Field of Science

2017 Nobel Prize picks

The nice thing about Nobel Prizes is that it gets easier to predict them every year, simply because most of the people you nominate don't win and automatically become candidates for the next year (note however that I said "easier to predict", not "easier to correctly predict"). That's why every year you can carry over much of the same list of likely candidates as before.

Having said that, there is a Bayesian quality to the predictions since the previous year's prize does compel you to tweak your priors, even if ever so slightly. Recent developments and a better understanding of scientific history also might make you add or subtract from your choices. For instance, last year the chemistry prize was awarded for molecular machines and nanotechnology. This was widely considered a “pure chemistry” prize, so this year’s prize is unlikely to be in the same area. Knowing the recent history of recent prizes for chemistry, my bets are on biological chemistry or inorganic chemistry as leading contenders this year.


As in previous years, I have decided to separate the prizes into lifetime achievement awards and specific discoveries. There have been fewer of the former in Nobel history and I have only two in mind myself, although the ones that do stand out are no lightweights - for instance R B Woodward, E J Corey, Linus Pauling and Martin Karplus were all lifetime achievement awardees. If you had to place a bet though, then statistically speaking you would bet on specific discoveries since there have been many more of these. So here goes:

Lifetime achievement awards

Inorganic chemistry: Harry Gray and Steve Lippard: For their pioneering and foundational work in the field of bioinorganic chemistry;work which has illuminated the workings of untold number of enzymatic and biological processes including electron transfer.

Biological chemistry: Stuart Schreiber and Peter Schultz: For their founding of the field of modern chemical genetics and their impact on the various ramifications of this field in chemistry, biology and medicine. Schreiber has already received the Wolf Prize last year so that improves his chances for the Nobel. The only glitch with this kind of recognition is that a lot of people contributed to the founding of chemical biology in the 1980s and 90s, so it might be a bit controversial to single out Schreiber and Schultz. The Thomson-Reuters website has a Schreiber prediction, but for rapamycin and mTOR; in my opinion that contribution, while noteworthy, would be too narrow and probably not sufficient for a prize.

Specific awards

John Goodenough and Stanley Whittingham for lithium-ion batteries: This has been on my list for a very long time and it will remain so. Very few science-based innovations have revolutionized our basic standard of living the way lithium-ion batteries have, and I cannot think of anyone else who deserves a prize for this as much as Goodenough. Just a few months ago there was a book about the making of the iPhone which featured him and his outsize impact on enabling our modern electronics age. As this recent New York Times profile noted, Goodenough is 94 and is still going strong, but that’s no reason to delay a recognition for him.


Generally speaking, recognition for the invention of specific devices have been rather rare, with the charged-coupled device (CCD) and the integrated circuit being exceptions. More importantly, a device prize was given out just three years ago in physics (for blue light-emitting diodes) so based on the Bayesian argument stated above, it might make it a bit unlikely for another device-based invention to win this year. Nonetheless, a prize for lithium ion batteries more than most other inventions would conform to the line in Alfred Nobel's will about the discovery that has "conferred the greatest benefits on mankind."

Franz-Ulrich Hartl and Arthur Horwich for their discovery of chaperones: This is clearly a discovery which has had a huge impact on our understanding of both basic biological processes as well as their therapeutic relevance.


Barry Sharpless for click chemistry, Marvin Caruthers for DNA synthesis:
I am grouping these two together under the heading of organic synthesis. Sharpless’s click chemistry has seen widespread enough use since it was developed. However, it’s worth contrasting it with two other kinds of novel reactions which were awarded the prize – olefin metathesis and palladium-catalyzed couplings. One of the reasons these two were recognized was because they had a huge impact on industrial synthesis of drugs, polymers, agricultural chemicals etc. I don’t know enough to know whether click chemistry has also had such a practical impact – it may not have since it’s still rather new – but I assume that this practical aspect would certainly play a role in the decision.

Of the two, I think Caruthers deserves it even more; the technology he invented in the 1980s has been chugging along for thirty years now, quietly fueling the biotechnology revolution. While perhaps not as monumental as sequencing, it’s certainly a close second, and unlike click chemistry its practical applications are uncontested. If Sanger could get a prize for figuring out the basic chemistry of DNA sequencing, then I don’t see why Caruthers shouldn’t get one for figuring out the basic chemistry of DNA synthesis. Caruthers could also nicely split the prize with Leroy Hood (below), who really pioneered both commercial DNA sequencers as well as synthesizers.

