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With the Nobel Prizes around the corner, it’s crystal ball time

Fernando Vergara/Associated Press/File 2015

If Bob Dylan can receive the Nobel Prize in literature, can science Nobels go to researchers whose work has a contemporary flair and direct relevance to what matters to the public?

In advance of next week’s prize announcements, 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.

The trio has been a recent favorite of Nobel prognosticators for breakthroughs in immuno-oncology, how immune cells destroy tumors (or fail to).

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Allison 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).

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Freeman and Sharpe discovered another immune-cell brake, called PD-1, which led to nivolumab (to treat melanoma and lung and other cancers), and pembrolizumab (for several cancers).

This year’s Warren Alpert Foundation Prize honored Allison, Freeman, and Sharpe — along with two other 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.

David Pendlebury, who has been making Nobel forecasts since 2002 — first for Thompson Reuters and now for Clarivate Analytics — put doctors Yuan Chang and Patrick Moore, of the University of Pittsburgh, on his list of possible recipients of the 2017 medicine Nobel. They discovered the cancer-causing human herpesvirus 8.

He also names Lewis Cantley of Weill Cornell Medical College, for discovering a cellular signaling pathway called PI3K and its role in cancer.

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Would these recent cancer discoveries be honored before earlier, more foundational ones? Dr. Bert 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 received 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 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 that Jacques Miller, 86, 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.

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“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.

The Nobel committee might decide credit for immuno-oncology is too difficult to untangle.

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.

MIT’s 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.

Sharon Begley can be reached at sharon.begley@statnews.com.
Follow her on Twitter @sxbegle.
Follow Stat on Twitter @statnews.