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
Over at The Curious Wavefunction, there's an interesting post on Isaiah Berlin's famous hedgehog/fox distinction (which goes back a long way) and how it applies to chemistry. Wavefunction makes the case, which I hadn't thought through in such detail, that chemistry has for a long time been a field for foxes. That is, our famous names tend to be people who jump around from area to area as their interests take them, rather than people who spend their careers digging into one particular problem.
At the outset, one thing seems clear: chemistry is much more of a fox's game than a hedgehog's. This is in contrast to theoretical physics or mathematics which have sported many spectacular hedgehogs. It's not that deep thinking hedgehogs are not valuable in chemistry. It's just that diversity in chemistry is too important to be left to hedgehogs alone. In chemistry more than in physics or math, differences and details matter. Unlike mathematics, where a hedgehog like Andrew Wiles spends almost his entire lifetime wrestling with Fermat's Last Theorem, chemistry affords few opportunities for solving single, narrowly defined problems through one approach, technique or idea. Chemists intrinsically revel in exploring a diverse and sometimes treacherous hodgepodge of rigorous mathematical analysis, empirical fact-stitching, back of the envelope calculations and heuristic modeling. These are activities ideally suited to foxes' temperament. One can say something similar about biologists.
I think he's right, and I think that that's rarely been more true than now. Whitesides, Schreiber, Sharpless. . .start listing big names and you get a list of foxes. As it did for Wavefunction, the most recent hedgehog that springs to my mind in organic chemistry was H. C. Brown, although if Buchwald continues to work on metal-catalyzed amine couplings for another forty years he could come close. Am I missing anyone? Nominations welcome in the comments.
I'm thinking Krzysztof Matyjaszewski as a hedgehog, although he publishes enough other stuff to make it clear that he has other interests - controlled radical polymerization is just the horse he's riding.
How much of that is funding-driven? If you focus on one area of synthetic chemistry how likely are your grants to be renewed without some nod toward the application of your work to other areas?
I think it's an organic chemist-centric point of view. Perhaps it depends on your definition of foxes and hedgehogs, but I'd say there are lots of supremely accomplished biochemists and physical chemists who are hedgehogs. By my interpretation, Mendeleev was a quintiessential hedgehog. I'd hope no one here would consider him second-rate or less.
I thought Brown had more than 1000 papers. And the later ones in JOC read like it, too. Another hedgehog possibility might be Katrizky? (To me, these don't really sound like endosements of the concept, but...) Better possibilities might be Overman with alkaloids (though he's switched from stereoselective Heck to aza-Cope-Mannich and his eponymous rearrangement) or J.D. White.
Maybe it's hard for people to tell "don't have any new ideas" apart easily from "I've found a really good technique and am trying to plumb its depths usefully"?
One that may not be immediately recognized as a hedgehog is K.C.
He has been working on cyclic ether natural products for over 20 years. And has been battling maitotoxin for as long.
It takes quite a hedgehog to continue to scale up the maitotoxin synthesis month after month to push forward milligrams of 30 + step pieces and then when one finds that the stereochemistry is wrong do it all over again.
The are quite a few molecules in his lab that have been kicked around for more than 15 years and have yet to fall. We don't read about them because he doesn't like to publish partial synthesis.
10. anon the II on April 13, 2011 10:03 AM writes...
I think Clark Still was the foxiest of the chemists that I can think of. I don't know what happened to him but someone said that he was off building experimental aircraft.
As with most stereotypes and metaphors this seems to be partially reflective of real situation however can't be taken too far. If one wants to apply to Pharma R&D would suggest med chem/discovery attracts more foxes while process/development tends to have a bit more hedgehogs. Some areas of research and personalities lend themselves to shorter term focus and other may be open to continuous expansion. The former may be better for higher level exploration potential with the latter more incremental progress having increased practical value. I had viewed Brown's work as a bit monotonousness yet a couple times was glad he/his Indian cadre provided particular key knowledge to use.
The very best scientists are those rare mutants that combine both species traits or have ability to transform between them as circumstances require.
