The Unsexy Science of This Year’s Nobel Prize in Medicine

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The distortion of incentives in science disfavors the style of groundbreaking research that led to this year’s prize.

By Michael White

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(Photo: thomasfisherlibrary/Flickr)

The Nobel Prize science committees have the considerable benefit of hindsight. When choosing who to recognize with science’s highest award, the Nobel committees can look back over the decades and identify scientific discoveries that turned out to be genuinely groundbreaking. Instead of having to evaluate today’s hot research trends, whose significance is uncertain and may be distorted by hype, the Nobel judges can wait on the test of time.

That ability to wait and see has produced an award this year that recognizes an important work of refreshingly unsexy science. On Monday, the Nobel Prize in Physiology or Medicine was won by Japanese scientist Yoshinori Ohsumi, who conducted his groundbreaking research in a way that runs counter to how biomedical science is usually performed today. Instead of working on a trendy topic, Ohsumi picked an important but understudied problem, whose relevance to human disease was not guaranteed. Rather than trying to quickly publish flashy results in high-visibility journals, he steadily published relatively incremental work in solid, field-specific journals. Ohsumi helped establish an important field of biomedical research because he took the long view and pursued it rigorously.

To survive in their careers, scientists have to quickly strike it big — or at least appear to — with a splashy result on a trending issue, published in one of a small handful of high-profile journals.

It’s no secret that the incentives in today’s scientific community don’t favor this kind of science. Multiple Nobel Prizewinners have said that their work would not be possible in today’s hyper-competitive, short-term-focused research environment. Randy Shenkman, who won the Medicine Nobel in 2013, commented that science today “is disfigured by inappropriate incentives.” To survive in their careers, scientists have to quickly strike it big — or at least appear to—with a splashy result on a trending issue, published in one of a small handful of high-profile journals. “The prevailing structures of personal reputation and career advancement mean the biggest rewards often follow the flashiest work, not the best,” Shenkman said.

Sometimes the best science does happen to be flashy as well, but Yoshinori Ohsumi’s work shows how good science often proceeds without seeming sensational. Ohsumi won the prize for reverse engineering a cellular garbage processing and recycling system that, we now know, plays a fundamental role in the routine functioning of our cells, and in their ability to adapt to environmental change. When Ohsumi began working on this problem in the 1980s, it was a niche field. The existence of a cellular recycling process — called autophagy (a Greek term meaning “self-eating”) — had been known since the early 1960s, but progress in understanding what it did and how it worked had been limited.

To crack this problem, Ohsumi turned to yeast cells, which are easy to manipulate genetically. This allowed him to use a tried-and-true method for biological reverse engineering, called a “genetic screen” — a technique in which you break genes by mutation to test whether those genes affect the process you are studying. Ohsumi used genetic screens, together with a clever technique for measuring autophagy, to build up a parts inventory for the molecular machinery that identifies, hauls away, breaks down, and recycles cellular garbage.

Ohsumi’s work, conducted over a decade, was important and interesting, but certainly not flashy. His papers were published in field-specific journals that are known to other scientists, but whose results are rarely picked up by the New York Times. After six years of steady progress, Ohsumi did publish a critical paper in a high-profile journal, Nature, in which he and his colleagues discovered that humans carry some of the same autophagy genes that were present in yeast. By that point, Ohsumi had laid a rigorous foundation for this field, which allowed it to flourish. Today, thousands of papers are published on autophagy each year, and the process now has a recognized role in human health and disease.

Young researchers pick trending topics and chase after big results, which too often turn out to be statistical flukes. In the process, researchers have incentives to “rush into print, cut corners, exaggerate their findings, and overstate the significance of their work.”

The steady, rigorous approach taken by Ohsumi is difficult to pursue today thanks to two trends that distort the incentives of scientists. The first is the pressure to publish quick, high-profile results, noted by Shenkman. To have a career in science — to get jobs, promotions, grant funding, and students — scientists are under pressure to publish flashy results in high-visibility journals as early in their careers as they can. The result is short-term thinking that often leads to poor science: Young researchers pick trending topics and chase after big results, which too often turn out to be statistical flukes. In the process, researchers have incentives to “rush into print, cut corners, exaggerate their findings, and overstate the significance of their work.” Related to this, there is growing evidence of a “publication bias” in science: Researchers publish more positive results than can possibly be true given the statistical tests used to define a positive result. In other words, much of what’s published may be noise, not signal.

The second harmful trend is the increasing emphasis on disease-related research, to the exclusion of basic biological studies. As several leaders of the biomedical research community have noted, a consequence of short-term thinking in science is “the inflated value that is now accorded to studies that claim a close link to medical practice,” at the expense of scientific progress and the achievement of longer-term goals. Yes, disease research is, without question, important if we want to actually treat or cure disease. But pressuring basic researchers to focus on topics that are obviously relevant to disease is a distorting incentive: Instead of asking what importantproblems are solvable, scientists are driven to ask what problems are fundable — and then they make too many promises about the medical benefits of a line of research that may currently be intractable.

Scientists, journal editors, and funding agencies don’t have the benefit of hindsight, as the Nobel Prize committees do. They have to choose what research to conduct, fund, and publish without knowing whether or not it will pan out. This is not easy, and hence the temptation to rely on superficial signs of significance: fast, big results; highly visible journals; and trending research topics. Yoshinori Ohsumi’s prize-winning work is a reminder that these signs of significance can be misleading––great science is not always flashy.

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