moment - minor family crisis. Can you also email Gene and get him to do the same? I don't have his new email address. We will be getting Caspar to do likewise.

A second issue is a concerted effort to shape what sorts of papers get into the scientific literature. Again, this does not seem to be a matter of interpretation; such messages as this, this, and this spell out exactly what's going on. You have talk of getting journal editors fired:

This is truly awful. GRL has gone downhill rapidly in recent years.
I think the decline began before Saiers. I have had some unhelpful dealings with him recently with regard to a paper Sarah and I have on glaciers -- it was well received by the referees, and so is in the publication pipeline. However, I got the impression that Saiers was trying to keep it from being published.

Proving bad behavior here is very difficult. If you think that Saiers is in the greenhouse skeptics camp, then, if we can find documentary evidence of this, we could go through official AGU channels to get him ousted. Even this would be difficult.

And of trying to get papers blocked from being referenced:

I can't see either of these papers being in the next IPCC report. Kevin and I will keep them out somehow - even if we have to redefine what the peer-review literature is !

Two questions arise: is this defensible, and does such behavior take place in other scientific disciplines? Personally, I find this sort of thing repugnant. Readers of this site will know that I tend to err on the side of "Publish and be damned", preferring to let the scientific literature sort itself out as ideas are evaluated and experiments are reproduced. I support the idea of peer review, and I don't think that every single crazy idea should be thrown out to waste everyone's time. But I set the "crazy idea" barrier pretty low, myself, remembering that a lot of really big ideas have seemed crazy at first. If a proposal has some connection with reality, and can be tested, I say put it out there, and the more important the consequences, the lower the barrier should be. (The flip side, of course, is that when some oddball idea has been tried and found wanting, its proponents should go away, to return only when they have something sturdier. That part definitely doesn't work as well as it should.)

So this "I won't send my work to a journal that publishes papers that disagree with me" business is, in my view, wrong. The East Anglia people went even farther, though, working to get journal editors and editorial boards changed so that they would be more to their liking, and I think that that's even more wrong. But does this sort of thing go on elsewhere?

It wouldn't surprise me. I hate to say that, and I have to add up front that I've never witnessed anything like this personally, but it still wouldn't surprise me. Scientists often have very easily inflamed egos, and divide into warring camps all too easily. But while it may have happened somewhere else, that does not make it normal (and especially not desirable) scientific behavior. This is not a standard technique by which our sausage is made over here.

What I've seen in organic chemistry are various attempts to steer papers to particular reviewers (or evade other ones). And I've seen people fire off angry letters to journal editors about why some particular paper was published (and why the letter writer's manuscript in response had not been accepted in turn, likely as not). The biggest brawl of them all was still going early in my career (having started before I was born): the fight over the nonclassical norbornyl cation, the very mention of which is still enough to make some older chemists put their hands over their ears and start to hum loudly. That one involved (among many others) two future Nobel Prize winners (H. C. Brown and George Olah), and got very heated indeed - but I still don't recall either one of them trying to get journal editors fired after publishing rival manuscripts. You don't do that sort of thing.

And that brings up an additional problem with all this journal curating: the CRU people have replied to their critics in the past by saying that more of their own studies have been published in the peer-reviewed literature. This is disingenuous when you're working at the same time to shape the peer-reviewed literature into what you think it should look like.

A third issue I want to comment on are the problems with the data and its analysis. I have deep sympathy for the fellow who tried to reconcile the various poorly documented and conflicting data sets and buggy, unannotated code that the CRU has apparently depended on. And I can easily see how this happens. I've been on long-running projects, especially some years ago, where people start to lose track of which numbers came from where (and when), where the underlying raw data are stored, and the history of various assumptions and corrections that were made along the way. That much is normal human behavior. But this goes beyond that.

Those of us who work in the drug industry know that we have to keep track of such things, because we're making decisions that could eventually run into the tens and hundreds of millions of dollars of our own money. And eventually we're going to be reviewed by regulatory agencies that are not staffed with our friends, and who are perfectly capable of telling us that they don't like our numbers and want us to go spend another couple of years (and another fifty or hundred million dollars) generating better ones for them. The regulatory-level lab and manufacturing protocols (GLP and GMP) generate a blizzard of paperwork for just these reasons.

But the stakes for climate research are even higher. The economic decisions involved make drug research programs look like roundoff errors. The data involved have to be very damned good and convincing, given the potential impact on the world economy, through both the possible effects of global warming itself and the effects of trying to ameliorate it. Looking inside the CRU does not make me confident that their data come anywhere close to that standard:

I am very sorry to report that the rest of the databases seem to be in nearly as poor a state as Australia was. There are hundreds if not thousands of pairs of dummy stations, one with no WMO and one with, usually overlapping and with the same station name and very similar coordinates. I know it could be old and new stations, but why such large overlaps if that's the case? Aarrggghhh! There truly is no end in sight... So, we can have a proper result, but only by including a load of garbage!

I do not want the future of the world economy riding on this. And what's more, it appears that the CRU no longer has much of their original raw data. It appears to have been tossed over twenty years ago. What we have left, as far as I can see, is a large data set of partially unknown origin, which has been adjusted by various people over the years in undocumented ways. If this is not the case, I would very much like the CRU to explain why not, and in great detail. And I do not wish to hear from people who wish to pretend that everything's just fine.

The commentator closest to my views is Clive Crook at The Atlantic, whose dismay at all this is unhidden. I'm not hiding mine, either. No matter what you think about climate change, if you respect the scientific endeavor, this is very bad news. Respect has to be earned. And it can be lost.

Comments (170) + TrackBacks (0) | Category: Current Events | General Scientific News | The Dark Side | The Scientific Literature

November 17, 2009

Warren DeLano

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Posted by Derek

I've been remiss in not mentioning this, but I just found out recently that Warren DeLano (the man behind the excellent open-source PyMOL program) passed away suddenly earlier this month. He was 37 - another unfortunate loss of a scientist who had done a lot of fine work and was clearly on the way to doing much more.

I notice that as I write this I have a PyMOL window open on my desktop; I use the program regularly to look at protein structures. Si monumentum requiris, circumspice.

Comments (8) + TrackBacks (0) | Category: Current Events | In Silico

November 13, 2009

Prof. Keith Fagnou

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Posted by Derek

As many readers may have heard by now, Keith Fagnou of the University of Ottawa has suddenly died from what appears to be H1N1 influenza.

I'm awaiting confirmation of that diagnosis, which is worrisome for all sorts of other reasons, but whatever the cause, this is a loss for synthetic chemisty. Prof. Fagnou had published many interesting and useful papers on catalysis of bond-forming reactions, an area that's been growing steadily in importance for years and shows no signs of faltering. We need all the smart, capable people we can get working on such things, and I'm very sorry that we've lost one. Condolences to his family, colleagues, and friends.

Comments (30) + TrackBacks (0) | Category: Current Events

November 11, 2009

Against Panic

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Posted by Derek

With the waves of layoffs going on, and all the nasty structural changes we're seeing in this business, it's easy to start feeling a toxic combination of fear and despair. And while I understand that, I'm going to try to briefly argue against it.

(1) I think that, in the years to come, that people are most definitely going to need medicines. And by that, I mean new ones, because there are a lot of conditions out there that we can't treat very well. As the world gets (on the average) older and wealthier, this need will do nothing but increase. In many cases, pharmaceutical treatment is cheaper than waiting and having surgery or the like, so there's a large scale cost-saving aspect to this, too.

(2) I also think that many of these medicines are still going to be small molecules. Now, biological products can be very powerful, and can do things that we can't (as yet) do with small molecules - mind you, the reverse is true, too. And I think that biologics will gradually increase their share of the pharma world as we find out more about how to make and administer them. But it is very hard to beat an orally administered small molecule for convenience, cost, and patient compliance, and those are three very big factors.

(3) What we're witnessing now is a huge argument about how we're going to make those small molecule drugs, where we're going to make them, and who will do all those things. And it's driven by money, naturally. We don't have enough new products on the market, which means that we have to sell the ones we have like crazy (which leads to all sorts of other problems, legal and otherwise). At the same time, we're having to spend more and more money to try to get what drugs we can through the whole process. These trends appear unsustainable, especially when running at the same time.

(4) But as Herbert Stein used to say, if something can't go on, then it won't. Right now, the only way out that companies can see is to cut costs as hard as possible (and market as hard as possible). Those both bring in short-term results that you can point at. Long-term, well. . .probably not so good. But in that same long term, we're going to have to find better ways of discovering and developing drugs. If we can improve that process, the fix can come from that direction rather than from the budget-cutting one.

(5) And those improvements don't have to be incredible to make a big difference. We have a 90% failure rate in the clinic as it stands. If we could just work it to where we only lose 8 out of 10 drug candidates, that would double the number of new drugs coming to the market, which would cheer everyone up immensely.

(6) The questions are: can we improve R&D in time? Can we improve it with the resources we have? I think that the demand (and thus the potential rewards) is too great for a solution not to be found, if there's one out there. And we still know so little about what we do that I can't imagine that answers aren't out there somewhere. Who's going to find them? How long will it take? Where are they? I've no clue. But that looks like the way out to me.

Comments (32) + TrackBacks (0) | Category: Business and Markets | Current Events | Drug Industry History

October 7, 2009

A Nobel for Ribosome Structure

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Posted by Derek

This was another Biology-for-Chemistry year for the Nobel Committee. Venkatraman Ramakrishnan (Cambridge), Thomas Steitz (Yale) and Ada Yonath (Weizmann Inst.) have won for X-ray crystallographic studies of the ribosome.

Ribosomes are indeed significant, to put it lightly. For those outside the field, these are the complex machines that ratchet along a strand of messenger RNA, reading off its three-letter codons, matching these with the appropriate transfer RNA that's bringing in an amino acid, then attaching that amino acid to the growing protein chain that emerges from the other side. This is where the cell biology rubber hits the road, where the process moves from nucleic acids (DNA going to RNA) and into the world of proteins, the fundamental working units of a day-to-day living cell.

The ribosome has a lot of work to do, and it does it spectacularly quickly and well. It's been obvious for decades that there was a lot of finely balanced stuff going on there. Some of the three-letter codons (and some of the tRNAs) look very much like some of the others, so the accuracy of the whole process is very impressive. If more proofs were needed, it turned out that several antibiotics worked by disrupting the process in bacteria, which showed that a relatively small molecule could throw a wrench into this much larger machinery.

Ribosomes are made out of smaller subunits. A huge amount of work in the earlier days of molecular biology showed that the smaller subunit (known as 30S for how it spun down in a centrifuge tube) seemed to be involved in reading the mRNA, and the larger subunit (50S) was where the protein synthesis was taking place. Most of this work was done on bacterial ribosomes, which are relatively easy to get ahold of. They work in the same fashion as those in higher organisms, but have enough key differences to make them of interest by themselves (see below).

During the 1980s and early 1990s, Yonath and her collaborators turned out the first X-ray structures of any of the ribosomal subunits. Fuzzy and primitive by today's standards, those first data sets got better year by year, thanks in part to techniques that her group worked out first. (The use of CCD detectors for X-ray crystallography, a technology that was behind part of Tuesday's Nobel in Physics, was another big help, as was the development of much brighter and more focused X-ray sources). Later in the 1990s, Steitz and Ramakrishnan both led teams that produced much higher-resolution structures of various ribosomal subunits, and solved what's known as the "phase problem" for these. That's a key to really reconstructing the structure of a complex molecule from X-ray data, and it is very much nontrivial as you start heading into territory like this. (If you want more on the phase problem, here's a thorough and comprehensive teaching site on X-ray crystallography from Cambridge itself).
Ribosomal%20structures.jpg
By the early 2000s, all three groups were turning out ever-sharper X-ray structures of different ribosomal subunits from various organisms. The illustration above, courtesy of the Nobel folks, shows the 50S subunit at 9-angstrom (1998), 5-angstrom (1999) and 2.4-angstrom (2000) resolution, and shows you how quickly this field was advancing. Ramakrishnan's group teased out many of the fine details of codon recognition, and showed how some antibiotics known to cause the ribosome to start bungling the process were able to to work. It turned out that the opening and closing behavior of the 30S piece was a key for this whole process, with error-inducing antibiotics causing it to go out of synch. And here's a place where the differences between bacterial ribosomes and eukaryotic ones really show up. The same antibiotics can't quite bind to mammalian ribosomes, fortunately. Having the protein synthesis machinery jerkily crank out garbled products is just what you'd wish for the bacteria that are infecting you, but isn't something that you'd want happening in your own cells.

At the same time, Steitz's group was turning out better and better structures of the 50S subunit, and helping to explain how it worked. One surprise was that there was a highly ordered set of water molecules and hydrogen bonds involved - in fact, protein synthesis seems to be driven (energetically) almost entirely by changes in entropy, rather than enthalpy. Both his group and Ramakrishnan's have been actively turning out structures of the ribosome subunits in complex with various proteins that are known to be key parts of the process, and those mechanisms of action are still being unraveled as we speak.

The Nobel citation makes reference to the implications of all this for drug design. I'm of two minds on that. It's certainly true that many important antibiotics work at the ribosomal level, and understanding how they do that has been a major advance. But we're not quite to the point where we can design new drugs to slide right in there and do what we want. I personally don't think we're really at that stage with most drug targets of any type, and trying to do it against structures with a lot of nucleic acid character is particularly hard. The computational methods for those are at an earlier stage than the ones we have for proteins.

One other note: every time a Nobel is awarded, the thoughts go to the people who worked in the same area, but missed out on the citation. The three-recipients-max stipulation makes this a perpetual problem. This is outside my area of specialization, but if I had to list some people that just missed out here, I'd have to cite Harry Noller of UC-Santa Cruz and Marina Rodnina of Göttingen. Update: add Peter Moore of Yale as well. All of them work in this exact same area, and have made many real contributions to it - and I'm sure that there are others who could go on this list as well.

One last note: five Chemistry awards out of the last seven, by my count, have gone to fundamental discoveries in cell or protein biology. That's probably a reasonable reflection of the real world, but it does rather cut down on the number of chemists who can expect to have their accomplishments recognized. The arguing about this issue is not be expected to cease any time soon.

Comments (46) + TrackBacks (0) | Category: Analytical Chemistry | Biological News | Current Events | Infectious Diseases

October 5, 2009

A Nobel for Telomerase

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Posted by Derek

As many had expected, a Nobel Prize has been awarded to Elizabeth Blackburn (of UCSF), Carol Greider (of Johns Hopkins), and Jack Szostak (of Harvard Medical School/Howard Hughes Inst.) for their work on telomerase. Blackburn had been studying telomeres since her postdoc days in the late 1970s, and she and Szostak worked together in the field in the early 1980s, collarborating from two different angles. Greider (then a graduate student in Blackburn's lab) discovered the telomerase enzyme in 1984. She's continued to work in the area, as well she might, since it's been an extremely interesting and important one.

Telomeres, as many readers will know, are repeating DNA stretches found on the end of chromosomes. It was realized in the 1970s that something of this kind needed to be there, since otherwise replication of the chromosomes would inevitably clip off a bit from the end each time (the enzymes involved can't go all the way to the ends of the strands). Telomeres are the disposable buffer regions, which distinguish the natural end of a chromosome from a plain double-stranded DNA break.

What became apparent, though was that the telomerase complex often didn't quite compensate for telomere shortening. This provides a mechanism for limiting the number of cell divisions - when the telomeres get below a certain length, further replication is shut down. Telomerase activity is higher in stem cells and a few other specialized lines. This means that the whole area must be a key part of both cellular aging and the biology of cancer. In a later post, I'll talk about telomerase as a drug target, a tricky endeavour that straddles both of those topics.

It's no wonder that this work has attracted the amount of attention it has, and it's no wonder either that it's the subject of a well deserved Nobel. Congratulations to the recipients!

Comments (20) + TrackBacks (0) | Category: Aging and Lifespan | Biological News | Cancer | Current Events

September 25, 2009

The Details of the Baucus Bill

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Posted by Derek

Since we were discussing the Baucus health care proposal here the other day, I thought that people would appreciate a chance to read through the provisions of the bill before forming an opinion of it.

Sorry! You can't. It's not online, and it won't even be online by the time the Finance Committee is through with it. Senator Baucus, though, would like you know know that it's because it's just too darn difficult to put it up.

So we'll just have to trust them. I suppose. We may get a chance to look things over before the House votes on anything. Unless some good reason comes up not to do that, of course. It has before.

Comments (23) + TrackBacks (0) | Category: Current Events | Regulatory Affairs

September 23, 2009

Pay Them Now, Or Pay For It Later

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Posted by Derek

Time for a brief comment on health care reform, now that Sen. Baucus has presented a bill to the Finance Committee (which, to be sure, I believe has already attracted over 500 proposed amendments). As is well known, the largest drug industry trade group, PhRMA, signed on to the whole idea of a large reform effort early, in exchange for a seat at the table (and a chance to make things go favorably). How's that working out so far?

As Steve Usdin at Biocentury writes, the answer is "fairly blatantly":

The parochial value of PhRMA’s controversial decision to cut a deal with the Senate Finance Committee and the White House became clear last week as details of the committee’s healthcare reform bill emerged that favor big pharma companies over their biotech siblings. The bill also pounds the medical device industry and slams laboratory service providers, sectors that didn’t agree on “voluntary” contributions to healthcare expansion. . .

. . .A 233-page summary of the America’s Healthy Future Act released by Finance Committee Chairman Max Baucus (D-Mont.) includes most of PhRMA’s healthcare reform wish list and has only one major provision pharma companies hope to kill: a commission with powers to constrain Medicare spending.

The tax put on medical devices by this bill has already been noted widely in the press, and I see that Sen. Kerry is already objecting to that provision - naturally enough, since Massachusetts has some big players in that area. The Senators from Guidant and Medtronics (also known as Indiana and Minnesota) are speaking up as well. The trade association for that industry (AdvaMed) apparently couldn't come to terms with Washington, so this tax is their reward - which, in a nutshell, is the sort of thing that keeps gradually turning me into a libertarian.

There are more examples. Biocentury goes on to detail an excise tax provision in the bill that's based on sales figures and market share. But this isn't calculated on total US sales, which is the method various biotech companies were pushing for. No, it's calculated by market share of sales to the US government, which (because of Medicare) tends to emphasize drugs for an older population. In general, if your drug is provided substantially through any government-supported program, (HIV medications come to mind), you're going to see a higher fee. Orphan drugs are exempt from the tax, which must gladden the hearts of several companies, though.

It's still way too early to get worked up over any specific provisions of any one bill, and there's plenty of room to wonder if anything substantial at all will get passed. But it is worth paying some attention to how the process works. When the same tactics are used in the private sector, the unfortunate phrase "protection racket" comes to mind. But government, well, that's different. Clearly.

Comments (28) + TrackBacks (0) | Category: Current Events | Regulatory Affairs

September 14, 2009

Norman Borlaug

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Posted by Derek

Norman Borlaug has died at the age of 95, and he's definitely worth remembering. His tireless work on improving agriculture saved hundreds of millions of people from being born to starvation. And it also kept the world from having to tear up even more natural habitats to plant food crops. Update: as pointed out in the comments, here's an excellent interview with Borlaug from 2000).

People tend to forget (or have never known) about the way the world has managed to escape the Malthusian trap over the last two or three hundred years. (A Farewell to Alms
is a book that makes this case at length, more here). And the way that birth rates drop once countries become more prosperous holds out the hope that we won't fall into an even greater version of the same thing. I think that once the Industrial Revolution happened, world population was going to explode eventually. Norman Borlaug was one of the key people who helped keep things together while that happened.

But what about natural, traditional means of growing crops, in harmony with the land and all that? It's easy to forget the agriculture is unnatural, and is a relatively recent invention. (In fact, perhaps it was that step, rather than the Industrial Revolution, that set the world on a path to an eventual population explosion. It just did so more slowly). Once we started clearing land and saving seed, we left the natural way of things behind. To put that another way, that's when the human race stop playing only the cards it had been dealt. And using the highest-yielding seed and the most well-thought-out ways of growing it will keep us from having to clear more of the land we have left.

Comments (30) + TrackBacks (0) | Category: Current Events

August 19, 2009

The PhRMA Deal

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Posted by Derek

I'm not always a fan of John Boehner, but I think he's on the right track with his letter to Billy Tauzin (PDF here from NPR's health care site). I understand that line about how in Washington, if you're not at the table you're on the menu. And I understand how the industry wants to get into the middle of the whole process to try to protect its interests. I just don't think that cutting this kind of deal is, in the end, doing that. And apparently Boehner agrees:

The Obama Administration tacitly acknowledged last week that the President will not be bound by the $80 billion limit PhRMA and its board of directors were led to believe had been secured in exchange for your organization's support of the Administration's health care takeover, and key Democrats in Congress, including Speaker Nancy Pelosi (D-CA) and Energy & Commerce Committee Chairman Henry Waxman (D-CA) have said explicitly they will not honor the agreement. In other words, now that the deal is publicly known and would be messy for your to reverse, Big Government is now changing the terms. . .because it can.

