The Missing Part of America’s Pandemic Response
Fighting COVID-19 demands new knowledge. But the country’s most important health-research agency has become sclerotic and overly cautious.
Many parts of the U.S. government, including its leading scientific agencies, are being blamed for the country’s chaotic and disorganized response to COVID-19. The CDC’s muddled and mistaken messaging about masks, testing, and the mechanism of viral spread sowed public confusion. The FDA’s extreme caution about approving boosters may have slowed the deployment of those vital measures. But a nation’s ability to weather a pandemic also depends upon its underlying ability to make major scientific discoveries, even—or especially—during moments of crisis. Success is not just a matter of luck; historically, the United States has made a series of strategic decisions that put researchers in a position to make timely breakthroughs. Yet amid the biggest health crisis in 100 years, the National Institutes of Health (NIH), the $42-billion-a-year engine of our nation’s biomedical-research infrastructure, has been strangely quiet.
In Washington, the NIH is a vanishingly rare entity: It enjoys bipartisan support. Since the end of World War II, its funding priorities have directed the research conducted at the nation’s medical schools, university science departments, and academic hospitals. It has furthered foundational research at the cellular and molecular levels, while also accelerating the progress of translational science—that is, the development of new treatments for use at patients’ bedside.
During the coronavirus pandemic, however, the NIH has appeared more a doddering, tired institution than a robust giant bestriding the gap between science and clinical care. Two and a half years after the coronavirus first surfaced, doctors, scientists, and the general public still need answers to essential questions about how to prevent and treat COVID-19—questions that America’s preeminent health-research agency is well placed to help answer. For instance, the NIH, the largest public funder of clinical trials in the United States, should also have been well positioned to create treatment guidance for doctors caring for patients hospitalized with a brand-new disease. The recent Infectious Diseases Society of America guidelines for treating hospitalized COVID patients cite more than 40 published clinical trials. By our count, only a handful were generated by the NIH. Unfortunately, such failures are not an anomaly.
To the agency’s credit, NIH scientists did play an important role in making the amazing mRNA vaccines a reality. The researchers Kizzmekia Corbett and Barney Graham and their team at the NIH’s Vaccine Research Center created a mechanism to stabilize the coronavirus’s spike protein so it could be properly recognized by the immune system—a discovery crucial in the development of the Moderna vaccine. Nevertheless, the vaccine’s history still highlights the risk-averse culture of the NIH. Despite its avowed commitment to innovation, the NIH did not support mRNA-vaccine research in the 1990s, when it was an ingenious but unproven idea. For years, the agency rejected grant proposals to fund the biochemist Katalin Karikó’s pioneering mRNA research. It was only through her persistence that, much later, she and her colleague Drew Weissman at the University of Pennsylvania were able to make discoveries foundational to COVID vaccines and the emerging field of mRNA therapeutics. Eventually, the NIH offered some modest support for their work. But if Karikó hadn’t been willing to labor for years outside a scientific mainstream whose boundaries the agency had helped to define, research by Corbett and Graham simply would not have had the same impact.
Full disclosure: Both of us have a stake in whether NIH succeeds. One of us, Gross, has applied for NIH grants—successfully in some cases and not in others—for research projects; the other, Emanuel, has been a secondary author on NIH-funded research and served as a department chair within the NIH for more than a decade. To our eyes, the contributions of Corbett and Graham show that the agency, though ailing, is not moribund. The agency’s defenders maintain that it is doing what it should be: focusing on basic science—fundamental questions without an expectation of short-term benefit—and yielding tremendous benefits to human knowledge. Yet the NIH’s limited COVID-related scientific productivity of the past two years highlights the drawbacks to this narrow approach. (We requested comment from the NIH but have not yet received a response.) Meanwhile, the recent creation of the Advanced Research Projects Agency for Health (ARPA-H)—a new, ostensibly independent unit established within the NIH and dedicated to high-risk, high-reward research—only underscores what's wrong with the status quo. ARPA-H's job is to identify large but solvable problems and make large, risky bets on novel ideas; like a venture-capital firm, it will have to accept frequent failures as the price of the occasional breakthrough success. Yet its creation is not sufficient to make up for NIH's recent woes. The new office's initial budget—$1 billion, about 2 percent of the NIH's—won't be enough to address deficits in clinical research or change the culture of the larger agency.
The NIH’s problems aren’t for lack of money. As early as March 2020, Congress provided the NIH an initial $940 million for COVID. To date, about $5 billion has been allocated to the agency for COVID-19 research. For comparison, the 2020 annual budget for the National Cancer Institute—the best-funded NIH institute—was $6.4 billion. But the COVID money has not had sufficient impact.
