WASHINGTON — Under the reign of Francis Collins, the National Institutes of Health was untouchable.
From virtually the moment President Obama appointed him in 2009, prominent figures in government and science have been enchanted by Collins, the Harley-riding, guitar-playing geneticist who brought newfound attention to the nation’s medical research agency.
In less than a decade, his agency’s budget ballooned from $29 billion to $42 billion. In an era when Democrats and Republicans agreed on nothing, the NIH’s popularity served as a rare unifier under three presidents.
When he retired last year, Collins was celebrated in an hourslong ceremony by Barack Obama, Yo-Yo Ma, George W. Bush, and the Dalai Lama. But his popularity obscured a debate raging in university laboratories and biotech boardrooms across the country: Is the biomedical sciences agency living up to its mission? Or, more fundamentally: What should its mission be?
The Biden administration’s search for Collins’ replacement, accordingly, has taken on outsize importance. It’s not just a key personnel decision: According to many NIH critics, it’s a once-in-a-generation chance to tackle the agency’s shortcomings and turn the government’s science strategy upside down. It’s also a process in which Collins, unexpectedly, will play a significant role: President Biden last month tapped him to serve as his science adviser in the wake of a workplace abuse scandal in the White House’s science office.
“Right now, NIH is a window into the past,” said Greg Simon, a veteran Democratic operative and onetime Pfizer executive who directed the Obama administration’s “Cancer Moonshot” effort in 2016. “It needs to be a window into the future. NIH needs to have an open, publicly involved process to redefine its mission.”
Much of the debate about the NIH centers on whether the agency should focus on “basic science” — fundamental research questions without immediate benefits to society — or on ambitious, instant-impact projects in the mold of Operation Warp Speed, the herculean government effort that developed Covid-19 vaccines in an astonishing nine months. The NIH has emphasized basic science since its inception in 1887, and the mission has largely remained constant even amid political tumult and an evolving scientific landscape.
The debate raises sweeping questions about the division of labor between industry and academia; the government’s role in bringing new medicines to market; and whether federally funded scientists should stay the course or throw out their decades-old playbook entirely. Taken together, the discussions highlight the critical moment for the agency and the future of American science — both in the wake of Covid pandemic, and as Biden searches for the agency’s next director.
“We need new voices, and we need new leaders,” said Esther Krofah, the executive director of FasterCures, a think tank funded by the nonprofit Milken Institute that focuses on accelerating biomedical research. “This is a good opportunity to make sure we’re meeting the moment.”
In the wake of Collins’ departure, and in the wake of the Covid-19 pandemic, calls for NIH reform have grown louder.
In a sense, the agency has been a victim of its own success: Its role in developing Covid vaccines, particularly Moderna’s, has become an oft-cited example of the critical role the agency plays in preserving Americans’ health. But it has also highlighted the rarity with which the NIH does anything fast.
“If we can move quickly, why don’t we? If we can move quickly, why can’t we move quickly on areas of unmet public health need? That’s the question that Covid is really forcing everyone to ask,” Krofah said.
There’s no shortage of opportunities: Over 100,000 Americans still die each year from ongoing public health crises like drug overdose, suicide, and cardiovascular disease. In fact, each of those conditions has an NIH institute that spends well over $1 billion each year on researching their underlying mechanisms and potential treatments.
But the federal government’s response to Covid-19, and the major role the NIH played, is clearly the exception, not the rule. When it comes to other, non-pandemic crises, critics charge that the NIH simply isn’t set up to effect change.
In particular, many blame the cornerstone of the agency’s structure: peer review, the system by which scientists review other scientists’ grant applications and determine which are most worthy of funding.
Even Collins, NIH’s staunchest defender, has acknowledged that the system is likely too conservative. Among other issues, the “study sections” that decide how to award funds often fail to include scientists from different disciplines and shy away from research that relies on new technology. Besides, critics say, leading researchers in a particular field are likely to fund projects in line with their own work, meaning that the innovative, off-the-beaten-path ideas that often lead to breakthroughs are at a distinct disadvantage.
