Four lessons from the pandemic to reboot the NIH

A model of COVID-19 is seen ahead of testimony from Dr. Francis Collins during a US Senate hearing.

Francis Collins retired as head of the NIH in December.Credit: Saul Loeb/Getty

The COVID-19 pandemic represented an important test for the US National Institutes of Health (NIH), the largest funder of biomedical research in the world. Many say that it passed admirably: the agency substantially contributed to the high-speed development of medicines and vaccines to fight SARS-CoV-2 by funding basic research and collaborating with pharmaceutical firms to coordinate clinical trials at a breakneck pace.

“It is an accomplishment for the ages,” says Shirley Tilghman, a molecular biologist and president emeritus at Princeton University in New Jersey, who has frequently written on the challenges faced by the NIH.

But as the dust settles on the frantic first years of the pandemic, she says it is worth reflecting on what lessons the agency can take away. The NIH is currently at a crossroads: the director post is vacant for the first time in 12 years, after the departure of geneticist Francis Collins in December.

To understand this pivotal moment, Nature spoke to researchers about how the NIH can continue to foster innovation and address some of the issues that have challenged it for decades. They say they hope that the NIH can channel the same sense of urgency and coordination that it brought to the COVID-19 pandemic to pressing health issues, that it should take more action to bolster the diversity of the biomedical workforce and that it should invest significantly more money into social and behavioral science and health-disparities research.

An NIH director could be named at any time, and although it’s unreasonable to expect them to solve everything, many researchers hope for an institutional reset on several key matters. “This is a moment of leadership shake-up,” says Eric Hekler, a social behavioral scientist at the University of California San Diego, who co-authored a commentary about restructuring the NIH, to be published in the American Journal of Public Health inJuly. “The next person appointed is going to have an influence on directing the next two — if not longer — years of how we engage in health sciences research.”

Fast innovation is possible

Composed of 27 institutes and centers and wielding a US$42-billion budget, the NIH has long been charged with having an approach to science funding that is too conservative. Many complain about bureaucratic red tape that slows the pace of scientific research.

Tilghman agrees with some of these concerns, but there are notable exceptions. In addition to the agency’s push to develop COVID-19 vaccines and therapeutics, she says the Human Genome Project “broke every rule” in the typical NIH playbook by setting a specific goal for a huge team of scientists and floating money more quickly than usual. It is worth considering, she says, whether there are scientific questions that could be approached in a similar way. For example, a concerted, agency-wide effort to search for a common understanding of neurological conditions, such as Alzheimer’s disease, could be fruitful, she says.

President Biden with Dr. Kizzmekia S. Corbett, Dr. Francis Collins, Jeffrey Zients, Dr. Anthony Fauci and Dr. Barney S. Graham.

The NIH helped to accelerate the development and testing of a COVID-19 vaccine.Credit: Saul Loeb/AFP via Getty

Many have pinned hopes for innovative health research on the Advanced Research Projects Agency for Health, or ARPA-H — a US$6.5-billion research agency proposed by US President Joe Biden that would fund high-risk, high-reward research in the life sciences . Congress agreed to put $1 billion towards the program in 2022 but has not yet passed legislation explicitly authorizing its creation. Last month, lawmakers sparred over whether the agency should be housed in the NIH or outside it; US health secretary Xavier Becerra eventually decided that ARPA-H would remain under the auspices of NIH, but its director will report directly to him instead of the NIH director.

Although ARPA-H will focus on more translational research, Tilghman says that the NIH should have an analog for funding high-risk, high-reward basic science. Greg Petsko, a biochemist at Harvard Medical School and Brigham and Women’s Hospital in Boston, Massachusetts, says that although the NIH serves a model organization in funding basic research, it could stand to update its mechanisms for doling out funds faster. One way, he says, would be to offer research institutions block grants and let them decide which projects to fund.

Improve workforce diversity

Funding projects faster is a good goal, says Omolola Eniola-Adefeso, a biomedical engineer at the University of Michigan in Ann Arbor, but underlying funding inequities based on a researcher’s institution, career stage, race or research area are an even more pressing problem. The agency has struggled, for example, to reverse racial disparities in funding since Donna Ginther, an economist at the University of Kansas in Lawrence, published a landmark analysis1 over a decade ago that found white researchers applying for NIH grants are much more likely than Black researchers to win them. Collins said the situation was “not acceptable” and committed the agency to action.

The NIH has invested resources to study where and how in the grant-selection process this bias manifests. It has offered a grant aimed at increasing faculty from underrepresented groups. It has introduced bias training for peer reviewers and launched an initiative to identify and address structural racism in the NIH and greater scientific community. But racial disparities persist, according to subsequent analyzes2. Only 1.4% of NIH senior investigators identify as Black, for example.

