Wednesday, October 10, 2012

Why I am discomfited by today's chemistry Nobel

Congratulations to Professor Robert Lefkowitz and Professor Brian Kobilka for the 2012 Nobel Prize in Chemistry "for studies of G-protein-coupled receptors." Their biochemical and structural work is groundbreaking and fundamental in nature -- and immediately useful, too. As Derek said, "At least a third of marketed drugs, after all, are GPCR ligands, so their importance is hard to overstate."

There's been a bit of back-and-forth in the chemblogo/Twittersphere about whether or not this is another "biology" prize for the Chemistry Nobel, and whether or not that is a good thing or a bad thing. The most eloquent defenders of the position that it is indeed a good thing include the two most eloquent writers in the chemblogosphere, Derek Lowe and Ash of The Curious Wavefunction. From Derek:
Biology isn't invading chemistry - biology is turning into chemistry. Giving the prize this year to Lefkowitz and Kobilka takes us from the first cloning of a GPCR (biology, biology all the way) to a detailed understanding of their molecular structure (chemistry!) And that's the story of molecular biology for you, right there. As it lives up to its name, its practitioners have had to start thinking of their tools and targets as real, distinct molecules. They have shapes, they have functional groups, they have stereochemistry and localized charges and conformations. They're chemicals. That's what kept occurring to me at the recent chemical biology conference I attended: anyone who's serious about understanding this stuff has to understand it in terms of chemistry, not in terms of "this square interacts with this circle, which has an arrow to this box over here, which cycles to this oval over here with a name in the middle of it. . ." Those old schematics will only take you so far. 
So, my fellow chemists, cheer the hell up already. Vast new territories are opening up to our expertise and our ways of looking at the world, and we're going to be needed to understand what to do next. Too many people are making me think of those who objected to the Louisiana Purchase or the annexation of California, who wondered what we could possibly ever want with those trackless wastelands to the West and how they could ever be part of the country. Looking at molecular biology and sighing "But it's not chemistry. . ." misses the point. I've had to come around to this view myself, but more and more I'm thinking it's the right one.
In Ash's comments on the prize, he comments that he's tired with this ages-old debate:
I have to say that the whole “But is this chemistry?!” meme is getting quite boring. Binding of a small molecule to a GPCR is as much of a molecular interaction as anything in chemistry. Plus, think about the downstream chemistry that GPCRs do, including phosphorylation and salt-bridge breakage. I thought chemists were supposed to rub their hands with glee at the reduction of biology to chemistry while biologists fret and fume. But I see the opposite, biologists being quite sanguine about proteins being awarded medicine Nobels while chemistry continue to complain about proteins (chemicals!) being awarded chemistry Nobels. As I have said before though, this very bickering shows the astonishing reach and diversity of the field. If you can’t even agree on a definition for your field, well, that means your field is truly omnipresent.
There are a number of questions/complaints that have been raised with this trend in the chemistry Nobels -- here are some that I have heard and agree with:
  • While chemists may have a more-and-more expansive definition of chemistry, do biologists agree with this redefinition/annexation? What have biologists said about this? 
    • If we asked Professors Lefkowitz and Kobilka last week if they were chemists, would they have said yes or no? Is this relevant? 
  • This is chemistry's one day to bask in the media spotlight. We have emphasized biological chemistry for the 6 of the last 13 Nobels (h/t SeeArrOh). Is this the right mix? 
    • What does this trend tell graduate students in other, non-life-science-oriented chemistry fields?
  • If you are using the tools of chemistry to do biology, are you a chemist? If you are not a chemist and yet advance the understanding of chemistry, should you be considered for the chemistry Nobel? (My answer: yes, certainly.) 
  • Isn't this just a sign that the Nobels, their strictures and the way they are awarded are a terrible way to highlight scientific merit and achievement? Should judged awards for science look more like the Heisman Trophy or the Westminster Dog Show
My main complaint against this trend of biology/biologists winning recent chemistry Nobel prizes is that it is beginning to distract from the non-life-sciences aspects of chemistry. Physical chemists, inorganic chemists, analytical chemists, polymer chemists (and yes, organic chemists too!) are all losing this zero-sum game, and missing out on their opportunity to tell the larger public that they exist and why they're important to humanity. We can always rely on the public to be willing to support (and fund!) disease cures and advances in human biology (and they have their own prize for Physiology or Medicine!), but gaining public acceptance or recognition for these other (more fundamentally chemistry?) fields is much more difficult. I think that's why I wince a little bit when it's yet another life scientist that gets to step up to the mike. 