Broadly, the system awards money to older, whiter researchers at elite institutions that critics say wield too much influence over the agency. Johns Hopkins University alone was awarded NIH grants totaling over $800 million in NIH funding in 2020. UCSF, UCLA, the University of Michigan, Duke, Stanford, and Columbia each received over a half-billion in NIH awards the same year. (Those sums exceed the amount Congress gives to entire NIH institutes. The National Institute on Minority Health and Health Disparities, for instance, has a budget of roughly $273 million.)
The average age of a first-time R01 grant recipient — the oldest and most common form of NIH funding — is 44, a trend that has only worsened in the past 30 years. Ninety-three percent of awards go to researchers who are white or of Asian descent; according to the agency, just 7% go to Black or Latino scientists.
“Hopkins and Harvard and MIT and Cal and others understand the system, and they help train their faculty to do well in that system,” said Sudip Parikh, the CEO of the American Association for the Advancement of Science, a D.C. advocacy group. “There’s nothing wrong with that, except for the fact that we don’t have a level playing field that creates a broader aperture for what is important science.”
And, on the issue of a bias against younger researchers, he continued: “We are killing our seed corn. As a 44-year-old scientist, getting your first R01 — that’s not OK.”
The agency’s massive bureaucracy, too, is seen as an obstacle. Attempts to streamline the NIH, however, have gone nowhere.
Harold Varmus, a cancer researcher who led the agency during the Clinton administration, advocated as director to reduce the number of NIH institutes to just six, a dramatic shakeup from its current 27.
His proposal went nowhere, and so have far more modest attempts at reform, like a merger of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. In September 2010, an agency committee voted 12-3 to merge the institutes, which have similar missions and study conditions with immense scientific similarities. Collins, though, rejected the move, and the institutes remain independent.
Some longtime NIH backers have even come to question whether the agency’s limitations allow their work to have any impact at all — a line of thought that Thomas Insel, who served as director of the National Institute of Mental Health for 13 years, controversially laid out in a recent book.
Despite advances in the scientific understanding of mental illness, he wrote, “Nothing my colleagues and I were doing addressed the ever-increasing urgency or magnitude of the suffering millions of Americans were living through — and dying from.”
Biden, too, has acknowledged there’s room for improvement in the U.S. scientific enterprise. And arguably his signature scientific proposal, a new high-stakes research agency known as ARPA-H, is in many ways an answer to the NIH’s limitations.
“I believe it is essential that we refresh and reinvigorate our national science and technology strategy to set us on a strong course for the next 75 years,” he wrote in an open letter to Eric Lander upon his appointment as Biden’s science adviser in January 2021. “This effort will require us to bring together our brightest minds across academia, medicine, industry, and government — breaking down the barriers that too often limit our vision and our progress.”
“The NIH leadership — like me — is too old, too white, and too male to be the group that guides them into the future.”
Greg Simon, a veteran Democratic operative who led Obama's Cancer Moonshot
When Collins stepped down in December, he was celebrated in an hourslong ceremony not only by the likes of Yo-Yo Ma, but by an array of the world’s most accomplished scientists. Quietly, though, some advocates of NIH reform were breathing a sigh of relief: If nothing else, Collins’ departure seemed to provide a natural opportunity for a reset.
In recent weeks, though, those advocates’ ambitions have run into a bizarre roadblock: Collins, the new White House science adviser.
It’s an unlikely landing spot for the longtime NIH director, who, upon stepping aside, had intended to return to his lab at the National Human Genome Research Institute. But the workplace-abuse scandal that led to the resignation of Lander — one of Collins’ longtime scientific collaborators — led Biden to call Collins back into service.
While his job at the White House is supposedly temporary, it nonetheless gives him a remarkable influence on all things NIH — chief among them, his replacement.
