The popularity contest of human genes

When will genomics cure cancer?

This is partly because there are significant barriers to studying something that no one has ever studied before. A researcher may spend years trying, for example, to create a range of laboratory rodents lacking the gene in question. They can create custom antibodies or other chemical reagents that can help track or visualize the gene. All this takes time, money and effort. "Many researchers identify an important gene and then spend their entire careers studying it," says Plon.

To do otherwise is risky. Stoeger has shown that over the past two decades, young researchers who focused on the least studied genes were 50% less likely to run their own labs. "These people are excluded from the biomedical workforce and then have no opportunity to create a laboratory exploring some of the unknown biologies," he says.

Stoeger and Amaral "have done a remarkable job in thoroughly analyzing why many important genes are ignored," says Purvesh Khatri of Stanford University. "Their findings underscore the need to change the way we study human biology."

Amaral attributes the imbalance of research to the erosion of funding from the National Institutes of Health, forcing scientists to fight for a decreasing number of grants and pushes them to conduct safer research. "When resources stop growing, the whole system asks people not to take risks," he says. NIH has grants to promote innovative, exploratory and high-risk research, but even these increase the same imbalances: half of the papers that emanate from them always focus on the same 5% of well-studied genes. Even so-called game change techniques like CRISPR have changed the landscape of gene popularity very little. "You get all these new tools, but you use them on the same set of genes that you used before," says Amaral.

And if (almost) each gene affects (almost) everything?

In the last decade, only six genes have escaped the darkness of the doldrums and have become increasingly popular, mainly because researchers have recently realized that they are medically important. C9Orf27, for example, has recently been identified as a common link between two neurodegenerative diseases: frontotemporal dementia and ALS. IDH1 is frequently mutated in brain cancers. SAMHD1 protects some cells from HIV. "It's clear that if motivated enough, the field can tack," says Shendure, "but I would have expected more exceptions.We do not want communism for genes, but we want to reduce activation energy to intensively attack the biology of genes that clearly deserve more attention.

Stoeger and Amaral have already created a wish list of genes that, based on their data, should be easier to study with modern methods and probably worthy of study. They also believe that agencies such as the NIH should create grants that encourage junior scientists to look for new and unpredictable lines of research and, above all, provide them with enough years of funding to offset the initial risk of following these pathways. "If we do not adopt targeted approaches to encourage the study of untested genes, the system will not change," Amaral says.