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About this Author
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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Monthly Archives

May 28, 2010

Scientific Discovery: Getting Older (And Less Lonely)

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Posted by Derek

The NBER (National Bureau of Economic Research) has been looking at the patterns of scientific publication and grant awards in the US, and has noticed some interesting trends. According to Inside Higher Ed, the study found (first off) that scientific publications are increasing at about 5.5% a year, and the report suggests that this might mean that any individual who reads at the same rate is seeing their own current knowledge decrease by the same amount.

I'm not so sure about that. While there are indeed more papers every year, the marginal utility of each new paper isn't necessarily very high - if I can switch into econ-speak myself. That's especially true if increased numbers of articles are due to new journals that end up (directly or indirectly) pulling things into the literature that wouldn't have even been published otherwise, simply because journals need to fill their pages. That said, the volume of interesting science done (and to be read about) each year is still increasing - I certainly can't deny that - but it would be a mistake to assume that "Scientific Journal Publications" are some sort of homogeneous good that can be measured as such.

Two other trends that were spotted make more sense to me: one is that the average number of co-authors is rising steadily. You wonder if that last part is just due to those physics papers that have six hundred people on them, but it seems to be the case across all disciplines. There are fewer and fewer solo scientific publications than there used to be, which confirms my own experience looking across the the chemistry literature.

Another trend is that fewer highly-cited big-news papers are coming from the younger end of the age distribution. The report says that "Peak productivity has increased by about 8 years, with the effect coming entirely from a collapse in productivity at young ages." The average ages for discoveries that later went on to win Nobels has been going up, as has the average age at which a scientist appears on their first patent. And that's worth thinking about - is it that our educational setup in the sciences sends people out into the fray at later and later ages? Or that the disciplines themselves have gotten more complicated, requiring a longer period before a substantial contribution can be made?

I think that a big factor is that younger scientists probably feel insecure working on high-risk high-reward projects. In academia, they're fighting for grant money and tenure, and I think that many people in that situation are careful about balancing "exciting and groundbreaking" against "likely to produce solid, publishable results". And industrial scientists tend to need more experience before they can make a big discovery as well, since the more applied fields have a larger body of specific knowledge built up.

The report contrasts these trends against the long-held image of the brave young researcher pushing toward a big discovery. I'd argue that the Nobel itself suffers from this problem, with its strict three-names-only rule. It's my impression that the committees that decide the prize have been having a harder and harder time of it over the years trying to find a way to stick to that. It has (inevitably) led to a number of deserving people getting left out - as well as a number of deserving discoveries that couldn't be narrowed down well enough. (Organic chemistry has the metal-catalyzed couplings as an example).

Finding ways to recognize large (often interdisciplinary) teams would be one step. Another change that might need to be made could include easing up a bit on the younger grant recipients, realizing that it's going to be increasingly difficult for them to hit things out of the park at that point in their careers. Could that also allow some of the better ones to work in tougher areas, with less fear of the consequences of failure?

Comments (22) + TrackBacks (0) | Category: Who Discovers and Why

May 27, 2010

Pfizer Halts a Trial Early - On Good News

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Posted by Derek

Pfizer was able to announce some good news today - their trial of Inspra (eplerenone) for patients with a particular combination of heart failure symptoms. The trial was halted early, but (for once) because the endpoints were reached so early that it would have been unethical to continue the placebo arm. It's always nice to hear about one of those; we don't get them that often.

The drug is an aldosterone antagonist which had already been approved several years ago for heart failure and hypertension, so it's not really a surprise that it worked in this population. But you never know, and Pfizer wanted to be able to get specifically recommended for patients of this type. And that they will.

Comments (13) + TrackBacks (0) | Category: Cardiovascular Disease | Clinical Trials

Max Gergel's Memoirs

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Posted by Derek

For once, I'm going to farm out a "Things I Won't Work With" post to someone else. For those who missed it in the comments, here's the link to the PDF of Max Gergel's extraordinary memoir "Excuse Me Sir, Would You Like to Buy a Kilo of Isopropyl Bromide?" Gergel founded Columbia Organic Chemicals, and if you want to see how it was done in the Old Days, this is the place to go. A sample:

". . .As we chatted, as if the thought had struck him for the first time, the old rogue said, "You know Gergel, I have a prep you could run for us which would make you a lot of money." Now this was the con working on the con. When my mother told me that a gentleman had called from town asking to visit Dr. Gergel there was no one at the plant except the two of us; when Parry, whom I already knew by reputation, sauntered in disguised as a simple country bumpkin I knew he was the director of research for Naval Research Labs, and his mission was to find someone foolhardy enough to make pentaborane. News travels. I met him at the door and told him that I was simply a lab flunky but would fetch Mr. Gergel, that my boss was extremely smart but had been prevented by the war effort (in which he had served valiantly and with distinction) from getting a PhD; that right now Mr. Gergel was extremely busy with priority reaction but would be able to see him in ten minutes—which gave me time to change my clothes and wash my face. He never realized that we were the same person. Parry chatted with me in the breezy, confidential voice that has been used by every con man since Judas Iscariot and told me that the only reason that the Navy was willing to farm out this fascinating project was simply luck of qualified personnel. That my splendid contribution to Manhattan District was well known by the military, that people spoke of me as a true Southern prodigy. (The old devil was so good that I listened with gradually increasing preparedness to make pentaborane, although I had been forewarned that it was dog with a capital "D". . .