Boehner goes on to say that Tauzin will surely "object to this letter and quarrel with its premise", which I think is a pretty sure bet. But stripped of the boilerplate that's found in the rest of it, I find that I agree with its key point very much, as stated above. I don't think that it's possible to do a PhRMA-style deal with an entity like the federal government. Because, you know, they can always change their minds, and what possible recourse do you have then?

Update: Yes, of course Boehner is a political opponent of President Obama, and has interests beyond purely philosophical ones in scuppering some of his grander plans. Both Boehner and Obama make me grit my teeth when I hear them talk about this issue, to tell you the truth, and boy howdy, there are plenty of other people in that category with them. And I realize that when I start talking politics, that many readers start to grit their own teeth in response.

Fear not, this is not going to turn into a political blog. But it's always been concerned with the drug industry, how it does what it does, and what its future might be. The current efforts at health care reform could well have an impact on these things, to put it delicately, so the topic has to come up. My free-market biases are pretty well known, though, so some readers may be able to save time by just skipping over what I write about it on the grounds that they probably have a good idea of what I'll have to say. I wouldn't blame anyone for doing that; vita brevis est. And I promise to not have the issue take over the site - I don't want to be a political blogger, either, really. . .

Comments (17) + TrackBacks (0) | Category: Current Events | Drug Prices | Regulatory Affairs

August 17, 2009

PhRMA's Negotiating Game

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Posted by Derek

Now for a bit on the pharma industry and the current fight over health care legislation. Does the industry want a new system to come into force, or not?

Depends on what that new system is, of course. But the industry is naturally trying to make sure that it has a hand in whatever passes. And here we come to a meeting of political interests. The administration would also prefer not to have the drug industry actively working against it, since drug companies have a lot of money to use for such purposes. Therefore, as anyone who knows politics could have predicted, a deal has been struck.

Or has it? As everyone has heard by now, Billy Tauzin, head of the industry's largest association (PhRMA), said that an understanding had been reached with Max Baucus of the Senate Finance Committee, with the approval of the White House. The industry would agree to come up with 80 billion dollars of savings, and the administration would then consider them to have done their part. More specifically, there would be no more talk of price negotiations for Medicare-approved drugs, of drug reimportation, or rebates for drugs prescribed to joint Medicare/Medicaid patients. The industry would also agree to support the new health plan by running ads (and, no doubt, by lobbying behind the scenes). Come, let us reason together.

It doesn't surprise me at all that such a quid pro quo would be worked out in advance - that's exactly how politics gets done. But what amazed me was that Tauzin would go around telling people. Predictably, many of the other players are now complaining, and PhRMA is reduced to saying that it's "counterproductive" to keep on talking about it.

Tauzin and PhRMA are also taking flak from their right - the Wall Street Journal blasted the whole idea of a deal the other day, calling it short-sighted. Congress could, after all, change the terms any time they can round up the votes, which would be any time it's convenient to blame the drug companies for something. I find myself more in this camp. I understand that PhRMA can't afford to stay out of this process (in which case the carving knives would come out sooner rather than later), but I think it's a sad business all the same, trading the threat of price controls now for the threat of price controls a little later on. Here's more complaining from National Review.

But that brings us back to Tauzin. I will work under the assumption that he's not an idiot, although I'm willing to listen to evidence for either side on that one. But if he isn't, why did he go around boasting of this wonderful backroom deal? All it seems to have done is endanger whatever agreement was reached. If my not-an-idiot stipulation is justified, though, the only reason I can see for doing this is as a tactic to get something even better. Did PhRMA look at the polls and decide the time was right to help torpedo everything? (And yes, I know the Rasmussen polls lean right, but I think they're picking up something real). Is that the game here?

Well, I get e-mails from people at PhRMA once in a while, and I'll probably get another one after I put this post up. Something tells me that I'm not going to get to hear what's really going on, but that doesn't stop a person from wondering.

Comments (50) + TrackBacks (0) | Category: Current Events | Drug Prices | Regulatory Affairs

July 30, 2009

Health Care Reform - Really?

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Posted by Derek

I haven't written about the various health care reform packages that are being hammered out and hammered through the various parts of Congress. That's partly because I began to think fairly early on in the process that we weren't actually going to see something happen as quickly as the administration wanted, which meant that there were still plenty of twists and turns left. I still think that's true - in fact, I have no idea when a final bill will ever get Frankensteined together for a vote, and no one else seems to have a good idea, either.

And since the main focus of this blog is pharmaceutical research, the first question I have to deal with is what effect such a bill will have on what I (and many of the readers here) do for a living. Absent a good idea of what the legislation will really look like, that's impossible to do in detail. But I can paint some broad strokes at this point, and they're probably not going to come as much of a surprise: I don't like what I see.

On the macro level, I don't like the administration's rhetoric on this issue. I do not believe that health care costs are crippling our economy, and the implication that they're tied to our current economic downturn seems specious. (And yes, that argument has been made, and more than once). Such an any-weapon-to-hand approach seems a bit different from what many people may have thought that they were voting for in the last election.

But I didn't vote for Obama, although I certainly wasn't crazy about the McCain-Palin ticket, either. My fears (expressed here) that he might turn out to be a zealous world-changing reformer have been amply confirmed. What do I have against zealous world-changing reformers, you ask? Why, I fear that the world is trickier than they are, for one thing. And too many of these people seem to come across as "If you people would just have enough sense to see that I'm doing this for your own good" types. At the rate we're going, that'll be the key phrase in a presidential speech right after Labor Day. (Mickey Kaus has been pointing out for some time now that this eat-your-peas-for-the-common-good approach is not doing the administration any favors).

The only big changes I'm in the mood for, generally speaking, are ones that give people more control over their own destiny, and if that's what we're seeing here, I've missed it. (I'm not alone). I guess that I just don't believe that systems this large and this complex are subject to wholesale intervention by the Wise and the Good. I worry that the Wise and Good will, in fact, decide that if they're truly going to control costs that they're going to ration health care in ways that people aren't necessarily expecting. Part of that rationing may well have to be either de facto (or flat-out de jure) price controls on pharmaceuticals and other parts of the system - and if applied thoroughly enough, these will be an excellent way of creating shortages of just the things that are being controlled, in the same way that price controls have always functioned. Some of those shortages will be silent ones: the things we don't discover.

Alternatively, we could end up with a Great Big Plan that doesn't really attempt to cut costs, or defers those cost savings into the glorious future. It's worth considering that, as far as I can see, every single attempt to run a large state-sponsored heath plan has ended up costing far, far more than even the most pessimistic initial estimates. And this time will be different. . . how, exactly?

And that leads us to the sort of bill that I think we're most likely to get: one that doesn't satisfy the biggest advocates of sweeping health care reform, since it's had to abandon the big proposals for the sake of political reality, but one that at the same time spends lots and lots more money, with no clear plan of how to raise these funds, all of that again for the sake of political reality. One, in short, that gives all the politicians involved a chance to pin "I Passed Health Care Reform!" buttons on their jackets while pissing off everyone who bothers to look at the thing closely, and one that commits us to spending oceans of money to accomplish not very much.

Perhaps I'm just in a bad mood. But that looks like what we're heading for.

Comments (72) + TrackBacks (0) | Category: Current Events | Drug Prices | Regulatory Affairs

July 10, 2009

Iran: Politics and Technology Update

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Posted by Derek

I wanted to make another brief excursion here, since (as many of you will have seen on the news), the situation in Iran is still very volatile indeed. The proxy-server efforts that I've spoken about here have been overtaken by events - plaintext proxies are basically out of the picture, thanks to countermeasures by the Iranian government.

But there are other ways to get information in and out, as the number of video clips from yesterday's protests make clear. For a roundup, see this post from Massachusetts's own Tehran Bureau: "Geeks Around the Globe Rally to Help Iranians Online". I'm glad to number myself among them.

One aspect of said geekdom is supporting Tor. I'm running a relay on my home computer - that's my machine, the relay named "levoglucosan" on this list of current routers. Setting up Tor took about five minutes to (but no real geek skills whatsoever, as opposed to getting the proxy servers going). Tor's getting a lot of use, as the Tehran Bureau post makes clear:

“Before the election we were seeing about one to two hundred new users [from Iran] per day,” says Andrew Lewman, executive director of The Tor Project.

“Right after the election and as the protests started we started seeing that spike up into 700 – 1,000 per day. Now we’re up to about 2,000 new users a day and around 8,000 connections sustained at any time, which is a huge, dramatic increase.”

The Canadians are doing their part via Psiphon, which has also had thousands of Iranian users recently. Another new effort is Haystack, a new anonymous-access tool which has been specifically designed to circumvent the Iranian regime's web filtering tools. It's modeled on Freegate, which has been giving the Great Firewall of China fits (and has also been useful in Iran, although they've had to cut access back to keep their Chinese bandwidth up). Haystack appears to have had its first test inside Iran yesterday, and appears to be working just as planned. With any luck, it'll soon be giving fits to the Iranian web censors, too: the kind of government that beats unarmed protestors in the streets, that breaks down doors in the middle of the night to haul people away just for suggesting in public that they don't like their leaders.

As a scientist, I believe in freedom of expression and freedom of inquiry. I've donated money and time to the efforts linked to above, and I'd like to urge that others do the same if they can.

Comments (1) + TrackBacks (0) | Category: Current Events

June 23, 2009

Proxy Server Update

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Posted by Derek

I appreciate the mail I've had on this subject, and wanted to provide a brief update for those who are interested. If you've set up a proxy server for Iran, you can submit it here - Austin Heap is the guy running this part of the effort. There's also a test page where you can see if you have things configured correctly. Anyone needing more technical details, please drop me a note - I'll either answer it myself or send you on to someone who can. I am, truth be told, not exactly one of the 1337-est haxors around, but one does what one can.

Comments (4) + TrackBacks (0) | Category: Blog Housekeeping | Current Events

June 19, 2009

Proxies and Politics Again

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Posted by Derek

Anyone who needs pointers on setting up an Iran proxy server, drop me an e-mail; I'll send over the information. There are quite a few technical updates, but I'll only inflict them on those who need 'em. And as for this news story, the Boston Globe reporter asked me "Hey, you're that In the Pipeline guy", aren't you?"

Comments (4) + TrackBacks (0) | Category: Current Events

June 17, 2009

Politics: Proxy Servers Revisited

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Posted by Derek

Just a quick update to my post the other day on proxies for the Iranian protestors. The San Francisco Chronicle has an article on Austin Heap, the fellow whose web site I linked to the other day. He and a number of collaborators are doing a lot of hard work trying to keep lines of communication open from inside Iran.

If any of you are trying the proxy server thing (as I am with my home machine), be sure to check this update. You'll need to make some adjustments, since the (current!) Iranian government isn't making this easy, naturally.

There are other information tunnels, which rapidly get to be beyond my own hardware resources and hacking skills, but many people seem to be at work on these. One interesting addition to the fray is the anti-Scientology group known as Anonymous. Since my opinion of Scientology is nearly as low as my opinion of the Iranian government, I can only welcome this meeting of the minds.

Comments (7) + TrackBacks (0) | Category: Current Events

June 16, 2009

Proxies for Iran (More Politics - Mixed With Technology)

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Posted by Derek

Many thanks to the people who've e-mailed me about the situation in Iran. My wife's relatives there are all OK (so far!); she's spoken to them several times. Things remain unstable and impossible to predict. It's been thirty years since huge crowds marched through the streets shouting "Death to the Dictator", so everyone's a bit out of practice.

One thing that the more technically inclined readers might consider doing is setting up proxy servers for use by the Iranian protesters. Two web sites that will give you details on this are here and here. The government is blocking all the obvious IP addresses for people trying to organize and get news out of the country, but anonymous proxies provide a lot of non-obvious routes onto the net. I'm trying to get something set up at home myself.

There are a lot of punches being thrown by both sides - for example, some people with proxy servers have reported a lot of denial-of-service garbage coming in from blocks of Russian and Chinese IP addresses. But if you configure things to accept only Iranian domains (those sites above have IP address lists) you should be able to screen that stuff. If you're up for it, please consider helping out. It's one of the few concrete steps I can think of from this distance. A general guide to the current cyberwarfare situation is here. Update - link went dead, but this new one will stay alive. BoingBoing has enough bandwidth!

Comments (20) + TrackBacks (0) | Category: Blog Housekeeping | Current Events

June 14, 2009

And Now Some Politics

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Posted by Derek

My Twitter account usually only gets my posts on this blog (the first 140 characters of them, that is). But those of you who follow me there have been flooded with updates of a very different kind for the last 24 hours or so. My Iranian-born wife and I have been watching the news carefully, as the Iranian election situation seems to be getting out of control. She's been translating Farsi-language updates, and I've been reposting them - there will probably be more of this over the next few days.

You can imagine where my sympathies lie, as a non-religious guy with libertarian leanings. Confusion and bad luck to the mullahs, to everyone who helped them steal this election, and to their henchmen beating members of the opposition in the streets. Freedom of speech, freedom of assembly, and freedom of electoral choice are easy to take for granted in some parts of the world, but none of them come easy.

And more to the usual subject of this blog: the Iranians have produced a lot of top-notch people in science, medicine, and engineering - I've seen and worked with many of them. But I'd love to be able to see what they could accomplish working from a free and stable country, and I hope I get the chance. We'll see.

If you're looking for news, #iranelection on Twitter is a firehouse of information, good and bad, and will lead you to plenty of other sites. The National Iranian American Council is an excellent source, and Andrew Sullivan is doing a fine job covering the situation, too.

Comments (16) + TrackBacks (0) | Category: Blog Housekeeping | Current Events

June 3, 2009

Will The Gentleman With the Pitchfork Please Speak Up?

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Posted by Derek

A few blocks from where I'm sitting, Biogen is having its shareholders meeting today. And since Carl Icahn is still trying very hard to gain leverage in the company's board, it seems to be turning into quite a spectacle over there. (More details).

They're supposed to reconvene at 2 PM for more voting. But from the sound of it, people are adjourning to go out and buy machetes and tire irons. We'll how things come out. . .

Comments (8) + TrackBacks (0) | Category: Business and Markets | Current Events

May 20, 2009

But You Can't Make Them Take It?

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Posted by Derek

Well, we can all study biochemical mechanisms in tumor cells every day of the week. And we can crank out tens of thousands of potential clinical candidates to hit them, run the assays, and then turn around and do it again. We can send things through all sorts of tox testing, take them to the clinic, try them against all sorts of terrible cancers, and amass enough data to make it through the FDA. Then we can let the oncologists continue to try variations, combinations, and regimens in the continuing search for something that works.

And every so often, we actually succeed. Childhood Hodgkin's lymphoma has one of the highest cure rates of all cancers. We can actually do something about that one (as opposed to, say, pancreatic cancer, which we can't do much about at all). Children who would otherwise die - and die slowly - now get a chance to live, to grow up.

But we can't, apparently, convince everyone of this. Many readers will have heard over the last few days of the case of Daniel Hauser of Minnesota, a 13-year-old diagnosed with Hodgkin's a few months ago. Instead of going in for rounds of chemotherapy, the boy (who has said that he doesn't believe that he's sick) and his family have opted for "Native American alternative therapy", and have fled from a court order. The boy's mother, who apparently does believe that he's sick, has said that she's treating him with "herbal supplements, vitamins, and ionized water".

These will, almost certainly, allow the lymphoma to kill him. Chemotherapy and radiation, on the other hand, will very likely allow him to live. If someone is bleeding to death from an arterial wound, anyone trying to heal them by invoking spiritual powers or alternative therapies would (and should) be shoved aside by any onlooker with a tourniquet. Daniel Hauser is bleeding to death as well: just more slowly, and in front of many more onlookers.

Comments (31) + TrackBacks (0) | Category: Cancer | Current Events | Snake Oil

May 12, 2009

Kumbaya

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Posted by Derek

Time, regrettably, for some politics. In case anyone’s wondering, my take on yesterday’s health care announcement by the Obama administration is perfectly stated here. I could not agree more.

In other words, I see the “historic announcement” as nothing more than political theater. Everyone got together, held hands, and pledged to voluntarily do some not-all-that-painful things to reduce costs, some of which (cost savings through better record keeping?) have already been underway for years. Even so, the chances of all of these being followed through are still low. And even if they were, the amount of money being saved is only a small fraction of what would be needed to pay for the administration’s stated health care goals.

None of this would bother me all that much, under normal circumstances. A lot of what goes on in Washington, at least in front of the cameras, is an elaborately choreographed dance. It’s related to real political dealing in the same way that a synchronized swimming exhibition compares to the 1956 Olympic water polo match between the Hungarians and the Soviet Union. But (like Megan McArdle in the Atlantic link above), I worry that the administration will now pretend that these savings are real. When they turn out to be (gasp!) insufficient, a crisis will be declared (you should never waste one, you know), and more persuasive measures will be used. You know, just as in the recent Chrysler “bailout”, a term I can only put in quotes. (Mickey Kaus perfectly sums up my feelings about that one, in that link and here).

Why should I care? After all, my industry should be more or less in the clear, since prescription drug spending is only about ten per cent of the nation’s health care costs, right? Well, my worry is that we’re a very visible (and often disliked) ten per cent, a nail that sticks up and that may well get hammered down pour encourager les autres. I hope I'm wrong. But I think that the Chrysler deal was just a curtain-raiser for an even bigger one in the same style for General Motors, and I hope I'm wrong about that one, too.

Comments (15) + TrackBacks (0) | Category: Business and Markets | Current Events | Drug Prices

April 30, 2009

Faking It on Facebook

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Posted by Derek

I have no Facebook presence to speak of (for better or worse), but if you do, and if you're involved in the pharma/biotech area, you might want to check out this report. Someone (or some group) has been setting up a whole network of fake identities there, and you have to wonder just what the motive is. Nature News has more.

Comments (6) + TrackBacks (0) | Category: Current Events

April 27, 2009

Don't Hit The Bunkers Just Yet

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Posted by Derek

Swine flu: is it time to panic yet? Actually, it never is, and this is a particularly useless time to start running in circles, despite the apparent non-stop coverage on the cable news channels. I had some exposure to those during my recent vacation, which only confirmed the complete ban on the damned things in my own house.

I’m reminded of a line from Michael Lewis’s article on New Orleans in the immediate aftermath of Hurricane Katrina. He described a neighbor as suffering from a severe information handicap: his TV was on. But I can’t get all superior about the Internet, either, since Drudge and others are running piled-up red headlines in the same manner. What’s the real situation?

As far as I can make out, it’s this: over the past many weeks, about one thousand cases of influenza have been reported in Mexico, with about seventy of them fatal. Travelers returned from Mexico have shown up ill in several other locations. But none of them have died – in fact, many of them don’t seem to be all that sick, and appear to be recovering without incident. This flu seems to have spread human-to-human in Mexico, but I’m not aware of any reports of that happening in other locations yet.

And here’s what we don’t know: the number of people actually infected in Mexico is unclear and will remain so. Seventy deaths in a thousand cases of flu is a very alarming figure, and that’s what’s driving all the attention. But we don’t know if that number should really be five thousand, or even ten. And we don’t know if all of those seventy patients even had influenza (or this strain of it) at all – the great majority of them don’t appear to have been serotyped.

So no, it’s not time to sound the sirens just yet. Odds are that this will wind down, just like many other outbreaks of influenza do. But we don’t know that for sure. If I had a nonessential trip to Mexico City scheduled, I’d postpone it. (Not that I’m looking to spend a lot of time in the city in general: one factor in the apparently high fatality rate there might be the awful air quality).

One thing an outbreak like this does, though, is to remind everyone that viral epidemics are potentially a real problem. I don’t think that this one is the Pandemic We’ve Been Waiting For, but that one might well be out there, and there’s no way to know when it might appear. If and when it does, we may not have many pharmacological weapons against it, for the reasons I’ve outlined here. For now, keep an eye on whether any of the cases outside Mexico develop into anything more serious than a day or two in bed, and whether any of these transmit to people around them. And don't watch any cable news. Here's the CDC's page on the outbreak, and here's the WHO.

Comments (34) + TrackBacks (0) | Category: Current Events | Infectious Diseases

April 7, 2009

Biogen Idec: What's Going On?

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Posted by Derek

Biogen Idec has continued to fight off Carl Icahn, opposing his nominees to the company's board and setting up a fight at the annual meeting later this year.

But this morning (as a correspondent has just pointed out to me) the company's stock has been taking off. It's up about 7%, with the broad market down, and all of this rise seems to have been since 11 AM. Someone's stepping up and buying a good amount of BIIB, for some reason. But who, and why?

Update: ah, here we go - rumors of Sanofi-Aventis or some other non-Ichan entity stepping in. We'll see if there's anything to it. . .

Comments (7) + TrackBacks (0) | Category: Business and Markets | Current Events

April 1, 2009

Sponsor A Gene?

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Posted by Derek

This has been forwarded on to me - if you find the idea of a gene sequence being sponsored by IKEA unusual, you should give the press release (and its associated links) a close look. . .