The slow pace of the NIH’s grant-funding mechanism is another factor undermining innovative research. The dreaded syndrome known as long COVID was first reported in May 2020. Estimates of how many Americans it afflicts range from 7.7 million to more than 20 million; according to the CDC, 20 percent of adults under age 65 who are infected by the coronavirus experience symptoms potentially attributable to long COVID. To bring life back to normal, the U.S. at least needs to know how frequently the syndrome occurs, who is at highest risk, how much vaccines protect people from it, and how to prevent and treat it. Yet only nine of about 240 currently registered long-COVID studies are funded by the NIH. In December 2020, Congress allocated more than $1 billion to the NIH for the study of long COVID; the NIH subsequently approved $470 million in September 2021 to create a research consortium, with a plan to have more than 200 recruitment sites up and running in early 2022. But two years after long COVID was first recognized, this study has enrolled less than 15 percent of the necessary participants.
Other countries, such as the U.K., were better able to support their scientists’ vision. The U.K.’s RECOVERY trial has yielded more insights about treating COVID than any other effort. Launched in March 2020 with less than $3 million—yes, million, not billion—and overseen by researchers at Oxford University, the study began enrolling thousands of patients almost immediately. The investigators built a study platform that incorporated centralized oversight, streamlined operations, randomly assigned consenting patients to test different treatments, and focused on identifying salient clinical questions with a sense of urgency. More than 170 hospitals in the U.K. participated. Consequently, more than 47,000 patients have been enrolled to date, and 15 treatments have been put through randomized controlled trials. It has been estimated that one of the RECOVERY studies alone—research that identified the steroid dexamethasone as the first drug to improve survival in hospitalized patients—has saved 1 million patients worldwide.
One problem with the NIH is that it emphasizes slow, safe studies focused on basic science rather than high-risk studies that might fail but that also might succeed in creating whole new fields, like the mRNA vaccines. Many studies show that younger researchers tend to break more new ground than more established ones do; Nobel Prize winners tend to make their discoveries in their late 30s and early 40s, not their late 50s and 60s. Yet the average age of first-time NIH-grant recipients has been going up and up, and is now 44 years. Indeed, the proportion of NIH grants going to what it classifies as early-stage researchers plummeted from about 55 percent in 1990 to less than 35 percent in 2020, while the proportion of grants going to older, later-stage researchers has increased from 10 percent to more than 25 percent in the same three decades.
Instead of embracing a diversity of researchers who employ a wide range of research approaches, the NIH’s vaunted peer-review system is inherently conservative. Its proposal-review committees disproportionately include scientists who have succeeded within the current NIH system. These well-funded researchers have no incentive to expand the range of research topics or reward new approaches that might eclipse their own laboratories’ work. That, in turn, leads to gaps in scientific understanding. Francis Collins, the agency’s most recent director, has acknowledged a profound underinvestment in research on human behavior: “I never imagined, a year ago, when those vaccines were just proving to be fantastically safe and effective, that we would still have 60 million people [unvaccinated].”
Moreover, the NIH has mostly retreated from clinical research. By some estimates, the pharmaceutical and medical-device industries now sponsor about six times as many clinical trials as the NIH. In practice, this dynamic narrows the type of clinical-research questions being investigated; only new drugs and other products that can sell on the market receive rigorous scientific scrutiny.
American lives depend on changing how the U.S. spends money on biomedical research. This is the perfect moment for the NIH to evolve. Collins, the agency’s director for 12 years, stepped down last year. The nomination and Senate confirmation hearings for his replacement are an excellent occasion to draw attention to how to transform the agency. Here are our top suggestions:
First, the NIH must invest in people, not projects. Venture capitalists invest in people rather than business plans, knowing that some new companies pivot three or four times before they find success. The NIH needs to modify its current approach of repeated short-term grant cycles for specific projects, which forces even the most stellar investigators to focus on studies with predictable results and to spend their time writing grants rather than in the lab or at the bedside.
Second, the NIH must invest in young, early-stage researchers with long-term grants that allow them to pursue their ideas without being tied to specific projects. And Congress should tie some of NIH’s funding to ensuring that the young investigators look like the country, not like retiring researchers. For decades, NIH has underfunded research by women and scholars of color. White grant applicants to the NIH are about 65 percent more likely to have their grants funded than Black applicants. Today, Black researchers receive less than 2 percent of all funding for the most coveted awards, investigator-initiated grants. That percentage has not perceptibly changed in the past decade.
Third, the NIH should rethink how it funds clinical research. Right now, it spends too much money on small, one-off studies conducted at individual academic-research centers. But pressing clinical questions are better answered when multiple research centers participate in collaborative work on large study platforms that can rapidly enroll and randomize patients by the hundreds or thousands.
America’s research enterprise has become sclerotic, cautious, focused on doing what it has always done and withdrawing from clinical research. The American public is paying for this decline in ambition. As the pandemic drags on, the Biden administration and Congress should fix the NIH’s culture. The country’s preeminent health-research agency needs to shake off its doldrums and embrace the very traits that are essential in generating outstanding science—creativity, persistence, and courage.