About this Author
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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Category Archives
November 17, 2009
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 (6)
+ TrackBacks (0) | Category: Current Events | In Silico
November 13, 2009
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 (24)
+ TrackBacks (0) | Category: Current Events
November 11, 2009
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
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).

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 (40)
+ TrackBacks (0) | Category: Analytical Chemistry | Biological News | Current Events | Infectious Diseases
October 5, 2009
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
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
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
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
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. . .
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+ TrackBacks (0) | Category: Current Events | Drug Prices | Regulatory Affairs
August 17, 2009
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
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
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
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.
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+ TrackBacks (0) | Category: Blog Housekeeping | Current Events
June 19, 2009
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
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
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!
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+ TrackBacks (0) | Category: Blog Housekeeping | Current Events
June 14, 2009
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.
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June 3, 2009
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. . .
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May 20, 2009
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.
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+ TrackBacks (0) | Category: Cancer | Current Events | Snake Oil
May 12, 2009
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.
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April 30, 2009
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.
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April 27, 2009
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.
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April 7, 2009
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. . .
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April 1, 2009
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. . .
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March 27, 2009
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.
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March 12, 2009
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".
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March 4, 2009
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.
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February 26, 2009
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.
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February 25, 2009
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.
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February 12, 2009
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. . .
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+ TrackBacks (0) | Category: Autism | Current Events | Press Coverage | Who Discovers and Why
February 3, 2009
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.
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January 8, 2009
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?)
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January 5, 2009
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.
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December 16, 2008
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.
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December 11, 2008
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
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
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
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
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
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
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
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
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.
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January 16, 2008
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.
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+ TrackBacks (0) | Category: Cancer | Current Events | Drug Industry History
January 9, 2008
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.
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October 12, 2007
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".
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+ TrackBacks (0) | Category: Current Events | General Scientific News
October 10, 2007
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!
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+ TrackBacks (0) | Category: Chemical News | Current Events
October 9, 2007
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.
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October 8, 2007
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.
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August 5, 2007
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?
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July 13, 2007
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.
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June 17, 2007
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.
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April 29, 2007
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.
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April 12, 2007
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.
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+ TrackBacks (0) | Category: Business and Markets | Closing Time | Current Events
February 26, 2007
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).
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+ TrackBacks (0) | Category: Current Events | Who Discovers and Why
February 23, 2007
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.
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February 21, 2007
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).
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+ TrackBacks (0) | Category: Current Events | Press Coverage | The Central Nervous System
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".
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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
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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
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.
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January 2, 2007
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.
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December 20, 2006
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.
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November 27, 2006
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.
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+ TrackBacks (0) | Category: Chem/Bio Warfare | Current Events | Toxicology
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.
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November 9, 2006
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!
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October 9, 2006
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. . .
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August 27, 2006
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.
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+ TrackBacks (0) | Category: Analytical Chemistry | Current Events
August 10, 2006
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
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.
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+ TrackBacks (0) | Category: Analytical Chemistry | Current Events
March 24, 2006
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.
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December 22, 2005
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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+ TrackBacks (0) | Category: Current Events | Intelligent Design
December 20, 2005
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
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
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
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
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
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
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
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
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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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
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
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
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
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
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
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
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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| Category: Chem/Bio Warfare | Current Events | Toxicology
January 6, 2003
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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