I came across the book in Duke's chemistry library in 1984, a few years after its publication, and read it straight through with my hair gradually rising upwards. Book 2 is especially full of alarming chemical stories. I suspect that some of the anecdotes have been polished up a bit over the years, but as Samuel Johnson once said, a man is not under oath in such matters. But when Gergel says that he made methyl iodide in an un-air-conditioned building in the summertime in South Carolina, and describes in vivid detail the symptoms of being poisoned by it, I believe every word. He must have added a pound to his weight in sheer methyl groups.

By modern standards, another shocking feature of the book is the treatment of chemical waste. Readers will not be surprised to learn that several former Columbia Organic sites feature prominently in the EPA's Superfund cleanup list, but they certainly aren't alone from that era.

Comments (19) + TrackBacks (0) | Category: Chemical News | How Not to Do It | Things I Won't Work With

Golden Ages Are Where You Find Them

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Posted by Derek

Remember Pfizer's "golden age of drug discovery", the one that it was entering back in April? News comes now that Martin Mackay, the company exec who gave Bloomberg News that quote, has left for AstraZeneca.

Mackay had been head of Pfizer's research for the last three years, and will be head of R&D in his new position. The news story linked to has various analysts talking about Pfizer's recent problems, and Mackay's effect on them, but I think that sort of thing is unfair. Three years (in most cases) is nowhere near enough time to say whether a head of research is making an impact on the drug pipeline. That's one of the biggest problems with managing in this industry - the long lead times before you get the real answers about anything.

At any rate, I wish good luck to Mackay in his new position, and the same to his successor at Pfizer, Wyeth's Mikael Dolsten. They, like all of us, need all the luck that they can get, golden age or no.

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

May 26, 2010

Albany Molecular Cuts - In the US, Anyway

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Posted by Derek

From their press release:

". . .As part of its strategy to increase global competitiveness and remain diligent in managing its costs, the company is also implementing significant cost reduction activities at its operations in the US. . .AMRI is reducing its US workforce by approximately 10%, or an estimated 80 jobs. This includes currently open positions that the company is not filling at this time.. . .Further, the company is suspending operations at one of its research laboratory facilities in Rensselaer, New York. Employees and equipment will be consolidated into nearby AMRI locations.

. . .These actions reflect the focus by our customers on cost of services amid a highly competitive environment coming primarily from Asia. This has led to a continued shift in demand for AMRI's services from the US to lower cost resources in Asia and Europe. While we remain cautiously optimistic about a return in demand for contract research outsourcing by the biopharmaceutical industry, softness in the US market has extended beyond our expectations. . .

AMRI's whole reason for starting was to save other companies money on chemical services. Given that, it's no surprise that they've been feeling the pressure in recent years, and the economic conditions out there must really be cranking things up. I hope that they're right about a return in demand - but I'm not so sure that there's going to be much of a return in demand at the prices that they used to get.

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

"Better Educated" in China?

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Posted by Derek

The Boston Globe has an interview with James Foster, the CEO of Charles River Labs, about their acquisition of WuXi. It's an overview of the whole outsourcing/consolidation story in the industry, which will be familiar to readers here. But an e-mail pointed me to one particular quote:

“For some period of time, there’ll be a wage benefit to using Chinese labor,’’ Foster said. “The labor is plentiful, cheaper, and better educated than in the States. It pains me to say so, but it’s true.’’

I assume that it doesn't pain him so much to say that the labor is plentiful and cheaper - rather, it's the "better educated" part. And that pains me, too, to be honest. Is it true? I'm sure that opinions are going to vary widely on that question - I've sent an e-mail to the people at Charles River asking if Foster's willing to go into more detail.

Update: I've heard back from them; through a spokesperson, Foster declines to comment further, citing the demands on his time during the WuXi merger. Good thing the Globe was able to talk to him, I guess!

Comments (68) + TrackBacks (0) | Category: Business and Markets

India's Research Culture

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Posted by Derek

R. A. Mashelkar of India's National Chemical Laboratory has a provocative opinion piece in Science on the research culture of his country. And it brings up a point that I don't think anyone could deny: that the attitudes of a society can affect (for better or worse) its ability to participate in scientific research:

Nobel Laureate Richard Feynman believed that creative pursuit in science requires irreverence. Sadly, this spirit is missing from Indian science today. As other nations pursue more innovative approaches to solving problems, India must free itself from a traditional attitude that condemns irreverence, so that it too can address local and global challenges and nurture future leaders in science. But how can the spirit of adventurism come to Indian science?

The situation has deep roots in Indian culture and tradition. The ancient Sanskrit saying "baba vakyam pramanam" means "the words of the elders are the ultimate truth," thus condemning the type of irreverence inspired by the persistent questioning that is necessary for science. The Indian educational system, which is textbook-centered rather than student-centered, discourages inquisitive attitudes at an early age. Rigid unimaginative curricula and examinations based on single correct answers further cement intolerance for creativity. And the bureaucracy inherited from the time of British rule over-rides meritocracy.

