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

Derek Lowe The 2002 Model

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

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

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July 22, 2014

The Broad Gets $650 Million For Psychiatric Research

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Posted by Derek

The Broad Institute seems to have gone through a bit of rough funding patch some months ago, but things are looking up: they've received a gift of $650 million to do basic research in psychiatric disorders. Believe it, that'll keep everyone busy, for sure.

I enjoyed Eric Lander's characterization of much of the 1990s work on the genetic basis of mental illness as "pretty much completely useless", and I don't disagree one bit. His challenge, as he and the rest of the folks at the Broad well know, is to keep someone from being able to say that about them in the year 2034. CNS work is the ultimate black box, which makes a person nervous, but on the other hand, anything solid that gets discovered will be a real advance. Good luck to them.

You might also be interested to know where the Stanley Foundation, the benefactors here, came up with over half a billion dollars to donate to basic medical research (and more to come, apparently). You'd never guess: selling collectibles. Sports figurines. Small replicas of classic cars, trucks, and tractors. Miniature porcelain versions of popular dolls. Leather-bound sets of great (public domain) novels. Order now for the complete set of Presidential Coins - that sort of thing. It looks to be a lot more lucrative than discovering drugs (!)

Comments (49) + TrackBacks (0) | Category: General Scientific News | The Central Nervous System

July 18, 2014

Chemistry Class For the "Food Babe"?

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Posted by Derek

I found this article from the Charlotte Observer on the "Food Babe" (Vani Hari) very interesting. A "menu consultant" for Chick-Fil-A, is she? Who knew?

I've come across a horribly long string of chemistry misapprehensions, mistakes, and blunders while looking at her site - she truly appears to know nothing whatsoever about chemistry, not that this would appear to bother her much. (Wavefunction has a good article on these). I noticed in the comments section of the newspaper's article that someone is apparently trying to crowdsource a fundraising drive to send her to some chemistry classes. I enjoy that idea very much, although (1) horse, water, drink, etc., and (2) she appears to have sufficient funds to do this already, were it of any possible interest to her. And more money coming in all the time. She may well make more money telling people that they're eating yoga mats than I do trying to discover drugs.

Comments (46) + TrackBacks (0) | Category: General Scientific News

July 9, 2014

No Scripps/USC

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Posted by Derek

The proposed Scripps/USC deal is off, according to reporters Gary Robbins and Bradley Fikes at the San Diego Union-Tribune. No details on what comes next, though - but something presumably does come next.

Comments (14) + TrackBacks (0) | Category: General Scientific News

July 2, 2014

All Natural And Chemical Free

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Posted by Derek

Yesterday's link to the comprehensive list of chemical-free products led to some smiles, but also to some accusations of preaching to the choir, both on my part and on the part of the paper's authors. A manuscript mentioned in the blog section of Nature Chemistry is certainly going to be noticed mostly by chemists, naturally, so I think that everyone responsible knows that this is mainly for some comic relief, rather than any sort of serious attempt to educate the general public. Given the constant barrage of "chemical-free" claims, and what that does to the mood of most chemists who see them, some comedy is welcome once in a while.

But the larger point stands. The commenters here who said, several times, that chemists and the public mean completely different things by the word "chemical" have a point. But let's take a closer look at this for a minute. What this implies (and implies accurately, I'd say) is that for many nonscientists, "chemical" means "something bad or poisonous". And that puts chemists in the position of sounding like they're arguing from the "No True Scotsman" fallacy. We're trying to say that everything is a chemical, and that they range from vital to harmless to poisonous (at some dose) and everything in between. But this can sound like special pleading to someone who's not a scientist, as if we're claiming all the good stuff for our side and disavowing the nasty ones as "Not the kind of chemical we were talking about". (Of course, the lay definition of chemical does this, with the sign flipped: the nasty things are "chemicals", and the non-nasty ones are. . .well, something else. Food, natural stuff, something, but not a chemical, because chemicals are nasty).

