Really, we at STAT love autophagy, the cell’s garbage disposal. Also those adorable little molecular machines. Discoveries about the former won the Nobel Prize in medicine last year for Yoshinori Ohsumi, while three inventors of the latter won the chemistry prize. But if Bob Dylan can win the literature Nobel, can science Nobels go to researchers whose work has a contemporary flair and direct relevance to what matters to the public?
We’re looking at you, Jim Allison of MD Anderson Cancer Center, Gordon Freeman of Dana-Farber Cancer Institute, and Dr. Arlene Sharpe of Harvard Medical School — or, we think the Nobel Committee choosing the medicine prize might.
That trio has been a recent favorite of Nobel prognosticators for breakthroughs in immuno-oncology, how immune cells destroy tumors (or fail to). Allison — with no thought to cancer, just curiosity about immune cells — discovered how surface molecules on immune cells, called CTLA-4, sideline them, and how disabling CTLA-4 can make the cells instead swarm and kill tumors.
That led to the first immune-based cancer drug, ipilimumab (for metastatic melanoma). Freeman and Sharpe discovered how another immune-cell brake, called PD-1, works with molecules on tumor cells called PD-L1 to squelch T cells. That led to nivolumab (to treat melanoma and lung and other cancers), and pembrolizumab (for several cancers). Although the immune drugs fail in many patients, immuno-oncology has revolutionized both the understanding of cancer biology and treatment of the disease.
This year’s Warren Alpert Foundation Prize honored this trio and two more scientists for key discoveries in cancer immunology. No more than three researchers can share a Nobel. That might make the Nobel committee decide credit for immuno-oncology is too difficult to untangle. But two other big awards, the Lasker in 2015 and the Breakthrough in 2014, honored Allison solo.
The immuno-oncology stars might also be hurt by a huge backlog of Nobel-caliber cancer research. The prize has never been awarded for developing molecular-targeted therapies like Gleevec and Herceptin (Brian Druker, Dennis Slamon), or for discovering cancer-causing genes (Robert Weinberg, Dr. Bert Vogelstein — or Mary-Claire King, for BRCA).
David Pendlebury, who has been making Nobel forecasts since 2002, first for Thompson Reuters and now for Clarivate Analytics, put Drs. Yuan Chang and Patrick Moore, of the University of Pittsburgh, on his list of possible winners of the 2017 medicine Nobel; they discovered the cancer-causing human herpesvirus 8. He also names Lewis Cantley of Weill Cornell Medicine, for discovering a cellular signaling pathway called PI3K and its role in cancer.
Would these recent cancer discoveries be honored before earlier, more foundational ones? Vogelstein, for instance, “has contributed so much,” Pendlebury said, especially to the understanding of how cancer arises from mutations, the very foundation of modern cancer biology. “It’s remarkable to me that he hasn’t been recognized” with a Nobel.
Phillip Sharp of the Massachusetts Institute of Technology, who won the 1993 medicine Nobel, has a hunch about why. “The Nobel committees hate cancer,” he said. They’ve given only two prizes for cancer genetics: One came 55 years after the winning discovery and the other, for cancer-causing oncogenes in 1989, may have filled the committees’ quota for this field.
“To give the medicine prize [for something in cancer biology] they have to have body counts” of the discovery saving many, many lives, Sharp said. For immuno-oncology and some other discoveries, “there aren’t enough yet.”
The Nobel committees get an estimated 300 nominations (from previous winners and other luminaries) every winter, so as past glories fade from the memories of nominators, long-ago breakthroughs are less likely to land before the committees. That means long odds on the discovery of how molecules as different as steroids and vitamins dock with hormone receptors to make a whole suite of physiological reactions happen (Ron Evans and Pierre Chambon), and of how adult brains give birth to new neurons, a finding that overturned decades of dogma (Rusty Gage).
It also suggests Jacques Miller needn’t be by his phone on Oct. 2, when the medicine Nobel is announced. He discovered what the thymus gland does and the function of T and B immune cells — in the 1960s, for goodness sake.
“He started the whole field of immunology,” Sharp said. “I’ve never understood why he hasn’t received a [Nobel] prize.” The omission is so egregious, “it will go down in the annals of Nobel prizes as a huge oversight,” said Pendlebury. Miller is 86. Nobels aren’t awarded posthumously.
The paradigm-shattering finding of how DNA wraps around proteins, which determines whether genes are expressed or silenced, has never gotten discoverers David Allis and Michael Grunstein a date with Sweden’s king, even though it served as the starting gun for the whole booming field of epigenetics and won the Gruber Genetics Prize last year.
How has brain imaging, which is to neuroscience what the electron microscope is to cell biology, not been Nobeled? As it happens, Clarivate, whose forecasts are based on how many times a scientist’s key papers have been cited by other researchers, named Karl Friston of University College London a contender for the 2017 medicine Nobel for discovering how to analyze raw data from brain imaging. If the committee wants to go that route, they should keep in mind that Seiji Ogawa, who discovered the principles that underlie fMRI, is 83.
Sharp doesn’t think it’s too early to honor discoveries about CRISPR, the bacterial immune system that can be tweaked to edit genomes. CRISPR-based genome editing has four key discoverers — Emmanuelle Charpentier, George Church, Jennifer Doudna, and Feng Zhang — so the rule of three is a problem, as is the bitter patent clash over who invented what (the Nobels loathe controversy). Sharp wonders if a Solomonic decision might be in store: the chemistry Nobel to Doudna and Charpentier, whose work was pure biochemistry, and medicine to Church and Zhang, who made CRISPR work in living cells, paving the way to medical uses.
But if you like long shots unknown to your office pool, may we suggest Kazutoshi Mori and Peter Walter? They discovered the “unfolded protein response,” a quality-control system that cells use when the proteins they make are, well, misfolded in a way that can cause harm. It’s just the kind of surprising key-to-life physiological mechanism, like autophagy, that Nobel committees love. Mori and Walter won the 2014 Lasker.