Comments (7) + TrackBacks (0) | Category: Current Events

March 27, 2009

Layoffs At Merck

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Posted by Derek

I’ve been hearing for a little while about impending layoffs at Merck. I decided, though, that this isn’t the environment to be putting up posts about rumors of job cuts – everyone’s jumpy enough already. But unfortunately, they aren’t rumors any more.

What I’m hearing about, in person and via e-mail, is what sounds like across the board R&D shrinkage For what it’s worth, the damage seems heavier (on a percentage basis) at West Point and in Montreal, but I haven’t heard of any R&D area yet that’s completely missed out. More details are welcome from those closer to the sites affected.

You’d have to think that these cuts have been in the works for a while, but that the Merck/Schering-Plough merger is what’s turned them into reality right now. Still, that’s a bit unusual – most of the time, with these mergers, the job cuts come from the new organization after the merger goes through. With one partner in the deal swinging the ax before that even happens, you wonder what’s going to go on once the two companies merge. Fewer cuts overall than people were estimating (or fewer on the Schering-Plough end? That would be a switch.) Or is this just a head start on something that needed deeper cuts for it to make any financial sense at all?

Either way, if anyone out there knows of some organizations that are in a hiring mood, please feel free to post those details in the comments section. One thing’s for sure – anyone who is trying to fill positions these days will see some good candidates.

Comments (178) + TrackBacks (0) | Category: Business and Markets | Current Events

March 12, 2009

Greedy Biotechs?

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Posted by Derek

Smack in the middle of the biotech district of Cambridge, at one of the busy intersections, is a whopping billboard. It’s one of those that rotate vertical segments between three faces, and for some weeks now, all three of them have proclaimed loudly “Stop Biotech Greed!” Variations on the theme include how much money biotech companies make, how the state should stop trying to encourage the industry and spend its money somewhere else, and so on. I’m sure the folks at Biogen enjoy seeing this thing switching between messages all day long; it’s right across from one of their buildings.

I wasn't at all sure who was funding this, because that billboard would presumably take more cash to lease than many activist groups have on hand. I do see occasional hand-made flyers against a proposed biological lab that Boston University wants to build, an issue that’s been fermenting around here for some time, but this was the first blast of anti-industry sentiment that I’d noticed. A quick look around provided the answer, though: the message is from the International Brotherhood of Electrical Workers, and the bottom of the dispute seems to be that several building project are going on that employ non-union electricians. And since a significant amount of the new construction in this area has to do with biotech and associated fields, well. . .

I suppose that they figured that attacking "biotech greed" will play better than a billboard saying "Hire Our Members Or We'll Insult You Again".

Comments (25) + TrackBacks (0) | Category: Current Events | Why Everyone Loves Us

March 4, 2009

Wyeth v. Levine: Pre-emption Goes Away

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Posted by Derek

The idea of preemption in drug liability cases has been coming up a lot in recent years. If the FDA approves a drug, does that Federal-level approval stop liability suits at the state level, or not?

The Supreme Court has ruled today in the Wyeth v. Levine case, which directly addresses this issue. And pre-emption now appears to be a dead issue, at least in my first reading:

". . .State tort suits uncover unknown drug hazards and pro-vide incentives for drug manufacturers to disclose safety risks promptly. They also serve a distinct compensatory function that may motivate injured persons to come for-ward with information. . .

. . .Wyeth has not persuaded us that failure-to-warn claims like Levine’s obstruct the federal regulation of drug labeling. Congress has repeatedly declined to pre-empt state law, and the FDA’s recently adopted position that state tort suits interfere with its statutory mandate is entitled to no weight. Although we recognize that some state-law claims might well frustrate the achievement of congressional objectives, this is not such a case.

We conclude that it is not impossible for Wyeth to comply with its state and federal law obligations and that Levine’s common-law claims do not stand as an obstacle to the accomplishment of Congress’ purposes in the FDCA. Accordingly, the judgment of the Vermont Supreme Court is affirmed."

And that, I would say, is that.

Comments (12) + TrackBacks (0) | Category: Current Events | Regulatory Affairs

February 26, 2009

Ranbaxy in Trouble

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Posted by Derek

There are reports this morning that the FDA is halting further review of drug applications from one of the largest generic drug manufacturers, India's Ranbaxy. It appears that some test results submitted to the agency have been found to be falsified. Update: here's the FDA's complaint (PDF).

I'm not seeing any details on what sorts of numbers look to have been cooked, or how the FDA caught on - more may come to light later. But it's for sure that this is trouble no company needs, and behavior no company should engage in. It's going to be especially hard in this case, because Ranbaxy (and India) have been trying to prove themselves as major, trustworthy players in the industry. I would have put the company in that category already, unfortunately, until this.

But it's important to remember that US companies have had their own compliance issues with manufacturing over the years - ask Schering-Plough about that, among others. Until we have more details about what's going on, I think it would be prudent to hold off on the "see what those cheap foreign plants will try to get away with" rhetoric. Who knows, that may come later.

Comments (39) + TrackBacks (0) | Category: Current Events | The Dark Side

February 25, 2009

Single, Simple Numbers: Use At Your Own Risk

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Posted by Derek

I wanted to link to this excellent article by Felix Salmon over at Wired. He's talking about the mathematical formula that convinced many people on Wall Street that they'd figured out how to price out correlated risks in debt securities. As we all now know, they'd done no such thing, even though trillions of dollars ended up riding on the whole idea.

The article's well worth reading just on those terms. But it's also worth thinking about for what it says about other fields where the risks - and the correlations between different risks - can't be well measured. Such as drug discovery and development! Many examples in Salmon's article can be extended directly to our own industry: what are the risks of each compound in Company X's pipeline failing? If a compound with a similar mechanism wipes out over at Company Y, how have the odds now changed? What about patent risks - if a Supreme Court decision makes everyone rethink issues of infringement or obviousness, how correlated are the patent-busting exposure around the industry? And so on. . .

The difference is that we haven't (quite) convinced ourselves over here that we've got it all figured out, and we haven't issued billions of dollars in derivative securities on top of our individual drug development programs. Not yet, anyway. But if you come away from a study of the current situation with a mistrust of any formula that people try to use to quantify complex systems down to one easy-to-use number, well, you've come out ahead.

Comments (15) + TrackBacks (0) | Category: Business and Markets | Current Events | Drug Development

February 12, 2009

Autism and Vaccines: Boiling Over Yet Again

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Posted by Derek

As you may well have heard by now, Ben Goldacre over at Bad Science has been involved in a wonderful altercation with both the anti-vaccination people there and with one of London’s big talk radio stations, LBC. And yes, this is happening just as Andrew Wakefield, one of the originators of the whole MMR vaccine flap, is being accused of falsifying data to make his case.

The full story can be found on Goldacre’s blog; see the link above for a starting point. The short version: LBC allowed Jeni Barnett, an outspoken opponent of vaccination, to vent her views for some 45 minutes in a prominent time slot. As Goldacre points out, she seems to have covered every possible anti-vaccine trope, despite the fact that some of them were mutually contradictory and many of them made little sense to start with. The British media – many parts of it, anyway – has not covered itself in glory on the whole vaccine-risk story, and this latest outburst was too much for Goldacre to take.

He posted the entire audio of the LBC show on his website, and that brought on threats of legal action from the radio station. And that move, as anyone who’s hung around the internet can tell you, made sure that the audio was immediately scattered around the world, with commentary, transcripts, and plenty of bad publicity. (You can find plenty of links to all of it here; I’m late to this particular party myself).

Goldacre makes an important point, one that’s been made before but has to be kept in mind when you’re listening to the news coverage of any disputed issue. He quotes Jeni Barnett as:

”. . . explaining endlessly that all she wanted to do was “start a debate” (because in the media everything is 50:50, and the truth lies exactly half way between the two most extreme views)

He's right; you run into that sort of thing all the time – readers who’ve had occasion to deal with Intelligent Design people and other creationists will recognize it immediately. “Teach the controversy” "Let's hear both sides of the debate", and all that. It’s another example of the disconnect between science works (or should work) and the political and social arenas. There are some big differences in the way disputes are resolved.

One of them is that, to a certain degree, questions do not remain open in scientific debate in the same way they do in politics. Fistfights are currently erupting over whether Keynes had a point about deficit spending in a recession (and if he did, how much is appropriate and in what way). Huge, ever-inflamed arguments take place over welfare, regulatory policy, defense spending, and other perennials. There are more than two sides to these kinds of issues. But come over here to the scientific world, where gravity really does diminish as the square of the distance between two objects; bacteria really do cause infections; sodium really reacts with water and yes, living organisms do evolve and change over time. Proclaiming that you disagree with these things just because you don’t like them, just think that they’re wrong, or don’t happen to believe them will get you nowhere in scientific debate. (That’s as opposed to political or religious debates, where those are all-too-common starting points).

But, at the same time, every question in science is potentially open. Look at all those facts I listed above – you can find ways around all of them. Gravity stops behaving in a perfect inverse-square way close to large masses. Not all bacteria cause infections, of course, and not all infections are caused by bacteria - and some bacteria that might kill one person could cause no problems for someone else. Sodium doesn’t do anything spectacular at all when it’s in the plus-one oxidation state, and even the metal probably doesn’t do much when exposed to water at, say, three degrees Kelvin. And organisms evolve at startlingly different rates and through a variety of mechanisms.

These two simultaneous principles – that questions really do get answered, but that the answers are always open to question – are what puzzle a lot of people about science. And they don’t fit well with the way that many people are used to arguing about issues. They can dwell on the first point and whack the scientific community over the head for having closed minds and unchallenged dogmas, or dwell on the second and claim that hey, they're all unproven theories, and here are some more theories to put on the table while we're at it.

But if you’re going to challenge some science that we think we understand, you’re going to have to bring the data. The bigger the topic, the better the evidence you’re going to need. You can do it – all kinds of cherished theories have gone down – but it’s not easy. If you’re going to claim that evolution doesn’t happen, or that we’re thinking about it all wrong, you’d better have some really impressive evidence (and coming up with an alternative with the same kind of explanatory power would help, too). If you’re going to claim that vaccines do more harm than good, or that they’re the cause of a specific terrible condition, you’d better have the numbers to back it up, not a mish-mosh of talking points.

Einstein’s work, for example, has stood up against all comers, taking on all kinds of extraordinarily painstaking experimental tests and passing every single one of them. If you’re going to beat relativity, you’re going to have to show up with absolutely epic skills. And that brings up a last point. When Einstein explained Mercury’s orbit (and more besides), he didn’t come in proclaiming that Newton was an idiot and that he’d gotten it all wrong. Isaac Newton, though an exceptionally weird human being, was very far indeed from being an idiot. No, relativity shows how under “normal” circumstances, Newton’s gravitational laws work wonderfully. Then it shows under what conditions they go off track, and predicts when that will happen and exactly to what degree. If you’re going to proclaim any new way of looking at the scientific evidence, you’re going to have to show how your breakthrough allows for something new to be seen, and you’re going to have to call your shots and be ready for the experimentalists to have a crack at you.

I find all this wonderfully exciting, and I've devoted my career to it. But it doesn't necessarily make for a quick TV or radio segment that will bring in a big audience, stir up a lot of noise and chatter, and (most importantly) raise the advertising rates. For that, you want politics, religion, or some tasty mixture thereof. . .

Comments (28) + TrackBacks (0) | Category: Autism | Current Events | Press Coverage | Who Discovers and Why

February 3, 2009

Their Crime? Collaborating With Other Scientists. . .

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Posted by Derek

Nature is rightfully drawing attention to the case of Arash and Kamiar Alaei, physicians (and brothers) from Iran, who have been sentenced to years in prison for supposedly "communicating with an enemy government". Their real crime seems to have been attending international conferences, talking about HIV as a public health problem in Iran, and doing so alongside representatives of US-based groups.

As the journal points out in an open letter, Mahmoud Ahmadinejad has been traveling around telling everyone about how wonderful scientific collaboration is. Watch their hands, not their lips, though. My sympathies go out to the Alaei brothers, along my hopes that international pressure might secure their release or make their appeals successful.

And my sympathies also go out to those scientists and physicians in Iran who have to work under such conditions - as the record of many expatriates shows, Iranians excel in such work when fools are not clapping handcuffs on them.

Comments (8) + TrackBacks (0) | Category: Current Events

January 8, 2009

Short Items: India, Sanjay Gupta, Satori Pharmaceuticals

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Posted by Derek

I have a few short links for everyone today. One series of posts that you might not have seen from Xconomy is a tour of the technological hot spots of India by Boston University's Vinit Nijhawan. It's interesting stuff for people like me who haven't been to the country, and he isn't shy about pointing out both the good and the bad about India's current situation. He's not focusing on the chemistry/pharmaceutical sector, but it's an interesting read in general. I would very much enjoy seeing a similar series written from China - perhaps the Xconomy folks are working on that one?

Next: if Sanjay Gupta really is going to be surgeon general (and why not?), it's worth watching his exchange with Michael Moore when Moore's movie "Sicko" came out. This is a 17-minute YouTube clip, and you may not make it through if you can't stand Michael Moore, but it has some good moments. Gupta is a *lot* more reasonable dealing the Moore than I would have been, but gets hammered on for his pains anyway.

And here's an interesting one, from a financial standpoint. Raising money for startup companies has, in the last few months, gone from the usual state of “not so easy” to “nearly impossible”. Everyone’s hoping for that to improve, but for now, this is a nasty time to try to float a new startup. That goes for follow-on financing, too, naturally, and that can hurt even more than troubles with start-up money. You can potentially delay the launch of your new venture – after all, no one else is getting anything off the ground, either – but if you’re already got a company going, the funds need to keep flowing. Companies that lined up more money in the middle of 2007 are shivering over the narrowness of their escape.

So it's impressive that an outfit called Satori Pharmaceuticals has made it through a full round of venture funding, and for Alzheimer's therapies, no less. That's a notorious graveyard for good ideas, but (at the same time) it's equally notorious for being hugely under-served. Good luck to them - they'll need it (and don't we all?)

Comments (20) + TrackBacks (0) | Category: Alzheimer's Disease | Current Events | Press Coverage

January 5, 2009

Well, Hose Me Down. . .

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Posted by Derek

Pfizer's Jeff Kindler says that the company: "is willing to acquire a large rival drug company to improve its financial health".

In other news, bears have expressed a willingness to defecate in forested areas.

Comments (20) + TrackBacks (0) | Category: Current Events

December 16, 2008

Layoffs. More Layoffs.

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Posted by Derek

I’m told by several people that today Bristol-Myers Squibb is announcing layoffs in research (and perhaps other areas). I don’t know how extensive these are, or how they’re spread across the New Jersey and Connecticut sites. What I do know is that accounting practices make these things especially rough, since a disproportionate number of such cuts take place before year’s end, which doesn’t do much for anyone’s holiday season. (Of course, I suppose it could be even worse – you could be working for Pfizer, and spend the holidays not knowing if your job was going to be there in January or not). In a smaller but deeper cutback, I also note that Entremed, a company that’s been struggling to survive ever since its turn in the spotlight with Judah Folkman’s anti-angiogenic peptides, has announced that sixty per cent of its employees will be let go. Since that includes the CEO and CFO, you have to conclude that the situation there is not good.

Having been through the layoff process myself, I know what the people involved are going through, and I wish them every hope of landing new positions. If anyone out there knows of companies that are hiring now in research, or even planning to, I’d be glad to list such in a separate post in order to provide some leads.

One other related item: I’ve heard from Linda Raber at C&E News who’s working on a "Careers in Pharma" story for them, and wants to write about all the chemistry layoffs this year. She’d like to hear from people who are willing to be quoted on what things have been like. (Update: you don't have to be identified - see the comments section for contact info!) I was quoted in a similar story after the Wonder Drug Factory layoffs, actually; this sort of piece is turning into more of a perennial than anyone would like.

Comments (53) + TrackBacks (0) | Category: Business and Markets | Current Events

December 11, 2008

Pfizer's Restructuring Grinds Along

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Posted by Derek

So, Pfizer: it seems as if they’ve been going on about cutting their research staff for months now. Well, its has been months, and the whole thing is turning into a rather bitter joke for people in Groton, from what I can tell. This current wave of restructuring has been rumbling along since back in the summer, and they told people about the layoffs in the fall. How long is all this going to take?

The latest announcement from the higher layers is that the company will announce its plans “sometime in January”. Lee Howard, a reporter at the New London paper The Day, has a copy of a letter from Pfizer’s Rod MacKenzie (head of discovery research worldwide) to employees, saying that because the changes in research are so complex, he won’t be able to communicate them by the end of the year. I’m not sure if the letter includes his greetings for a Merry Christmas and a Happy New Year; maybe that one will arrive in time for Valentine’s Day. Here's the article, the comments to which erupt in a lot of vituperative town-vs-gown New London crossfire.

From what I’m hearing, the coming changes are going to be quite profound in chemistry. Pfizer seems to be dividing its chemists up into people who think up molecules, and people who make them, with no real overlap. You’re probably thinking sure, that’s how the Germans and the Swiss tend to do it, the PhDs in the offices and the BS/MS folks out at the hood. But apparently there are PhDs on the “make the molecules” side in Pfizer’s new scheme, although I think the “design the molecules” side will have no one who isn’t. At any rate, the traditional medicinal chemist, someone who has an idea for a new molecule and then goes out to the lab and makes it, will seemingly have no place at Pfizer. You do one, or you do the other.

And I’ve heard from several sources that major outsourcing will be a big part of the new system as well. The “drug designers” will also be resource managers, spending their time figuring out what compounds and series to ship over to China, and what to have the local groups work on. As readers here well know, I think that outsourcing definitely has its place, but Pfizer seems to be going even further down that road than the rest of the industry – how well that’s going to work is an open question. A lot of the outsourcing work I’ve seen over the years has been. . .OK. Used judiciously, that’s fine, but I don’t know if I’d want to base whole programs on it if I didn’t have to.

I think it’s safe to say that morale and productivity in the labs in Groton must be drooping a bit these days. How could it not be, with everyone waiting for months to see who’s going to be let go, and in this economic climate? I understand that it’s a big organization, and that figuring out what to do is a complicated job. I certainly wouldn’t want it. But the way this is being done has not reflected well on the company’s management and how it treats its employees. But we’ll just have to add this one to the existing lists in both categories. . .

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November 4, 2008

We Interrupt This Science. . .For Some Politics

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Posted by Derek

Election day. I’ve had a lot of requests from people who want to know how I’m going to vote. Before I started blogging, my reply to that was usually a variation on “None of your business”, but then I got into the sideline of telling people my opinions on things every working day. So that answer won’t do.

But what answer will, this year? My political leanings are, I think, fairly clear to anyone who’s read this blog for a while. Economically, I’m a capitalist, for sure. I believe that wealth can most certainly be created, most effectively through human creativity. I would prefer that people be allowed to keep as much of the fruits of their labors as possible, to do with as they wish. I’m a free-trader as well. Tariffs and subsidies do not make me happy. I believe in Adam Smith’s invisible hand, and in comparative advantage, which is why I continue to defend outsourcing even as it takes away jobs in my own industry, in my own country. I think that Schumpeter was right about creative destruction, but he never said it was fun.

In public and social policy, I believe that there should be strong, enforced laws at the limits of behavior – but I try to set those limits fairly wide, out at the “as long as you’re not harming anyone else” line. I think that inside that boundary people should be allowed to do as they damned well please, even if the results don’t please me much. Often, they don’t – but my tastes are not a matter of law. I’m not religious at all, so I feel no need to enforce what I might see as God’s will on anyone. My first (but not sole) requirement for my tolerance of someone else’s religious beliefs is whether they can stand me not sharing them. Not everyone can.

And as for elections, well, I have a low opinion of politicians in general. I realize that this is unfair to the elected officials who are genuinely hard-working public servants, but those people are rather thin on the ground. Ah, politics: watching the game played while growing up in Arkansas did me a lot of good. And studying history has given me no reason to think the game has ever changed. Why should it? Human nature hasn’t. (Any political scheme that proposes to change that should cause you to flee at all speed). No, people are what they are, and the best of them simply don’t go into politics, as a rule.

So, in a President, I’m not looking for charisma or charm – in fact, I rather fear both qualities. I’d like to see enough eloquence to keep someone out of the laughingstock category, but no more, if possible. In general, I’m not looking for someone whose appeal is based on looking good on TV. (Unfortunately for my opinions, our current system for picking presidents largely values the opposites of all these). As for intelligence, I’m looking for someone smart enough to pick advisors who are smarter and more capable than they are themselves. But feeling so smart that you think you’re actually on top of what’s going on is a recipe for disaster. No one at that level is master of events, or really even of their own fate.