So I think it's true that approaches that start off by arguing the definition of "chemical" are doomed. It reminds me of something you see in online political arguments once in a while - someone will say something about anti-Semitism in an Arab country, and likely as not, some other genius will step in with the utterly useless point that it's definitionally impossible, you see, for an Arab to be an anti-Semite, because technically the Arabs are also a Semitic people! Ah-hah! What that's supposed to accomplish has always been a mystery to me, but I fear that attempts to redefine that word "chemical" are in the same category, no matter how teeth-grinding I find that situation to be.

The only thing I've done in this line, when discussing this sort of thing one-on-one, is to go ahead and mention that to a chemist, everything that's made out of atoms is pretty much a "chemical", and that we don't use the word to distinguish between the ones that we like and the ones that we don't. I've used that to bring up the circular nature of some of the arguments on the opposite side: someone's against a chemical ingredient because it's toxic, and they know it's toxic because it's a chemical ingredient. If it were "natural", things would be different.

That's the point to drop in the classic line about cyanide and botulism being all-natural, too. You don't do that just to score some sort of debating point, though, satisfying though that may be - I try not to introduce that one with a flourish of the sword point. No, I think you want to come in with a slightly regretful "Well, here's the problem. . ." approach. The idea, I'd say, is to introduce the concept of there being a continuum of toxicity out there, one that doesn't distinguish between man-made compounds and natural ones.

The next step after that is the fundamental toxicological idea that the dose makes the poison, but I think it's only effective to bring that up after this earlier point has been made. Otherwise, it sounds like special pleading again: "Oh, well, yeah, that's a deadly poison, but a little bit of it probably won't hurt you. Much." My favorite example in this line is selenium. It's simultaneously a vital trace nutrient and a poison, all depending on the dose, and I think a lot of people might improve their thinking on these topics if they tried to integrate that possibility into their views of the world.

Because it's clear that a lot of people don't have room for it right now. The common view is that the world is divided into two categories of stuff: the natural, made by living things, and the unnatural, made by humans (mostly chemists, dang them). You even see this scheme applied to inorganic chemistry: you can find people out there selling makeup and nutritional supplements who charge a premium for things like calcium carbonate when it's a "natural mineral", as opposed (apparently) to that nasty sludge that comes out of the vats down at the chemical plant. (This is also one of the reasons why arguing about the chemist's definition of "organic" is even more of a losing position than arguing about the word "chemical").

There's a religious (or at least quasi-religious) aspect to all this, which makes the arguments emotional and hard to win by appeals to reason. That worldview I describe is a dualist, Manichean one: there are forces of good, and there are forces of evil, and you have to choose sides, don't you? It's sort of assumed that the "natural" world is all of a piece: living creatures are always better off with natural things. They're better; they're what living creatures are meant to consume and be surrounded by. Anything else is ersatz, a defective substitute for the real thing, and quite possibly an outright work of evil by those forces on the other side.

Note that we're heading into some very deep things in many human cultures here, which is another reason that this is never an easy or simple argument to have. That split between natural and unnatural means that there was a time, before all this industrial horror, when people lived in the natural state. They never encountered anything artificial, because there was no such thing in the world. Now, a great number of cultures have a "Golden Age" myth, that distant time when everything was so much better - more pure, somehow, before things became corrupted into their present regrettable state. The Garden of Eden is the aspect this takes in the Christian religion, but you find similar things in many other traditions. (Interestingly, this often takes the form of an ancient age when humans spoke directly with the gods, in whatever form they took, which is one of the things that led Julian Jaynes to his fascinating, although probably unprovable hypotheses in The Origin of Consciousness in the Breakdown of the Bicameral Mind).

This Prelapsarian strain of thinking permeates the all-natural chemical-free worldview. There was a time when food and human health were so much better, and industrial civilization has messed it all up. We're surrounded by man-made toxins and horrible substitutes for real food, and we've lost the true path. It's no wonder that there's all this cancer and diabetes and autism and everything: no one ever used to get those things. Note the followup to this line of thought: someone did this to us. The more hard-core believers in this worldview are actually furious at what they see as the casual, deliberate poisoning of the entire population. The forces of evil, indeed.

