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 year’s prediction story did) one of those is due and deserving. The trouble is, as MIT’s 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. They’re 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 technique’s 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 don’t 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 humanity’s towering achievements.” (Sheltzer correctly predicted 2018’s 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 aren’t chosen all that, well, scientifically. For medicine, a five-member Nobel Committee for Physiology or Medicine at Sweden’s 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 scientist’s 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. That’s 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 year’s award for how cells sense changing oxygen levels was pretty abstruse and might shape this year’s 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 Parkinson’s, cochlear implant, statins …” Pendlebury said. We wouldn’t 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 Medicine’s 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 that’s guess #1,” Sheltzer said.

Unless … “We’ve 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. STAT’s 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). They’ve 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 cancer’s 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 Arnold’s 2018 Nobel for chemistry, so we’re skeptical, but who knows?

Let’s 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 it’s 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 Šikšnys 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 don’t 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 CSHL’s Sheltzer. “It’s a question of when, not if. Zhang/Doudna/Charpentier/Horvath/Barrangou shared the Gairdner. Pick 2 or 3 of them?”

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