All this said, I can’t say that I’m very thrilled with the prospect of either presidential candidate this year – nor is this the first election during which I’ve had that feeling. My economic preferences would tend to make me more Republican – but our current Republican president has spent money like pouring water on the ground, so what does that avail me? I agree with McCain more than Obama on foreign policy, but his statements on the current economic mess have been, to my mind, disgraceful. But then again, Obama’s have been disgraceful, too, as far as I’m concerned. Of course, one has to get elected, and to get elected one has to run around spouting all kinds of nonsense. I learned from my father to watch their hands, not their mouths: actions over words. But McCain’s actions are hard to predict, and as for Obama, someone who came up through Chicago politics is probably capable of things that would even raise the eyebrows of a guy from Arkansas.

I find no comfort further down the ticket. Sarah Palin has not shown herself, to my mind, as qualified to be president. I appreciate the fact that many didn’t think that Harry Truman was, either, and I realize that we’ve gone through several periods where the VP would probably have been disastrous if called on to serve (think Spiro Agnew, John Nance Garner). But no, while I understand the political reasons why McCain chose Palin, I think the choice reflects poorly on him in a larger sense. But on the other side of the ballot, Joe Biden often seems to me like the worst sort of blowhard hack, the walking embodiment of almost everything I can’t stand about national politicians. (Charles Schumer narrowly takes my prize in that category, in case you’re wondering). No, choosing Biden tells me nothing good about Obama.

I think it would do the Republicans a lot of good to be thoroughly out of power for a while, although the thought of Sarah Palin as a rising star in the party is not encouraging. But I think that having the Presidency and both houses of Congress will tend to bring out the worst in the Democrats. What to do? Whatever I do, it’s mostly going to be an exercise for my own conscience. I now live in Massachusetts; Obama will take this state even if an asteroid hits. Back in 1992, I spent so long in the polling booth that people were rattling the door as if it were a public restroom. Bush (Sr.), Bill Clinton, Ross Perot – I kept looking at the names, and finally realized that I couldn’t vote for any of them (admittedly, it took the least time for me to eliminate Perot). I finally voted Libertarian, in the serene hope and confidence that they would not win. But I'm not sure I can run that trick on myself again this year. . .

Update: this is why I generally don't write about politics - this post was no fun to write, and it's probably not much fun to read, either. Be assured that I'm not planningn to take the blog in this direction more than once every few years - the internet is full of political opinions, and doesn't need any more from me. Back to science tomorrow, I promise!

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October 24, 2008

BlackLight Power Responds

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Posted by Derek

After my post the other day, I’ve heard from some folks at Blacklight Power, including their founder, Randell Mills. He says that I have a number of details wrong about their system, and wrote with more information. I’ll quote from Mills:

”We do not add water to R-Ni. Any water present after drying is in the form of Bayerite or Gibbsite (Al(OH)3) which is quantified by XRD and TPD. Regarding the Rowan University team validation, the maximum theoretical heat from the measured content was 1% of the observed energy as stated with the analytical results given in the Rowan report which is on-line at our website.”

He also takes exception – as well he might – to my line about the correlation of the company’s activities to their fund-raising needs, stating that Blacklight currently has no need to raise any money at all. And as for the NMR figure that I could make no sense of, that appears to have been mislabeled. The one I was looking at, Mills says, is indeed a solution NMR and was actually Figure 45 in the document. Figure 58, he says, has now been fixed, although I have to say that it still looks like a duplicate of Figure 45 this morning at this link. Update: here's the correct version,

But as best I understand it now, the fundamental claim of the Blacklight work is that formation of their lower-energy states of hydrogen is extremely exothermic. Alkali metal hydrides, they say, are particularly good catalysts for this, giving you hydrinos and sodium metal (see equations 32 through 34 in their PDF). So the Raney nickel in these experiments is being used as a source of atomic hydrogen, and forming small amounts of sodium hydride on its surface gives you a system to see all this in action. Figure 17 would seem to be one of these, and Figure 21 is the same thing on a kilo scale.

I’ll not comment on these just yet, but will continue to see if I can make sense of what’s going on. I’ll invite readers to do the same if they wish, and to post queries about the stuff in the comments here (or to e-mail them to me). We’ll come back for another round as the process goes on.

Mills has been good enough to offer to help me out with any aspects of the data that they’ve published, and to get in contact with the company should I be in the area, which is a good sign, and much appreciated. They’re also supposed to have a video of the reaction up shortly, and we’ll see what we can learn from that as well. Against all this, I have to put the fact that I still find the physics behind the company quite odd and improbable. And one has to remember that the track record of odd, improbable physics breakthroughs that promise huge supplies of energy is. . .not good. And that’s putting it very mildly indeed.

But all it takes is one. And all Blacklight has to do to quiet the skeptics (many of whom are much more vitriolic than I am) is to throw that big switch at some point and have the kilowatts (or megawatts) come streaming out. That’ll do it, for sure, and the company assures everyone that this is their goal. I wish them luck with it, because a huge and unexpected new source of energy would be a good thing indeed. I’m actually glad to live in a country where ideas this wild can raise tens of millions of dollars, but (for the time being) I’m also glad that none of that money is mine.

Update: I'm already getting queries about how I can come down on the likes of Kevin Trudeau or Matthias Rath but not give Blacklight the same treatment. One reason is that Blacklight doesn't seem to be trying to extract money from the general public, which is, of course, Kevin Trudeau's whole reason for living. Another related reason is that Rath, Trudeau and their ilk are preying, in many cases, on people who are already ill and urging them to do things which will actually make them worse. Blacklight, as far as I can tell, is not urging people to chop down their power lines and send off for Home Hydrino Kits.

I find Blacklight's physics weird and unconvincing, too. But proposing weirdo physics theories is no crime.

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October 22, 2008

Blacklight Power: What on Earth?

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Posted by Derek

Today, thanks to a story in the New York Times, we take up the unusual case of Blacklight Power. You may have heard of them before - I had, and I didn't realize that they were still around. Their founder, Randell Mills, has been telling people for years now that there is another energetic state of hydrogen, which he calls the “hydrino”, and that transitions to and from this state can be used to generate power.

My competence in physics isn’t sufficient to wade through Blacklight’s thicket of equations – but what competence I have in the subject strongly suggests that the company is very likely delusional (or, less charitably, hoping to delude others). A “state below the ground state” for hydrogen atoms, based on fractional Rydberg coefficients, seems. . . highly unlikely, to put it mildly. This is a perfect example of extraordinary claims that call for extraordinary evidence.

And that’s where the Times article comes in. According to it, the company has send samples of Raney nickel, apparently enriched in their putative hydrinos, to Rowan University down the road from them in New Jersey. When reacted with water, calorimetry of this system appears to show a release of heat “far beyond anything anticipated”. (It should be noted that this is a burst of heat when the water is added, as you’d expect, not some sort of sustained reaction. Its application to electric power generation is unclear). Update: Blacklight has responded, pointing out that I have several details of this experiment wrong - see this later post.

I know, I know – we’ve been down this road before, and more than once. Breeding even more skepticism is Blacklight’s history (link thanks to Glenn Reynolds at Instapundit). The company has been around since at least the early 1990s, and appears to have been promising various breakthroughs Real Soon Now the whole time. The timing of these announcements would seem to correlate more closely to the company’s financial demands than to their scientific accomplishments. Update: Blacklight disputes this statement, too, saying that they're not raising money This is not a totally unfamiliar business model in the drug industry, to be sure, but neither are most drug companies proposing revolutions at the level of the hydrogen atom. No, Occam’s Razor doesn’t leave much stubble behind when you run it over Blacklight Power.

But when people start talking Raney nickel, they’re heading into my territory, and the territory of many of this site’s readers. The Times names associate professor Peter Jansson at Rowan as the faculty member who’s conducting the tests, and I’ve written him this morning, as one scientist to another, to ask for more details and comment, if possible. We’ll see what can be learned.

Blacklight, for their part, have this PDF available. This part would appear to be what’s being tested at Rowan:

”To achieve high power, R-Ni having a surface area of about 100 m2/g was surface-coated with NaOH and reacted with Na metal to form NaH. Using water-flow, batch calorimetry, the measured power from 15g of R-Ni was about 0.5 kW with an energy balance of delta-H = -36 kJ compared to delta-H of roughly 0 kJ from the R-Ni starting material, R-NiAl alloy, when reacted with Na metal. The observed energy balance of the NaH reaction was -1.6 x 10 to the 4th kJ/mole H2, over 66 times the -241.8 kJ/mole H2 enthalpy of combustion.”

I'll wait for more details before commenting on this, but it's clearly rather odd. Also in the rather-odd category are some of the figures in the Blacklight PDF - take a look at Figure 58, for example, which is labeled "MAS NMR spectra relative to external TMS Of NaCl, KCl, and CsCl showing the expected trend of increasing intensity of H2 (1/4) at 1.1 ppm relative to the H2 at 4.3 ppm down the column of the Group I elements."

Well, fine - but hold on a minute. MAS is "magic angle spinning", which is a solid-state NMR technique - and that NMR spectrum is clearly taken with a lot of DMF around. The dimethylformamide peaks are labeled as such, and it looks like a solution spectrum, not a solid-state one. Second, where's the trend? I see no series presented, just a single spectrum of something, with no labels to suggest various alkali metals. What's more, although I can't find a value for the NMR chemical shift of hydrogen gas in DMF, it's known to be 4.5 in deuterochloroform, so their 4.3 ppm is reasonable. But there's no peak at 4.3 to compare that big 1.1 ppm peak to - what am I looking at here? Update: Blacklight has informed me that this figure was mislabled, and that they're correcting the error

We shall see - maybe. I'll report back if I hear from the group at Rowan. For now, I remain skeptical. I would truly enjoy the discovery a new energy source, but the history of this field does not inspire confidence.

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October 8, 2008

A Green Fluorescent Nobel Prize

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Posted by Derek

So it was green fluorescent protein after all! We can argue about whether this was a pure chemistry prize or another quasi-biology one, but either way, the award is a strong one. So, what is the stuff and what’s it do?

Osamu Shimomura discovered the actual protein back in 1962, isolating it from the jellyfish Aequoria victoria. These were known to be luminescent creatures, but when the light-emitting protein was found (named aequorin), it turned out to give off blue light. That was strange, since the jellyfish were known for their green color. Shimomura then isolated another protein from the same jellyfish cells, which turned out to absorb the blue light from aequorin very efficiently and then fluoresce in the green: green fluorescent protein. The two proteins are a coupled system, an excellent example of a phenomenon known as FRET (fluorescence resonance energy transfer), which has been engineered into many other useful applications over the years.

Fluorescence is much more common in inorganic salts and small organic molecules, and at first it was a puzzle how a protein could emit light in the same way. As it turns out, there’s a three-amino-acid sequence right in the middle of its structure (serine-tyrosine-glycine) that condenses with itself when the protein is folded properly and makes a new fluorescent species. (The last step of the process is reaction with ambient oxygen). The protein has a very pronounced barrel shape to it, and lines up these key amino acids in just the orientation needed for the reaction to go at a reasonable rate (on a time scale of tens of minutes at room temperature). This is well worked out now, but it was definitely not obvious at the time.

In the late 1980s, for example, the gene for GFP was cloned by Doug Prasher, but he and his co-workers believed that they could well express a non-fluorescent protein that would need activation by some other system. He had the idea that this could be used as a tag for other proteins, but was never able to get to the point of demonstrating it, and will join the list of people who were on the trail of a Nobel discovery but never quite got there. Update: Here's what Prasher is doing now - this is a hard-luck story if I've ever heard one Prasher furnished some of the clone to Martin Chalfie at Columbia, who got it to express in E. coli and found that the bacteria indeed glowed bright green. (Other groups were trying the same thing, but the expression was a bit tricky at the time). The next step was to express it in the roundworm C. elegans (naturally enough, since Chalfie had worked with Sydney Brenner). Splicing it in behind a specific promoter caused the GFP to express in definite patterns in the worms, just as expected. This all suggested that the protein was fluorescing on its own, and could do the same in all sorts of organisms under all sorts of conditions.

And so it’s proved. GFP is wonderful stuff for marking proteins in living systems. Its sequence can be fused on to many other proteins without disturbing their function, it folds up just fine with no help to its active form, and it’s bright and very photoefficient. Where Roger Tsien enters the picture is in extending this idea to a whole family of proteins. Tsien worked out the last details of the fluorescent structure, showing that oxygen is needed for the last step. He and his group then set out to make mutant forms of the protein, changing the color of its fluorescence and other properties. He’s done the same thing with a red fluorescent protein from coral, and this work (which continues in labs all over the world) has led to a wide variety of in vivo fluorescent tags, which can be made to perform a huge number of useful tricks. They can sense calcium levels or the presence of various metabolites, fluoresce only when they come into contact with another specifically labeled protein, used in various time-resolved techniques to monitor the speed of protein trafficking, and who knows what else. A lot of what we’ve learned in the last fifteen years about the behavior of real proteins in living cells has come out of this work – the prize is well deserved.

I want to close with a bit of an interview with Martin Chalfie, which is an excellent insight into how things like this get discovered (or don't!)

Considering how significant GFP has been, why do you think no one else came up with it, while you were waiting for Doug Prasher to clone it?

"That’s a very important point. In hindsight, you wonder why 50 billion people weren’t working on this. But I think the field of bioluminescence or, in general, the research done on organisms and biological problems that have no immediate medical implications, was not viewed as being important science. People were working on this, but it was slow and tedious work, and getting enough protein from jellyfish required rather long hours at the lab. They had to devise ways of isolating the cells that were bioluminescent and then grinding them up and doing the extraction on them. It’s not like ordering a bunch of mice and getting livers out and doing an experiment. It was all rather arduous. It’s quite remarkable that it was done at all. It was mostly biochemists doing it, and they were not getting a lot of support. In fact, as I remember it, Doug Prasher had some funding initially from the American Cancer Society, and when that dried up he could not get grants to pursue the work. I never applied for a grant to do the original GFP research. Granting agencies would have wanted to see preliminary data and the work was outside my main research program. GFP is really an example of something very useful coming from a far-outside-the-mainstream source. And because this was coming from a non-model-organism system, these jellyfish found off the west coast of the U.S., people were not jumping at the chance to go out and isolate RNAs and make cDNAs from them. So we’re not talking about a field that was highly populated. It was not something that was widely talked about. At the time, there was a lot of excitement about molecular biology, but this was biochemistry. The discovery really was somewhat orthogonal to the mainstream of biological research."

Here's an entire site dedicated to the GFP story, full of illustrations and details. That interview with Chalfie is here, with some background on his part in the discovery. Science background from the Nobel Foundation is here (PDF), for those who want even more).

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October 7, 2008

Nobel Season 2008

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Posted by Derek

So we come upon Nobel season again. As I do every year, I'm going to throw the comments section open for nominations for who should (and who shouldn't!) get the prize in Chemistry this year. We may well have a trapdoor open on us again, since some years the committee uses the Chemistry prize as a dumping ground for spare biology prizes, but we'll see how it goes.

If we do get a chemistry prize this time, my money is against my own field, synthetic organic chemistry. In fact, long-term, I'm betting against it, unless the work has a hook into some broader story. That could be nanotechnology, drug discovery (wouldn't that be nice?), advances in materials science, energy storage or conversion, and the like. But I don't see many (any?) prizes being given out for straight organic synthesis, the way E. J. Corey's was. I think that the time for that has indeed passed.

But there's room for a prize or two in synthetic methods, I have to say, a sort of H. C. Brown-type prize. A lot of people have waited to see if palladium couplings would get one, for example. I think that metal-catalyzed couplings are definitely worthy of the recognition - they've taken over the world to a degree that younger chemists can't realize - but I don't know if the Nobel committee has ever been able to unravel the prize distribution to where they feel safe with it.

That's a problem in several areas (drug discovery being another example where credit is often spread around). Individual researchers can end up in the same boat, which is the usual opinion about, say, George Whitesides of Harvard. He's done a lot of very interesting work over the years, but it's been in several rather different areas. I think we can use all of those sorts of scientists we can get, myself, but the profile doesn't match up well with what the Nobel folks are looking for.

So, place your bets, folks. For reference, the Thomson/Reuters folks have a short list of their own, based on literature citations: Charles Leiber of Harvard for nanotech, Roger Tsien of UCSD for green fluorescent protein, and Krzysztof Matyjaszewski of Carnegie Mellon for atom-transfer radical polymerization.

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September 25, 2008

Pfizer: As We Speak?

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Posted by Derek

I'm hearing reports that Pfizer is telling employees in various therapeutic areas right now that there will be deep cuts coming, and that more details will be coming out in about two weeks (individual-level layoff notices, etc.) I gather that obesity research is being hit hard, and some others as well - but any details from people in a position to know would be appreciated.

This is a heck of a time to be laid off, that's for sure. Here's hoping that things aren't as bad as I'm hearing. . .

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July 2, 2008

More Pfizer Layoffs?

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Posted by Derek

Unfortunately, I’m getting reports of significant chemistry layoffs coming this fall at Pfizer’s Groton facility. Rumors of all sorts seem to be going around: one indication is that this is going to hit both PhD and associate chemists, as opposed to some earlier reorganizations there which mostly seemed to let lab heads go. The timing is also uncertain, but September/October seems to be the average of what I’m hearing. I assume that biology and other areas will feel the tremors, too, but I have no information about them. There's nothing on the news wires about any of this, so it's not at the official announcement stage, but people seem to be getting braced.

I’m not happy to hear about this kind of thing, but I can’t say that it’s a surprise, either. Pfizer is going to be having a rough time of it for years to come, what with the Lipitor patent expiration coming closer. And as fate would have it, the company will get to feel that one about as hard as possible, because the various things that were going to cushion the blow haven’t worked out so well.

Think about it – Celebrex was the whole driving force for the Pharmacia/Upjohn acquisition, and just look at it now. Compared to what it was supposed to be by 2008, it’s in terrible shape. Then you have the gigantic failure of torcetrapib, the CETP inhibitor that was going to extend the Lipitor franchise and make it even bigger. That was in late 2006, and the echos have not died away even now. And then there’s the ruinous failure of Exubera, the inhaled insulin that was going to be a runaway best seller all its own. (Oh, it really was, although it’s hard to remember that - a reader sent me a 2006 analyst report (Hambrecht) which is just giddy with expectations – Pfizer’s 1.2 billion sales projection is clearly way too low, you see, and the brokerage’s own 2.5 billion might be conservative. Heck, 5 billion in sales is “very achievable” by 2010, so you’d better load up now, because the ship is sailing, the train’s leaving the station, and so on. . .ah, Wall Street.)

So, Pfizer’s buffers are exhausted, but the big beaker of fuming nitric acid is still going to unload on schedule. It’s going to be a tough place to work, and it’s going to be a tough stock to own. If you have a chance to do anything about either of those situations, I’d look into it.

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May 29, 2008

Nullius in Verba

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Posted by Derek

Since I was talking the other day about the analytical habit of mind, this is a good time to link to an article by someone who has it like few other people alive: Freeman Dyson, who is thankfully still with us and still thinking hard. At the moment, he seems to be thinking about something that involves chemistry, physics, economics, and plenty of politics.

He has an article in the latest New York Review of Books that is one of the most sensible things I have ever seen on the issue of global warming. I strongly urge people to read it, because it’s a perspective that you don’t often see. (It ends, in fact, with a small note of despair at how seldom that particular viewpoint comes up). I found it particularly interesting, as you might guess, because I agreed with it a great deal.

Dyson stipulates at the beginning that carbon dioxide levels are, in fact, rising, and that they have been for some time. And he also is willing to stipulate that this will lead, other factors being equal, to a rise in global temperatures. He doesn’t get into the details, although there are endless details to get into, but goes on to make some larger points.

One of them is economic. One of the books he’s reviewing, by economist William Nordhaus, is an attempt to work out the best course of action. Nordhaus is not denying a problem, to put it mildly: his estimate comes out to about 23 trillion dollars of harm in the next hundred years (in constant dollars, yet) if nothing is done at all. The question is, how much will the various proposed solutions cost in comparison?

His numbers come out this way: the best current policy he can come up with, a carefully tuned carbon tax that increases year by year, comes out to only 20 trillion of damage, as opposed to 23 – that is, plus three trillion constant dollars. The Kyoto Protocol, turned down by the US Senate during the Clinton years, comes out to 22 trillion dollars of harm (one trillion to the good) if the US were to participate, and completely even (no good whatsoever) without the US. The Stern Review plan, endorsed by the British government, comes out to 37 trillion dollars of total harm, and Al Gore’s proposed policies come out down 44 trillion dollars: that is, twenty-one trillion dollars worse than doing nothing at all.

As Dyson correctly points out, these latter two proposals appear to be “disastrously expensive”. And the problem with such courses of action are that this money could be used for something better: Nordhaus also calculates the effect of finding some reasonably low-cost method to cut back on carbon dioxide emissions, such as a more efficient means of generating solar or geothermal power, the advent of genetically engineered plants with a high carbon-sequestering ability, etc. That general route comes out to roughly 6 trillion dollars of total harm, which is seventeen trillion better than doing nothing (and thirty-eight trillion better than the Full Albert). That’s by far the most attractive solution, if it can be realized. But doing an extra ten or twenty trillion dollars of damage to the global economy will make that rather unlikely, if we choose to do that.

