What’s in the cards for this year’s Nobel Prizes? – STAT

Were not saying that discovering molecular drivers of cancer or cancer-causing genes doesnt deserve the Nobel Prize in medicine or physiology. But for Dr. Brian Druker (whose work led to the targeted leukemia drug Gleevec), Dr. Dennis Slamon (Herceptin), and Mary-Claire King (the BRCA breast- and ovarian-cancer gene), 2019 is probably not their year to be summoned to Stockholm: The 2018 medicine Nobel honored immuno-oncology, and according to STATs Nobel crystal ball, cancer wont win two years in a row.

With the naming of the science Nobels fast approaching the medicine prize will be announced on Oct. 7, physics on Oct. 8, chemistry on Oct. 9 polls, betting pools, and number crunching are in full swing, using approaches from toting up how many predictor prizes a scientist has won to calculating the periodicity of awards, meaning how many years pass before a specific subfield is honored again.

Past laureates, who get to submit nominations every year after their own anointing, have their favorites and, sometimes, their hunches, wrong though they usually are. As 2018 chemistry winner Frances Arnold of the California Institute of Technology said, Its not helpful to second-guess these things!

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Indeed, the Nobels are known for some head-scratching choices over the decades, though less in the science prizes than in peace and literature. Nevertheless, some experts have developed systems that do pretty well. Since 2002, David Pendlebury of Clarivate Analytics has made 50 correct predictions (though usually not in the right year) by analyzing how often a scientists key papers are cited by peers.

Using that strategy, Pendlebury thinks the chemistry Nobel could go toinventors of DNA sequencing techniques: Marvin Caruthers of the University of Colorado, Leroy Hood of the Institute for Systems Biology, and Michael Hunkapiller, CEO of DNA sequencing goliath Pacific Biosciences.Without their [1980s] inventions, Pendlebury said, there would be no map of the human genome.More on that below.

In medicine, Pendlebury likes the chances of Hans Clevers of the Netherlands Utrecht University for research on the Wnt signaling pathway. Wnt controls how stem cells differentiate and how some cancers develop. If Wnt wins, then the private biotech Samumed (valuation: $12 billion) can say its investigational Wnt-targeting drugs are based on Nobel-winning research.

Pendlebury also has his eyes on John Kappler and Philippa Marrack of National Jewish Health in Denver for discovering T-cell tolerance, a mechanism by which the thymus eliminates T cells that would attack the self. That advanced understanding of autoimmune diseases such as rheumatoid arthritis and lupus, and is so basic and important one wonders, Why no Nobel yet?

In 2019, the answer might be, because the 2018 prize honored the hybrid of immunology and cancer, so immunology might have to wait another decade for its next turn. Thats sad news for Jacques Miller, who has never received a Nobel for discovering the function of the thymus and the fact that immune cells include T and B cells in the 1960s. Look how many Nobels were given for immunology based on Millers work, said MITs Phillip Sharp, who shared the 1993 medicine Nobel. There is just a lot of good science that will never get recognized.

If immunology and cancer are off the table, it opens a lane for optogenetics, the revolutionary mashup of genetic engineering and neuroscience. Here, Pendlebury likes Ernst Bamberg of the Max Planck Institute of Biophysics in Germany, Karl Deisseroth of Stanford University, and Gero Miesenbck of the University of Oxford in the U.K. Honoring optogenetics would be wonderful on many levels, starting with the power of the technique to identify neural circuits involved in virtually any function and disease. (The Nobel committees like techniques that enable others to make cool discoveries, Sharp said.)

Even more fun, a prize for optogenetics could open the floodgates of controversy. The key discoveries have so many fathers (alas, optogenetics has no mothers) that picking any three, the maximum for a Nobel, would likely trigger weeks (maybe years!) of carping about who got left out. As it happens, on Thursday the $500,000 Warren Alpert Prize will honor optogenetics, but the winners are Deisseroth, Miesenbck, MITs Edward Boyden (Deisseroths former postdoc), and Peter Hegemann of Germanys Humboldt University. If science had cage matches, we could root for one between Bamberg, Boyden, and Hegemann for the third slot in an optogenetics Nobel.

