Francis Collins Cannot Exclude a Lab Leak

Francis Collins had already announced he would step down as director of the National Institutes of Health by the end of 2021 when Lex Fridman sat down with him. Appointed and reappointed by Barack Obama, Donald Trump, and Joe Biden, he oversaw 27 institutes and centers, including NIAID, which made him Anthony Fauci’s boss. Before NIH he had led the Human Genome Project. Fridman opens by saying science at its best is a source of hope, and that it has been painful to watch it become a source of division during the pandemic.

He starts with the hardest question. Collins had called for a thorough, expert-driven, objective inquiry into the origins of COVID-19. Is there a reasonable chance the virus leaked from a lab? “I can’t exclude that,” Collins says. He thinks it is fairly unlikely. He wishes there were more ability to ask questions of the Chinese government and to see laboratory records that have never been shared. Most likely, he argues, this was a natural origin: a virus that started in a bat, perhaps traveled through an intermediate host still unidentified, and found its way into humans.

Will science ever know? Collins thinks it might, if investigators find that intermediate host. There has not yet been a thorough enough search to declare the hunt a failure. He asks the audience to remember the timescale. With SARS it was 14 years before the civet cat was identified as the intermediate host. With MERS it was quicker: camels. With SARS-CoV-2 there has been some looking, but the political tension between the United States and China means that if looking is going on, “we’re not getting told about it.” The question is scientific, he says, with political implications.

Doing great science in a pandemic under those tensions is, in his word, unfortunate. Pasteur said science knows no country, and Collins’s whole career in genetics depended on international collaboration. The Human Genome Project put 2,400 scientists in six countries to work together, not worrying about credit, giving all the data away. Collins was the person supposed to keep that coordinated. China was part of it — its first real entry into a big international big-science project — and it did its part. “It’s very different now,” he says.

Fridman turns to the 2014 U.S. pause on gain-of-function research, lifted by NIH in December 2017, and asks Collins to argue both sides. Collins first wants to slow the language down. The term, he says, is causing such confusion that he needs a minute. In ordinary science, researchers do gain-of-function experiments all the time. NIH’s clinical center is running cancer immunotherapy trials in which a patient’s immune cells are taken out, treated with gene therapy that revs up their ability to find the cancer, and given back as what he calls “little ninja warriors.” That is a gain of function, and it can save a life.

He reaches for a still more ordinary example: the eyeglasses on his face. They are a gain of function; without them he would not see Fridman clearly. The kind of work now under very rigorous, carefully defined oversight is different. It applies when you work with an established human pathogen known to be capable of causing a pandemic, and you enhance or potentially enhance its transmissibility or virulence. That subset has a name: EPPP, enhanced potential pandemic pathogen. The standard was worked out over three years by the National Science Advisory Board on Biosecurity and must be reviewed by a panel that goes well beyond NIH.

Most of the time, he says, the risk is not worth it. Only three times in the last three or four years have experiments been given permission to go forward, and they were all influenza. If you are worried about the next pandemic, knowing more about the coming enemy is useful, including for influenza and coronaviruses like SARS, MERS, and SARS-CoV-2 — but only if it can be done safely. Lab accidents happen. SARS itself leaked from laboratories, and people got sick. That is why the oversight is stringent.

Collins wants to be “really clear” about the work at the Wuhan Institute of Virology, done as a sub-award on an NIH grant to EcoHealth in New York. Those experiments, he says, did not meet the standard that requires the stringent EPPP oversight. In the everyday scientific use of “gain of function,” someone might say they qualified. In the specific use that applies to a potential pandemic pathogen, absolutely not. Nothing went on there, on his account, that should not have happened under the oversight then in force.

There was a process failure. The grantee institution failed to notify NIH about an experiment it was supposed to report, in which researchers mixed and matched viral genomes and got a somewhat larger viral load. It was still not EPPP. It was all bat viruses, not human pathogens, and it did not cross the threshold. Anyone willing to look at what EPPP means and what those experiments were, he says, would have to agree.