And there are enough small reinforcing bars of truth to make all of this hold together quite well. There's no doubt that industrial poisons have sickened vast numbers of people in the past: mercury is just the first one that's come to mind. (I'm tempted to point out that mercury and its salts, by the standards of the cosmetics and supplements industries, are most certainly some of those all-natural minerals, but let that pass for now). We've learned more about waste disposal, occupational exposure, and what can go into food, but there have been horrible incidents that live on vividly in the imagination. And civilization itself didn't necessarily go about increasing health and lifespan for quite a while, as the statistics assembled in Gregory Clark's A Farewell to Alms make clear. In fact, for centuries, living in cities was associated with shorter lifespans and higher mortality. We've turned a lot of corners, but it's been comparatively recently.

And on the topic of "comparatively recently", there's one more factor at work that I'd like to bring up. The "chemical free" view of the world has the virtue of simplicity (and indeed, sees simplicity as a virtue itself). Want to stay healthy? Simple. Don't eat things with chemicals in them. Want to know if something is the right thing to eat, drink, wear, etc.? Simple: is it natural or not? This is another thing that makes some people who argue for this view so vehement - it's not hard, it's right in front of you, and why can't you see the right way of living when it's so, so. . .simple? Arguing against that, from a scientific point of view, puts a person at several disadvantages. You necessarily have to come in with all these complications and qualifying statements, trying to show how things are actually different than they look. That sounds like more special pleading, for one thing, and it's especially ineffective against a way of thinking that often leans toward thinking that the more direct, simple, and obvious something is, the more likely it is to be correct.

That's actually the default way of human thinking, when you get down to it, which is the problem. Science, and the scientific worldview, are unnatural things, and I don't mean that just in the whole-grain no-additives sense of "natural". I mean that they do not come to most people as a normal consequence of their experience and habits of thought. A bit of it does: "Hey, every time I do X, Y seems to happen". But where that line of thinking takes you starts to feel very odd very quickly. You start finding out that the physical world is a lot more complicated than it looks, that "after" does not necessarily mean "because", and that all rules of thumb break down eventually (and usually without warning). You find that math, of all things, seems to be the language that the universe is written in (or at least a very good approximation to it), and that's not exactly an obvious concept, either. You find that many of the most important things in that physical world are invisible to our senses, and not necessarily in a reassuring way, or in a way that even makes much sense at all at first. (Magical explanations of invisible forces at least follow human intuitions). It's no wonder that scientific thinking took such a long, long time to ever catch on in human history. I still sometimes think that it's only tolerated because it brings results.

So there are plenty of reasons why it's hard to effectively argue against the all-natural chemical-free worldview. You're asking your audience to accept a number of things that don't make much sense to them, and what's worse, many of these things look like rhetorical tricks at best and active (even actively evil) attempts to mislead them at worst. And all in the service of something that many of them are predisposed to regard as suspicious even from the start. It's uphill all the way.

Comments (52) + TrackBacks (0) | Category: General Scientific News | Snake Oil | Toxicology

June 30, 2014

Don't Learn to Science?

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Posted by Derek

In keeping with the discussions around here about STEM jobs and education, I wanted to pass along this link from Coding Horror: "Please Don't Learn to Code". It's written by a programmer, as you might guess, and here's his main point:

To those who argue programming is an essential skill we should be teaching our children, right up there with reading, writing, and arithmetic: can you explain to me how Michael Bloomberg would be better at his day to day job of leading the largest city in the USA if he woke up one morning as a crack Java coder? It is obvious to me how being a skilled reader, a skilled writer, and at least high school level math are fundamental to performing the job of a politician. Or at any job, for that matter. But understanding variables and functions, pointers and recursion? I can't see it.
Look, I love programming. I also believe programming is important … in the right context, for some people. But so are a lot of skills. I would no more urge everyone to learn programming than I would urge everyone to learn plumbing. That'd be ridiculous, right?

I see his point. He goes on to say that more code is not necessarily what we need in the world, and that coding is not the proper solution to many problems. On a less philosophic level, the learn-to-code movement also makes it seem as if this is the short path to a job, which is not quite aligned with reality, either.