And there are other effects. To quote Dyson:

” The practical consequence of the Stern policy would be to slow down the economic growth of China now in order to reduce damage from climate change a hundred years later. Several generations of Chinese citizens would be impoverished to make their descendants only slightly richer. According to Nordhaus, the slowing-down of growth would in the end be far more costly to China than the climatic damage.”

But there’s a factor that neither of the books he reviews mentions: that atmospheric carbon dioxide exchanges, on a relatively fast time scale, with the Earth’s vegetation. About eight per cent of it a year cycles back and forth, and that hold out hope for a biotech solution. Engineered organisms could fix this carbon into useful forms, or (failing that) just take out out of circulation completely. But we need to go full speed ahead on research to realize that.

The last part of his review addresses a larger question. Environmentalism, he states, is now more of a religious question than anything else. (Other people have realized that, and many who do bemoan the fact, but Dyson has no problem with it, saying that the ethics of environmentalism are “fundamentally sound”.) But here’s his problem:

”Unfortunately, some members of the environmental movement have also adopted as an article of faith the belief that global warming is the greatest threat to the ecology of our planet. That is one reason why the arguments about global warming have become bitter and passionate. Much of the public has come to believe that anyone who is skeptical about the dangers of global warming is an enemy of the environment. The skeptics now have the difficult task of convincing the public that the opposite is true. Many of the skeptics are passionate environmentalists. They are horrified to see the obsession with global warming distracting public attention from what they see as more serious and more immediate dangers to the planet. . .”

The distressing thing, as he mentions, is that many organizations (including, I'm sorry to say, the Royal Society among other groups of scientists), have decided that the issue is settled and that anyone dissenting from this view is to be slapped down. As for me, I’m not completely convinced by the current climate data, so I probably am to the right even of Dyson on this issue. Here he is, though, willing to stipulate that most of the basic assumptions are true, but finding no place for someone who can do that and still not see global warming as the Single Biggest Issue Of Our Time.

I know how he feels: I consider myself an advocate of the environment, but I think the best way to preserve it is to do more genetic engineering rather than less. Better crops will mean that we don’t have to plow up more land to feed everyone, and we won’t have to dump as many insecticides and herbicides on that land we’re using. That means that I also think the best way to preserve unspoiled spaces is to do less organic farming, and not more: organic farming, particularly the hard-core varieties, uses too much land to generate too little food, and it does so mainly to give people in wealthy countries a chance to feel good about themselves.

And I think the best way to preserve wild areas and biodiversity is to have more free trade and economic development, not to slow it down. Richer countries have lower birth rates, for one thing. (I actually think that the planet would be better off with fewer people on it, but I’m not willing to achieve that goal by killing off a few billion of us).

And finally, economic growth is what’s giving us the chance to find technologies to get us out of our problems. I know that there’s another way to look at it – that the technology we have got us into this problem, and that we should reverse course. But I don’t think that’s even possible, or desirable. I’d rather have engineered plants cleaning out the atmosphere, and I’d rather have electricity from fusion or orbiting solar arrays. I’d rather find cheaper ways to get some of our fouler industries off the planet entirely, and mine the asteroids and comets. I’d rather people get richer and smarter, with more time and resources to do what they enjoy. How we’re going to do any good by putting on hair shirts and confessing our sins escapes me.

Comments (62) + TrackBacks (0) | Category: Business and Markets | Current Events | General Scientific News

January 16, 2008

Judah Folkman

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Posted by Derek

So Judah Folkman is no longer with us. He's considered to be the father of the idea that many tumors help to make their own blood supply, through angiogenesis, and that this could be a way to impede their growth. Since his first papers on the topic were published back in 1971, I think he does indeed get the credit. And he should not only get the credit for having the idea, but for publishing it and sticking with it. (Here's an interview with Folkman where he talks about this and much more).

Interestingly, it had been noted as long ago as 1941 that transplanted tumors in animals managed to link in to the existing blood supply through the formation of new vessels, but no one knew what to do with this result. (Here's a history of the field from a few years ago). It's not surprising that it took so long for the idea to catch on, though. It was by no means clear back in 1971, much less 1941, how blood vessels could be raised up by signaling from their target tissue. It wasn't until much later that the signaling pathways for blood vessel growth were discovered. Vascular endothelial growth factor, for example, was only found in 1983, and its functions didn't become clear until 1989 (timeline).

Folkman's death (which took place in the Denver airport, of all places) has brought back memories of the (in)famous Gina Kolata article on Folkman's work in the New York Times from 1998, a front-pager which featured James Watson's notorious quote about how Folkman was going to cure cancer in two years. I wrote about that one in the early days of my blog, and again here when Entremed finally gave up on the compounds that Kolata and the Times had hyped to the skies. The year 2000 came and went without a cancer cure, and many more years are going to go by as well. That's because, as I and many others never tire of pointing out, cancer isn't a single disease, and will never have a single cure. It's like looking for a cure for bad writing - it comes in so many different varieties, for so many different reasons, and therefore needs many different fixes.

Comments (6) + TrackBacks (0) | Category: Cancer | Current Events | Drug Industry History

January 9, 2008

Ah, Politics

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Posted by Derek

I’ve got a big post ready to go on the subject of money and the drug industry, but since I figure everyone has a political hangover this morning, I’ll wait until tomorrow to put that one up. I was up in New Hampshire last weekend with my wife and kids, and I’m surprised that we didn’t trip over one candidate or another. Their campaign signs decorated every snowbank in Nashua, that’s for sure – I even saw a “Duncan Hunter 2008” one, which I should have loaded into the trunk as a collector’s item.

It’s far too early for me to talk about the various candidates in terms of their attitudes toward research and towards my industry – most of these people are going to be gone soon, anyway – but I will say that the lackluster showing (so far) of John Edwards pleases me. The idea of an Edwards presidency gives me the shakes, frankly (I see that he scares Alex Tabarrok, too).

At least this time he’s not promising that if he’s elected that the halt and the lame shall forthwith rise on the healing powers of stem cells. He did that in 2004, and in much stronger tent-meeting tones than that last sentence. It’s not that stem cells will never bring anyone up out of a wheelchair – I very much hope that that’s possible, and who knows, it may well be. But it’s not going to take place during the timetable of one presidential administration, that’s for sure.

No doubt everyone running for president is in favor of research, and of science in the abstract. (Well, OK, maybe we can make an exception for my fellow Arkansan Mike Huckabee, when it comes to some scientific theories). Their attitudes toward the drug industry, though, make for a much livelier spread of opinion. There will be time enough to talk about that once we’re down to the single candidates, though.

Comments (27) + TrackBacks (0) | Category: Current Events

October 12, 2007

Unnatural, And Proud Of It

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Posted by Derek

The Haber-Bosch ammonia synthesis doesn’t intrude itself into the public consciousness much, but this year’s Nobel gave it a bit of a push. One thing I’ve noticed, though, is that whenever the topic of artificial fertilization comes up, it always kicks up a small dust storm of comment around it.

These vary widely in the reasonableness. Pointing out that artificially fixed nitrogen moved agriculture from (ultimately) a solar-powered base to (largely) a fossil-fuel base is both accurate and a good starting point for further discussion. See the comments to the Nobel post for an example – a person can argue that the Haber process didn’t require fossil fuels per se, or that we use more of them cooking the food than we do growing it (which may be true), or that we use more of them moving the food around (which I think is almost certainly true, and which opens up another set of questions) and so on.

Other good topics for discussion are how close various parts of the world were to a Malthusian food crisis when the ammonia synthesis came along, the other industrial effects of relatively cheap ammonia, the tradeoff of intensive fertilized farming in smaller areas versus more traditional routes in larger ones, etc. But if you’d like an example of an unreasonable comment, I’ll let this one over at Megan McArdle’s Atlantic Monthly blog stand in for a lot of similar fuzzy-mindedness:

"Higher yields due to the petroleum rich Haber-Bosch method also mean faster soil erosion and increased need of rotation etc. Combined with applying this method for inefficient livestock agriculture - it has destroyed NOT saved the rainforest and other ecosystems. Chemical fertilizer in ecology are like statism for the economy. You can force short-term results but nothing more!

At least 800 million people still go hungry.. their way forward into a sustainable future is less livestock agriculture and (more) organic natural farming.

Haber-Bosch is on the same environmental level as coal, oil! Not good, not sustainable, ideologically toxic for survival. We have to get rid of it pronto if we want our children to have "a nice life".

. . .All the social sciences, all the non-biological sciences like chemistry and physics should drop immediately what they are doing and learn more about their mother (and forget as much as possible about their "father" - you know who I mean?)!"

It’s hard to know where to start with this sort of thing. But I think I’ll do what Richard Dawkins did for Prince Charles a few years ago. Dawkins’s “You’re an idiot” style of debate isn’t always productive (for example, I think he does more harm than good to his cause as an atheist), but in this case I think the board across the nose was a good idea. He pointed out that if we’re going to use “naturalness” as a criterion, then agriculture isn’t going to make the cut, either. And that doesn’t mean factory farming and Roundup-Ready seeds; that means agriculture of any kind beyond remembering where the good patch of wild blueberries is and getting there before the bears do:

I think you may have an exaggerated idea of the natural ness of "traditional" or "organic" agriculture. Agriculture has always been unnatural. Our species began to depart from our natural hunter-gatherer lifestyle as recently as 10,000 years ago - too short to measure on the evolutionary timescale.

Wheat, be it ever so wholemeal and stoneground, is not a natural food for Homo sapiens. Nor is milk, except for children. Almost every morsel of our food is genetically modified - admittedly by artificial selection not artificial mutation, but the end result is the same. A wheat grain is a genetically modified grass seed, just as a pekinese is a genetically modified wolf. Playing God? We've been playing God for centuries!

The large, anonymous crowds in which we now teem began with the agricultural revolution, and without agriculture we could survive in only a tiny fraction of our current numbers. Our high population is an agricultural (and technological and medical) artifact. It is far more unnatural than the population-limiting methods condemned as unnatural by the Pope. Like it or not, we are stuck with agriculture, and agriculture - all agriculture - is unnatural. We sold that pass 10,000 years ago.

Dawkins is correct. We live in an unnatural world, and that goes for a lot of prehistory, too. Our world has been unnatural ever since we started applying our intelligence to it. When humans first started building shelters to get out of the cold and rain, I suppose you could say that this is no more than what an animal does when it digs a den. Killing a mammoth partly in order to use its bones for a house is a step beyond that, but in the same league as what beavers do to birch trees. But clearing land, planting seeds in it, tending and harvesting a crop, and saving some of its seeds to plant again is another order of living. Just because it all happened a long time ago (and because no one yet knew how to write it down) doesn’t make it any more in tune with ancient natural harmonies or whatever. (Try this PDF on for size).

We've been trying to fertilize the soil for thousands of years with whatever was on hand - manure, dead fish, the ashes of the plants that were burnt to make the field. And we've been modifying the genetic profile of our food crops over that same time with awe-inspiring persistence and dedication. (Good thing, too). No, when we move from that to artificial fertilizers and genetically engineered seeds, we’re talking about differences in degree rather than differences in kind. Large differences in degree, true, and worth discussing they are, but not on the basis of either their antiquity or their "naturalness".

Comments (21) + TrackBacks (0) | Category: Current Events | General Scientific News

October 10, 2007

Ertl Wins: Down With Witchcraft

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Posted by Derek

As some had speculated, the Nobel in chemistry did take a turn toward physical chemistry this year, for the first time in some while. Gerhard Ertl has won for his work on reactions that take place on solid surfaces, an extremely important (and extremely difficult) field of research.

It’s hard because chemists and physicists have an easier time of it with bulk phases – all solid, liquid, or gas. When you start mixing them, or start trying to understand what happens where they meet, things get tricky. The border between two phases is very different from what’s on either side of it. The key zone is only a few atoms thick, and the interesting stuff there happens extremely quickly.

But some of the most important chemical reactions in the world take place down there. Take the Haber-Bosch process for producing ammonia – “Right,” I’m sure some readers of today’s newspaper are saying, “you take the Haber-Bosch process, whatever it is, and get it out of here.” But by making ammonia from nitrogen in the air, it led to (among other things) the invention of man-made fertilizers. That reaction has kept billions of people from starving to death, and kept huge swaths of wilderness from being turned into farmland. (Read up on Norman Borlaug if you haven’t already for more on this).

You can Haber-Bosch yourself some ammonia simply enough – just take iron powder, mix it with some drain cleaner (potassium hydroxide) and stir that up with some alumina and finely ground sand (silica). Heat it up to several hundred degrees and blow nitrogen and hydrogen across it; ammonia gas comes whiffing out the other end. Now, bacteria do this at room temperature in water, down around the roots of bean plants, but bacteria can do a lot of things we can’t do. For human civilization, this is a major achievement, because nitrogen does not want to do this reaction at all.

The industrial process was discovered in its earliest form nearly one hundred years ago, and was the subject of a Nobel all its own. But no one knew how it worked, which is a good example of how difficult surface interface work can be. You can see what has to happen eventually: the triple bond between two nitrogen atoms has to be broken and replaced by three bonds to hydrogen, whose own H-H bond is also broken. But that nitrogen triple is one of the strongest bonds in all of chemistry, so how is it breaking? Do the nitrogen molecules soak into the iron somehow, and if so, what does “soak in” mean on an atomic level, anyway? Do they sit on the surface, instead – and if they do, what keeps them there? Is that triple bond still in force when that happens, or has it started to break? If so, what on earth is strong enough on the surface of iron powder to do that? Where’s the hydrogen during all this, and how does its single bond get broken? What happens first, and why do you need the hydroxide and the other stuff? And so on.

Ertl and others had long studied hydrogen’s behavior on metal surfaces, while helping to figure out how catalytic hydrogenation works. (That was a reaction accurately described to me as an undergraduate in 1981 as “witchcraft”, and Ertl is one of the people who have helped to exorcise it). So they’d seen how hydrogen got broken into individual atoms and spread between iron atoms on the surface – the surprise for him and his co-workers was that nitrogen turned out to do the same thing, breaking that fearsome triple bond in the process. The biggest step in the whole mechanism happened very early. By running the reaction forward and in reverse (turning ammonia back into nitrogen and hydrogen, an otherwise perverse act for the most part), they were able to work out all the individual steps and the energies involved. Along the way, they figured out what the potassium hydroxide was doing in there, too (donating some key electrons to the iron atoms).

Observing this and other surface processes has pushed the limits of several spectroscopic techniques, such as Auger electron spectroscopy (AES), low-energy electron diffraction (LEED), various forms of photoelectron spectroscopy, and others. Ertl's work has been notable for using a wide variety of methods, since there's no one tool that can give you the answers to questions like these.

He and his associates have studied many other surface reactions, such as the sorts of things that go on in the catalytic converters in exhaust systems. Metal-surface reactions like this are crucial to industrial civilization, and their importance is, if anything, growing. If we're ever going to get fuel cells to work economically, use hydrogen as an energy medium, or do a better job cleaning up industrial wastes, we're going to be using such things. And keeping them in the category of witchcraft won't cut it. It never does. Congratulations to Gerhard Ertl!

Comments (23) + TrackBacks (0) | Category: Chemical News | Current Events

October 9, 2007

Nobel Chemistry Odds

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Posted by Derek

Paul Bracher over at Chembark has posted an extensive list of Nobel odds, just in time for tomorrow's announcement. For the record, I think that if it's a more biologically-oriented award - and hey, in recent years that's just what it's been - then Roger Tsien et al., for green fluorescent protein, is my guess. If it's straight organic chemistry, then my guess is Suzuki/Heck/ and whoever else they can decide on for transition-metal coupling reactions. In physical chemistry, I'd have to go with Richard Zare, for laser studies and various instrumental techniques.

Keep in mind, though, that my track record is pretty ugly. Of course, so is everyone else's.

Comments (7) + TrackBacks (0) | Category: Current Events

October 8, 2007

Nobel Season

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Posted by Derek

The Nobel in Medicine has gone this year to the inventors of gene-knockout techniques for mice, which seems well-deserved, considering how much has been learned through such experiments. This is, in fact, one of those discoveries that you'd think was already recognized by a Nobel if you hadn't been keeping count, which is as good a criterion as any. (It's rather odd, for example, that gene knockouts were recognized after RNA interference, don't you think, since a good ten or fifteen years separate the two in real life?)

Wednesday morning is the announcement of the Chemistry award, so I'm throwing open the gates of speculation, as I do every year around here. Our track record (mine and the predictions in the comments) has not been very good, but nobody has a good batting average when trying to read the minds of the Nobel committees. I feel pretty safe in saying that this year will be a "real" chemistry prize - we're one out of the last four, compared to overflow from the nonexistent Nobel in molecular and cell biology.

So, who's it going to be? Last year's uninformed gossip is here, and there's plenty more over at Chembark. Put your bets down, but only with money you can afford to lose. . .

Update: Still more speculation, and even more.

Comments (6) + TrackBacks (0) | Category: Current Events

August 5, 2007

The Choir Hears It Again

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Posted by Derek

Over at Life Sciences Daily, Ogan Gurel has a post on the recent FDA Avandia vote that's worth reading. That's not so much for the Avandia news, which we all know about now - the main focus of the piece is on the Center for Medicine in the Public Interest (CMPI) and their blog, Drugwonks.

I don't have a permalink up to Drugwonks, partly for the reasons that Gurel goes into. I should disclose, though, that I've met the people behind CMPI (Robert Goldberg and Peter Pitts), and have accepted their hospitality while attending a CMPI-sponsored conference last spring. I got along with both of them just fine. But that said, I don't think that their web site is as effective as it could be.

I think that whoever writes the posts there is trying for a lively, irreverent tone, but (as Gurel goes into a great amount of detail to show), a lot of the entries slide over into ad hominem invective. Now, I'm no stranger to that form of argument myself - any of my pieces on Kevin Trudeau would furnish a number of examples, and I enjoyed writing every one of them. (In fact, I reserve to right to back up and insult him again, when the opportunity arises).

But the weapon should fit the offense. There's almost nothing too nasty to say about Kevin Trudeau, but Steve Nissen (the cardiologist who's raised the alarm on Avandia and several other drugs) is no Kevin Trudeau. He's a very competent guy, with a set of strongly held opinions which he backs up with publications in high-ranking journals. Agree with him or not (and I've come down both ways in the past myself), he's a serious person making serious arguments. And they deserve serious responses, not the sort of raspberries and hoots coming from some of the Drugwonks posts.

And the thing is, I assume that the whole purpose of a think tank (like CMPI) is to influence debate. The tone of their blog, though, suffers from the same defects that make most political blogs (left or right) nearly unreadable to me. Conclusions are assumed without argument, choirs are preached to, poses struck - if you didn't agree with the point of view before you started, there's nothing there to convince you. Actually, if you didn't agree with the point of view before, you probably didn't even look at the site at all.

I've never felt the need to hang around sites where people do little more than cheer each other on about the rightness of their cause. I'd rather someone tell me something I didn't know, or show me a new way to think about an issue and why it might be correct. Perhaps that's the scientist in me. Are there other people who are more convinced by this sort of thing, from either end of the debate?

Comments (6) + TrackBacks (0) | Category: Current Events

July 13, 2007

Pour Encourager Les Autres

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Posted by Derek

There have been a couple of drug safety issues here in the US over the last few years - you may have heard about one or two of them. Less well known, unless you're in the industry, have been the fines that some companies have paid for deficiencies on their manufacturing end. Schering-Plough's $500 million dollar one about five years ago is one of the most memorable, but there have been others.

But other countries have different approaches to drug safety. And if their regulatory apparatus breaks down in some way, they have, well. . .different approaches to enforcement. Don't look for a Washington think-tank to advocate this method any time soon, although there are times that I'm really glad that it won't come to a vote.

Comments (5) + TrackBacks (0) | Category: Current Events

June 17, 2007

Access To Science

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Posted by Derek

Via Pharyngula, I came across this impassioned blog post on the problems that amateurs (and their children) have getting chemicals, lab equipment, and other science supplies these days. Regulatory attempts to cut down on access to potential explosives and company attempts to dodge potential lawsuits seem to be the main culprits.

I sympathize, and I just hope that the situation isn't as dire as it's made out to be. This isn't a new problem, though. Chemistry kits were already being drained of their more exciting components even in the early 1970s - my father went out and got me some supplemental chemicals back then, including a couple that I probably shouldn't have had. But from the sound of things, it's hard to even do that much under current conditions.

Even outside the hazardous parts of science, there's a general problem with a lot of equipment designed for kids being total junk. As an amateur astronomer, for example, it's not even safe to get me started on some of the telescopes that are sold as ideal for a young observer. And what's even more frustrating is that (compared to my childhood) good telescopes are more affordable and available than ever. There's no excuse for the unk. The situation isn't good in microscopes, either. As far as I can tell, you really have to go to the online surplus and auction sites and buy a used real microscope, if you can find a good one, because the ones marketed as starter instruments are trash.