The biggest reason it did not cross: EPPP applies only to agents that are known human pathogens of pandemic potential. These were wild-derived bat viruses, not shown to be infectious to humans. Researchers took four of them and moved spike-protein genes around to see which would bind better to the ACE2 receptor. That does not get across the line. The more troubling claim — that this is how SARS-CoV-2 got started — is, he says, “absolutely demonstrably false.” The bat viruses had only about 80 percent similarity to SARS-CoV-2, decades away in evolutionary terms. It is “really irresponsible” to claim otherwise.

Fridman presses the gray area. Unexpected results are the point of experiments, and the public has a right to hear that uncertainty. Collins says he is comfortable discussing the gray area. What makes him uncomfortable is people deciding for themselves what the threshold is on the basis of a political argument. The line was laid out explicitly after three years of deliberation. If it needs to be reconsidered, reconsider it. Do not take an experiment already done and announce that the threshold is no longer what it was. That, he says, does a disservice to the whole process.

He insists the ethics of this work have not been ignored. The issue has been front and center for a decade or more, including two major meetings of the National Academy of Sciences. In January 2020, just before COVID changed everything, NIH had already charged the same biosecurity advisory board to reconvene, look at three years of experience, and ask whether the threshold was too easy or too hard. Then the pandemic arrived, and the infectious-disease experts on the board said they did not have time. Collins thinks the time is now right, and that the discussion should be as public as one can imagine. If the conclusion were that these experiments should not be done under any circumstances, that would be the conclusion. So far it has not been.

Looking out a hundred years, Fridman asks whether cheaper synthetic biology makes a leaked man-made virus one of civilization’s greatest threats. Collins does worry. The tightest oversight covers federally funded research, and there is no reason to think that is the only place such work would go on. There is no equally stringent international oversight. It would take a seriously deranged group, he argues, because bioweapons that kill only your enemies and spare you are a fantasy — humans are too alike. He does not see an imminent risk, but suppliers already flag oligonucleotide orders that match smallpox. International tracking, he wishes, were stronger. On ethics more broadly, the world lacks an enforcement mechanism: look at human germline genome editing, which has bully pulpits and governments deciding for themselves.

What about incompetence rather than evil? Fridman’s father, a physicist, worked at Chernobyl. Collins does not dodge it. SARS leaked from a lab in China two or three times, and in some instances people died; it was fortunately contained quickly. You still need to study viruses to keep them from causing broader pandemics, and you must insist on the BSL-2, 3, and 4 framework. You cannot count on every human being to do exactly what they are supposed to. That accident risk, he says, has to be in the mix when someone decides whether a given pathogen experiment is worth supporting.

Collins is Fauci’s boss, and he has stood behind him. Should Fauci be fired because so many people in politics have called for it? Absolutely not. To do so would hand a victory to people who want to make up stories and destroy someone. Nothing in the way Fauci has been targeted, Collins says, is based on truth. The argument is circular: they decided they do not like Tony, they make things up, they twist comments about gain of function — where Fauci was referring to the specific policy definition — and they say he lied to Congress. “That’s simply not true.”

Critics also dislike that medical recommendations changed over more than a year and call it flip-flopping. The science changed, Collins replies. The Delta variant changed everything. You do not want Fauci saying the same thing he said a year ago; that would be wrong. It was the best they could do then. People do not understand that, or they do not want to. The campaign has been hammered so often that Fauci now needs 24/7 security against people who want to do him violence. Treating that as a reason to fire him, Collins says, would hand the evil forces the victory. He will not do that.

Fridman tries a harder ask. Collins has a humility, perhaps because he is a man of God, that garners trust. As the face of science in a catastrophe, does a leader also owe the public that extra work of winning trust back? Collins’s answer is that the best way you give people trust is to tell them the truth. He does not think more humility from Fauci would change the fact that attackers need a target to distract from their own party’s failings. If Fauci were out of the scene and Collins were placed in that role, he expects the same targeting would ratchet up. He is less visible, not more virtuous in delivery.

On masks specifically, Fauci has said multiple times that the early recommendation not to wear them had two reasons: a shortage needed in hospitals, and a lack of realization that the virus could heavily infect asymptomatic people. As that changed, he changed. Did he make an error? Collins says no: he was making a judgment based on the data then. As a scientist, the temptation is a full brain dump of knowns, unknowns, and needed experiments. That will not play in a sound bite on the evening news. You distill it to the best recommendation you can make at that time. A century ago, a discussion about masks also led to panic. The calculation is complicated, and it does not go away.

