Dust off the crystal ball: It’s time for STAT’s 2020 Nobel Prize predictions – STAT

Posted: October 4, 2020 at 2:16 pm

The mistake Nobel Prize prognosticators yours truly included make is to look through the greatest hits of biochemistry, biology, and medicine (the areas STAT covers) nuclear hormone receptors! microRNAs! and figure (as last years prediction story did) one of those is due and deserving. The trouble is, as MITs Phillip Sharp, who shared the 1993 medicine Nobel, told me, There is just a lot of good science that will never get recognized.

So focusing on the greatest hits to forecast the science winners who will be announced next week is too simplistic. Theyre all contenders, but the smart money looks for other criteria. Like toggling between discoveries of what cells and molecules do and inventions of techniques that reveal what they do, or between disciplines, or (for medicine) between something that directly cures patients and something about the wonders of living cells.

By that criteria, it might be a techniques turn, since the last such winner in medicine was for turning adult cells into stem cells, in 2012. Could this be the year for optogenetics, which allows brain scientists to control genetically modified neurons with light? I dont think optogenetics has made a big enough impact outside of neuroscience yet, said cancer biologist Jason Sheltzer of Cold Spring Harbor Laboratory, who dabbles in Nobel predictions, but who knows.

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The last Nobel for DNA sequencing was way back in 1980, he pointed out, and since then we have seen the complete sequencing of the human genome, one of humanitys towering achievements. (Sheltzer correctly predicted 2018s medicine Nobel for immuno-oncology pioneer James Allison. The Human Genome Project could win it for the officials who led it, like Francis Collins of the National Institutes of Health and Eric Lander of the Broad Institute. Would Craig Venter, who led a competing private effort, make it to Stockholm, too? Let the betting commence!

Just to be clear, science Nobels arent chosen all that, well, scientifically. For medicine, a five-member Nobel Committee for Physiology or Medicine at Swedens Karolinska Institute sifts nominations and selects candidates. The 50-member Nobel Assembly votes, this year on Oct. 5. So you can get head-scratchers from, say, 20-18-12 or similarly split votes if, say, genetics fanciers split their votes among two contenders. (If you want to know if that happened, hang on until 2070: Nobel records are secret and sealed for 50 years.) For chemistry, chosen on Oct. 7 this year, the five-member Nobel Committee of the Royal Swedish Academy of Sciences likewise sifts nominations and recommends finalists to the academy for a vote.

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Besides invention and discovery switching off in the medicine Nobel, there certainly seems to be periodicity in terms of disciplines taking turns, said David Pendlebury of data company Clarivate Analytics. He has made 54 correct Nobel predictions (usually in the wrong year, but in 29 cases within just two) since 2002 by analyzing how often a scientists key papers are cited by peers and awarded predictive prizes like the Lasker or Gairdner awards.

Neuroscience won the medicine Nobel in 2000, 2004, 2014, and 2017, immunology in 2008, 2011, and 2018, for instance. Infectious disease and cancer win every decade or two, and so are probably also-rans for 2020. Thats why STAT said last year that the 2018 medicine award for immuno-oncology made cancer an unlikely 2019 winner. Yet William Kaelin, Peter Ratcliffe, and Gregg Semenza won for discovering how cells sense and adapt to oxygen availability, through gene regulation, which is tangentially related to cancer. Go figure.

For the medicine prize, periodicity also applies to toggling between super-basic molecular biology and stuff that actually cures people (not year by year, but generally). Last years award for how cells sense changing oxygen levels was pretty abstruse and might shape this years choice.

Prizes with a more clinical focus have been 2003 (MRI), 2005 (H. pylori and ulcers), 2008 (HIV), 2015 (roundworm and malaria therapy), and 2018 (immuno-oncology), [so] maybe a clinical type of prize this year, [such as] hepatitis C treatment, brain stimulation for Parkinsons, cochlear implant, statins Pendlebury said. We wouldnt be surprised at a hep C win for Charles Rice of Rockefeller University and Ralf Bartenschlager of Heidelberg University (2016 Lasker winners) for the super-basic discoveries that led to drugs that cure the viral disease.