The pandemic has helped to reveal the risks of such funding gaps: Black, Indigenous and other people of color have disproportionately been killed or made ill by COVID-19. Those disparities reflect a lack of representation in the sciences. Eniola-Adefeso points to the use of pulse oximeters, which measure blood oxygen saturation and were a primary tool for identifying severe COVID-19 cases; studies suggest that the technology works poorly in people with dark skin3. “The people [who] are at the table doing biomedical research do not come close to representing the people who we are designing those technologies for,” says Eniola-Adefeso, who argued in February 2021 that the NIH should “fund Black scientists”4.

She says that the NIH does have ways to approach racial equality. She says it’s time that the agency withdraws the grant-review criterion based on the resources and reputation of an applicant’s institution, because it strongly favors institutions that have historically been well funded.

Another inexpensive option would be a specific fund for underrepresented researchers whose grant-application scores end up in the ‘grey zone’, in which NIH program officers have the discretion to fund or reject their project, says Olivia Rissland, a molecular biologist at the University of Colorado School of Medicine in Aurora. Sometimes, winning their first grant can make all the difference to a researcher. “A whole bunch of things open up, and then they are on a much more sustainable path,” says Rissland, who serves as an adviser for the Good Science Project, an organization that advocates for improving the funding and practice of science.

COVID-19 also threatens to exacerbate funding and workforce disparities. Rissland worries about how agencies such as the NIH will account for scientists’ radically different experiences of the pandemic — especially given that it has disproportionately affected women and communities of color. A survey conducted in October 2020 found that feelings of pandemic-related burnout were worse for female faculty members, who often bear a disproportionate load of family care. Rissland is concerned that, if the agency doesn’t take these concerns seriously, many of these women could leave academia in the next few years.

Integrate the social sciences

The pandemic forced funders and researchers to accelerate speed of biomedical research — but it also exposed the importance of public buy-in.

Despite the availability of highly effective vaccines and therapeutics in the United States, just two-thirds of the country has been fully vaccinated and less than half has received a booster dose. Collins has said that not addressing vaccine hesitancy is one of his chief regrets as the former NIH director, and that he wishes the agency incorporated more insights from behavioral social-science research into confronting the problem.

William Riley, a social psychologist who served as director of the NIH Office of Behavioral and Social Sciences Research until December, agrees. “If we don’t do more research in that area, when the next pandemic comes along, we still won’t have a good understanding of how to address vaccine misinformation,” he says.

Beyond funding social and behavioral science, some researchers think the agency needs to re-evaluate how it approaches research questions in general.

Hekler says that the institutes in the NIH are too siloed and focused on improving outcomes in their own narrow fields, adding that this reductive approach often ignores the built-in complexity of how health conditions interact and co-occur. For example, many of the underlying drivers of cancer elevate the risk of cardiovascular disease and vice versa, he says.

In his forthcoming commentary, Hekler and his colleagues propose restructuring the NIH with these principles in mind. They suggest that the agency incorporate institutes that focus on drivers of health and the process of conducting science.

Hekler is not the first to propose reforms to the 27 institutes, but change has come slowly to the agency — in part owing to its immense bureaucratic sprawl. Petsko agrees that the NIH is currently organized with an outdated understanding of medicine. If it were to be created from scratch today, he’d prefer it to ideally be organized by biological pathways and processes, such as cell growth and death, instead of by organ. But with the current model of basic-research funding working well, Petsko says he would be reluctant to advocate for such a major reorganization.

Don’t ignore the politics

Jeremy Berg, a data scientist at the University of Pittsburgh in Pennsylvania, and the former director of the National Institute of General Medical Sciences, says he hopes that whoever is picked as the next director focuses on evaluating the current distribution of funds to each institute and whether the structure of the agency is serving it well.

But there might be barriers to significant change. After geneticist Eric Lander resigned as Biden’s science adviser following allegations of bullying and harassment, Biden tapped Collins to serve on an interim basis until a permanent adviser is nominated and confirmed. That means Collins has a role in choosing his NIH successor — which Eniola-Adefeso says is counter to what the agency needs right now. “There’s a lot of recycling of mindsets at NIH that prevents them from seeing what we on the outside are seeing,” she says.

The agency’s next leader will have to contend with an unprecedented level of political vitriol and mistrust of science, partly spurred by COVID-19. That means the director has to be an excellent communicator, says Rissland. “The NIH can’t be an insular ivory tower,” she says.

Ultimately, says Carla Williams, a behavioral scientist at Howard University in Washington DC, it’s unreasonable to expect that the director will solve the agency’s longstanding problems without a significant infusion of money and collective action. “When we talk about policy change at this level, we can’t expect a panacea or a magic pill,” she says.

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