Sam Danishefsky. Hedgehog. Aren't most synthetic organic guys hedgehogs? All they do is synthetic organic… The natural products look different, but the approach is exactly the same. Wasn't that the whole idea of "The Logic of Chemical Synthesis"
And there you are—E.J. Corey, the father of all synthetic organic hedgehogs.
Thanks for the plug Derek. Clark Still and Peter Schultz are definitely high on the fox list. Both also came close to being snared by the hedgehog camp.
I think the broad strokes that paint mathematicians like Wiles as hedgehog need to be counter balanced. It is probably fair to say that the most revered mathematicians (now and in history) are so due to the frightening span of their work (names like Erdos, Tao, Gauss etc. come to mind) and their ability to see connections between fields to derive astounding new results.
It's difficult to compare chemists to these people (since chemists employ armies of grad students and postdocs). Even so, "span" in chemistry is often just a reflection of someone who is jumping on the latest funding trends, and the results we see are more a type of fashion than knowledge.
Do we really need George Whitesides latest paper microlfuidic device? Did Schultz's para-iodo tyrosine do anything for finding new crystal structures? Schriber's "chemgoogle"...?
I am not trying to nitpick at bad examples from large bodies of work, I am saying that some of the work from these prolific authors is indeed knowledge....a lot (most) of it is really just fashion.
"Clark Still and Peter Schultz are definitely high on the fox list. "
I though Schultz was high on the "most likely to be the spawn of Satan list" (Corey has already been approved by necronomical divination).
What's so pathetic about the average chemists mindset is that he can only see the tree in the forest.
Any chemist who works in a non-theoretical field is able to steal the ideas of hundreds or thousands of his underpaid workers and lay claim to big cash prizes and a stable existence.
I'll bet even an average chemist could mange comparable careers to the so called greats given enough resources.
It's why half the readers of this blog are destined for the unemployment line.
I wonder how grand Schreibers career would have been had he been at Univ of Kansas?
22. newnickname on April 13, 2011 3:16 PM writes...
#17 Re: Danishefsky. I see hedgefox. Starting with Stork in '67 (isoxazole annelation), he then did vinyl picoline annelation and kept going until he did "Danishefsky Diene" for annelation. After using it for 4+2 = 6 carbocycles, he branched out to show that it could be used for all kinds of other things: (4+2)-1 = 5 carbocyles (pentalenes), lactones, hetero-DA to make pyrans, and so on. But he's done a few other things without using his diene, as well.
#17 and #22
Half of what Danishefsky does these days is immunological research. He even has people working for him on 2 campuses: Columbia and MSKCC. So no, you chose the wrong synthetic organic chemist to use as your example.
I expected Dave Gin to also move more toward immunology at MSKCC, but unfortunately that can't happen anymore.
Chemistry is a creative science in the sense that you synthesize something which everyone can see, while often to see the creativity in solving a mathematical theorem or of quantum physics problem is not easy for non-specialists. Nature too uses chemistry, especially chemical synthesis for various biological purposes. So it is very difficult for majority of organic chemists not to get inspired for using their creations for yet better purposes. Therefore, I think it is not much of a problem if we see many foxes around, though some hedgehogs would definitely add their charm to the diversity of researchers.
1. opsomath on April 13, 2011 8:56 AM writes...
I'm thinking Krzysztof Matyjaszewski as a hedgehog, although he publishes enough other stuff to make it clear that he has other interests - controlled radical polymerization is just the horse he's riding.
Permalink to Comment2. SP on April 13, 2011 9:14 AM writes...
How much of that is funding-driven? If you focus on one area of synthetic chemistry how likely are your grants to be renewed without some nod toward the application of your work to other areas?
Permalink to Comment3. Monte Davis on April 13, 2011 9:18 AM writes...
Speaking of Erlenmyers, catch the video profile of a lab-glassware blower that was featured on Boing Boing the other day:
http://vimeo.com/22299035
A dwindling (if not yet dying) breed.
Permalink to Comment4. Rick on April 13, 2011 9:22 AM writes...
I think it's an organic chemist-centric point of view. Perhaps it depends on your definition of foxes and hedgehogs, but I'd say there are lots of supremely accomplished biochemists and physical chemists who are hedgehogs. By my interpretation, Mendeleev was a quintiessential hedgehog. I'd hope no one here would consider him second-rate or less.