I grew up with access to a fair telescope, a fine microscope, a good chemistry outfit, and more (model rockets, etc.) - which (now that I look back) was pretty good going on the part of my parents, considering where and when I had these things. I'm making sure that my kids have similar opportunities. There's no substitute for being able to use your hands if you're interested in science growing up. I hope that it's still possible.

Comments (16) + TrackBacks (0) | Category: Current Events

April 29, 2007

Time To Conduct Some Business

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Posted by Derek

It's been nearly three months since my former workplace closed its laboratory doors. By now, many of my co-workers have landed positions, although certainly not all. The experiences have varied widely: some of the associates were able to move to new positions so quickly that they hardly skipped a day of commuting, while other people are still updating their CVs and hustling up every connection they can.

I wanted to put in a brief plug, then, for some former colleagues who have reacted to the closure of the Wonder Drug Factory by striking out on their own. They've started a service company called Cheminpharma, which supports all sorts of chemistry related to pre-clinical drug discovery efforts: medicinal chemistry, synthesis of intermediates, reference compounds etc. They have a site in Connecticut and synthesis capacity in India, and they'd welcome any queries:

Uday Khire (Ph.D., MBA)
Cheminpharma
25 Science Park at Yale,
150 Munson Street, New Haven, CT 06511
Phone: 203-773-1737 (O), 203-231-3060 (cell)
E-mail: uskhire@gmail.com

I hope that they can make a go of it - by publishing that e-mail address, I've at least ensured that they'll get lots of spam, anyway. Works for me! With any luck, they'll hear from some people with more need for med-chem than your average Nigerian scam artist has.

Comments (7) + TrackBacks (0) | Category: Current Events

April 12, 2007

Layoffs - Again

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Posted by Derek

I've heard from more than one source that Pfizer has laid off a large number of research staff this week in Groton. This seems to have taken people by surprise in many cases, since the expectation was just that everyone would find out where they were on the new organization charts. Well, in a way, they did.

As mentioned in a comment to this post, the company seems to want to get more people out in the lab. They're aiming for a 4:1 ratio of associates to PhDs in chemistry, where the cuts seem to have been deeper. That would (to my knowledge) probably be the highest average ratio in the industry. Pfizer seems to be approaching this through both the numerator and the denominator: I've heard of associate-level chemists who had CVs in with the company getting recent messages about some planned hiring.

But for now, there are more researchers (chemistry and biology) out of work. The Northeast, I have to say, is getting rather saturated with drug industry job-seekers. The region is still processing my own site's closure, so I have a great deal of sympathy with the Pfizer folks who are being turned out now.

Comments (47) + TrackBacks (0) | Category: Business and Markets | Closing Time | Current Events

February 26, 2007

Hedgehogs in Stockholm

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Posted by Derek

F. Albert Cotton's recent demise brings up a question that traditionally comes up in the fall, during Nobel season. Cotton himself never won the prize, although his name came up constantly in the list of contenders. There's a group of scientists (a select one) in every Nobel-bearing discipline that fills this role. Some of these people eventually get Nobel recognition, of course, and when that happens a good number of onlookers are relieved that ol' So-and-So finally got it, and another host are surprised, because they'd already sort of assumed that ol' So-and-So had received one years before.

But as time goes on, it seems to become clear that some eminent people are just not going to win, and I'd have to have put Cotton in that category. The Nobel committee had years in which to act on his behalf; they never did. The question then is why. Theories abound, some of them conspiratorial (and thus unprovable for another hundred years or so), but most trying to discern what makes some work Nobelish and some not.

One of the strongest arguments is that doing a lot of good work across several areas can hurt your chances. It seems to help the committee settle on candidates when there's a clear accomplishment in a relatively well-defined field to point at. Generalists and cross-functional types are surely at a disadvantage, unless they can adduce a Nobel-worthy accomplishment (or nearly) in one of their areas. That's not easy, given how rare work at that level gets done even when you've devoted all your time and efforts to one thing.

The current example in organic chemistry is George Whitesides at Harvard. He's an excellent chemist, and has had a lot of good ideas and a lot of interesting work come out of his group. But it's all over the place, which is something I really enjoy seeing, but the Nobel folks maybe not as much. Just look at this bio page from Harvard, and watch it attempt to pull all his various research activities under some sort of canopy. It isn't easy.

To drag the late Isaiah Berlin into it again, Whitesides clearly seems to be a fox rather than a hedgehog. Hedgehogs tend to be either spectacularly wrong or spectacularly right, and that last category smooths the path to greater formal recognition. For more on fox/hedgehog distinctions in other disciplines, see Daniel Drezner (international relations), Andrew Gelman (statistics), and Freeman Dyson (physics), and for an application of the concept to drug research, see here. Which sort of creature does Whitesides stock his research group with? Paul Bracher would know.

(Readers are invited in the comments to submit their own candidates for scientists who always seem to be on the Nobel list, but haven't won, and any alternate theories about why this happens).

Comments (23) + TrackBacks (0) | Category: Current Events | Who Discovers and Why

February 23, 2007

F. A. Cotton, 1930-2007

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Posted by Derek

F. A. Cotton died this week, and another gigantic name in chemistry departs. As an inorganic chemist, he was technically outside my field, but no one's really outside the range of influence of someone like that. If you're an organic chemist, you use organometallic reagents and catalysts, and if you use those, you owe F. A. Cotton some appreciation. 50 years of research, 1600 papers, some extremely influential books - he really cleared some brush, and we're unlikely to see his kind again.

Comments (7) + TrackBacks (0) | Category: Current Events

February 21, 2007

CMPI Conference: Critical Path

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Posted by Derek

The last panel of the day (I missed a good part of one in between, unfortunately) is on the FDA's Critical Path initiative and personalized medicine in general. It's moderated by Greg Simon of FasterCures, and features Michelle Hoffman of Drug Discovery and Development, Robert McBurney of BG Medicine, Gualberto Ruaño of Genomas, John Swen of Pfizer, and Janet Woodcock of the FDA.

Hoffman makes the point that some of the hyper-sceptical reporting of drug and medical issues is a reaction to the genomics hype of a few years ago. (I know, some of you out there who've seen stories that were ripped right from an idiotic press release are wondering where this sceptical reporting is, but I think she's talking about, say, the New York Times.

McBurney spoke about his academic background, saying that he cares even more about data now than he did back then, since millions of dollars are riding on the results. He also mentions the genomic craze, using a good analogy - that a caterpillar and the corresponding butterfly have exactly the same genetic sequence. "I have the same genome I did when I was born," he said, "but some things have changed along the way". His company has recently signed a deal with the FDA to look at preclinical liver toxicity, wirh funding from several large drug companies.

Ruaño is speaking about reverse genomics, "bedside to bench" work for figuring out drug and tox mechanisms. He's summarizing a recent paper in Mol. Psych. on the metabolic effects of antipsychotic drugs - the weight gain and prediabetic symptoms seen in a subset of patients. He and his company did a large parallel search for DNA markers between the patient populations on the two ends of the weight-gain distribution. As it turned out, in olanzapine-treated patients, an ApoE marker was higher in the heavy group, and and ApoE4 one was higher in the lean. For risperidone-treated patients, the leptin receptor and the NPY5 receptor fit the same pattern. They're starting to use their markers prospectively to predict how new patients will respond.

That leads into John Swen's view from Pfizer. He makes the point right at first that he doesn't blame the media for the overhyping of new technologies, as opposed to the people promoting them. (He's got a point, although I'd share the blame out a bit more - compare Michelle Hoffman's view at the beginning of this post). His view of the Critical Path initiatives is that it's going to be long slog to get biomarkers and transitional medicine to work out - worth it, certainly, but not something that's going to start delivering in a short time frame. (No argument here!) He also thinks that we could be doing a lot better than we are in things like new clinical trial designs (which is interesting coming from a company that's run the first large published Bayesian clinical trial).

And finally, Woodcock of the FDA is being asked about how the whole Critical Path initiative is going to fare at its current level of funding. She also feels that the media are very cynical about the sorts of technologies that are being promoted, which corroborates the over-reaction theme. She also says that the parts of the scientific community that are "more vested in the reductionist model" are also pushing back a bit. (My take is that the minute something useful comes out of the whole personalized medicine field, most of the critics will shut up with great alacrity. Success has a thousand fathers, for sure, and nowhere more than in a drug company). She largely dodges the funding question, saying that's it not really the agency's job to lobby for funds, but says that the biggest obstacle she faces right now is getting enough reviewer time to evaluate proposals properly. She thinks that the single best use of the money, though, is personalized medicine (which I find a bit arguable at this point, but eventually she may well be right).

Comments (6) + TrackBacks (0) | Category: Current Events | Press Coverage | The Central Nervous System

CMPI Conference: Lunch With the FDA

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Posted by Derek

Now I'm listening to Andy von Eschenbach, the new FDA commissioner, who's giving a speech on communication and regulation. I think I can refer to him as "Andy", since I'm eating a ham and cheese sandwich in front of him (not to mention blogging his speech).

The main thing I've taken away is that the agency plans to announce some new outlets and methods to disclose information - he's not ready to say what those are yet, but promises that details will be forthcoming. Now questions are coming from the floor - the first one is on direct-to-consumer ads and the recent recommendations by the Institute of Medicine. von Eschenbach answers by saying that the FDA has to recognize the right to free speech, but has to make sure that things are factual. (Not the time to get into a discussion of commercial speech, clearly).

Answering another question, von Eschenbach seems to want to move the FDA away from a reactive stance on drug-safety issues. That's probably a good idea, but considering the kinds of events that bring these things to the front page, reaction is surely always going to be a big part of the process.

Now there's a question about the adverse event reporting system - how to make it useful without overloading people. (This was a feature of the second panel discussion). He's answering that adverse events are only part of the problem - there's unexpected efficacy as well, and any system needs to be able to pick up on all sorts of events. (I agree, but I think that the former will always far outweight the latter).

Now a representative of PhRMA is asking about transparency - as an MD, he's contrasting the open discussion at at mortality and morbidity conference among physicians with what takes place at the FDA/national press level. von Eschenbach replies that acquiring the data is only the first step, and that transforming raw information into knowledge needs to be more transparent. He's saying that the general public wants the end product, not so much all the raw data. (I'd add that these days there will always be people, far between but very committed and vocal, who will want to see the raw numbers, too).

An attendee from Pharmaceutical Executive magazine asks about making sure that different points of view are considered, and on whistleblowers in general. von Eschenbach's reply is that he'd like to have things run so that people wouldn't feel the need to go outside the usual processed. "If people wanted Andy von Eschenbach to do everything himself," he says, "there would just be the Andy Agency". He expects people to adhere to the way the FDA does business, and wants them to come to him if they have a problem.

Steve Projan of Wyeth is now saying that the FDA doesn't seem to have the resources to do what it wants to do, and asks about the renewal of the PDUFA legislation. (There's a whole panel on that in the afternoon). von Eschenbach's reply isn't very specific, as probably befits an issue that's the subject of current legislative wrangling. He regards PDUFA fees as straight fee-for-service, and regards them as useful, but only one part of his resourcing.

The last two questions are on drug labels - the questioner is asking about the inclusion of genomic information on warfarin and tamoxifen labels. And the final question is on regulation of diagnostic test regulation, and the burden on direct-to-consumer genetic tests - the questioner is saying that many primary care physicians aren't that well trained in genetics, and that these tests might as well go to the consumer rather than using the MD as a gatekeeper. "Uh. . .how much time do I have left?" says von Eschenbach, mock-nervously.

He answers that drug labels are changing constantly, and that the agency has to be certain that any infomation that's given out so broadly is really accurate and valuable. He says that the various "omic" disciplines are going to have to make sure that they've got very well established data before it can go on a drug label, but that he knows that this is coming on. As for the regulatory burden on tests, he seems leery of turning these things loose on the public, and would rather have these "integrated into the medical model".

Comments (1) + TrackBacks (0) | Category: Current Events | Press Coverage

CMPI Conference: Panel on the Politics of Drug Evaluation

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Posted by Derek

The second panel is going on now, moderated by Steve Usdin of BioCentury, and featuring Helen Boucher of Tufts, Frank Burroughs of the Abigail Alliance, Scott Gottleib of the American Enterprise Institute, and Steve Projan of Wyeth.

One subject that's coming up a lot (as it did in the first panel) is the associate of SSRI therapy with suicide (or suicidality). That's a good example of the tricky nature of drug regulation, crossing over from pre-approval to marketed compounds. Some of the earlier panelists (and questioners from the audience) bemoaned the media coverage on the issue - the current panel is talking about it as an example (some parts good, some bad) of how to study ongoing safety issues, with a big problem being who's going to pay for such things. Surveillance, everyone agrees, is probably the best way to get useful data on drugs and their performance in the real world, but (as has been pointed out), no one wants to hear about how that's surely going to drive up drug costs.

Other areas coming up are antibiotics (and the dearth of new ones) and off-label use of cancer therapies (and other drugs) and how much to regulate it.

The conflict between openness and giving lawyers bait to sue everyone is also being discussed - tort reform has been referred to more than once, as you'd figure. The debate about whether you want to report only data that's reached statistical significance has shown up as well (I think that the alternative is chaos, personally, but not everyone agrees).

Steve Projan made a good point about the problems with Ketek (which, as others have noted, haven't had anywhere near the coverage that the Vioxx problems did). As he says, if you drop Ketek and switch to ampicillin, you'll end up killing more people through anaphylactic shock.

Note: post edited after original version, to incorporate more info - DBL

Comments (0) + TrackBacks (0) | Category: Current Events | Press Coverage

CMPI Conference: Panel on Media Coverage

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Posted by Derek

Well, I'm sitting in the audience now at the CMPI conference. My panel was the first of the day, and was pretty lively. Moderated by Rob Pollock of the Wall Street Journal, it featured Ed Silverman of the Newark Star-Ledger (and now of the very useful Pharmalot, Paul Coplan (who does risk managment at Wyeth), Tim Hunt (public affairs at Biogen-Idec), and Paul Seligman (safety policy at the FDA), and Diedtra Henderson of the Boston Globe.

Vioxx was a big point of discussion, as an example of media reporting on medical and pharma issues. There was a noticeable split between the reporters on the panel and the pharma people on this - the discussion was civil, but you could see the differences in opinion on how well the issue had been covered. With Biogen represented, the Tysabri withdrawal (and return) was also a big topic.

I suppose the main point I'd make in reference to that split came when Ed Silverman mentioned that a good thing that came out of the Vioxx coverage was that it started debate, and that that was always a good thing. I agreed with him, up to a point, adding, though, that I thought that informed debate was more useful. My problem with much of the Vioxx coverage was (as I said about that Michael Crichton op-ed the other day) that it made people feel as if they'd been informed when they hadn't been.

There was general agreement that risk/reward (especially absolute risk versus relative risk) was a key concept in reporting these things, but that it could be difficult to get across to a general readership. The other agreement was the companies should try to be as open as possible about clinical data and adverse events, with (naturally) different ideas about where the cutoff of possibility would fall.

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January 9, 2007

That Smell

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Posted by Derek

You know, I was seeing some more headlines about the powerful natural-gas smell in New York City the other day, and a thought crossed my mind:

You organic chemists over that way, at Columbia, NYU, Hunter College, etc. . .just by chance, did any of you happen to run a great big alkanethiol reaction? Or dump, for some odd reason, a liter or two of the neat stuff down a convenient waste pipe?

Just asking. How much ethanethiol would it take to stink out Manhattan, anyway? Depending on wind conditions, it might not be as much as you'd think.

Comments (8) + TrackBacks (0) | Category: Current Events

January 2, 2007

And The Winner Is. . .

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Posted by Derek

I didn't do any year-end awards around here, but the folks at ChemBark are charging ahead. If you were a reader of Paul Bracher's previous site, you'll have no doubt about who his Chemical Villian of the Year might be. The other awards are coming out as well, and are worth checking out.

Comments (0) + TrackBacks (0) | Category: Current Events

December 20, 2006

Injustice

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Posted by Derek

Many readers are probably aware of this story, but those who aren't should be. A court in Libya has (re)sentenced six foreign medical workers to death for allegedly infecting hundreds of Libyan children with HIV. That sounds insane on the face of it, and (as you would well imagine) the evidence for any such thing is just not there.

Instead, this seems to be a problem with poor hygiene in the health care system in Benghazi, which is not something that stretches the imagination like, say, a deliberate plot to infect Libyan children does. The molecular biology evidence is that this is a local strain of the virus which was already spreading before the medics even arrived in the country. Nonetheless, the Libyan courts seem determined to make a huge case out of this, and the Libyan media (state-run, needless to say) have been whipping up the crowds.

No one can say how this will play out, because there are still many slow, painful steps to go in the Libyan legal process, which certainly seems rather baroque for a country not exactly used to the rule of law. With Libya trying to open up to the West and bring in foreign investment, a horribly circus like this would seem to be just what they don't need. But it's already been dragging on for a couple of years now, in the face of all evidence and reason.

As I've said before, one of my general rules is that questions which begin with "I wonder how come they. . ." are often answered with "money". And that's probably the case here. Speculation is that all of this will come down to paying Libya some sort of "compensation". That's a nice word for what's really just an ugly, immoral shakedown - the sort of thing that the better class of gangster might feel is beneath them. Not the government of Libya, however. The Libyan people deserve better. The medics in this case, for their part, deserve to be freed immediately.

Comments (5) + TrackBacks (0) | Category: Current Events

November 27, 2006

The Litvinenko Case: More On Polonium and Alpha Particles

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Posted by Derek

So, what actually happens, down at the molecular and cellular level, when a person is exposed to alpha radiation? If it’s coming from outside the body, not all that much. The outer layer of dead skin cells is enough to soak up most of the damage, and it’s not like alpha particles can make it that far through the air, anyway. This is good news for Londoners worried about exposure (I note that reports have at least three sites there showing traces of radioactivity). I strongly discourage anyone from standing around next to an alpha source, but there are a lot worse things that you can stand next to - a gamma or fast neutron source, for example, either of which will penetrate your tan and keep on going.

But inside the body, that’s a different story. Alexander Litvinenko was given polonium in his food or drink, and from there the stuff distributes fairly widely across many tissues. At lower radioactive doses, that pattern is probably a good thing. When you have a radionuclide that concentrates in a particular tissue, like iodine in the thyroid, a dose that would be bearable across the entire body can cause a lot of local damage when it piles up. At higher doses, though, the situation can flip around. People can survive with damaged thyroid glands, or after total bone marrow transplants or the like. But general tissue damage is much harder to deal with.

Polonium ends up concentrating in the kidneys, to the extent that it concentrates anywhere, and attempts have been made to minimize radiation damage there. But by then an awful lot of destruction has occurred elsewhere – the blood-forming tissues, the linings of the gastrointestinal tract and the blood vessels themselves, and others. Note that these are all fast-dividing cell populations.

Zooming in, the mechanisms for all that mayhem are complex, and they’re still not completely understood. The first thing you can imagine is the alpha particle smacking into something, which to a first approximation is exactly what happens. They don’t get far – less than 100 micrometers. But along the way they can bash into quite a few things, losing some energy each time, which shows up as flung-off electrons, various strengths of photons, and doubtless some good old kinetic bouncing around. Eventually, when the particle slows down enough, it drags off a couple of electrons in passing and settles down as a peaceful atom of helium. That leaves some positive charges to account for, though, since those electrons were otherwise employed before being press-ganged, and this ionization (along with that caused by those stray electrons along the way) is one of the major sources of cellular damage.

All this can take place either in the nucleus or out in the cytoplasm, with different effects. This sort of thing can damage the cell's outer membrane, for one thing, which can lead to trouble. In the nucleus, one of the more dramatic events is sudden double-strand DNA breakage. That's never a good thing, since the strands don't always get put back together correctly. A couple of years ago, a group from the Netherlands was able to come up with dramatic images of chromosome breakage along the tracks made by alpha particles in living cells.

Then there’s also the complication of the “bystander effect”. Untouched cells in the vicinity of one that has taken an ionizing radiation hit also show changes, which seem to be at least partly related to an inflammation response. This seems to happen mostly after damage to the nucleus.

All this focused destruction has long since drawn the attention of people who actually want to kill off cells, namely oncology researchers. Alpha sources conjugated to antibodies are a very big deal in cancer treatment, and a huge amount of work is going on in the area. The antibodies can, in theory, deliver the radiation source specifically to certain cell types, which soak up most of the exposure.

So there's a use for everything. But one of those uses, this time, was assassination. Alexander Litvinenko's killers knew exactly what they were doing, and exactly what would happen to him. I hope that they're eventually found and dealt with proportionately.

Comments (9) + TrackBacks (0) | Category: Chem/Bio Warfare | Current Events | Toxicology

Polonium Poisoning

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Posted by Derek

I was going to write up a piece on thallium poisoning, until word came out over the long weekend that the Russian spy case was instead an instance of polonium poisoning. That's a very different matter indeed.