Records of Nobel committee deliberations remain secret for 50 years, so its anyones guess if theyre influenced by other big prizes. But the latter do seem to have predictive value. Thats one reason David Allis of Rockefeller University and Michael Grunstein of Hebrew University, who in the 1990s discovered one way genes are activated and quieted (through proteins called histones), are favorites (again) for a medicine Nobel. Theyve shared a slew of awards, including a 2018 Lasker and a 2016 Gruber Prize in Genetics, so 2019 could (finally) be their year, especially since there hasnt been a Nobel for gene expression since 2006, and the Allis/Grunstein discovery basically launched the hot field of epigenetics.

Sharp points to another scientist who made seminal contributions to the understanding of genes off/on switches: Yale Universitys Joan Steitz, who in 1979 discovered small noncoding RNAs that control gene expression.

For his crystal ball, biologist Jason Sheltzer of Cold Spring Harbor Laboratory looks at periodicity, a strategy that helped him correctly predict last years medicine win for immune-oncology pioneer James Allison. Fields like infectious disease, immunology, and cancer win every 10 to 20 years, and so are probably off the table for 2019. But the last Nobel for DNA sequencing was way back in 1980, Sheltzer points out, and since then we have seen the complete sequencing of the human genome, one of humanitys towering achievements.

The problem is, hundreds of scientists worked on the Human Genome Project. Last year the Nobels honored the organizers of the project that discovered gravitational waves, so with similar reasoning the medicine or chemistry prize might go to Dr. Francis Collins, now director of the National Institutes of Health and the guy who herded all those cats to get the genome project done, and/or to the Broad Institutes Eric Lander, whose lab churned out much of the sequence. A third might be Craig Venter, the outsider whose private sequencing efforts raced the Collins/Lander government project to a bitter draw.

But if this trio wins, Pendleburys DNA-sequencing three (Caruthers, Hood, and Hunkapiller) wont. To complicate things even further, among the leading vote getters in an online poll for the chemistry Nobel is Shankar Balasubramanian of Cambridge University, who helped developed next-generation DNA sequencing. The Nobel committees grapple with questions of credit all the time: who did it, who did it first, who had the greatest impact, said chemist Peter Dorhout, past president of the American Chemical Society. I wouldnt want to be them.

For that and other messy reasons, when asked if sequencing has a shot at a Nobel, Sharp didnt hesitate: No, he told STAT.

Gene editing, on the other hand, last won in 1993, so it could be time for a new editing prize, Sheltzer tweeted. CRISPR in particular, [Jennifer] Doudna [of the University of California, Berkeley] will win for either chemistry or medicine.

The wisdom of the crowd agrees with him. Sigma Xi, the scientific research honor society, has been asking members to vote for most likely laureates in bracketology-style matchups. Doudna made the final four in chemistry. (Sigma Xi will announce the winner of its contest Thursday.) The other three finalists: Harvards Stuart Schreiber for research on signal transduction and master regulators of cell function such as the gene mTOR, now a hot target for cancer and other drugs; John Goodenough of the University of Texas for inventing lithium-ion batteries, and Stanfords Carolyn Bertozzi for basically developing bio-orthogonal chemistry, in which reporter molecules label biomolecules within cells.

Since STAT covers only life sciences, we have nothing to say about Goodenoughs chances (but thank you for making smartphones, digital cameras, and Teslas possible!), and agree that Schreiber and Bertozzi are stars. But the Doudna pick is a minefield. If she wins it alone, there will be hurt egos galore, starting with her collaborator Emmanuelle Charpentier of the Max Planck Institute for Infection Biology and including Virginijus iknys of Vilnius University. iknys is often called the forgotten man of CRISPR because Doudna and Charpentier had been running the table of prizes for their work turning a bacterial immune system into a DNA editor until he shared last years $1 million Kavli Prize in nanoscience.

If the Nobel committees prefer to keep firestorms of controversy for the peace prize (Greta Thunberg or Donald Trump?), they have many safe but stellar choices. Pierre Chambon and Ronald Evans have never won for discovering nuclear hormone receptors, where molecules as different as steroids and vitamins dock to make a whole suite of physiological reactions happen, Sharp points out. He also thinks Victor Ambros of the University of Massachusetts and Harvards Gary Ruvkun could bounce up this year for discovering microRNAs DNA-regulating molecules that turn out to control embryonic development, cancer, cell differentiation, and more. The pair has also snared a pile of predictor awards, including a Lasker, a Gairdner, a Breakthrough, and a Gruber Genetics Prize.

To all the many scientists whose work deserves a Nobel but who will not get an early-morning call from Stockholm next week, Sharp offers this quasi-consolation: Life is not fair.

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What's in the cards for this year's Nobel Prizes? - STAT