Permalink to Comment5. Ed on April 13, 2011 9:26 AM writes...
Ian Paterson and the boron aldol in polyketide synthesis spring to mind as an obvious hedgehog approach.
Going strong since 1985?
Permalink to Comment6. Rick on April 13, 2011 9:30 AM writes...
Oh yeah, foxiest chemist ever: Linus Pauling. No doubt about it. Whitesides, Schreiber, Sharpless are mere kits compared to Pauling.
Permalink to Comment7. Curryworks on April 13, 2011 9:44 AM writes...
Matyjaszewski is a fox he started in anionic polymerization and did a total change of program when ATRP was discovered.
To attest to his foxiness how do you publish 700+ papers and not work on one subject.
Permalink to Comment8. Hap on April 13, 2011 9:53 AM writes...
I thought Brown had more than 1000 papers. And the later ones in JOC read like it, too. Another hedgehog possibility might be Katrizky? (To me, these don't really sound like endosements of the concept, but...) Better possibilities might be Overman with alkaloids (though he's switched from stereoselective Heck to aza-Cope-Mannich and his eponymous rearrangement) or J.D. White.
Maybe it's hard for people to tell "don't have any new ideas" apart easily from "I've found a really good technique and am trying to plumb its depths usefully"?
Permalink to Comment9. Rob on April 13, 2011 10:02 AM writes...
One that may not be immediately recognized as a hedgehog is K.C.
He has been working on cyclic ether natural products for over 20 years. And has been battling maitotoxin for as long.
It takes quite a hedgehog to continue to scale up the maitotoxin synthesis month after month to push forward milligrams of 30 + step pieces and then when one finds that the stereochemistry is wrong do it all over again.
The are quite a few molecules in his lab that have been kicked around for more than 15 years and have yet to fall. We don't read about them because he doesn't like to publish partial synthesis.
Permalink to Comment10. anon the II on April 13, 2011 10:03 AM writes...
I think Clark Still was the foxiest of the chemists that I can think of. I don't know what happened to him but someone said that he was off building experimental aircraft.
Permalink to Comment11. Anonymous on April 13, 2011 10:22 AM writes...
Peter Schultz is way foxier than Schreiber.
Permalink to Comment12. anonymatic on April 13, 2011 10:24 AM writes...
Where's Chris Walsh???
Permalink to Comment13. CMCguy on April 13, 2011 10:26 AM writes...
As with most stereotypes and metaphors this seems to be partially reflective of real situation however can't be taken too far. If one wants to apply to Pharma R&D would suggest med chem/discovery attracts more foxes while process/development tends to have a bit more hedgehogs. Some areas of research and personalities lend themselves to shorter term focus and other may be open to continuous expansion. The former may be better for higher level exploration potential with the latter more incremental progress having increased practical value. I had viewed Brown's work as a bit monotonousness yet a couple times was glad he/his Indian cadre provided particular key knowledge to use.
The very best scientists are those rare mutants that combine both species traits or have ability to transform between them as circumstances require.
Permalink to Comment14. Anon on April 13, 2011 10:33 AM writes...
Peter Schultz may be a "Wolf in Fox clothing"?
Permalink to Comment15. Anonymous on April 13, 2011 11:10 AM writes...
@Rob #9
Permalink to CommentK.C. is a hedgefox. Or is it a foxhog? Either way, he's an exception to either rule, but unquestionably top shelf.
16. Anonymous on April 13, 2011 11:11 AM writes...
Taylor Swift is definitely a FOX.
Permalink to Comment17. JSR on April 13, 2011 11:26 AM writes...
Sam Danishefsky. Hedgehog. Aren't most synthetic organic guys hedgehogs? All they do is synthetic organic… The natural products look different, but the approach is exactly the same. Wasn't that the whole idea of "The Logic of Chemical Synthesis"
And there you are—E.J. Corey, the father of all synthetic organic hedgehogs.
Permalink to Comment18. Curious Wavefunction on April 13, 2011 12:03 PM writes...
