When will genomics cure cancer?
That’s partly because there are substantial barriers to studying something that no one else has studied before. A researcher might spend years trying to, for example, engineer a line of laboratory rodents that lack the gene in question. They might create bespoke antibodies or other chemical reagents that can help track or visualize the gene. This all takes time, money, and effort. “Many investigators identify an important gene and then spend their whole career studying it,” says Plon.
To do otherwise is risky. Stoeger showed that over the past two decades, junior researchers who focused their attention on the least studied genes were 50 percent less likely to eventually run their own lab. “Those people get pushed out of the biomedical workforce, and then don’t get a chance to set up a lab that explores some of the previously unknown biology,” he says.
Stoeger and Amaral “have done a remarkable job of comprehensively analyzing the reasons why many important genes are ignored,” adds Purvesh Khatri from Stanford University. “Their results underscore the need to change how we study human biology.”
Amaral blames the research imbalance on the erosion of funding from the National Institutes of Health, which forces scientists to compete for a dwindling number of grants and pushes them toward safer research. “When resources stop growing, the entire system is telling people not to take chances,” he says. The NIH does have grants that are meant to promote innovative, exploratory, high-risk research, but even these end up augmenting the same imbalances: Half of the papers that emerge from them still focus on the same 5 percent of well-studied genes. Even supposedly game-changing techniques like CRISPR have altered the landscape of gene popularity very little. “You get all these new tools but you end up using them on the same set of genes that you were using them on before,” says Amaral.
What if (almost) every gene affects (almost) everything?
Within the past decade, only six genes have escaped the doldrums of obscurity and become newly popular, mainly because researchers recently realized that they are medically important. C9Orf72, for example, was recently identified as a common link between two neurodegenerative diseases—frontotemporal dementia and ALS. IDH1 is commonly mutated in brain cancers. SAMHD1 protects certain cells from HIV. “It’s clear that if sufficiently motivated, the field can tack,” says Shendure, “but I still would have expected more exceptions. We don’t want communism for genes, but we do want to lower the activation energy for intensively attacking the biology of genes that clearly merit 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 are probably worthy of attention. They also think that agencies like the NIH should create grants that encourage junior scientists to pursue new and unpredictable lines of research, and, crucially, provide them with enough years of funding to offset the initial risk of heading down those paths. “If we don’t take targeted approaches to incentivize the study of unstudied genes, the system is not going to change,” Amaral says.