20 comments:

  1. "organic chemists are losing this zero-sum game, and missing out on [the] opportunity to tell the larger public...why they're important to humanity"

    The simplest explanation is that they aren't important to humanity.

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  2. Inorganic's doin' alright: 2010, 2005, 2001, etc.

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  3. For too long, chemists have seen the importance of their work as self evident. What do we teach freshmen in chemistry? Raoult, Henry, and Le Chatelier (1800's). What do we teach sophomores? Markovnikov and Grignard (late 1800s/early 1900s)—great scientists to be sure. Meanwhile, our 'biology' colleagues are teaching freshmen about PCR (chemistry Nobel 1993) and stem cells (physiology Nobel 2012). They learn about ribosomes, GFP, and GPCRs (chemistry Nobels in 2009, 2010, and 2012). The learn about histones and nuclear receptors (good candidates for future Nobels in chemistry). Most chemistry departments (perhaps because of the ACS) teach the same stale curriculum that they did 20 years ago, which is at best, a slight modification of what they taught 40 years ago.

    Biologists have shed many once popular sub-fields. Know any good zoologists? Taxonomists?

    Chemists can keep doing what they've always done (general chemistry, organic chemistry, inorganic chemistry, and physical chemistry (and perhaps biochem) as classically defined). But they do so at their peril. And the 'biologists' will continue to do some of the most interesting work studying systems at the molecular level.

    The organic chemists seem to get their hides chapped most easily when a Nobel gets awarded to a 'biologist'. It's worth asking "what are the fundamental unanswered questions in organic chemistry?" Note, this is not the same as "what can't we do as well as we would like (yield, ee, steps)?", which is probably best characterized as an engineering problem. This is not to say that process chemistry/engineering is not valuable (it is), but is it the forefront of science?

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    1. I don't think we get our hides chapped easily, I just think there are a lot of us (especially in the blogosphere) and so our complaints are probably overrepresented.

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    2. I am an organic chemist by training, and the complaints are not just in the blogosphere. In my (chemistry) department I heard several complaints at the coffee machine about this year's prize (with additional references to prior bad acts by the committee). There are lots of organic chemists to be sure. Not too long ago, at steady-state, the top academic groups ran with ~25(+) students, and others worked with ~15 (because hands are important). The world has changed. There may be a few groups that can work with 20+ trainees, and most of them may get good jobs in the US. But the model that was successful for several decades (get a PhD in organic chemistry and have a job waiting for you in pharma and a good chance at long-term job security) is not sustainable. In my opinion, those that ignore this are blind, and they are not doing their advisees any favors.

      I still ask "what are the fundamental unanswered questions in organic chemistry?" And again, I offer the caveat: "what can't we do as well as we would like (yield, ee, steps)?", which is probably best characterized as an engineering problem.

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    3. Chemists could have answer the question: "Can life evolve from nothing?" No life - no biology. At that time world was ruled by physics and chemistry. And both possible answers are equally interesting, but surely they are out of scale of the Nobel Prize.

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  4. To Anonymous at 540 pm: Physics teaches freshman about Maxwell (1800s), Newton (1600s!!), etc. but these are not worthless pursuits. Physics is still at the forefront of science, and guess what, so is chemistry. There is a lot of novel and groundbreaking chemistry, but it is seemingly ignored by the Nobel committee.

    I'm not sure where you come away with the idea that chemistry teaches the same thing as 20 years ago. I, in my classes (intro and inorganic), teach many topics discovered or developed in the past 20 years. Yes, we still teach about Le Chatelier, but physics still teaches Maxwell. These are fundamental principles that students need.

