The first warnings that new scientists in the US were becoming a threatened species were sounded by the head of National Institutes of Health in 1979. Almost 40 years later, the current director, Francis Collins, is writing about “The Issue That Keeps Us Awake at Night,” expressing the same concerns. While efforts to increase NIH funding opportunities for early-stage investigators have been moderately successful, they have not stemmed the worries that the pathway to success for new investigators is still too discouraging. Earlier this year, a new initiative, “The Next Generation of Biomedical and Behavioral Sciences Researchers: Breaking Through,” was announced and proposed changes to address prolonged training, an overly narrow career focus, and the lack of opportunities for independent research earlier in a career.
The major problem for budding scientists is that it is increasingly difficult to get grants. The average age for first-time independent awardees has risen to the mid-40s, and up to 88 percent of applications are rejected each review cycle. The pipeline is narrow (only 10 institutions account for more than half the training awards in pediatrics, for instance), the peer review system may be faulty, and the whole enterprise is biased in favor of low-risk research. In 2017, fewer than 1,000 applicants were successful in getting one of the K-type awards meant for scientists at the early stages of their careers, and only 3,000 applied.
Were the NIH to adopt a more entrepreneurial approach, . . . the pipeline for new biomedical and physician scientists would markedly increase.
Over these same 40 years, another issue has arisen. Articles in the scientific and lay press contend that the US is falling behind in the area of biomedical discovery, under headlines such as “America is losing biomedical research leadership to Asia” and “The NIH is in danger of losing its edge in creating biomedical innovations.” New ideas are becoming scarcer, or coming from other countries.
The responses to these two interconnected problems—the disappearance of new scientists and of new breakthroughs—generally fall into two categories: throw more money at it, or tweak the system. But because these haven’t solved this crisis of people and ideas over all these decades, we need to look at them in a different way.
I once wrote a business plan for a startup, and it resembled nothing more than a research grant. From that perspective, the NIH is a very large, very conservative, bank. As the trustee of the public’s money, it is notoriously risk-averse, as, to ensure a guaranteed return, there must be ample existing research data (equivalent to years of sales data) and a stellar Biosketch research CV (the business equivalent is a compelling resume). All of this favors new applicants to have been trained in well-established labs in well-known universities, and who are generally proposing the next, well-supported step in whatever their mentors have been doing. The peer reviewers, like bank investment officers, are often professionally or socially acquainted with the young applicant’s mentor. No one is shocked that funded grants for new investigators resemble spin-offs from already profitable companies. Keeping the pipeline so careful and tight, however, risks losing people and ideas.
I suggest that we should look to the other technological revolution that sprang from American ingenuity, entrepreneurship and investment, through which we can find a new direction to shake biomedical science out of its malaise. From the late 1980s into the ‘90s, hundreds, if not thousands, of young inventors and programmers in Silicon Valley produced plans for a new device or service or application. Armed with only code or a garage-built prototype, they got nowhere with the traditional investing sources. They turned instead to technology investors, now famous for being very, very rich and very, very prescient, except that these investors were smart, not clairvoyant. At this earliest stage, they took their pot of investment funds and divided them into many small sums, knowing that most would be lost but a few would rise up to justify a second round of larger investments, and maybe a third round, and eventually a Google or Apple or Facebook would emerge to change everything.
What I suggest is that the NIH (alone or perhaps with other funders such as pharmaceutical firms or even technology investors) create a similar, very early phase investment fund. Just 3 percent of the yearly NIH budget could support 20,000 annual $50,000 grants. These would be awarded to new investigators who present a plausible hypothesis and a feasible plan to test it, but no preliminary data or fancy pedigree. They would get their salaries from their home institutions, which would share the risk. This kind of seed planting would give funders from NIH, foundations, and others far better information about which new lines of inquiry might be worthy of the next funding round, for example, an R21-type of B round of funding, and which ones are not ready for the next stage. The traditional pathway for new investigators would still be open. What this program would do is give support to the cohort of young scientists who currently are leaving academic research for positions in teaching or industry.
One could argue that the NIH’s RO3 grant program, which offers up to $100,000 over two years, already does this. These grants, though, are offered by less than half of the NIH centers and institutes, new investigators are discouraged from applying, and in 2017, there were only 466 new RO3 grants awarded totaling less than 0.1 percent of the total NIH budget. The combined totals for the K01, K08, K12, K22, and K23 programs for new young investigators in 2017 were 712 new grants for $126,000,000. A recent study, though, showed that even with this careful, conservative system of vetting, only a third of those selected for the K programs received subsequent R awards.
My proposal would require very different application reviews from what the NIH study sections now do, and it would be a challenge to the review system and its culture. Without an increase in the NIH overall budget, adopting it would mean a billion dollars less for RO1s and program projects. But were the NIH to adopt a more entrepreneurial approach, using a modest amount of the funds that the Congress allocates, the pipeline for new biomedical and physician scientists would markedly increase. It would shorten the timeline toward independent funding. It could uncover more innovative and riskier ideas, and it could improve a lack of diversity in race, gender, and ethnicity in research. Finally, it might make research more fun again, maybe enough that some talented people would stick around science for long enough that one of them might become the next Francis Collins.
Henry J. Rozycki is the vice chair for research at the Children’s Hospital of Richmond at Virginia Commonwealth University.