For starters, polonium isotopes (like most radioactive substances) are much more hazardous as radiological agents than as chemical ones. Unraveling the two isn't always easy, but this case is pretty clear. It's likely that polonium is chemically toxic, since it's in the same series as selenium and tellurium (which both are), but it's also likely that any reasonable dose would kill a person from alpha radiation rather than from whatever enzyme inhibition, etc., that might also ensue. People have been dosed with fairly robust amounts of tellurium and survived, albeit uncomfortably, but I can't imagine that anyone has been exposed to a systemic dose of a hard alpha emitter and pulled through.

This takes us into the long-standing arguments about the toxicity of such isotopes. Readers who remember the anti-nuke days of the 1970s and 80s may recall the statements about plutonium's incredible toxicity, generally expressed in terms of how miniscule an amount would be needed to kill every human being on the planet. Left unsaid in those calculations was that said plutonium would have to be dosed intermally in some bioavailable form. More Pu was surely vaporized in the atmospheric bomb tests of the 1950s, without depopulating the Earth to any noticeable extent. (See the arguments here, for example).

Here, though, we have a case of that exact bioavailable dosing of a strong radioisotope, with the unfortunate effects that you'd predict. There were some experiments early in the atomic research era where patients were dosed with radioactive isotopes. Oddly, the polonium experiments may have been the only ones that stand up to ethical scrutiny. A good review of what's known about polonium exposure, at least as of 1988, can be found here.

One thing that many people may not realize is that every person on the planet has some polonium exposure. There are many people who equate "radioactive" with "man-made", but those categories don't completely overlap. Polonium is a naturally occurring element, although certainly not in high abundance, but there's enough for Marie Curie to have isolated it. It's part of the radioactive decay series of U-238, and as a daughter radionuclide is a contributor to the toxicity of radium and radon exposure. You've had it - but not like this.

Comments (17) + TrackBacks (0) | Category: Current Events | Toxicology

November 9, 2006

Help Wanted - I Hope

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Posted by Derek

Well, here's a post I didn't think I'd be writing, although the possibility (given my industry) has always been there. The Wonder Drug Factory has decided to totally rearrange their research divisions, and we've been informed that our site is slated to close. Several hundred people will be losing their jobs, and I'm one of them. I don't agree with the decision (hey, I never think it's a good idea to turn me out on the street), but "out of my hands" doesn't begin to describe it. By all appearances, things will be shut down by the end of the year.

So the job search is on, and I'm going to start it by using whatever size platform I've built here. As for my background and experience, well, si curriculum vitae requiris, circumspice. I'm told by colleagues that reading my site is a pretty good simulation of having me around in person, so (for better or worse), that's what you'd be getting. I can provide a more traditional CV on request, of course, with the accompanying lists of patents, publications, and previous projects.

For family reasons, I'd prefer to stay in Connecticut, but I'll obviously start looking farther afield depending on what's out there. Industrial drug discovery is my strong point, naturally, but I'm certainly willing to listen to other ideas (academia, etc.) I can be contacted at derek-lowe@sbcglobal.net. I also want to mention that I have a number of very capable colleagues, at all levels of experience. Recruiters and search firms, give me a call - I can put you on to some excellent prospects: chemists, biologists - we've got 'em all. Or more accurately, we had them all, until today.

I'd been reasonably optimistic as the clouds gathered here over the last few months, but at the same time I've been preparing for this event, which is within error bars of the worst case. As for my attitude toward such things, I can tell you that Epictetus said it a long time ago:

Work, therefore to be able to say to every harsh appearance, "You are but an appearance, and not absolutely the thing you appear to be." And then examine it by those rules which you have, and first, and chiefly, by this: whether it concerns the things which are in our own control, or those which are not; and, if it concerns anything not in our control, be prepared to say that it is nothing to you. . .

When therefore we are hindered, or disturbed, or grieved, let us never attribute it to others, but to ourselves; that is, to our own principles. An uninstructed person will lay the fault of his own bad condition upon others. Someone just starting instruction will lay the fault on himself. Some who is perfectly instructed will place blame neither on others nor on himself.

Losing this job has not been in my control. Finding another one is. Here goes!

Comments (61) + TrackBacks (0) | Category: Business and Markets | Current Events | Drug Industry History

October 9, 2006

Here and There

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Posted by Derek

A few miscellaneous notes this morning: I had an e-mail from a reader who asks "Why is Imclone stock worth anything at all?" He was referring to the competition they're now facing from Amgen, and the managerial turmoil that's been going on for months now. For my part, I think that IMCL is worth something, but I sure don't think it's worth $29.44/share, which is where I went short on Friday. (In the future, if I write about them, I'll make note of that fact each time in the interest of disclosure). I realize that this puts me on the other side of the fence from Carl Icahn, a person whose stock-picking judgment I might normally defer to. But in this case, I think I may know more about cancer therapies than Icahn does. We'll find out.

On an unrelated topic, I have a request. Does anyone know of a commercial source for a library of diverse phenyl carbamates? I realize that that's not the usual sort of diversity library - if I were after secondary amines, the offers just wouldn't stop. I can find scattered examples from various suppliers, but if someone had a bunch already collected, it would be a great time-saver. Any ideas?

But finally, though, physics is more on my mind than chemistry this morning. I'm digesting the unpleasant implications of this map, courtesy of the US Geological Survey. . .

Comments (2) + TrackBacks (0) | Category: Cancer | Current Events

August 27, 2006

Floyd Landis: Could His Cortisone Treatments Exonerate Him?

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Posted by Derek

After my article on the role of carbon isotope testing in the Floyd Landis case, a question has come up several times in the comments and in my e-mail: since it's well-known that Landis was taking cortisone for his hip, could this have skewed the isotope ratios in his testosterone?

I doubt it very much, and here's why: first off, around 95% of the circulating testosterone in the male body is produced in the testes. For Landis's isotope ratios to be off a significant amount through something involving his own metabolic pathways, this is the only place that's worth looking.Testosterone and the other steroids are produced from cholesterol. The testes and other steroidogenic tissues have a stockpile of cholesteryl esters ready to be used for steroid synthesis, so it's going to be an uphill fight to alter things by any route, given that reserve.

Now it's time to dive into some biochemistry for the next few paragraphs - follow along if you like, or jump down to near the end if you don't want to see a lot of structures. OK, in steroid synthesis the first thing that happens is the chewing off of a side chain on the D ring to form pregnenolone, which is then turned into progesterone. That's the starting material for both testosterone and cortisol/cortisone. (Note that those last two are interconverted in the body by the 11-HSD enzymes).

Going down these different pathways, testosterone and cortisol end up with rather different structures. Cortisol's more complex. If you flip back and forth between those links in the previous paragraph, you'll see that the A and B rings are the same in both, but the C ring of cortisol has an extra hydroxyl group at C11, and it also has some oxidized side chain left at C17, which has been completely chopped off in testosterone. The question is, can you get from cortisol back to something that could be used to make testosterone?

I can believe the side-chain transformation much easier than the C-11 deoxygenation. Here's the metabolic fate of cortisol. Note that all these metabolites still have an oxidized C-11 - if anything is going to be recycled into testosterone, that C-11 is going to have to be reduced back down. And if there's a metabolic pathway that does that to any degree, I can't seem to find out anything about it. If it's a feasible pathway at all, it must be very minor indeed. If any steroid experts can shed light on this, I'd be glad to hear the details. (There's also the question of how long such intermediates would be available, versus their half-life before further metabolism and excretion, but that's a whole other issue).

No, if Landis's carbon isotope ratios are off significantly - and we haven't seen the official numbers yet - then it's hard for me to see how the cortisone injections could have much to do with it. We'll be stuck, in that case, with either conspiracy theories or with the conclusion that Landis used testosterone, and if it comes to that, I know which one I'm most likely to believe.

Comments (22) + TrackBacks (0) | Category: Analytical Chemistry | Current Events

August 10, 2006

Airplanes and Chemicals

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Posted by Derek

I've already been asked about today's news of a plot to bring chemical explosives on to commercial flights in Britain. Naturally, like most other chemists, I have opinions and speculations about how people might do this, but I'm going to keep them to myself. I've no desire to be used as reference material for such things, unlikely though that might be. If there are later disclosures (unlikely) about the compounds and methods used, I may comment on them then, but I'm not going to add to the available information about homemade explosives for terrorism.

And in the spirit of honi soit qui mal y pense, it is my sincere wish that anyone who investigates such things blow themselves up very early in their R&D program.

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August 1, 2006

Testosterone, Carbon Isotopes, and Floyd Landis

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Posted by Derek

The New York Times broke the story today that the testosterone found in Tour de France champion Floyd Landis's blood was not from a natural source. Just how do they know that, and how reliable is the test?

The first thing an anti-doping lab looks for in such a case is the ratio of testosterone to the isomeric epitestosterone - too high an imbalance is physiologically unlikely and arouses suspicion. Landis already is in trouble from that reading, but the subject of the Times scoop is the isotopic ratio of the testosterone itself. And that one is going to be hard to get away from, if it's true.

Update: people are asking me why athletes don't just take extra epistestosterone to even things out. That they do - that's the most basic form of masking, and if Landis's ratio was as far off as is being reported, it's one of the odd features about this case. But the isotope test will spot either one, if it's not the kind your body produces itself - read on.

Steroids, by weight, are mostly carbon atoms. Most of the carbon in the world is the C-12 isotope, six protons and six neutrons, but around one per cent of it has an extra neutron to make it C-13. Those are the only stable isotopes of carbon. You can find tiny bits of radioactive C-14, though, and you can also get C-11 if you have access to a particle accelerator. Work fast, though, because it's hot as a pistol.

So, testosterone has 19 carbon atoms, and if on average every one out of a hundred carbon atoms is a C-13, you can calculate the spread of molecular weights you could expect, and their relative abundance. One out of every ten thousand molecules would have two C-13 atoms in there somewhere, one out of every million or so would have three, and so on. A good mass spectrometer will lay this data out for you like a deck of cards.

But here's the kicker: those isotopic forms of the elements behave a bit differently in chemical reactions. The heavier ones do the same things as their lighter cousins, but if they're involved in or near key bond-breaking or bond-making steps, they do them more slowly. It's like having a heavier ball attached to the other end of a spring. This is called a kinetic isotope effect, and chemists have found all sorts of weird and ingenious ways to expoit it. But it's been showing up for a lot longer than we've been around.

The enzymatic reactions that plants and bacteria use when they take up or form carbon dioxide have been slowly and relentlessly messing with the isotope ratios of carbon for hundreds of millions of years. And since decayed plants are food for other plants, and the living plants are food for animals, which are food for other animals and fertilizer for still more plants. . .over all this time, biological systems have become enriched in the lighter, faster-reacting C-12 isotope, while the rest of the nonliving world has become a bit heavier in C-13. You can sample the air next to a bunch of plants and watch as they switch from daytime photosynthesis to nighttime respiration, just based on the carbon isotope ratios. Ridiculously tiny variations in these things can now be observed, which have led to all sorts of unlikely applications, from determining where particular batches of cocaine came from to figuring out the dietary preferences of extinct herbivores.

So, if your body is just naturally cranking out the testosterone, it's going to have a particular isotopic signature. But if you're taking the synthetic stuff, which has been partly worked on with abiotic forms of carbon derived from a different source (see below), the fingerprints will show. (Update: yes, this means that the difference between commercial testosterone and the body's own supply isn't as large as it would be otherwise, since the commercial synthesis generally starts from plant-derived steroid backbones. But it's still nothing that a good mass spec lab would miss). If the news reports are right, that's what Landis's blood samples have shown. And if they have, there seems only one unfortunate conclusion to be drawn.

Chem-Geek Supplemental Update: for the folks who have been wondering where exactly the isotopic difference comes in, here's the story: synthetic testosterone is made from phytosterol percursors, typically derived from wild yams or soy. Those are both warm-climate C3 plants, which take up atmospheric carbon dioxide by a different route than temperate-zone C4 plants, leading to noticeably different isotope ratios. That's where all the isotope-driven studies of diet start from. The typical Western industrial-country diet is derived from a mixture of C3 and C4 stocks, so the appearance of testosterone with a C3-plant isotopic profile is diagnostic.

Comments (299) + TrackBacks (0) | Category: Analytical Chemistry | Current Events

March 24, 2006

Explosion News

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Posted by Derek

It's a busy news day. Word is this morning (EST) that there's been a huge explosion at a chemistry building at the ENSC of Mulhouse, in Alsace in eastern France - an old and well-known chemical engineering school. One faculty member appears to have been killed, and there are several injuries. The building looks to have been severely damaged, and local residents are saying that the explosion was heard all over town and felt like an earthquake.

I've been looking at some news reports, but no one's reporting on what caused the blast. This sounds like much more than a typical batch-of-something-in-the-hood going up, though, that's for sure. If any readers can shed some technical light on this in the comments, I'd be grateful.

Comments (5) + TrackBacks (0) | Category: Current Events

December 22, 2005

Poor Put-Upon Intelligent Design

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Posted by Derek

I was driving last night and listening to NPR, when they broadcast a commentary by Joe Loconte of the Heritage Foundation. This was bemoaning the Dover decision tossing Intelligent Design out of the local Pennsylvania school curriculum, and I'm afraid I ended up adding some loud and vulgar commentary of my own while hearing it.

Loconte's analogy was to the Big Bang theory in cosmology. He claimed that when the theory was proposed, that some of the objections to it were because of its similarities to the creation account in Genesis. I wasn't aware that the Big Bang was considered too religious, but it seems that this was the case for some physicists. That's quite an irony, though, considering some of the religious objections to it now. (Here's a rundown from everyone's favorite creationist web site, Answers In Genesis, certainly the first time I've ever linked to them. Hours of entertainment await you there, though, I have to admit.)

And you can see where the rest of the commentary went. We should make room for seemingly heretical theories in science, even if they seem to have religious overtones, because the orthodox dogma of the scientists can indeed be overthrown, yea verily, just as it was with the Big Bang theory. Loconte has sounded this note before, many times - see this CNN transcript where he goes on about the "high priests of evolution" and the "divergence of views within the scientific community" on the issue.

But Loconte neglected to mention that Big Bang cosmology won its case by providing empirical evidence, and plenty of it. And this was done completely within the framework of scientific discovery - making testable predictions, for one thing.

And that's where the analogy with ID breaks down. If Intelligent Design has made any testable predictions, I've missed them. If it's advancing due to further research, I've missed that, too. Loconte has made the error, which is unfortunately common in those with no scientific background, of assuming that ID is just another scientific theory because it claims to be. "I can't see how something this complicated could have happened except by God doing it" is not a basis for scientific discovery. For that, you want something like "I can't see how something this complicated could have happened. Let's look at all the evidence we can get and follow it no matter where it leads."

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December 20, 2005

The Dover Decision Comes Down

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Posted by Derek

The last time I touched on Intelligent Design around here, things were pretty lively, and I promised not to return to the topic until the Kitzmiller decision came down. Well, here it is (PDF).

Good luck getting that link to load today, though. I think that this one from the York Dispatch is working better. From what I've read so far, Judge Jones has completely hammered the ID case flat:

". . .The Board contacted no scientists or scientific organizations. The Board failed to consider the views of the District's school teachers. The Board relied solely on legal advice from two organizations with demonstrably religious, cultural, and legal missions, the Discovery Institute and TMLC. Moreover, Defendants' asserted secular purpose of improving science education is belied by the fact that most if not all of the Board members who voted in favor of the biology curriculum change conceded that they still do not know, nor have they ever known, precisely what ID is. To assert a secular purpose against this backdrop is ludicrous. . .Defendants have unceasingly attempted in vain to distance themselves from their own actions and statements, which culminated in repetitious, untruthful testimony. . .

. . .Those who disagree with our holding will likely mark it as the product of an activist judge. If so, they will have erred as this is manifestly not an activity Court. Rather this case came to us as the result of the activism of an ill-informed faction on a school board, aided by a national public interest law firm eager to find a constitutional test case on ID, who in combination drove the Board to adopt an imprudent and ultimately unconstitutional policy. The breathtaking inanity of the Board's decision is evident when considered against the factual backdrop which has now been fully revealed through this trial. The students, parents, and teachers of the Dover Area School District deserved better than to be dragged into this legal maelstrom, with its resulting utter waste of monetary and personal resources. . ."

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November 30, 2005

Merck Update

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Posted by Derek

Despite an AP story today that named a Merck/Banyu research site in Japan, It looks like it's the Merck research site in England (Terlings Park, Harlow, Essex) that will close, as some rumors already had it. A comment was left to the post below that seems to confirm things, and I believe that it's authentic.

I'm sorry to see it. They've been doing good work there for a long time - a large part of the Substance P story that I spoke about here was done at Terlings Park, for example. Here's hoping that Merck doesn't have to cut more in the future.

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November 28, 2005

Merck, Finally

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Posted by Derek

Everyone's been waiting for it, and today the ax finally dropped at Merck. It had to. The company still has over six thousand Vioxx lawsuits piled up, and one of their biggest moneymakers (Zocor, simvastatin) is going off patent (and that's not their only patent problem). Their advanced research pipeline has taken a terrible pounding the last couple of years, too, with the loss of a couple of Phase III compounds and the post-approval death of Pargluva.

It's not easy to tell from the press release, but it looks as if many of the 7,000 jobs that Merck is cutting will come from manufacturing. They're closing five production sites outright and trimming some others over the next two years. Discovery isn't being spared, though, since Merck's also closing a basic research site. (That's how you know things have gotten bad at a big pharma company). No details on which one yet, but I think we can assume that it's not going to be Rahway, and I don't see how it can possibly be West Point, PA either.

That would mean that the folks at Merck-Cambridge and Merck-La Jolla (Update: whoops - that one's been closed since June) must be pretty jumpy, and I don't blame 'em. I listened to a fair amount of the company's conference call from this morning, and a spokesman said that the employees at each site designated for closure would be notified over the next two days. There won't be any public announcements until then.

As someone who's been through some rounds of closures and layoffs (a memorable one of which happened at almost this exact time of year, come to think of it), my sympathies go out to Merck's employees. I don't believe that their company has ever been through something like this before. I'm sorry to see y'all joining the club. And you people at Pfizer, I'm afraid that your membership will be up for renewal soon. . .

Update: here's a list of Merck's research sites. . .

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November 7, 2005

Intelligent Design, Molecule By Molecule

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Posted by Derek

[Update: reading this post, I can see that I was in a pretty testy mood when I wrote it last night. Intelligent Design does that to me. So if you're not in the mood to be ranted at, come on back tomorrow and I'll see what I can do for you. . .]

Further update: comments have now been turned off, to keep this one from rising from the grave. No doubt I'll post on ID again eventually, so everyone will have another opportunity to ventilate their opinions.

OK, one more on this topic, and then we'll try to give it a rest until the Dover school board decision comes down. (The comments to the yesterday's post are still rolling right along, though, as you'd expect from a debating ground like this one). The article by Jerry Coyne I linked to yesterday gives some good anatomical arguments against intelligent design. But I wanted to zoom down to the molecular level for a minute, since after all, I am a chemist.

DNA is a wonderful molecule, no doubt about it. And to someone like me, who believes that the evidence for evolution is overwhelming, it's also a fine illustration of how it works on a molecular level. Others, though, no doubt see in its intricacies the hand of a creator. What, I wonder, are we then to make of the degraded remnants of old viral DNA in our genome? Designed in there, or not? Or what about the long stretches that seem to do nothing but repeat the same few base-pair letters over and over - dozens, hundreds, or thousands of times? Doubtless the Designer would have his reasons, but perhaps some of these would have been better implemented with repeats that aren't so prone to breakage and mismatch. Hundreds of terrible diseases result. (That page is only the barest sample. It's an awful topic to research). It's almost as if these things persist as the residue of ancient random choices or something.

Moving on to what are supposed to be the normal genes, we find entire books can be written on the horrible consequences of tiny changes in the genetic code. Take the so-called Swedish and Dutch mutations in the amyloid precursor protein. Switch the DNA a bit, and you get a new amino acid in the protein. Get the wrong one, and you die, most terribly, from early and rampaging Alzheimer's disease with complications. Those particular mutations have been in families for hundreds of years now - we've tracked them through the generations. They're still with us because the people involved live long enough to have children - many of whom are destined to die the same terrible way - before the underlying disease finishes them off. It's almost as if the consequences of a mutation were more severe when it affects reproductive fitness.

Mysterious ways, mysterious ways. No doubt that accounts for why we (and guinea pigs, and Peruvian fruit bats) can't make our own vitamin C, the way the other mammals can. Or why our livers respond to the excess of free fatty acids in type II diabetes by. . .making more sugar, which is exactly what the body doesn't need. There must surely be a reason, too, a good well-designed one, for autoimmune diseases: having our bodies tear themselves to pieces on a cellular level; I can't wait to hear why that feature was built in. It's almost as if once we've had children, just about anything can happen to us.

I'll stop there. I could go on for pages. Suffice it to say that when I look at the biochemistry of living systems, I see an amazingly complex system, wonderful to behold. And it's held together with duct tape, chewing gum, and weathered pieces of wood - whatever was handy, and whatever worked. It's almost as if it's just been tinkering along for a billion years.