I suppose I can support learning a tiny bit about programming just so you can recognize what code is, and when code might be an appropriate way to approach a problem you have. But I can also recognize plumbing problems when I see them without any particular training in the area. The general populace (and its political leadership) could probably benefit most of all from a basic understanding of how computers, and the Internet, work. Being able to get around on the Internet is becoming a basic life skill, and we should be worried about fixing that first and most of all, before we start jumping all the way into code.

Now let's apply that to learning about chemistry and biology. It's not going to be a very comfortable exercise, because I (and many of the people who read this site) have put a lot of time and effort into learning an awful lot of chemistry and biology. I've written before about the problem of how much science the "average" person should know, and the least controversial answer is "More than they do now". After that, the arguing starts.

It would be nice if everyone knew enough to make some of the ridiculous scams out there harder to work. "Eat whatever you want and still lose 10 pounds a week with this miracle fat-burning supplement!" would be greeted with "Hey, isn't that thermodynamically sort of impossible?". "New Super-Ionized Oxygenated Water Reverses Aging!" would meet with "How do you "super-ionize" water? And how much oxygen can it hold, anyway? And wouldn't that be, like, bleach?" It would be good if people had a slightly better idea of what causes cancer, how diabetes works, a bit better understanding of toxicology, and so on.

But then we're already supposed to be teaching everyone some of the basics, and it doesn't necessarily seem to be going all that well (evidence, both hopeful and not, can be found here and here). Everyone's supposedly exposed to some simple astronomy, but surveys always show a depressing amount of confusion, when it comes to the earth, moon, and sun, which one of them is going around which. Everyone's supposed to have been exposed to the idea of cells making up living organisms, to DNA, and so on, but you can still seemingly get away with all kinds of off-kilter claims about such things when talking to a lay audience.

Some readers will remember the "Why Are You Forcing My Son to Take Chemistry" guy from the Washington Post. I wish that I could argue that chemistry, and a good dose of it, is prima facie a requirement for any reasonably competent citizen, but I'm not quite there yet. But I'm also sure that being completely ignorant of chemistry is a good indicator of someone whose worldview is incomplete and could use some shoring up. You need some knowledge in these areas, but we could start with getting across the stuff we're trying to get across already.

What I am sure of, though, is that a certain amount of science and math really is necessary, and not just for the bare facts. My daughter, when she was learning the quadratic equation, asked me the classic question "Why am I learning this? When will I ever use it?" My response to her was that I, too, had rarely had recourse to the quadratic equation as it stood. But at the same time, learning these things was good for the mind. I told her that when I went to the gym, it wasn't because I was planning on having to do more repetitive squats with a weighted bar on my back any time soon. But strengthening my back and legs was a good thing in general, and helped out with a lot of other things in my day-to-day life, in both the short and long terms. The same with the mind. Memorized the quadratic formula was not a great deal of use in and of itself, but that realization she had, in one of those thrown-ball problems, that the height of the ball was at the origin at just two points (at the beginning and the end of its flight), and that was why solving for time at that height gave you two solutions - that flash of understanding, I told her, was the feeling of mental muscle being built up, capacity that she would need for more than just her math homework. Everyone could do with some of that exercise.

Comments (35) + TrackBacks (0) | Category: General Scientific News

June 21, 2014

Scripps Update

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Posted by Derek

I'm told now that after a number of faculty at the Scripps Research Institute have objected to the proposed deal with USC, that UC-San Diego is ready to explore some sort of merger deal. Going down North Torrey Pines Road would seem to be logistically easier than going to Los Angeles, but there are other considerations as well. This could go on for a while!

Comments (28) + TrackBacks (0) | Category: General Scientific News

June 17, 2014

Scripps Merging With USC?

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Posted by Derek

This news broke last night: that USC might be acquiring Scripps. It all looks to come down to tight federal money: that's where most of the funding comes from, and institutions that rely on grants (and overhead from grants) to survive are having to cut back. (There were, for example, a number of layoffs earlier this year at the Broad Institute in Cambridge, for just that reason).

As you can see from that story, I was called last night for comment about this, and I have to say, I was very surprised (although maybe not as surprised as the reporter was when I started quoting Tennyson). The loss of several big names over the last few years has made it clear that there were some difficulties inside Scripps, which made quite a contrast to the era when they burst on the organic chemistry scene by making huge offers to a number of star professors. But I couldn't think of another example where one department more or less takes over another one, and I especially couldn't think of anything happening at this level.