Collins can totally empathize with people hesitant to take a COVID vaccine or to give it to their children, especially when they are barraged by conflicting information. He has spent much of the past year trying to listen better, because officials keep assuming they know the basis for someone’s hesitancy and often do not. The variety of reasons is broad. A big concern is that the work was done too fast and corners were cut. Another is long-term effects nobody will know about for years. You can say that has not been seen with other vaccines, and there is no particular reason to think this one is different — but you cannot absolutely say there is no chance. His heart goes out to the confused and fearful. He has no sympathy for people who keep distributing information that is demonstrably false. “They’re taking lives.”

What worries him beyond COVID is another epidemic: the loss of the anchor of truth. Truth as a way to decide whether to vaccinate yourself or your children seems to have lost its primacy, replaced by a strongly expressed opinion or a Facebook post from two hours ago. The same substitution shows up in other fights, including whether the 2020 election was fair. Polarization is bad enough; having no way to resolve it by asking what is true makes him deeply worried, and he is usually an optimist. Fridman offers a less bleak reading: 21st-century audiences distrust an authoritarian tone, and in the battle of ideas humility and love win. Collins is with him. That answer, he notes, is very biblical.

Fridman then brings up Joe Rogan, ivermectin, and NIH’s own page saying there is insufficient evidence for or against the drug. Collins unpacks it. The concern about Rogan is not limited to taking ivermectin. More serious is being fairly publicly negative about vaccines while people are dying: 700,000 COVID deaths, and Kaiser estimates of at least 100,000 unnecessary deaths among the unvaccinated. Promoting that attitude as the pandemic rages is, he says, simply irresponsible. Ivermectin captured imaginations to the point that some people took livestock doses and got pretty sick. A recent review of the studies, he says, concludes it probably does not work. ACTIV-6, a trial his public-private partnership is running, had about 400 patients randomized to ivermectin or placebo and might have a careful answer within a month.

Fridman pushes back: Rogan is not saying ignore science; he is saying it is okay to ask questions about risk and benefit, including for healthy young people and children, and he often cites anecdotal harm. Collins agrees skepticism is healthy, then wants the next step to be the data. He tells of a six-foot-six professional wrestler, solid muscle, who almost died of COVID and became a vaccine spokesman because the virus does not care how healthy you are. The average person in the ICU with COVID-19, he says, is under age 50. Seven hundred children have died; some had obesity, a lot did not. Younger people are less susceptible, kids even less so, but it is not zero. If the vaccine is really safe and really effective, you probably want everybody to take advantage of it. Everyone is dropping their risk; some more than others.

Collins is totally worried about variants. Delta took over the world in a couple of months because of its extreme contagiousness. Viruses would be beautiful if they were not terrifying. Anyone who wants to understand evolution in real time, he says, should study SARS-CoV-2: Alpha, Beta, Gamma, Delta, sweeping through populations on fairly minor differences in fitness. The live question is whether Delta is it — so fit that nothing else can displace it. He does not know. The United Kingdom already has Delta AY.4, a sublineage that seems to be taking over the Delta population as if it were a little more contagious. That might be the first hint of something new: not a completely different virus, but Delta plus.

The big fear is a variant so different that vaccine protection fails, and nobody knows how different that has to be. So far it has been a pleasant surprise. After two doses, and more so after a booster, the immune system is clever enough to make a diversity of antibodies covering small changes. Even Beta, B.1.351 from South Africa, the most different so far, still looks pretty good. That will not always hold if something gets far from the original Wuhan virus. The good news is mRNA lets you redesign a shot quickly and run a few thousand people through a trial to confirm antibodies. Collins does not want to have to do that. Lives would be at risk in the meantime. Variants do not appear unless the virus is replicating in a person, so the way out is to cut infections.

His cocktail of solutions is not one thing. In the United States it means getting 64 million unvaccinated adults vaccinated, getting kids vaccinated, getting boosters into people who are due, and keeping indoor masking and distancing until the country is really done — which it is not. This is a worldwide pandemic. Low- and middle-income countries have for the most part not even started with vaccine access. That, he worries, is where the next variant will probably arrive, and it will cross the world quickly, as the last 22 months have shown repeatedly.