    Biology has recently reinvented itself due to molecular advancements. This does not make it a more noble (no pun intended) pursuit.

    Plus the curriculum in the first two years of chemistry is dictated primarily by pre-meds and biologists, since most students fall into these categories. Blame those jerks.

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  5. Andre,

    I don't dispute that established laws are important. However, most chemistry texts the I am aware of spend significant time discussing 'settled' science. Maxwell, Newton, and Le Chatelier could, in principle, be overturned, but I don't know of anyone working on it.

    The gen chem text my department uses today is nearly identical to the one I used 20 years ago. Same author, more color, different order of chapters, and $60 more expensive. Organic is pretty much the same (radicals appear later, there's more color, and there's a chapter on organometallics).

    Biology texts are much different today than they were 20 years ago. They talk about ribosome structures, siRNAs, etc.

    You're right that the classics are terrific (we still teach Plato), but we don't consider it modern philosophy.

    We can blame the pre-med/biologists/jerks for our early curriculum, but that's a cop out. You are right that : "Biology has recently reinvented itself due to molecular advancements." and you are right that "This does not make it a more noble (no pun intended) pursuit."

    The former is a good scientific argument (we know more, so we adapt and teach differently). The latter is true as well, and is commonly used as a defense of traditional philosophy (yes, Derrida's view of deconstruction exists, but that doesn't diminish the work of Hegel).

    We can teach modern chemistry, or the history of chemistry. Both have value. However, modern sciences typically receive more funding/attract more newcomers than the humanities.

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    1. So are you saying to fold more materials (or something else) in? I sort of came into chemistry the other way (BS/MS materials science, a few years in industry, currently a chemistry PhD student) and have benefited a lot from going into grad school knowing about things that aren't generally part of a traditional chemistry curriculum like colloids, crystal structures beyond bcc, fcc, hcp, and primitive cubic, polymers, microscopy, and structure-property relationships in the solid state, all of which are either available as electives in many materials departments (colloids, microscopy), or are part of the core curriculum (everything else).

      I'd like to see some of this changed in the standard undergraduate curriculum, but where do you put it? My instincts say to track students based on what they think they want to do while not having the tracks irreversibly diverge until after the core of general, organic, physical, and inorganic are done. That way if someone is interested in biochem, they can take several molecular or cell biology courses in addition to higher level biochemistry, organic, and analytical courses, whereas someone like me who wants to work on materials could pass on something like analytical (which I have in fact done, with absolutely no adverse effects on my career) while taking extra courses in organic, inorganic, physical, crystallography, electronic and magnetic properties, rheology etc.

      That being said, we still needed to take and use general chemistry.

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    2. I don't buy that chemists are teaching "history of chemistry" in introductory classes (unless they are seriously lagging in their curriculum). When I have taught (and when I was taught 15 years ago) students didn't learn about Henry's Law or Raoult's law, they learn derivation, applications and limitations of the ideal gas law. We mention the name Le Chatelier (mainly because the name appears on standardized exams that students will take pre-graduate) but we focus on thermodynamics. These aren't archaic ideas, and mastery is needed if you want to excel in chemistry, biochemistry, or biology.

      I guess the main point is that biology education is fundamentally different than chemistry or physics. These are math intensive subjects that require mastery of techniques and methods that may be a hundred or more year old, but that does not make them or the science as a whole less modern or less worthy. Biology may teach about advanced cutting edge things, but how do students really understand the RNA and whatever and the molecular bases of the processes until they take the chemistry and physics that underpin it? They spend a year memorizing cartoons of molecules in processes, then in advanced years, after learning about molecular structure and thermodynamics, go back and learn why/how the interactions occur.

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    3. Different anon here...

      So what *are* the new, revolutionary concepts/ideas/molecules in mainstream/"traditional" chemistry in the last 20 years? The chem nobels that have been given to inorganic recently have been from research done in the 70s and early 80s.