Like Pendlebury, Sheltzer believes in predictive prizes. I looked back at the last 20 years of Nobel Prizes in medicine/physiology, he said. Eighty-three percent of them had won at least one of three prizes before the Nobel: the Lasker, the Gairdner, or the Horwitz Prize. Of the five people who have recently won all three, only one works in a field so far ignored by the Nobel committees, he said: Yale School of Medicines Arthur Horwich, a pioneer of protein folding and chaperone proteins. In addition to the Gairdner in 2004, Horwitz in 2008, and Lasker in 2011, he received the $3 million Breakthrough Prize in 2019. So thats guess #1, Sheltzer said.

Unless Weve had a few [medicine] awards that you could classify as cell biology recently oxygen sensing in 2019, autophagy in 2016, even immune regulation is kinda cell biological, Sheltzer acknowledged. So I think a genetics award is more likely than one to Horwich, whose discoveries about how cells fold the proteins they synthesize are central to the understanding of life. STATs nickel says look no further than the 2015 Lasker Basic Medical Research Award: It honored Evelyn Witkin of Rutgers and Stephen Elledge of Harvard for discovering how DNA repairs itself after being damaged.

Might David Allis of Rockefeller and Michael Grunstein of UCLA finally get the call to Stockholm? They discovered one way genes are activated (through proteins called histones). Theyve shared a 2018 Lasker and a 2016 Gruber Prize in Genetics, and basically launched the hot field of epigenetics. I think a prize related to epigenetic control of transcription by DNA and histone modifications could be in order, Kaelin told STAT.

For physiology or medicine, Pendlebury likes Pamela Bjorkman of Caltech and Jack Strominger of Harvard for determining the structure and function of major histocompatibility complex (MHC) proteins, a landmark discovery that has contributed to drug and vaccine development, as well as Yusuke Nakamura of the University of Tokyo for genome-wide association studies that led to personalized approaches to cancer treatment (personally, we doubt this is cancers year again), and Huda Zoghbi of Baylor College of Medicine for work on the origin of neurological disorders.

In chemistry, Pendlebury likes Moungi Bawendi of MIT, Christopher Murray of the University of Pennsylvania, and Taeghwan Hyeon of Seoul National University for synthesizing nanocrystals, a cool new way to deliver drugs, and Makoto Fujita of the University of Tokyo for discovering supramolecular chemistry, in which lab-made molecules self-assemble by emulating how nature makes them. That has some overlap with Frances Arnolds 2018 Nobel for chemistry, so were skeptical, but who knows?

Lets address the elephant in the Nobel anteroom, and the chatter that the revolutionary genome editing technique CRISPR will win for chemistry. (Its value in medicine is still TBD, but its stellar biochemistry.)

The discovery of the CRISPR-Cas9 system is certainly worthy of a Nobel Prize, Kaelin said. I suspect the challenge here will be to get the attribution right. Perhaps there could be a chemistry prize for the basic mechanism and a medicine prize for application to somatic gene editing in human cells.

By attribution, he means, who gets CRISPR credit? Only three people can share a Nobel. But CRISPR has more mothers and fathers than that. Jennifer Doudna of the University of California, Berkeley, and her collaborator Emmanuelle Charpentier have won a slew of predictive prizes for their work turning a bacterial immune system into a DNA editor, but dark horse Virginijus iknys of Vilnius University shared the 2018 $1 million Kavli Prize in nanoscience for his CRISPR work. And Feng Zhang of the Broad Institute is more widely cited than the above three, Pendlebury said, a marker of what colleagues think.

CRISPR citations built up more to Feng Zheng et al. than to Doudna and Charpentier, but I dont think that matters as much as judgments about priority claim, Pendlebury said. There are more than three to credit and I do think that is problematic. Bad feelings are not something the Nobel Assembly wants to generate, I am sure.

CRISPR will win, said CSHLs Sheltzer. Its a question of when, not if. Zhang/Doudna/Charpentier/Horvath/Barrangou shared the Gairdner. Pick 2 or 3 of them?

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Dust off the crystal ball: It's time for STAT's 2020 Nobel Prize predictions - STAT

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