It doesn't look like a done deal yet, and even if it does go forward, how things will work is unclear. (It's also unclear what this means for the Scripps branch in Florida). More on this as it develops.

Comments (41) + TrackBacks (0) | Category: General Scientific News

April 1, 2014

Freeman Dyson on the PhD Degree

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Posted by Derek

From this interview:

"Oh, yes. I’m very proud of not having a Ph.D. I think the Ph.D. system is an abomination. It was invented as a system for educating German professors in the 19th century, and it works well under those conditions. It’s good for a very small number of people who are going to spend their lives being professors. But it has become now a kind of union card that you have to have in order to have a job, whether it’s being a professor or other things, and it’s quite inappropriate for that. It forces people to waste years and years of their lives sort of pretending to do research for which they’re not at all well-suited. In the end, they have this piece of paper which says they’re qualified, but it really doesn’t mean anything. The Ph.D. takes far too long and discourages women from becoming scientists, which I consider a great tragedy. So I have opposed it all my life without any success at all. . ."

Comments (68) + TrackBacks (0) | Category: General Scientific News

March 3, 2014

Sydney Brenner on the State of Science

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Posted by Derek

Via Retraction Watch, here's an outspoken interview with Sydney Brenner, who's never been the sort of person to keep his opinions bottled up inside him. Here, for example, are his views on graduate school in the US:

Today the Americans have developed a new culture in science based on the slavery of graduate students. Now graduate students of American institutions are afraid. He just performs. He’s got to perform. The post-doc is an indentured labourer. We now have labs that don’t work in the same way as the early labs where people were independent, where they could have their own ideas and could pursue them.

The most important thing today is for young people to take responsibility, to actually know how to formulate an idea and how to work on it. Not to buy into the so-called apprenticeship. I think you can only foster that by having sort of deviant studies. That is, you go on and do something really different. Then I think you will be able to foster it.

But today there is no way to do this without money. That’s the difficulty. In order to do science you have to have it supported. The supporters now, the bureaucrats of science, do not wish to take any risks. So in order to get it supported, they want to know from the start that it will work. This means you have to have preliminary information, which means that you are bound to follow the straight and narrow.

I can't argue with that. In academia these days, it seems to me that the main way that something really unusual or orthogonal gets done is by people doing something else with their grant money than they told people they'd do. Which has always been the case to some extent, but I get the impression it's more so than ever. The article also quotes from Brenner's appreciation of the late Fred Sanger, where he made a similar point:

A Fred Sanger would not survive today’s world of science. With continuous reporting and appraisals, some committee would note that he published little of import between insulin in 1952 and his first paper on RNA sequencing in 1967 with another long gap until DNA sequencing in 1977. He would be labelled as unproductive, and his modest personal support would be denied. We no longer have a culture that allows individuals to embark on long-term—and what would be considered today extremely risky—projects.

Here are Brenner's mild, temperate views on the peer-review system and its intersection with academic publishing:

. . .I don’t believe in peer review because I think it’s very distorted and as I’ve said, it’s simply a regression to the mean.

I think peer review is hindering science. In fact, I think it has become a completely corrupt system. It’s corrupt in many ways, in that scientists and academics have handed over to the editors of these journals the ability to make judgment on science and scientists. There are universities in America, and I’ve heard from many committees, that we won’t consider people’s publications in low impact factor journals.

Now I mean, people are trying to do something, but I think it’s not publish or perish, it’s publish in the okay places [or perish]. And this has assembled a most ridiculous group of people. I wrote a column for many years in the nineties, in a journal called Current Biology. In one article, “Hard Cases”, I campaigned against this [culture] because I think it is not only bad, it’s corrupt. In other words it puts the judgment in the hands of people who really have no reason to exercise judgment at all. And that’s all been done in the aid of commerce, because they are now giant organisations making money out of it.

I don't find a lot to disagree with there, either. The big scientific publishers have some good people working for them, but the entire cause is more and more suspect. THere's a huge moral hazard involved, which we don't seem to be avoiding very well at all.