“I’d rather have a much more independent search,” said Keith Yamamoto, the vice chancellor for science policy and strategy at the University of California, San Francisco. “To ensure fresh thinking about priorities and approaches, it would seem better for the search not to be orchestrated by the outgoing director.”
Simon, the former Cancer Moonshot director, went further, calling for Collins to recuse himself from the search entirely, and for many directors of the 27 institutes that compose the NIH to join him in retirement.
“The NIH leadership — like me — is too old, too white, and too male to be the group that guides them into the future,” he said.
Beyond their ability to run a $42 billion biomedical research agency, the Biden administration’s selection of a director is likely to signal the White House’s views on several critical research questions. Hanging in the balance, potentially, are major policy decisions about the NIH’s future partnerships with industry, its relationship with major research universities, and its role in “translational” research — projects that put scientific advances to real-world use, like developing new drugs or medical devices.
Little is known about the search, especially in the wake of Lander’s departure. But there is near-consensus in Washington that the next director is unlikely to be a white man. In the agency’s 135-year history, all but one of its 16 directors have been men, and all have been white.
The next NIH director is also unlikely to be a current agency insider, according to longtime agency insiders who spoke about the search process on the condition of anonymity. The current acting director, longtime Collins deputy Larry Tabak, is not viewed as a candidate for the role, nor is Ned Sharpless, the director of the National Cancer Institute, NIH’s largest and most independent component. Some insiders, speaking on the condition of anonymity, have floated Nora Volkow or Gary Gibbons — the directors of the drug addiction and heart, lung, and blood institutes, respectively — though neither is seen as a likely choice, either.
Among the most pressing questions is whether the next director should come from industry, academia, or government.
NIH has been “very successful in its mission of making progress toward advancing basic science,” Krofah said. But the ideal selection, she added, would be someone who “brings a bit more private-sector experience, to help NIH think more deeply around innovation.”
It’s also unclear whether Collins will formally take over Lander’s role spearheading the NIH director search process. Both, however, are academics through and through — Collins has spent decades at NIH, and Lander spent nearly two decades at the Broad Institute of MIT and Harvard.
Biden, though, has left no doubt that he still values Collins’ input immensely — not just via his emergency appointment to the science adviser role, but with his words at the NIH’s retirement ceremony in December, even before that appointment.
“Doc, the bad news for you is, you ain’t getting rid of me, man — I’m going to keep calling you all the time,” Biden said then. “You just point me in the direction, and I’ll follow.”
The NIH, of course, is not without its defenders.
In fact, a vast coalition of advocacy groups exists in Washington in large part to lobby on the agency’s behalf.
Major organizations like Research!America, the Association of American Medical Colleges, and United for Medical Research, among others, have long advocated for increased NIH funding. Universities and drug companies have long been happy to fund those groups to make the case: Academia reaps the benefits directly, and biopharma waits in the wings to commercialize new discoveries first made by NIH-funded researchers.
More broadly, the agency is viewed worldwide as the gold standard for government-backed biomedical research. Altogether, 168 NIH-funded researchers have been awarded Nobel Prizes, either individually or as part of a team.
The NIH is a major driver of economic growth, too, both via the technologies it helps discover and in the jobs it helps create. One recent estimate from United for Medical Research showed the NIH as being responsible for over a half-million jobs and $91 billion in economic activity each year.
The agency remains immensely popular in Washington among Democrats and Republicans alike; even GOP lawmakers normally reticent to expand the size of government agencies refer to NIH’s repeated budget increases as “life-saving, cost-saving.”
During Covid, too, the NIH gained a new celebrity in Anthony Fauci, the director of its infectious diseases research institute. Though he’s become a polarizing figure in right-wing circles, Fauci’s constant presence on network TV gave the NIH a larger public footprint than in recent memory. Collins, too, became a TV mainstay.
Even a few of the NIH’s bench scientists gained a cult following — namely, Kizzmekia Corbett, an immunologist in Fauci’s institute who, in conjunction with other researchers and the drug company Moderna, helped develop a vaccine that entered Phase 1 trials just 66 days after the virus’ genetic sequence was first released.
