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Derek Lowe The 2002 Model

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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: Twitter: Dereklowe

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February 26, 2007

Hedgehogs in Stockholm

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Posted by Derek

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

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

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

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

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

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

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


1. Paul on February 27, 2007 12:19 AM writes...

OK, I'll start. The cross-coupling synthetic chemists deserve one, but might not get it because there are so many of them and JK Stille died. The Teflon people at Dow deserve one, but might not get it because academia is favored relative to industry and Roy Plunkett died. The steroid/birth control people deserve one, but that's a touchy subject and Russell Marker died. JD Roberts deserves one for bringing NMR to organic chemistry, but the NMR phenomenon already won for physics and MRI won in medicine. DNA synthesis (Carruthers and Hood) should win one, and I don't know why it hasn't (Mullis/PCR?). Roger Tsien will win one for fluorescent probes. Lippard/Holm/Gray might win one for bioinorganic chemistry. Much like the sportswriters who continue to not vote Art Monk into Canton, te Nobel Committee is at risk of making itself irrelevant.

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2. Insider on February 27, 2007 3:56 AM writes...

This might help the debate:

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3. curiousGeorge on February 27, 2007 5:12 AM writes...

Lippard was a student of Cotton's. Once removed is better than none at all.

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4. Another Kevin on February 27, 2007 7:58 AM writes...

Did anyone else read this posting and think of Susan Lucci (Erica in _All My Children_) who was nominated for an Emmy in _eighteen consecutive years_ without winning one? (She finally did win one.)

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5. Jonathan Gitlin on February 27, 2007 10:07 AM writes...

Salvador Moncada should arguably have been included in the Nobel Prizes for both Prostaglandins and also Nitric Oxide. The latter exclusion is particularly galling, since his contribution to the discovery was at least as significant as Furchgott, Murad or Ignarro. I believe he accused the Karolinska Institute of racism, claiming that it was because he's Honduran.

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6. JSinger on February 27, 2007 11:08 AM writes...

...DNA synthesis (Carruthers and Hood) should win one, and I don't know why it hasn't...

In general, Hood's contributions to genomics are incredibly overlooked. He was barely mentioned in the human genome hype, despite being the most important person in the creation of high-throughput molecular biology. I assume there's a political reason, but don't know what it is.

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7. SRC on February 27, 2007 12:42 PM writes...

Lippard was a student of Cotton's. Once removed is better than none at all.

So was Holm, for that matter.

My candidate: Harden McConnell.

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8. Liberal Chemist on February 27, 2007 12:59 PM writes...

To go back to an earlier point in this post I feel that there is also a bias against "pure" chemists (if there ever was such a beast). It almost feels that with the large number of molecular biologists (and let's face it molecular physicists) that have been awarded the big prize in recent years that there should have been a new prize category created. As long as the spectrum of suitable candidates is so broad we will have to recognize the work vital to the greatest number of people working in the discipline and quite frankly chemistry has been overwhelmed by biochemistry and the numbers will never support an award to a straightforward chemist working outside the umbrella of sub-disciplines linked to biochemistry or medicinal chemistry. Perhaps "never" is a bit extreme given Kroto and Smalley but you get my point.

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9. Bioorganic Chemist on February 27, 2007 2:16 PM writes...

Frank Westheimer might be an even better example than Whitesides. Let's see: stereospecific enzymatic mechanism of NADH/NAD reduction/oxidation, mechanisms of phosphate hydrolysis and enzymatic decarboxylation, photoaffinity labeling, molecular mechanics and the use of empirical force fields in structure calculations (the "Westheimer method"), mechanisms of chromic acid oxidation and aromatic nitration, electronic effects in organic synthesis, ... Uninteresting things like initiating the entire field of bioorganic chemistry.

Westheimer has even famously addressed this: "I must say, I like to go on to new things. I would like to think that I initiated a lot of different projects, but certainly have not developed any one of them as thoroughly as would be possible, maybe not so thoroughly as would be desirable. If you do many different things, that's the way it's going to be. Whether I would have made a larger contribution to chemistry if I had done fewer things and exploited them better, well, no one will ever know."
(Quote from C&EN, 1987)

Dick Heck is another example of somebody developing a lot of chemistry and leaving much of it to others to exploit: for developing C-C bond formation using Pd, describing "Sonogashira couplings" (before Sonagashira; Cu-free variant as well), couplings to vinyl boronic acids (prior to Suzuki), carbonylations, as well as alkene couplings (Heck reaction) and other contributions, including groundbreaking mechanistic studies in organometallic reactions. Perhaps the Nobel Committee needs the cover that the "sexy" depends on chemistry. Human genome sequencing was dependent on fluorescent bases synthesized by aryl halide-alkyne couplings.

Heck and Westheimer are still alive, so maybe there's hope. On the other hand, if you got a few crystal structures published over the last few years, then I'm sure that your contribution to science and society was greater than Westheimer's or Heck's.

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10. Derek Lowe on February 27, 2007 2:19 PM writes...

I'm detecting some sulfurous fumes in that last comment's last paragraph. . .

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11. Paiute on February 27, 2007 3:36 PM writes...

Two thoughts:

1. Maybe the Nobels need an old-timers committee. Works for Cooperstown.

2. Passed over for the Al Nobel? You may still win an Ig Nobel. And the ceremony is way more fun.

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12. lazlo on February 27, 2007 3:50 PM writes...