Comments (35) + TrackBacks (0) | Category: General Scientific News | The Scientific Literature

February 17, 2014

Down With P Values

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Posted by Derek

I'd like to recommend this article from Nature (which looks to be open access). It details the problems with using p-values for statistics, and it's simultaneously interesting and frustrating to read. The frustrating part is that the points it makes have been made many times before, but to little or no effect. P-values don't mean what a lot of people think that they mean, and what meaning that have can be obscured by circumstances. There really should be better ways for scientists to communicate the statistical strength of their results:

One result is an abundance of confusion about what the P value means. Consider Motyl's study about political extremists. Most scientists would look at his original P value of 0.01 and say that there was just a 1% chance of his result being a false alarm. But they would be wrong. The P value cannot say this: all it can do is summarize the data assuming a specific null hypothesis. It cannot work backwards and make statements about the underlying reality. That requires another piece of information: the odds that a real effect was there in the first place. To ignore this would be like waking up with a headache and concluding that you have a rare brain tumour — possible, but so unlikely that it requires a lot more evidence to supersede an everyday explanation such as an allergic reaction. The more implausible the hypothesis — telepathy, aliens, homeopathy — the greater the chance that an exciting finding is a false alarm, no matter what the P value is.

Critics also bemoan the way that P values can encourage muddled thinking. A prime example is their tendency to deflect attention from the actual size of an effect. Last year, for example, a study of more than 19,000 people showed that those who meet their spouses online are less likely to divorce (p < 0.002) and more likely to have high marital satisfaction (p < 0.001) than those who meet offline (see Nature http://doi.org/rcg; 2013). That might have sounded impressive, but the effects were actually tiny: meeting online nudged the divorce rate from 7.67% down to 5.96%, and barely budged happiness from 5.48 to 5.64 on a 7-point scale. To pounce on tiny P values and ignore the larger question is to fall prey to the “seductive certainty of significance”, says Geoff Cumming, an emeritus psychologist at La Trobe University in Melbourne, Australia. But significance is no indicator of practical relevance, he says: “We should be asking, 'How much of an effect is there?', not 'Is there an effect?'”

The article has some suggestions about what to do, but seems guardedly pessimistic about the likelihood of change. The closer you look at it, though, the more our current system looks like an artifact that was never meant to be used in the way we're using it.

Comments (30) + TrackBacks (0) | Category: General Scientific News

February 6, 2014

Crowdfunding Independent Research

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Posted by Derek

I've written about Ethan Perlstein's work here before, and now I note that the Wall Street Journalhas an article about his crowdfunding research model.

Ethan O. Perlstein for years followed a traditional path as a scientist. He earned a Ph.D. in molecular biology from Harvard, spent five years doing postdoctoral research at Princeton and led a team that published two papers on pharmacology.

But last year, Dr. Perlstein was turned down by 27 universities when he sought a tenure-track position to set up his own lab. Hundreds of candidates had applied for a small number of positions, the universities said, a situation made worse by cuts in federal research funding.. . .

. . .Still, Dr. Perlstein's approach is unusual because he isn't raising money to support a discrete project or product. "Ethan is doing basic research," said Jessica Richman, co-founder of Ubiome, a health and wellness startup that raised more than $350,000 through crowdfunding on a site called Indiegogo. "He is selling the idea that he is an independent scientist doing research."

Dr. Perlstein plans to launch his public appeal for Perlstein Lab this week on a site called AngelList. Perlstein Lab will focus on finding drugs to treat lysosomal storage diseases, in which cells fail to produce and recycle waste. The materials accumulate in cells and can cause a range of problems, including death.

Here's his profile page on AngelList, which seeks money from what the SEC calls "qualified" investors (high net worth individuals). I think that's probably a good idea - anyone who's done "angel" type investments before will have a more realistic idea of the chance of any return (you'd hope). Crowdfunding research, in general, is something that interests me a great deal, although it's easy to think of potential problems.

Comments (12) + TrackBacks (0) | Category: Business and Markets | General Scientific News

October 29, 2013

Humble Enzyme Dodges Spotlight

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Posted by Derek

Here's the latest biochemical news from The Onion, which is at least as reliable as some journals. What I think I like the best is that the person who wrote this clearly understood some details about amylase and about enzyme function in general. An alternative science career?