The medicine prize

As is traditionally the case, several of the above discoveries and inventions can be contenders for the medicine prize. However we have left out what is potentially the biggest contender of all until now.

Jennifer Doudna, Emmanuelle Charpentier and Feng Zhang for CRISP-Cas9: I don't think there is a reasonable soul who thinks CRISPR-Cas9 does not deserve a Nobel Prize at some point in time. In terms of revolutionary impact and ubiquitous use it almost certainly belongs in the same shelf that houses PCR and Sanger sequencing.

There are two sets of questions I have about it though: Firstly, whether an award for it would still be rather premature. While there is no doubt as to the broad applicability of CRISPR, it also seems to me that it's rather hard right now to apply it with complete confidence to a wide variety of systems. I haven't seen numbers describing the percentage of times that CRISPR works reliably, and one would think that kind of statistics would be important for anyone wanting to reach an informed decision on the matter (I would be happy to have someone point me to such numbers). While that infamous Chinese embryo study that made the headlines last year was quite flawed, it also exposed the problems with efficacy and specificity that still bedevil CRISPR (these are problems similar to the two major problems for drugs). My personal take on it is that we might have to wait for just a few more years before the technique becomes robust and reliable enough to thoroughly enter the realm of reality from one of possibility.

The second question I have about it is the whole patent controversy, which if anything seems to have become even more acrimonious since last year, reaching worthy-of-optioning-movie-rights level of acrimonious in fact. Doudna also wrote a book on CRISPR this year which I reviewed here; while it’s generally fair and certainly well-written, it does downplay Church and Zhang’s role (and wisely omits any discussion of the patent controversy). Generally speaking Nobel Prizes try to stay clear of controversy, and one would think that the Nobel committee would be especially averse to sullying their hands with a commercial one. The lack of clear assignment of priority that is being played out in the courts right now not only tarnishes the intellectual purity of the discovery, but on a more practical level it also makes the decision to award the prize to all three major contenders (Doudna, Charpentier and Zhang) difficult.

Hopefully, as would be fitting for a good novel, the allure of a Nobel Prize would make the three protagonists reach an agreement to settle their differences over a few beers. But that could still take some time. A different way to look at the whole issue however is to say that the Nobel committee could actually heal the divisions by awarding the prize to the trio. Either way, a recognition of CRISPR is likely going to be one of the most publicly debated prizes of recent times.

The bottom line in my mind: CRISPR definitely deserves a prize, and its past results and tremendous future potential may very well tip the balance this year, but it could also happen that the lack of robust, public vindication of the method and the patent controversy could make the recognition seem premature and delay the actual award.

Mary-Claire King: For the discovery of the BRCA1 breast cancer gene. Not only did this discovery revolutionize the treatment and detection of breast cancer, but it really helped to solidify the connection between genetics and cancer.

Craig Venter, Francis Collins, Eric Lander, Leroy Hood and others for genomics and sequencing: The split here may be pretty hard here and they might have to rope in a few consortiums, but as incomplete and even misleading as the sequencing of the human genome might have been, there is little doubt that it was a signal scientific achievement deserving of a Nobel Prize.

Alec Jeffreys for DNA fingerprinting and assorted applications: Alec Jeffreys is another perpetual favorite on the list and one whose invention has had a huge societal impact. I have never really understood why he has never been awarded the prize; the societal impact of DNA fingerprinting is almost as great as the contraceptive pill (for which Carl Djerassi was unfortunately never recognized).

Ronald Evans and Pierre Chambon for nuclear receptors: After GPCRs, nuclear receptors are the biggest targets for drugs, and GPCRs have already been recognized a few years ago. The third discoverer of nuclear receptors, Elwood Jensen, sadly passed away in 2012.

Bert Vogelstein, Robert Weinberg and others for cancer genes: This again seems like a no-brainer to me. Several medicine prizes have been awarded to cancer genetics so this certainly wouldn't be a novel idea, and it's also clear that Vogelstein and Weinberg have done more than almost anyone else in identifying rogue cancer genes and their key roles in health and disease.

The physics prize: There should be zero doubt in anyone’s mind that this year's Nobel Prize in physics will be awarded to Kip Thorne and Rainer Weiss for their decades-long dogged leadership and work that culminated in last year's breakthrough discovery of gravitational waves by the LIGO observatory. I would both love and hate to be in their position right now. It's a dead ringer, and the only reason they missed it last year was because the discovery came after the nomination. Sadly Ron Drever died of dementia this year. For those wanting to know more about the kind of dedication and personality clashes these three men brought to the project, Janna Levin's book which came out earlier this year is a great source.