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November 6, 2005

The Dover Decision

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Posted by Derek

Friday was the end of arguments in the Kitzmiller v. Dover Area School District trial on the teaching of "intelligent design" in the local 9th-grade biology class. We won't see a decision in the case for a while (perhaps by the end of the year), and no one knows how broadly the judge in the case might be inclined to rule.

I don't see how there could be much uncertainty in my position on this matter, but just in case: I think that "intelligent design" is pernicious nonsense. I understand why some people believe it, but the argument from incredulity doesn't do much for me. If I threw up my hands at everything that seemed to complicated for me to explain, I'd be out of a job, and rightfully so. My scientific predecessors kept trying to explain mysteries - good for them! - and I'm not going to stop looking for answers, either.

Since the organization defending the ID position has said that they want to "use the courts to change the culture", here's hoping that they get an enormous bucket of cold water poured on them. I was a college student in Arkansas when Judge Overton ruled in McLean v. Arkansas, an attempt to mandate the teaching of "creation science", and his opinion still makes fine reading. It put the brakes on that whole approach to ridding curricula of evolution, but eventually such selection pressure led to the spread of this latest mutation. "Intelligent Design" is clearly the scion of "creation science" - try as I might, I don't see how anyone but a fool can believe otherwise. If it too gets struck down, we can all expect yet another variation in another few years as the anti-evolution forces continue to evolve.


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November 3, 2005

Merck Off the Mat

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Posted by Derek

Everyone will have heard the news that Merck won their second Vioxx court case in New Jersey this morning. This came as a relief to me and to people like me, for several reasons. The immediate one was just that Merck had survived this latest round, of course. This wasn't a particularly strong case, and I had hopes that Merck would prevail, but you never know how juries are going to run.

And that brings up the second reason: if Merck had lost this one, they could expect to lose plenty more. The plaintiff in this case survived his heart attack, had a history of heart trouble and had other risk factors, and doesn't seem to have been a diligent user of Vioxx at all, which he only took for two months. I'm sure that hundreds (thousands?) of other cases could be found that rise to roughly this level, and Merck would likely be crippled by losing them. Now the focus shifts to a Federal court case in Houston, which starts later this month. I hate to put it in these terms, but this next one is going to be something of a tiebreaker.

I'm not saying that Merck should necessarily win every case, though. Vioxx does seem to carry some cardiovascular risk, Merck does seem to have charged ahead with it, and so many people took it that there must have been some people injured. But the FDA did approve the drug, let's not forget, and it's quite possible to argue that its benefits still outweigh its risks. And even if Merck were to win every trial from here on, they'e still be out a huge amount in legal fees. They've taken a beating, both in their reputation and in their finances, and that's not going away.

So no, I don't think Merck should be able to suddenly make all their troubles go away (not that that's going to happen). But neither do I think that they should be driven into the ground like a tent peg by repeated legal hammer-blows. Drug companies should be punished when they screw up. But destroying them for it, in a chancy industry like this one, will just ensure that we don't have many working drug companies.

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October 5, 2005

Metathesis Nobel!

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Posted by Derek

As several of my readers had speculated, this year's Chemistry Nobel has gone to Grubbs, Schrock, and Chauvin for the olefin metathesis reaction. So, what the heck is that?

First things first. You're not going to be able to make people think you know about this stuff without a quick hint. It looks as if that word should be pronounced like something from a philosophy course (meta-thesis), but chemists put the accent on the second syllable and almost skip over the third: meh-TA theh-sis. What this reaction does is rearrange carbon-carbon double bonds (alkenes). Like many chemical mechanisms, that's something that happens by itself under harsh conditions, and makes some pretty harsh mixtures of gunk, but doing in a controlled and predictable way is another thing entirely.

This PDF from the Nobel people does a fine job of outlining the chemistry - page 7, in particular, shows the various reactions that you can do. (Here's a less comprehensive HTML look.) Two alkenes can be blended into a new one, which is useful. Many of the applications of the reaction have been with cyclic compounds: if the two alkenes are in the same molecule, the blending reaction forms a new ring. (This Ring-Closing Metathesis process became an instant fad within the organic chemistry community during the mid-1990s, with everyone trying it out to see what it could do.) And you can run the process in reverse - if you have a ring with an alkene in it, the reaction can break it open into two separate ones.

"Big deal", you might say. Actually, it is. Carbon-carbon bonds are the hard currency of organic chemistry. They're tough to handle, but that's what what you have to do to alter the framework of any organic compound. Any clean, predictable way of forming and breaking them is going to be instantly useful. (There still aren't enough reactions that can do that, and if you can find another one, you can go to Stockholm, too). Olefin metathesis is being used all over the place, from polymers to pharmaceuticals. It runs on the benchtop, and in the production plant - it's a good one.

One more thing about this prize: the Nobel committee has done a good job of assigning credit here. Chauvin was the first to work out how a metathesis reaction runs, even though people didn't have a very good way of doing the chemistry. Schrock was the first person to come up with a catalyst that would allow the reaction to run in the real world, but it had some limitations. And Grubbs came up with the catalyst systems that were easy to handle (meaning you could take them out of the bottle in ordinary air!) and worked on a wide range of compounds. This is a fine mix of basic and applied work, and I'm glad the the Nobel recognizes all of it. Congratulations to Yves Chauvin, Richard Schrock, and Robert Grubbs!

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October 2, 2005

A Piece of the Action

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Posted by Derek

Does anyone know where a man can put some of his hard-earned research dollars down on a Nobel Prize bet? The Chemistry prize is going to be announced early on Wednesday, so time is tight.

Last year there was a German site taking bets, but they seem dormant. Here's their previous chemistry prize page, which will do for a list of potential names this year, too, since none of them delivered. It's a bit top-heavy with organic chemistry names, I'd say, which is perhaps one reason it didn't perform that well. The Chemistry prize is often used as a way to spread the Medicine (or Physics) prizes around a bit - I'd think a smart customer would want to cover some of those possibilities with a field bet.

But where? Money can be placed on the Peace and Literature prizes. That's understandable, since many more people feel as if they know something about these subjects. (Some of the past awardees make it painfully clear that you don't have to know anything about either one). You can place an interesting bet on a future Physics prize (or lack of one) here. But sporting chemists seem to have no place to turn. . .

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August 21, 2005

Okay, One More Merck Point

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Posted by Derek

You know, there is one more thing about the Merck case I'd like address. This is brought on partly by the general press coverage of whether Merck knew this or hid that, and partly by an intensely irritating comment to Friday afternoon's post.

You would think, to hear the way some people talk, that no one at Merck ever took Vioxx. That they just launched it onto the market with an evil cackle and a shout of "Caveat emptor", then sat back to watch the money roll in. Actually, employees of Merck very likely took Vioxx at a rate above that of their cohorts in the general population - employee discounts, you know. I've no doubt that this applies to Merck's marketing department, to their clinical development groups, and to their toxicologists. Why shouldn't they take their own company's drug if they're in need of a COX-2 inhibitor?

It's not very far to the conspiracy theories that pop up about cancer, about HIV, about every awful disease you can imagine. "You know," some fool will whisper to you, "that the drug companies really have a cure for it. They're just waiting until more people get sick. In fact, they're probably making sure that as many people get it as possible."

It's difficult for me to express coherently my contempt for that idea. Let me assure you that employees of pharmaceutical companies, and their relatives, and their friends, are potential heirs to every disease that this world offers, just like everyone else. I might add that it's particularly hard to watch someone you know suffer and die from a disease that you've been working for years to treat, but still have nothing to offer for.

So enough of this division between Merck and the rest of the world. Merck is a large company, with tens of thousands of people in it. Many of them took Vioxx. No small number of those people probably worked on it. I'd like to hear how that pulpit-pounding Texas attorney would work them into his world view.

Update: For plenty of good commentary on the legal aspects of the Merck verdict, see Ted Frank's post at Point of Law.

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No More Merck For A Couple of Days

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Posted by Derek

I'm glad to hear that the punitive damages in the Merck case will be automatically reduced under Texas law. But the jury award will still set a public precedent, which I fear that later juries will be tempted to see and raise. Hey, if the Texas fellow was worth $253 million, who's to say that the next plaintiff isn't worth even more? There may be a tendency to dig deep into the pile of money while it's still there. Ay, what a depressing topic. I hope that everyone who dislikes the drug industry is enjoying this; someone should be.

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August 19, 2005

Judgement Day

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Posted by Derek

A during-the-working day update, and I don't think I've ever done that for good news. Merck has been found liable in the first Vioxx trial. The jury has awarded 24 million dollars in outright damages, and $229 million in punitive damages. (If you'd like a strictly utilitarian, economic response to that award, start by pricing out what $253 million dollars of life insurance will cost - that is, if you can get anyone to not hang up the phone on you.) Merck, of course, is going to appeal.

It shouldn't be any surprise to find out that I think that this is terrible news. While I think Merck really pushed Vioxx too hard, as have the other companies with COX-2 inhibitors, I don't see a way to justify that large an award. This might open the door to a number of such awards, and Merck could end up spending its money fighting for its life rather than trying to bring new drugs to market. Enough of these losses, followed by losses on appeal, could sink the company completely.

I know, I know. They should have thought about that before flogging Vioxx to everyone that could bend their finger joints, right, right. But if every new drug we take to market is going to have a reasonable chance of ruining the company, why bother? And I know the answer to that one, too: "just make sure they're safe." What tiny words "sure" and "safe" are. You wouldn't think that they could cause the trouble that they do.

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January 30, 2005

Welcome to the World, I Hope

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Posted by Derek

Although I generally don't comment on current political events here, I wanted to congratulate the Iraqis who voted in their election this weekend. From a scientist's point of view, it would be a fine thing if they (and the other countries in the region) could have their affairs in good enough order to join the research efforts that are going on in so many other countries.

You don't necessarily have to be a rich country to do some useful science, if you pick your targets well. Cuba, of all places, seems to have a pretty respectable expertise in biotech and vaccines. And (to be frank) the position of many Middle Eastern countries in the rankings of world science isn't due to lack of money. The Gulf States, for example, could bankroll some serious projects - but, for the most part, they don't. (I'm not going to comment on the large physics engineering project that seems to be underway in Iran!)

I'm showing my biases here, because I think that scientific research is one of the greatest endeavors of the human race. The more hands and minds we have working on the big problems, the better the chances of solutions. But the Middle East (broadly defined, and with the conspicuous exception of Israel) is a desert for science. Most of the countries in that part of the world are hardly visible in the scientific literature - in this PDF article, you'll see that this entire region (along with Africa) is completely ignored. In my field, I see occasional papers from Egypt and Iran, but that's just about it.

There are plenty of competent (and potentially competent) people in these countries - just look at what some of them have accomplished as expatriates. The social, economic, and educational problems in these countries are (among other things) a tremendous waste of human potential. We need it, they need it, and I hope that eventually it finds an outlet.

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December 1, 2004

Strangers on a Train

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Posted by Derek

Sean Carroll over at Preposterous Universe is one of those half-physics half-astronomy guys. He mentions that when he's on an airplane, the conversation takes a totally different turn depending on which field he claims. (Hint: people have some idea of what an astronomer does. . .) But Chad Orzel of Uncertain Principles hasn't been able to hide behind physics, because of the field's known ability to bring the cranks out from under chairs and behind curtains.

How does a medicinal chemist fare? Pretty well compared to those disciplines, actually. I've been afraid, at times, of inducing a rant about rapacious drug prices from total strangers, but that's never really happened. What I've found is that people are very interested in what I do, although they know almost nothing about it. I get a lot of questions - those experiences, in fact, are one of the things that started me blogging.

Now, introducing yourself as an organic chemist (which is also a fair statement) gives me a chance to reproduce Carroll's experience. That'll generally quiet people down very quickly, because odds are they've either never had a chemistry course or have less-than-fond memories of one. The most commone response is: "Organic chemistry! Man, I hated that!" But at least it doesn't breed cranks. . .what would they do, shove twenty-page syntheses of tetrodotoxin at you, with notes in green ink all around the margins?

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October 30, 2004

Special Off-Topic Weekend Irrelevancy

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Posted by Derek

Just in case there's anyone who hasn't had enough of the whole topic, the reasons for my (not-all-that-ringing) Bush endorsement are duplicated in greater detail by Megan McArdle guest-blogging on Instapundit. Her thoughts are an extremely close match to my own on most of the topics she covers (you'll particularly note the congruences on foreign policy and health care.)

So if you want to pick apart my choice, start by picking apart hers for practice. Hey, in a few days we'll know one way or another. . .I hope.

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October 25, 2004

Actually, It's Everything Else That's Off-Topic

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Posted by Derek

Here we are, with one week to go before the election. Several bloggers that I read regularly have called on the other opinion-spouters in this business to state who they're voting for, so readers can know where they're writing from. Since I talk about the politics of health care and drug industry (in between lab stories and bizarre patents, that is) I think I should go ahead and turn over my cards. The point of a blog is to have an opinion, after all, which opinion is expressed both in what I choose to write about and overtly within the writing itself.

So it shouldn't come as a surprise to regular readers that I will be casting my vote for President Bush next week. I'm not exactly going to be whistling as I walk into the booth, though, because Bush has done several things that would, under other circumstances, be deal-breakers for me. The limits on federal funding for embryonic stem cell research are one example. Since the issue turned into a political football it's been distorted past recognition, but while recognizing that embryonic stem cells are not going to suddenly send people leaping out of wheelchairs, and realizing that private money can (and is) funding such research, I still dislike the limits that the Bush administration has proposed. I understand their reasons, but I disagree with them and I worry about the precedent that they set.

Another problem has been the administration's wobbly attitude toward free trade. I don't like seeing tariffs anywhere on much of anything, so the steel and textile actions of the last few years don't sit well with me. I think that free trade is the closest we come to getting something for nothing in this world, and I worry every time someone messes with it for political advantage. (If I thought that Sen. Kerry would be any better, my decision to vote for Bush would be that much harder.)

Next we come to the nominal subject of this blog, pharmaceutical research. As you'd expect, Sen. Kerry's constant hammering on the drug companies make it next to impossible for me to consider voting for him. His proposals would significantly raise my chances of being tossed out into the street, unable to make a living at my chosen trade. And given the state of the industry, those odds are already quite large enough, thanks. I recognize that some of Kerry's statements are just campaign rhetoric, and that a Republican-controlled Congress would be unlikely to act on many of his plans. But it seems foolhardy to vote for someone on the assumption that he doesn't really mean what he says.

So under other circumstances, I'd be back to my situation in 1992. I was disappointed in Bush(41), did not trust Clinton (remember, I'm from Arkansas), and considered Ross Perot to be dangerously unstable. I took an awful long time in the voting booth, and finally cast a protest vote for the Libertarians, which required a bit of nose-holding even then. Ah, those 1990s. But this much too serious a year for protest votes. It would take a truly un-Libertarian amount of coercion to get me to vote for them this year.

My personal worries are about continued pharmaceutical employment, but the biggest issue in this election is foreign policy. And I simply cannot trust Senator Kerry's instincts in that area. I have disagreements with some of the things that the Bush administration has done and how it's done them, but those are nothing compared to the ones I can see having with a Kerry presidency. I believe that he, as well as many of his supporters, are living with a view of the world that correlates rather weakly with reality. And yes, I well realize that they believe the same thing about people like me.

There you have it. I'm not necessarily trying to bring anyone around to my point of view, since I don't think there's much convincing left to do at this late date. But now you know where I'm coming from, and can adjust your dials accordingly.

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July 4, 2004

Happy Fourth of July

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Posted by Derek

July 4th here: my two small children are splashing around in an inflatable pool out in the yard while I check the whole pork shoulder that's been cooking since about seven in the morning. More soaked hickory chips go in. (Where I grew up on the Delta, you can spot the barbecue restaurants because they always look as if they're on fire.) I'll have it with beans and my wife's cole slaw, and there's watermelon and homemade strawberry ice cream for dessert.

My wife and her mother are drinking tea out under an oak tree, beyond the kids's splash radius. Next to them, on a green picnic table, I've set up my old microscope, a medical student model that my parents gave me when I was ten. Earlier we were looking at some pond droplets, my son and daughter dripping with pool water as they peered at rotifers and nematodes.

My son has already announced that he wants some scissors when we go back inside, because he wants to cut some of the signatures out to keep from the newpaper's annual full-page reproduction of the Declaration of Independence. He and his sister especially like John Hancock's, of course, and the smart remark he made when he signed it. This year I pointed out Ben Franklin's signature, and related his line about all hanging together or all hanging separately, but I could tell that it didn't register - as it well shouldn't, but I couldn't resist.

They haven't grasped that people back then fought under terrible conditions - aren't they all - to be rid of a king and what he represented. And they don't realize how strange it was for a people to throw off the rule of a king and then, somehow, to avoid ending up under his replacement. (Meet the new boss!) George Orwell famously said that if you wanted to imagine the future, to picture a boot stamping on a human face, forever. But that's an even better summary of the past. Just look at it.

What's even stranger is that for over two hundred years we've continued to avoid all the kings, emperors, sultans, First Citizens, mullahs, all the other graspers and grabbers who long to be at the thick end of the whip. They're in long supply, unfortunately. My wife and her mother, out there in the yard, are both exiles from Iran. They can tell you all about it, starting in the days of the Shah. Then they'll go on to the days after the Shah's portraits were crowbarred down and another loser's stuck right up on the same spot so the paint job wouldn't look funny.

It's safe to say that none of us here in the back yard have any desire to be part of a restored Caliphate. The fellows who want to be in charge of it don't look like the sort who would look kindly on this scene, and not just because of the pork shoulder. And there are plenty of others who would find it necessary to shape things up around here if they were in charge, for that matter.

That'll serve as a test, then: anyone who'll leave us to our own devices this July Fourth - those people are the ones welcome here, strangely enough. If you don't give a damn, then sit down and have some strawberry ice cream. But if you think it's your duty to set us straight, then I've got a section of the newspaper for you to study. It has some holes cut out of the bottom part, but the main points are still there.

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April 6, 2004

Osmium Tetroxide, Of All Things

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Posted by Derek

This morning brings the news, via ABC, that the recently discovered bomb plot in London involved a quantity of osmium tetroxide. That's a surprise.

I know the reagent well, but it's not what anyone would call a common chemical, despite the news story above that calls it "easily obtained." It's quite odd that someone could accumulate a significant amount of it, and it's significant that anyone would have thought of it in the first place. It's found in small amounts in histology labs, particularly for staining in electron microscopy, but that's generally in very dilute solution. If these people had the pure stuff, well, someone's had some chemical education, and probably in my specialty, damn it all.

The reagent is used in organic synthesis for a specific (and not particularly common) reaction, the oxidation of carbon-carbon double bonds to diols. I've done that one myself once or twice. OsO4 comes in and turns the alkene into a matched pair of alcohols, one on each carbon, and it stops there. Other strong oxidizing reagents can't help themselves - they find the diol easier to attack than the double bond was, and go on to tear it up further. There was a recent paper in the literature on the mechanistic details, actually, going into just why the osmium reagent stops where it does.

Unfortunately, the alkenes it could attack are unsaturated fatty acids and such, as found in lipoproteins and cell membranes. Exposed tissue is vulnerable. Breathing a large amount of the vapor can kill a person through irritation of the lungs, but it's not as bad that way as the better-known agents like phosgene. A bigger problem is the cornea of the eyes, and the reagent is mostly feared for its ability to bring on temporary (and in some cases, permanent) blindness.

There's no doubt in my mind that any terrorist with the stuff was going for that effect. Could it have worked? Well, it's a solid at room temperature, but a hot day will melt it. The stuff sublimes easily; it has a high vapor pressure. Just being around the solid crystals is enough to get you overexposed to the vapors. I don't know how much of the reagent these people had, but I tend to think (again, contrary to the ABC story) that an explosion would have dispersed it to the point that it was just down to irritant levels. I wouldn't want to find out, though.

If they were planning to use it in a non-explosive gas attack, that's another matter. But the vapors are said to be very irritating, with a distinctive chlorine-like smell - which I cannot verify, thank God. It's not like no one would have noticed that there was some nasty chemical in the air. I think that they could have done some damage, certainly. But what disturbs me more than the reagent itself is the thinking behind it. . .

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January 6, 2003

And Another Thing. . .

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Posted by Derek

I've been staying away from all the Clonaid / Raelian hoo-hah. As soon as I realized who was behind this, I rolled my eyes and braced for the worst. I first read about the Raelians in Donna Kossy's extraordinary book Kooks (which I see is now in a second edition, which I must purchase very soon indeed.) With that as background, it's hard to take anything these people say seriously.

My opinion of the human clone claims can be easily expressed: bullshit. Look, you fools: extraordinary claims require extraordinary evidence. Come up with multiple blood samples now for DNA microsatellite analysis, in full view of multiple witnesses, or shut up. This is an important issue, and watching all of you hit each other with pies and try to cram yourselves back into the midget car isn't very instructive.

There. I feel better now.

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