Comments (10) + TrackBacks (0) | Category: General Scientific News

October 7, 2013

The 2013 Medicine/Physiology Nobel: Traffic

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Posted by Derek

This year's Medicine Nobel is one that's been anticipated for some time. James Rothman of Yale, Randy W. Schekman of Berkeley, and Thomas C. Südhof of Stanford are cited for their fundamental discoveries in vesicular trafficking, and I can't imagine anyone complaining that it wasn't deserved. (The only controversy would be thanks, once again, to the "Rule of Three" in Alfred Nobel's will. Richard Scheller of Genentech has won prizes with Südhof and with Scheller for his work in the same field).
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Here's the Nobel Foundation's scientific summary, and as usual, it's a good one. Vesicles are membrane-enclosed bubbles that bud off from cellular compartments and transport cargo to other parts of the cell (or outside it entirely), where they merge with another membrane and release their contents. There's a lot of cellular machinery involved on both the sending and receiving end, and that's what this year's winners worked out.

As it turns out, there are specific proteins (such as the SNAREs) imbedded in intracellular membranes that work as an addressing system: "tie up the membrane around this point and send the resulting globule on its way", or "stick here and start the membrane fusion process". This sort of thing is going on constantly inside the cell, and the up-to-the-surface-and-out variation is particularly noticeably in neurons, since they're constantly secreting neurotransmitters into the synapse. That latter process turned out to be very closely tied to signals like local calcium levels, which gives it the ability to be turned on and off quickly.

As the Nobel summary shows, a lot of solid cell biology had to be done to unravel all this. Scheckman looked for yeast cells that showed obvious mutations in their vesicle transport and tracked down what proteins had been altered. Rothman started off with a viral infection system that produced a lot of an easily-trackable protein, and once he'd identified others that helped to move it around, he used these as affinity reagents to find what bound to them in turn. This work dovetailed very neatly with the proteins that Scheckman's lab had identified, and suggested (as you'd figure) that this machinery was conserved across many living systems. Südhof then extended this work into the neurotransmitter area, discovering the proteins involved in the timing signals that are so critical in those cells, and demonstrating their function by generating mouse knockout models along the way.

The importance of all these processes to living systems can't be overstated. Eukaryotic cells have to be compartmentalized to function; there's too much going on for everything to be in the same stew pot all at the same time. So a system for "mailing" materials between those regions is vital. And in the same way, cells have to communicate with others, releasing packets of signaling molecules under very tight supervision, and that's done through many of the same mechanisms. You can trace the history of our understanding of these things through years of Nobel awards, and there will surely be more.

Comments (15) + TrackBacks (0) | Category: Biological News | General Scientific News

September 30, 2013

A War On Expertise?

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Posted by Derek

I see that Popular Science is shutting down the comments function on their web site. Like a lot of news organizations, I think that their signal/noise was pretty low in the comments. (And that prompts me to express, again, my appreciation for the commenters on this blog - one of the first questions I get when I talk to anyone else who runs a web site is how on Earth the comments section around here stays so readable and sane!)

They're citing some experiments that seem to show that fractious comments sections actually make the original posts above them seem less reliable, and that may be how it works. In reality, my impression is that if a site seems to have a lot of fist-waving in the comments section, that pretty soon most readers don't even bother with it, and the only ones that show up are there for the fights. I'll say this for the Popular Science folks - they're not doing this for monetary/traffic reasons, because wildly argumentative comments sections also drive traffic from the people who just can't stay away (and hit "Refresh" over and over in the process).

Here's the key quote from their article:

A politically motivated, decades-long war on expertise has eroded the popular consensus on a wide variety of scientifically validated topics. Everything, from evolution to the origins of climate change, is mistakenly up for grabs again. Scientific certainty is just another thing for two people to "debate" on television. And because comments sections tend to be a grotesque reflection of the media culture surrounding them, the cynical work of undermining bedrock scientific doctrine is now being done beneath our own stories, within a website devoted to championing science.