Fridman is surprised, annoyed, and frustrated that rapid at-home testing was not a core part of the solution from the beginning. Nobody is against testing. America is good at mass manufacture. A cheap daily test gives people information and the freedom to decide what to do with it, without sharing the result with anyone. He believes people will stay home when the test is positive. Collins is “so completely with you.” NIH is running a trial in Georgia, Indiana, Hawaii, and Kentucky that blankets a community with free testing and watches spread, including through wastewater.

The country got off to a bad start. For the first several months, testing lived in big-box laboratories: send a sample through the mail, get a result back sometimes five days later, after you have already infected a dozen people. It was the wrong model, but it was what they had. People insisted on PCR because home antigen tests would have false positives and false negatives. No test is perfect, Collins replies, but a test that is not acceptable or accessible is the worst setting.

With a billion dollars from Congress, NIH created RADx, Rapid Acceleration of Diagnostics, and turned itself into a venture-capital shop. Every small business or academic lab with a home-testing idea was invited in and thrown into a “shark tank” of business experts, engineers, and people who understood supply chains and manufacturing. At the time of the taping, about two million tests a day were coming out of that program, including most of the home tests on pharmacy shelves. He wishes they had done it faster. In December he expected about 410 million tests for the month, and with one or two more platforms approved — NIH was helping FDA as a validation lab — they could be at half a billion tests a month. Fridman calls it a dream. Collins calls it a happy story, and he had been waiting for one.

Fridman raises an accusation, first flagged to him by Rogan, that NIH funded a paper with images of sedated puppies whose heads were inserted into small enclosures containing disease-carrying sand flies. Collins says the story is not true, or at least the citation of NIH as a funding source on that paper is not correct. The larger question stands: how does a director of an agency funding vast research ensure ethical fortitude when the line is gray? In 2015 Collins announced NIH would no longer support biomedical research involving chimpanzees. A National Academy of Sciences panel was asked whether invasive chimpanzee work was still essential. The conclusion was that it was not, and that these closest relatives should be retired to sanctuary.

Many of the animals had been purchased because they were expected to be good hosts for HIV, and they were not. They were kept around in primate laboratories while people invented other things to do that were not scientifically compelling. Collins took flak from parts of the scientific community for caving to animal-rights groups. He thinks the decision was right. Companion animals are harder still; everyone’s heart hurts at harm to a dog or a cat. Oversight groups decide, with public as well as scientific input, whether a study is justified and how to avoid pain. That is a consensus of what people think is acceptable, not a claim that every step is ethical by a standard everyone would sign.

Dogs are the only host for some diseases, including leishmaniasis — the subject of the paper NIH did not fund — and lymphatic filariasis, an NIH-supported experiment in Georgia in which dogs are infected with a parasite because that is the only model for whether a treatment will work. Collins will defend that. If carefully reviewed animal research can save a child from a terrible disease, it does not make him comfortable, but it still seems the right choice. Declaring all animal research off the table is also unethical, he argues, because it dooms people for whom that work might have been the remaining hope. Outside medicine, factory farming troubles him far more.

A few weeks before the interview, Collins announced he would step down at year’s end, remaining at NIH in another capacity. No other NIH director, he notes, had served more than one president after being appointed. Being carried from Obama through Trump and into Biden was unheard of. Scientific organizations benefit from new vision, and 12 years is a long time for the same leader. If he was not going to stay for Biden’s full term, he needed to signal now so a successor could be found, nominated, and confirmed. He decided at the end of May. The job is exhausting: for the last 20 months, 100 hours a week. He does not think he is done, and he would like time to find out whether there is another calling.

What is he proud of? Gene editing that is now curing sickle cell disease, unthinkable in 2009. Single-cell biology. The BRAIN Initiative, which he announced in the East Room with Obama: about 600 investigators, a *Nature* issue devoted to a cell census of the brain, and more than half the investigators engineers, not traditional biologists. Precision cancer treatment and immunotherapy pulled from a backwater into some of the hottest science. And COVID vaccines in 11 months, built on decades of basic work on mRNA, spike proteins, structural biology, immunology, and genomics — something 2009 Collins would never have imagined. He describes his role as midwife, using the director’s convening power to pull together people who do not share a scientific language.