He points out that India's greatest scientific names (and there are some heavy hitters) got there in spite of such pressures, not because of them. It's not like this issue hasn't been aired out in India before; I've had Indian colleagues say much the same things to me. And these attitudes can be found in many countries, of course - you can find them here in the US. Mediocre researchers the world over keep their heads down, avoid projects that make their bosses (or themselves) nervous, and keep within the bounds of the literature.

The key, though, is to make sure that people who want to try risky ideas are able to do it. If they're inhibited by pressure from their bosses or their peers, the productivity of a whole country's science can suffer. Not everyone is capable (or willing) to go out on the edge, but it's crucial that the people who can and will are able to do so. That's where we've excelled in the US, where we have an entire infrastructure (the venture capital system) for funding things that are probably not going to work. It's not like we're perfect at this process, but we're better than many others.

But India appears to be moving in the right direction - Mashelkar goes into some details on the way that scientific education is changing. The next step will be to give risk-tolerant investors ways to back the good ideas that emerge. That's a tough one, and a lot of countries have been unable to quite get there. Sometimes the needed investors aren't there, or aren't quite well-capitalized (or willing) enough, or there aren't enough good ideas floating around, or there are no good ways to get the ideas and the money together. Personally, I think India's going to get there, and that it'll be a good thing for the country, and for the rest of the world.

Comments (22) + TrackBacks (0) | Category: Business and Markets | Who Discovers and Why

May 25, 2010

A Word to the Wise

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Posted by Derek

Today's entry on an embarrassingly wrong structure in Bioorganic and Medicinal Chemistry Letters has a number of people in the comments talking about experiences they've had reviewing for the journal. I've done reviews for them myself, naturally, as well as for other journals. I have too few examples to judge from, but (so far) I have managed to kill off papers at other journals, but I have never managed to kill off a manuscript at BOMCL. I have - apparently like some other people - recommended in the past that a paper be published (if at all) only with major revisions, only to see it sail through basically untouched.

I hope I'm not being unfair here, because there are a lot of hard-working people at the journal. And similar stories can, I'm sure, be told about every other journal (in every other discipline). But I think that BOMCL gets so many manuscripts that their workload is very high. Unfortunately, the journal also publishes a great deal of what it gets. We're unlikely to see the real figures any time soon, but I'd have to guess that the percentage of papers rejected is definitely lower than average.

I also realize that I'm open to accusations of conflict of interest here, since I'm on the editorial board of a competing journal, ACS Medicinal Chemistry Letters. What I can promise is that I will, in fact, work to keep any papers that I consider inadequate out of those pages (and, at the same time, to encourage good work to go there). I've tried to do that with BOMCL, too, in my capacity as reviewer, but it just hasn't always worked out.

But perhaps this is something I can do for them: to point out, publicly, that their credibility as a venue for medicinal chemistry results has suffered recently. When people get the impression that work is being sloppily reviewed at a given journal, they wonder how much they should trust the other papers that get published. Bioorganic and Medicinal Chemistry Letters has been around for twenty years now, and has published some very useful stuff over the years. There's a real place for it in the publishing world. But it's been better than it has been recently, and it should be better than it is. I hate to say this. But someone should.

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

May 24, 2010

What's the Condensation Record?

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Posted by Derek

There are probably some other reactions of the same order as this one - but does anyone know a higher one? I'm talking about this four-component condensation reaction, reported from a lab in Iran, which actually makes semi-useful looking oxadiazoles. Anyone know of a five-component condensation? A real one, I mean, that makes a real product, as opposed to dark gooey stuff. Those, I can imagine.

Comments (18) + TrackBacks (0) | Category: Chemical News

Great Moments in Heterocyclic Chemistry

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Posted by Derek

Something definitely went wrong with this paper: check out the thiophenes, which look through the whole paper just like they do in that abstract. It's another who-let-that-through moment for Bioorganic and Medicinal Chemistry Letters. Perhaps it's all a plot, to get you to read every paper in the hopes that something bizarre will turn up. . .

Comments (25) + TrackBacks (0) | Category: The Scientific Literature

Martin Gardner, RIP

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Posted by Derek

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

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

Comments (11) + TrackBacks (0) | Category: Current Events

May 21, 2010

Friday Book Recommendation

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Posted by Derek

I'm going to be off helping out with my daughter's field trip today, so it's not like there are going to be a lot of posts around here. But I did want to mention this book, "The Elements", by Theodore Gray.

That's this guy, Theodore Gray of Wolfram Research and of Wooden Periodic Table fame. He's clearly a wild man for chemical elements, and good for him. Now what someone needs to do is a coffee-table book on photogenic chemical compounds - dissolving potassium permanganate, crystals of chromium (III) chloride, hunks of copper (II) sulfate. It would (as those examples suggest) be mostly inorganic chemistry, but what the hey. . .

Comments (25) + TrackBacks (0) | Category: Book Recommendations

May 20, 2010