I know where they're coming from, but I'm not so sure about that "again". My belief is that there hasn't been a time when evolution was not controversial with many people, nor climate change/global warming. The internet, it's true, gives everyone with a point of view a chance to ventilate, so it brings this sort of thing to the surface much more easily than in the past. (Look back a few decades, and ask yourself what was available to someone with a strong opinion. Letters to the editor? Soapbox in the park? Handling out flyers on the corner?)

And I don't think that there's been any big, coherent, "decades-long war on expertise". If there is, then there always has been. It makes a person feel better to believe these things, but that's the sort of self-congratulatory thinking that I believe one has to avoid. "I'm too smart for the crowd, the mob - a member of a persecuted minority just because I see the truth. . ." That doesn't do anything to help your own reasoning.

No, most people don't understand scientific topics, but most people never have. If anything, I'd be willing to bet that the population today is more literate in these matters than ever before. The sorts of people who go hunting through web sites looking for things to confirm their own opinions have always been with us. As have groups who'd rather obfuscate topics than debate them, for reasons of their own. We just have a better look at the whole process these days.

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September 26, 2013

Nobel Speculation Time

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Posted by Derek

As we approach October, Nobel Speculation Season is upon us again. And Ash is right at Curious Wavefunction - making the predictions gets easier every year, because you get to keep the lists you had from before, with maybe a name or two removed because they actually won. Paul at Chembark usually does a long post on the subject this time of year, but he seems to have his hands full (understandably!) getting his academic lab set up and teaching his courses the first time through.

The Thomson Reuters people have made their annual predictions, based on citation counts and such measures, and so far every other article I've seen in the press is based on their lists. Some years I speculate myself, so for what they're worth, here's my 2011 list, here's 2010, here's 2009, 2008, and 2006.

What's the landscape like this year? Thomson/Reuters have made a bold case for Sharpless/Folkin/Finn for the Huisgen-style "click" chemistry. I know that the thought has crossed my mind before (and shown up in the comments here before as well, several times). A second Nobel for Sharpless would be quite a feat, and it really says something that people consider it a possibility. John Bardeen got Physics twice, and Sanger got Chemistry twice. Marie Curie's the only person to win in two different sciences. (And yes, there's Pauling, the only winner of two unshared prizes, but one of them was Peace, which has too often been a real eye-roller of an award). R. B. Woodward, had he lived, would certainly have won Chemistry twice, since there was an award for the Woodward-Hoffman rules after his death.

Thomson/Reuters also proposes Alvisatros/Mirkin/Seeman for a DNA nanotechnology prize in chemistry, and Bruce Ames for the Ames mutagenicity test. (Man, it feels strange to link to something that I blogged about eleven years ago!) Of those two, I think Ames is a better bet, since he really did change the field of toxicology forever. It would make more sense for a physiology/medicine prize, but we all know how things go. On the other hand, I think that the DNA nanoparticle work will be given a chance to have a greater real-world impact before it gets a prize.

I like the Wavefunction picks a lot, too. He's looking at single-molecule spectroscopy for a physical/analytical chemistry prize, and he points out that surface plasmon resonance and solid-state NMR (among other NMR methods) haven't won, either. Considering the 2002 prize to Fenn for electrospray MS, these are very plausible, although I have to say that LC/MS (considering the way it's taken over the analytical world in the last 20 years) made that one a clear choice. His other top picks are nuclear receptors, electron transfer in biological systems, chaperone proteins, cancer genetics, and some sort of chemical biology prize. I wouldn't be a bit surprised at any of those - like the palladium-coupling prize, the biggest problem will be figuring out who to award some of these to, not determining whether they're worthy of winning.

My own guess? From the Thomson/Reuters and Wavefunction lists, I like Ames, nuclear receptors, single-molecule spectroscopy, and chaperone proteins. Just behind those are electron transfer and then the triazole click work. I don't see an organic synthesis prize at all; I think this is going to be physical/analytical if it's going to be inside the traditional bounds of chemistry. And with that in mind, the committee might just use the chemistry prize for Venter et al. on DNA sequencing methods, or for Solomon Snyder et al. on neurotransmitters. We shall see!

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September 25, 2013

MacArthur Awards in Chemistry