Talking science with Obama felt like talking to a sponge. Fridman had heard the president distinguish narrow AI from strong AI in a way that passed the “BS test.” Collins’s explanation is that Obama listened to experts and then asked the best questions in a room full of scientists — not because he knew the answers, but because he knew which questions to ask. The curiosity was genuine, almost a kid in a candy store who had snuck into the office. Out of conversations like that came All of Us, a million-strong American cohort sharing electronic health records and genomes. Out of a different kind of convening came the Accelerating Medicines Partnership. Academic scientists thought pharma scientists were not that smart and only wanted money; pharma thought academics only wanted papers. Both stereotypes were wrong.

AMP started with three open-access projects — Alzheimer’s, diabetes, and rheumatoid arthritis and lupus — with NIH covering half the cost and industry required to put skin in the game. Parkinson’s, schizophrenia, and bespoke gene therapy for ultra-rare diseases followed; heart failure would make seven. That background made ACTIV possible when COVID arrived: about 100 people, half industry and half government and academia, who dropped everything. AMP took two years to start. ACTIV took two weeks. They kept the lawyers out of the room. The group designed vaccine master protocols and the 30,000-participant trial size, and ran at least 20 therapeutic agents, including monoclonal antibodies that work, in record time. Fridman calls the public-private dance a source of hope. Collins calls it science’s finest hour in a long time.

Collins was not a person of faith growing up. He became a believer in his twenties, as a medical student, after noticing he had never thought through the meaning of life, why we are here, what happens when you die, and whether there is a God. Science is not so helpful on those questions. Atheism, his former position, felt like the least supportable choice because it asserts a universal negative, which scientists are not supposed to do. Agnosticism felt like a cop-out. He kept going, found the person of Jesus Christ answering questions he could not otherwise answer, and somewhat kicking and screaming became a Christian. People predicted his head would explode. The two worldviews have not been incompatible for him. COVID vaccines are both an amazing scientific achievement and an answer to prayer. Sam Harris wrote a *New York Times* op-ed calling his NIH nomination a terrible mistake. Collins’s reply is that he has a testimonial.

The late Christopher Hitchens, a devout atheist, was his friend, called him one of the greatest living Americans, and noted that Collins was sequencing the genome of the cancer that would kill him. They got off to a rough start at a highbrow dinner when Hitchens deeply insulted a question Collins asked. Collins’s reaction was to figure out how to have a more civil conversation. Then came admiration, jousting, and “iron sharpens iron” over a glass of Scotch. When Hitchens got cancer, Collins became an ally on treatment options and perhaps helped him stay around an extra six months. Afternoons in a downtown apartment, over wine, talking science, Thomas Jefferson, or faith: Collins knew it would always be interesting.

Is he afraid of death? He is not afraid, not looking forward to it, and not in a rush, because he still has things to do. He is 71. He is not ready to become a full-time golfer. Sixteen years earlier he wrote *The Language of God* to explain how, from his perspective, science and faith are complementary if you are careful about which question you are asking. People tired of Richard Dawkins at one end and young-earth creationists at the other seemed hungry for a way the two could get along. He started the BioLogos foundation, stepped away to become NIH director, and watched it flourish. Legacy talk makes him uneasy; it feels self-promoting. The day he announced his departure felt a little like attending his own funeral, and the stories people told him about a difference he had made were enough. He does not want a monument.

Fridman asks the most difficult question, the one that perhaps sent Collins toward God: what is the meaning of life, in three sentences, with a couple of minutes left. Science does not help. Collins believes we are here for a blink of an eye, and that existence somehow goes on beyond that in a way he does not entirely understand. In the blink we are called to make the world a better place, to love people, to give altruistic instincts more room and selfish ones less — to live out the Sermon on the Mount. Once he read it, he could not unread it. The meaning of life is to strive for that standard, knowing you will fail over and over, and that God forgives you. Hopefully, to put a little bit of love out into the world.