There is another recognition that I have always thought has been due: a recognition of the ATLAS-CMS collaboration at the LHC which discovered the Higgs boson. A prize for them would emphasize several things: it would put experiment at the center of this important scientific discovery (there would have been no 2013 Nobel Prize without the LHC) and it would herald a new and necessary tradition of awarding the prize to teams rather than individuals, reflecting the reality of contemporary science. The Nobel committee could also recognize the international, collaborative nature of science and actually award the prize to the entire LIGO team and not just to Thorne and Weiss, but that’s unlikely to happen.

It also seems to me that a Nobel Prize for chaos theory and the study of dynamical systems - a field that surprisingly has not been recognized yet - should include any number of pioneers featured for instance in James Gleick's amazing book "Chaos", most notably Mitchell Feigenbaum.

Literature

My interest in fiction has picked up again over the last few years so I am going to venture a few guesses here. Unlike the science awards, Nobel Prizes for literature are usually more of lifetime achievement awards rather than awards for specific books; in fact nobody has won the prize for writing just one book, no matter how transformational it might have seemed.

More accurately, the literature prize is usually given for writers who have consistently explored specific themes in their work. For instance, Naipaul and Coetzee were recognized for vividly exploring issues of post-colonial identity, Tony Morrison was recognized for exploring issues of black identity and Bertrand Russell was recognized for extolling the virtues of individual freedom and rationality. It thus makes sense to think in terms of themes when considering potential literature Nobel Laureates.

My personal favorite pick for the prize is Haruki Murakami. Interestingly, my introduction to him came not through his novels but through his amazing book on running which was a great driving force for my own running efforts. But whether it’s in that book or in his novels, Murakami is quite stunning at exploring existential angst, isolation and anxiety in a world where technology is supposed to function as a palliative that connects humans together. His prose is characteristically Japanese; spare, stark and straight to the point. More than most writers I know, I think Murakami deserves to be recognized for his substantial body of work with unifying themes.

Among other people who have traditionally been on nomination lists are Salman Rushdie, Milan Kundera, Philip Roth, Cormac McCarthy and Joan Didion. I think all of these are great writers, but Cormac McCarthy would top the list for me, again because he has produced a consistent body of work that investigates raw themes of Americana in devastatingly brief and searing prose. Rushdie’s “Midnight’s Children” is brilliant, but I honestly don’t think his other work really is up to Nobel caliber. Roth is also an eminent contender in my opinion, and I would be happy to see him receive the award. Joyce Carol Oates is another favorite, but frankly I haven’t read enough of her work to form an informed judgement. In any case, it’s now been twenty four years since an American won the prize, and there are certainly a few worthy contenders by this point.

Far and away, I personally think the most creative writer in English alive today is Richard Powers; he's one of those few novelists to whom I would apply the "genius" label. His sentence constructions and metaphors defy belief and for sheer imaginative prose I cannot think of his equal. Unfortunately, while he has a cult following, his novels are rather challenging to become widely read, and generally speaking the Nobel Committee does simple rather than complex.

So that's it from my side. Let the bloodbath games commence!

15 comments:

  1. I just don't see any way that it shouldn't go to Goodenough. Right now I see at least 5 Li ion battery powered devices in the room I'm in. He completely changed society with his discoveries

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    1. For me Goodenough has been a no-brainer for a long time. He pretty much checks every box.

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  2. Even easier than recycling a Nobel prediction list is to criticize someone else's.

    Other invention prizes in Physics in the last 50 years:
    2014 "for the invention of efficient blue light-emitting diodes..."
    1992 "for his invention and development of particle detectors, in particular the multiwire proportional chamber"
    1989 hydrogen maser & ion traps
    1986 electron microscope & scanning tunneling electron microscope
    1978 Kapitsa "for his basic inventions..."

    On Cas9/CRISPR, I have yet to hear off a system in which it doesn't work. That is in the sense of Cas9 being a programmable DNA-binding protein and nuclease. So much attention is focused on gene editing, which can be trickier to implement, but again there is yet a paper saying "we tried really carefully and can't get Cas9 editing to work in system X". Run a PubMed search & you'll find Cas9 working in a variety of bacteria, archea, plants, fungi, invertebrates and vertebrates. As a research tool, Cas9 has had a spectacular impact & there is no sign whatsoever that we anywhere near "peak CRISPR".