      Suggestions:

      N-heterocyclic (shelf-stable) carbenes (arduengo)
      Quintuple bond (power)
      New oxidation states of main group and f-block elements
      Modern CH activation protocols
      ...

      I need help from organic / physical guys!

      Interestingly, Whitesides wrote an article in 1990 predicting what will be discovered in chemistry in next 20 years:

      Whitesides, G. Angew. Chem. Int. Ed. Engl. 29 (1990) 1209-1218
      http://web.uni-plovdiv.bg/plamenpenchev/mag/files/ang_chem3.pdf

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  6. I enjoyed reading this article and the following discussion. i am preparing for graduate studies in inorganic chemistry - although most of my education thus far has been the fundamental "classics" I think there is certainly a place for them.

    A lot of the advances in chemistry have led to advances in biology. The same could be said for Math --> Physics --> Chemistry --> etc... I think its just the nature of science and maybe one day the lines of distinction between biochemistry, physical biology, etc will become less clear. I don't think its a bad thing, as a unified force working on problems I think we can solve them better by taking a multidisciplinary approach.

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  7. Lev,

    Excellent science is excellent science, no matter which discipline lays claim to it (or disavows itself of it).

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  8. As a biochem graduate, who did a PhD in protein crystallography, before dabbling in molecular biology and then specialising in biophysics, I have of late been asked "how do I label what I do."

    The simplest answer is "scientist" - classical barriers between disciplines are not immutable. Indeed, it could be argued that the most important insights are to be gained by bringing the firepower of two disciplines to bear on a single problem. Which is why biologists doing chemistry (or indeed chemists doing biology) have been particularly successful at gaining gongs.

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  9. During a literature search today, I noticed there's a banner on certain ACS publications congratulating the two prize winners.

    It got me wondering if the two doctors are even ACS members. It would be rather embarrassing if they weren't. Not surprising, but embarrassing.

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  10. Thanks for the plug, and I appreciate the angst that other kinds of chemists experience in not being able to communicate the excitement of their research to the public. But in a simple sense the Nobel Prizes simply reflect the dominance of a particular field. The twenty-first century is widely regarded as the century of biology and a lot of the most exciting discoveries in the last decade have been in biochemistry. This trend will likely continue.

    The first comment on this thread was snark but it has a shred of truth in it. Although organic chemists are of overwhelming importance to humanity, you can't expect straight organic synthesis to win a lot of Nobels simply because the golden age of organic synthesis has passed (although there certainly are individual problems in the field that are exciting). I think we will see lots of prizes for nanotechnology (including materials science) after the field really matures; as of now I think the field is too young to gather prizes, unlike biochemistry which has had a head start of a hundred years. I would give it about twenty years. So the best thing is not to despair and continue to make advances in your individual research areas since this is the only way that they can win prizes and be recognized. It's truly unfortunate that our fields need to win Nobel Prizes for public recognition, but such is the way of the world.

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    1. Nanotech is already winning prizes. Kroto et al for C60 1996 and Geim & Novoselov for graphene 2010.

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  11. Yet a different Anon here. I worked in a GPCR lab a few years ago. It was split 70-30 between chemists (synthetic chemists, molecular modelers and physical chemists) and biologists. To me, the initial discovery might seem like it was a biology question, but the end result is very much part of the chemistry field.

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  12. Realistically, most of the major breakthroughs in pure organic/inorganic/physical areas long ago happened. And analytical has rarely won the prize since the early days since it is basically an applied science and has to have a huge impact to pull it off. I think Fenn and Tanaka are the only analytical types to have won it recently if I recall and even that was for the areas they opened in bio.

    That leaves the interdisciplinary areas (biomedical, environmental, energy, etc.) as the ones that can have the impact the prize committee looks for. Of those bio/med just moves much faster than the others. I'm sure at some point there will be one or more related to climate just like Rowland did for CFCs. But it will require someone figuring out aerosols or having a viable CO2 or geoengineering solution first. Likewise someone will get it for fuel cells or alt fuels or fusion! if any of those are ever really viable. But until that happens, bio-related stuff will dominate.

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