Chemistry is becoming drained of 'big-picture", far reaching ideas. Particularly synthesis. Slave-ship labs with the PI pounding the drum to uncover another intermediate is the depressing reality. If you've been there you know what I'm talking about. Biochemistry is likely to recieve a greater share of future chemical prizes. Whitesides fits the latter category and I wouldnt be surprised to see him mentioned in the future.
Why anyone would mention Roger Tsien for a prize is beyond me. His lab is 'patents first', people and science second. He's gotten quite rich though, funneling the people's research dough into his private for-profit projects.

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13. AA on February 27, 2007 4:00 PM writes...

it seems a little odd to me that the Nobel selections are so hedgehog oriented in the last decade or so... what happened to awarding it for "outstanding contributions to such and such field" in general (as was done for woodward)? there some people (of whom westheimer and whitesides are prime examples) who has so clearly made huge impacts in a number of fields that they are clearly masters of chemistry/biology/biochemistry etc however they prefer to see themselves. is it wrong for the committee to award the prize to someone as a sort of congratulations to a career that has made some seminal contributions?

an example from organic chem is Corey winning for retrosynthesis. to me, this has always seemed like an excuse to give a nobel to someone who is obviously a fox but under a hedgehog pretense. Retrosynthesis may have been set down in writing by Corey, but it is impossible to think that the other major practitioners of total synthesis in his day (Woodward, Stork, Robinson etc) were not already thinking in those terms. My guess is that the committee said "we'll give a prize to an organicer this year. who's the biggest name in the field?". Corey's domination of so many aspects of organic chem made him the obvious choice and they picked "retrosynthesis" as an easy excuse to give it to him, rather than having to say "Corey is the #1 guy so he got it by default".

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14. Sili on February 27, 2007 5:46 PM writes...

Having read AA's comment (No. 13) I was reminded that Einstein got his Nobel for explaining the Photoelectric Effect. (Though admittedly in that case it was because Special Relativity was still considered too speculative.)

Point being, that other Prizes have been awarded on ... a pretence for a lack of a better word.

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15. Wavefunction on February 27, 2007 5:56 PM writes...

Stork should have won along with Corey. Now his chance is gone. As far as your list is concerned, again, Freeman Dyson had a shot with Feynman. He would have gotten it if Tomonaga had not shown up.
John Slater never got the prize when he should have; Pauling completely overshadowed him. G N Lewis was always a contender and never got it.
I think Westheimer and Breslow should get it for bioorganic chemistry. Breslow still might, but Westheimer will need to stay fortified with pills.

As Paul mentioned above, the Nobel committee is running the risk of making itself irrelevant. They are like the Oscar guys, who might never have awarded Scorsese.

My opinion about the Nobels is simple; those who receive it (usually) deserve it, but there are many more of the same caliber who would never get it.

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16. MadGenius on February 28, 2007 12:03 AM writes...

Seymour Benzer??

maybe behavioural genetics doesn't really fit into the Nobel category of Medicine/Physiology.

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17. Hap on February 28, 2007 5:22 PM writes...

One has to wonder if the emphasis on large, daring intellectual leaps by the Nobel committee and the people who make it up has something to do with the occurrence of the crystal structure/modeling problems in the subsequent story. The comments indicate that the author used a low-res crystal structure and a lot of modeling to determine a (speculative) protein structure. If intellectual leaps rather than consistency and sturdiness in reasoning are valued, than this seems like reasonable behavior - one will leap on the data present, even if imperfect and speculative, to try to arrive at a notable result before anyone else. Perhaps this ensures that lots of research is undertaken that might wait in limbo (or forever) for better data, but it also means that lots of effeort and money is wasted on overprosecution of guesses based on preliminary and/or bad data.

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18. TMS on February 28, 2007 6:37 PM writes...

Dick Heck has been nominated at least twice and I think he has EJ in his corner.

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19. richard blaine on February 28, 2007 9:38 PM writes...

Probably many Pipeline readers already know this, but Teflon was discovered by Roy Plunkett at Dupont, not Dow. If you're not familiar, look up the story on the Chemical Heritage website. A wonderful example of serendipity in chemical research.

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20. richard blaine on February 28, 2007 9:42 PM writes...

An interesting parallel thread could be "industrial scientists who deserve the Nobel but will probably never get it because their work is too practical." My nominee would be Stephanie Kwolek of Dupont, who invented Kevlar. (And by dogged pursuit of the molecule, not serendipity.)

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21. Paul on March 1, 2007 4:50 AM writes...

My bad on that.

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22. Jim Hu on March 3, 2007 2:13 AM writes...

Paul, regarding DNA: what about Khorana's prize? Also Michael Smith who shared with Mullis in 1993.

Regarding Carruthers, it wouldn't be unreasonable given the importance of the chemistry to the current scale of oligo synthesis. But they might feel they've covered chemical synthesis of DNA.

Your mentioning Hood leads to the obvious genomics candidate who some will be reluctant to honor: Venter.

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23. wlm on March 3, 2007 3:54 PM writes...

I like the fact that the Nobel is generally awarded for a specific accomplishment, even when the accomplishment spans a number of years (the development of biomolecular NMR by Wuthrich, for instance). There are other ways to honor illustrious careers, like membership in the National Academy.

As for those who arguably deserve a Nobel but haven't received one: how about Evans, Smithies and Capecchi for knockout mouse technology? Or Holm and Beinert for iron-sulfur clusters? Maybe Snyder for his opiate receptor or nitric oxide work?

I've mentioned that I think Woese should get a Nobel for his work on rRNA phylogenies. But someone (in comments to a previous Nobel post) pointed out that he was given a Crafoord Prize, which presumably rules out a Nobel.

As for Venter, you could make the case that he, Ham Smith, and whoever came up with their assembly algorithm deserve it for the first non-viral genome. Still, Venter seems like such a loathsome person that I find it hard to summon much enthusiasm for the idea.

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