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The Dayside : Risky business

By: Charles Day
18 April 2014

Earlier this month I chanced on an interview with Sydney Brenner, a distinguished molecular biologist. The occasion of the interview was the death last year of one of Brenner's former colleagues, Frederick Sanger, who remains the only scientist to receive two Nobel Prizes in Chemistry: the first, in 1958, for sequencing the amino acids in insulin and other proteins; the second, in 1980, for sequencing DNA.

Brenner's interviewer was Elizabeth Dzeng, a PhD student at the University of Cambridge. Although she and Brenner discussed Sanger's legacy, the bulk of their conversation covered what Brenner sees as problems with the current research enterprise.

Frederick Sanger at home in Cambridge in 1958, the year he was awarded his first Nobel Prize in Chemistry. CREDIT: Associated Press

Frederick Sanger at home in Cambridge in 1958, the year he was awarded his first Nobel Prize in Chemistry. CREDIT: Associated Press

The interview is well worth reading. For a flavor of Brenner's critique, here's a passage from a tribute that Brenner wrote for Sanger in Science:

A Fred Sanger would not survive today’s world of science. With continuous reporting and appraisals, some committee would note that he published little of import between insulin in 1952 and his first paper on RNA sequencing in 1967 with another long gap until DNA sequencing in 1977. He would be labeled as unproductive, and his modest personal support would be denied. We no longer have a culture that allows individuals to embark on long-term—and what would be considered today extremely risky—projects.

Brenner made some of his notable discoveries in the 1950s and 1960s when he belonged to a small research group at Cambridge University that later became the Laboratory of Molecular Biology. Eleven members of the LMB, including Brenner himself, have been awarded Nobel Prizes.

In Brenner's view, the way to move science forward is to identify bold, talented researchers and give them funding to pursue their ideas while they are still young. To fund such a program, Brenner advocates skimming, say, 1% of a funding agency's research budget and giving it to people like him—"successful gamblers," in his words, "who have done all this who can have different ideas about projects and people, and you let us allocate it."

Brenner is in the fortunate position of being able to do just that. He told Dzeng that he has set up two labs in Singapore for young Singaporeans who

have all been sent abroad to get their PhDs at places like Cambridge, Stanford, and Berkeley. They return back and rather than work five years as a post-doc for some other person, I’ve got a lab where they can work for themselves. They’re not working for me and I’ve told them that.

At least one other lab is in the works.

Dzeng did not ask Brenner what happens if his bets on young Singaporean scientists don't pay off, but I can guess how he might have replied. After perhaps citing his previous track record of picking winners, he would probably say that some risks are worth taking.

What are those risks, exactly? It's hard to believe that Brenner's talented young Singaporeans will not produce worthwhile science. The risk, perhaps, is that they might not produce a breakthrough. Or that they might produce one breakthrough early in their careers and then nothing of similar import for the rest of their lives.

But not taking the risk to fund bold, innovative science is itself risky. In an editorial published in Science in 2012, James Langer, a former president of the American Physical Society, complained,

In my area of condensed-matter and materials physics, the U.S. National Science Foundation (NSF) can fund only about 10% of the individual-investigator proposals it receives. [The Department of Energy (DOE) has similar difficulties.] Each proposal is sent to a group of peer reviewers, who rank it on a scale ranging from “excellent” to “poor.” NSF then funds only those proposals that receive the uniformly highest reviews. One less-than-“excellent” review, no matter how misguided, is usually enough to doom a proposal. Any proposal that is truly innovative, interdisciplinary, or otherwise unusual is almost certain to be sent to at least one reviewer who will be less than enthusiastic about it. Sensible investigators know not to submit such proposals; as a result, some of the most urgent research areas are disappearing.

Since Langer's editorial appeared, he and I have been corresponding sporadically about how to raise the odds that bold ideas receive funding. Brenner's solution—of trusting successful mavericks to allocate a portion of total funding—is worth considering, although I worry that it might rely too much on whom the maverick happens to know.

The only other way to embolden funding agencies to take risks could be to give them more money.

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