For the agency, Covid-19 provided public evidence that its science yields tangible benefits, even if the typical journey from “bench to bedside,” as it is known, can take decades.
Indeed, many Americans benefit from NIH research every day, even if they don’t know it. According to a 2018 study, the agency’s science aided in the development of all 210 drugs approved for use by the Food and Drug Administration during a recent six-year stretch. CRISPR, the paradigm-shifting gene-editing technology now in use in numerous clinical trials, was first discovered by NIH-funded research.
As a result, even research experts who are highly critical of the NIH bureaucracy acknowledge that the agency’s basic model is working. Criticisms that the NIH isn’t doing enough to translate science into tangible human benefit aren’t quite right, they argue: While it may be an important job for the government, it simply isn’t what NIH does best.
“My own view is that the NIH should stay the course,” said Yamamoto, the UCSF vice chancellor. “It needs to communicate more clearly that knowledge discovery is the primary mission, and that the government needs to develop other mechanisms — ARPA-H, et cetera — to help de-risk bold ideas for industry to develop.”
“My goodness, we don’t need it to be that everything requires a 30-person team based at Hopkins or MIT that does super exciting scientific research, but doesn’t cure anybody of anything.”
Sudip Parikh, CEO of AAAS
There is little disagreement about either NIH’s successes or its shortcomings. But actual proposals for rethinking the U.S. government’s biomedical research strategy have gained little traction — until now.
Biden, in particular, kicked off his tenure by proposing an agency meant to “end cancer as we know it” — the Advanced Research Projects Authority for Health, or ARPA-H.
The new agency, designed in the mold of the Pentagon science agency DARPA, is in many ways the anti-NIH. Instead of funding basic science research, it would award contracts to essentially develop prototypes for transformational new technologies. Instead of evaluating its work over the course of years, it would evaluate its work over the course of months. Instead of allowing institute directors to remain in their jobs for decades, it would impose strict term limits for project managers, and would pull the plug on funding for projects that don’t hit critical benchmarks.
The NIH and the infrastructure behind it, however, have proven unwilling to share the stage. From the beginning, Collins pushed for ARPA-H to exist as a unit of his larger agency, as opposed to an independent research office like DARPA.
The new agency’s biggest boosters, however, have warned that ARPA-H could fail spectacularly if it’s created under the NIH umbrella.
“It should be independent,” Geoffrey Ling, a former DARPA science official and major ARPA-H proponent, said during a congressional hearing last month. “It needs to be independent. Because you need people there who are going to have the determination, have the drive, have the urgency, to get the job done.”
The debate has come to serve as a symbol of entrenched NIH bureaucracy. The immense agency simply has too much inertia, experts charge, to allow for significant change — as evidenced by dead-end attempts to reduce the number of institutes or fund more aggressive research proposals.
Even the agency’s successful reforms have taken decades to implement: Most recently, a new rule that will require nearly all NIH-funded scientists to make their data publicly available. While it’s a landmark step that will make the agency more transparent and could help address science’s reproducibility crisis, critics lament that it took nearly two decades to implement.
More broadly, Simon said he fears the NIH won’t change unless Congress or the White House forces it to. Absent other reforms, he said, simply increasing the agency’s budget or making simple asks won’t be enough.
“Spending more to do the wrong things will not make them the right things,” he said. “That’s what we learned when we doubled their budget in the Clinton administration. They didn’t start funding newer things with newer people. They gave the old dogs twice as much money. It was a complete and utter failure.”
This time, he and other advocates hope that the NIH can throw out at least part of its playbook.
“There’s another CRISPR out there,” Parikh said. “Basic science won’t let me down. But my goodness, we don’t need it to be that everything requires a 30-person team based at Hopkins or MIT that does super exciting scientific research, but doesn’t cure anybody of anything.”
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