Thanks for the plug Derek. Clark Still and Peter Schultz are definitely high on the fox list. Both also came close to being snared by the hedgehog camp.
Permalink to Comment19. leftscienceawhileago on April 13, 2011 12:59 PM writes...
9.
An interesting paper that is uncharacteristic of K.C.'s lab, back when "self replication" was a hotter topic:
http://www.nature.com/nature/journal/v369/n6477/abs/369218a0.html
I think the broad strokes that paint mathematicians like Wiles as hedgehog need to be counter balanced. It is probably fair to say that the most revered mathematicians (now and in history) are so due to the frightening span of their work (names like Erdos, Tao, Gauss etc. come to mind) and their ability to see connections between fields to derive astounding new results.
It's difficult to compare chemists to these people (since chemists employ armies of grad students and postdocs). Even so, "span" in chemistry is often just a reflection of someone who is jumping on the latest funding trends, and the results we see are more a type of fashion than knowledge.
Do we really need George Whitesides latest paper microlfuidic device? Did Schultz's para-iodo tyrosine do anything for finding new crystal structures? Schriber's "chemgoogle"...?
I am not trying to nitpick at bad examples from large bodies of work, I am saying that some of the work from these prolific authors is indeed knowledge....a lot (most) of it is really just fashion.
Permalink to Comment20. John on April 13, 2011 2:12 PM writes...
"Clark Still and Peter Schultz are definitely high on the fox list. "
I though Schultz was high on the "most likely to be the spawn of Satan list" (Corey has already been approved by necronomical divination).
What's so pathetic about the average chemists mindset is that he can only see the tree in the forest.
Any chemist who works in a non-theoretical field is able to steal the ideas of hundreds or thousands of his underpaid workers and lay claim to big cash prizes and a stable existence.
I'll bet even an average chemist could mange comparable careers to the so called greats given enough resources.
It's why half the readers of this blog are destined for the unemployment line.
I wonder how grand Schreibers career would have been had he been at Univ of Kansas?
Permalink to Comment21. Peter on April 13, 2011 2:38 PM writes...
I'm not sure I believe in the fox/hedgehog model for chemists -- but if I had to nominate a hedgehog, I think Dave Collum is a good example.
Permalink to Comment22. newnickname on April 13, 2011 3:16 PM writes...
#17 Re: Danishefsky. I see hedgefox. Starting with Stork in '67 (isoxazole annelation), he then did vinyl picoline annelation and kept going until he did "Danishefsky Diene" for annelation. After using it for 4+2 = 6 carbocycles, he branched out to show that it could be used for all kinds of other things: (4+2)-1 = 5 carbocyles (pentalenes), lactones, hetero-DA to make pyrans, and so on. But he's done a few other things without using his diene, as well.
Permalink to Comment23. Chemjobber on April 13, 2011 3:33 PM writes...
Is Grubbs a hedgehog or a fox? I'd say hedgehog, but I don't really know the scope of his work outside of metathesis.
Permalink to Comment24. Tok on April 13, 2011 3:37 PM writes...
#17 and #22
Half of what Danishefsky does these days is immunological research. He even has people working for him on 2 campuses: Columbia and MSKCC. So no, you chose the wrong synthetic organic chemist to use as your example.
I expected Dave Gin to also move more toward immunology at MSKCC, but unfortunately that can't happen anymore.
Permalink to Comment25. Chemist on April 14, 2011 3:22 AM writes...
Chemistry is a creative science in the sense that you synthesize something which everyone can see, while often to see the creativity in solving a mathematical theorem or of quantum physics problem is not easy for non-specialists. Nature too uses chemistry, especially chemical synthesis for various biological purposes. So it is very difficult for majority of organic chemists not to get inspired for using their creations for yet better purposes. Therefore, I think it is not much of a problem if we see many foxes around, though some hedgehogs would definitely add their charm to the diversity of researchers.
Permalink to Comment26. SteveM on April 14, 2011 12:41 PM writes...
Robert Woodward seems like the quintessential fox.
First Reserpine and then the Woodward-Hoffman Rules. That guy was something...
Permalink to Comment