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    1. Oh indeed, definitely some important Nobels for invention. I was referring explicitly to inventions that resulted in great commercial benefits and impacted daily life. Thanks for the info on CRISPR. How specific have been these editing applications in terms of off-site effects?

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    2. The human therapeutics get scrutinized the hardest on off-target effects. Some of the research uses probably need a look -- you'd hate to have a result be due to off-target issues -- but a lot are either intolerant or unaffected.

      Intolerant would be bacterial gene editing -- bacterial and archeal chromosomes seem to have little tolerance for double-stranded breaks. One person in the field told me his group had success with a promoter-less Cas9 construct -- the background transcription was sufficient.

      But to me the real beauty of Cas9 et al is the spectacular modularity -- which enabled the immediate generation of nuclease-null mutants -- plus its high tolerance for fusing to other domains. Just using a nuclease-dead version gives you a programmable repressor. Fuse it to a polymerase-recruitment domain and you have an activator. Fuse it to a fluorescent protein and you have a way to specifically stain loci in vivo. Fuse it to epigenetic modifiers and you can edit that. Throw in some light-sensitive domains or inducible dimerization domains and you can make all these properties inducible.

      Cas9 is also spectacularly useful in vitro, such as the CATCH technique which allows capturing large fragments for input into PacBio or Oxford Nanopore long read DNA sequencing.

      Even in the editing, a lot of the applications are probably relatively tolerant of off targets. Things like knocking-in a wide variety of BRCA variants seen in genetic tests to determine which actually impinge on gene function. Or, say with Cas9 library screens, multiple guides can be used to defend against off-target effects.

      The modularity of the protein is also enabling mutagenesis and structural biology to understand the roots of specificity and generate mutants with even higher fidelity. Perhaps those can't eliminate off-target cutting, but I suspect in a few years it will be considered a very minor hindrance to medical applications

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    3. Very informative, thanks Keith. Echoing my recent post, it would be good to map CRISPR's DOA.

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    4. +1 for Keith. CRISPR/Cas9 toolkit works so well that we now advise people to downplay this part in their position and grant applications. I sit on half a dozen grant panels and the same number of SABs and recruitment panels. The technology is present under some guise in close to 100% of projects that include a molecular and cellular component.

      I think the patent issue is the most severe one, and also the noise generated by people who should not be in contention. For instance, a lot of emphasis by supporters of people like Church is put on the homologous recombination. But a lot of what we do with the system uses nuclease dead Cas9 as noted by Keith.

      For me, the only ones who tick the boxes either for the bacterial immunity and for the applications are JD and EC. The latter should also get a bonus for being lest belligerent and more interested in science than in money.

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  3. But, mTOR is discovery due to Swiss-American Michael N. Hall, right? It is just that FK-506 and Rapamycin came along and all fit into groove. It takes away nothing from Stu, but he was still an organic chemist then in comparison to other biologist including Prof. Hall. MTor deserves its own Nobel.

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    1. Yes, I would think mTOR deserves it own prize.

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  4. "In any case, it’s now been twenty four years since an American won the prize, and there are certainly a few worthy contenders by this point."

    Well, Bob Dylan won last year.

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    1. Correct, I was thinking of "mainstream" writing (although that does seem to change with time!).

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  5. As for Cas9, I never understood why Georges Church is not considered to be a strong pretender for the Nobel prize ? His Science paper literally came out in the same issue as Zhang's paper. He has a strong claim about being one of the person who enabled Cas9 for eukaryotic cells.

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  6. My problem with Zhang and Church with regards to Cas9/CRISPR:
    Once the original in vitro story by Doudna and Charpentier was out, the application in cells was very obvious, and, as it turned out, pretty trivial.
    Were Zhang and Church hit by a meteorite, gene editing would have been nevertheless published within months.
    On the other hand, there were the guys in Lithuania which, if I remember correctly, sent a very similar story than Doudna/Charpentier to Cell even earlier only to be flatly rejected. The story eventually came out in PNAS, but in the meantime the Jinek paper came out.

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    1. I agree that the Lithuanians should be strong contenders. Whether the extension to eukaryotes is obvious or not is at the heart of the patent controversy I believe.

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  7. OUTSIDE THE BOX PREDICTIONS
    NOBEL MEDICINE : JAPANESE FOR FUNCTIONAL MRI (fMRI)
    PHYSICS: KIP THORNE ET AL
    LITT: MURAKAMI
    CHEM: SOLAR ENERGY GUYS

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