A rebuttal to NIH leadership's screed against pandemic preparedness.
Dr. Angela Rasmussen joins Inside Medicine for a tag-team response to a poorly reasoned essay by NIH Director Dr. Jay Bhattacharya and his deputy, Dr. Matthew Memoli.
Late last week, NIH Director Dr. Jay Bhattacharya and his Principal Deputy Director, Dr. Matthew Memoli, published an essay in City Journal1 that argues, basically, for a head-in-the-sand approach to pandemic preparedness.
This isn’t that surprising coming from Dr. Bhattacharya. He co-authored “The Great Barrington Declaration”—pandemic fan fiction that, if implemented, would have cost countless American lives by voluntarily increasing the number of Covid-19 infections during the pre-vaccine era, all in the futile pursuit of herd immunity. Now that Dr. Bhattacharya is running the NIH, his ideas on the topic warrant substantial scrutiny.
That’s what we’ll do today.
Once again, I’m using the Fiskkit.com approach, a website that lets readers annotate articles, line by line. This time, however, I’ve enlisted help from virologist (and co-editor-in-chief of the scientific journal Vaccine) Dr. Angela Rasmussen, someone I knew would add much more technically detailed analyses and debunking. She happens to have been involved in some of the most important genetic studies tracing the origins of the SARS-CoV-2 virus in the market in Wuhan, so she’s the perfect partner for this. Dr. Rasmussen also authors a sharp Substack entitled “Rasmussen Retorts,” which I highly recommend.
So, buckle up, kids. It’s about to get messy. But you’re sure to learn a lot.
Note #1: We went long. We know that you might not read every word. But we feel that it is important to document expert thinking/analysis about the realtime and potentially catastrophic mistakes that our national leaders are making on pandemic preparedness.
Note #2: Every sentence in the Bhattacharya/Memoli essay appears bolded in quotes below, and is followed by rebuttals or comments by me, Dr. Rasmussen, or both. If you’d like to read this on Fiskkit, you can do so here.
Note #3: Newsletters are the perfect forum for time-intensive deep-dives like this. If you haven’t yet done so, please consider subscribing to and supporting our work. Thank you!
Let’s get to it…
The headline: NIH Directors: The World Needs a New Pandemic Playbook.
The sub-headline: The old one failed to cope with Covid and may even have caused it.
“Over the past two decades, scientists developed a pandemic preparedness playbook that has failed catastrophically.”
Faust: Jay has long talked about the need for nuance in these discussions. Here, he spurns that and declares our strategy to have been a catastrophic failure. Does he still believe that his proposed approach—The Great Barrington Declaration—which advocated for trying to use herd immunity among the young and healthy as a way to end the Covid-19 pandemic in 2020, would have worked? Because that would have been an even larger failure, as there would have been many, many more people who got infected before getting the chance to get vaccine protection.
So, the pandemic preparedness playbook (such that it is; more on that below) both needs improvement and is responsible for the benefit of Covid-19 vaccines that saved millions of lives.
Rasmussen: Failures in the US COVID-19 response are not the same thing as “a pandemic preparedness playbook that has failed catastrophically,” particularly considering that Bhattacharya and Memoli falsely assert that said playbook may have caused the pandemic. This is unsupported by evidence.
“It grew out of the fears aroused by the global emergence of highly pathogenic avian influenza in 2003 and the swine flu pandemic of 2009. The U.S. National Institutes of Health (NIH)—which we now lead—made massive investments that failed to cope with the Covid pandemic.”
Rasmussen: The Vaccine Research Center at NIH was able to begin developing mRNA vaccines targeting SARS-CoV-2 spike on January 10, 2020, because of NIH-funded research into mRNA vaccine technology and virology research on SARS-related coronaviruses. After SARS-CoV-1 emerged in 2003, NIH invested in developing vaccines and testing the 4 different structural proteins of SARS-CoV-1 for their immunogenicity (ability to elicit protective immune responses). Further NIH investments when MERS-CoV emerged in 2012 led to a MERS-CoV mRNA vaccine that entered clinical trials. Because of all this work that preceded the emergence of SARS-CoV-2, we were able to make vaccines that saved millions of lives within a year. This is a very clear example of how NIH-funded research did contribute significantly to coping with the Covid pandemic.
“Worse, the playbook itself may have caused it”
Faust: While a lab leak is possible, there has never been a shred of credible evidence to support conclusions that this is how the pandemic started. Meanwhile, there is compelling evidence (bordering on proof), that illegal animals being sold in a market in Wuhan were the source of the virus.
Rasmussen: All current evidence demonstrates that SARS-CoV-2 emerged into the human population via the wildlife trade at the Huanan Wholesale Seafood Market in Wuhan, China. There is no evidence supporting the assertion that NIH-funded pandemic preparedness activities or virology or vaccine research caused the pandemic. All existing data are consistent with zoonotic emergence. None of the available evidence is consistent with a virus emerging from a laboratory. I co-authored several key papers on pandemic origins presenting the evidence. Several other key papers are here:
Here are some other popular press articles I have written on this topic:
“The pandemic preparedness playbook is breathtaking, even utopian, in its ambition”
Faust: Exploring how to avoid or better mitigate a pandemic using science and research is not breathtakingly ambitious. It’s what the public expects experts to do. What they mean by utopian is unclear, but in the next section, they outline their problems with its approach. From that, it appears that they believe the risks (which are real) are impossible to overcome. That’s both wrong and, frankly, insulting to the ingenuity and care of the scientific community.
Rasmussen: I understand the concept of “utopia” as a perfect society in which everyone is happy, healthy, and living their best lives. In my opinion, a society that applies evidence-based public health policies to prepare for and prevent mass casualties from pandemics does sound pretty ideal. There is always room to improve and refine pandemic preparedness and prevention plans, but to suggest that it’s a breathtakingly ambitious undertaking is not how I think of a core function of national public health capacity. It’s telling that Bhattacharya and Memoli view planning strategies to mitigate the damage of significant public health threats like pandemics as a grand and possibly idealized fantasy and not a central objective of public health.
“It entails three basic steps.”
Rasmussen: The entire US pandemic preparedness and prevention plan spanned multiple agencies in the US government and was much more complex than “it entails three basic steps,” since they go on to say those steps were: 1. Go virus hunting; 2. Recklessly grow those viruses and make them more dangerous; 3. Make vaccines for these newly created pathogens and collude with Big Pharma to get rich. It is a completely invented scenario that this describes the US “pandemic preparedness playbook.” It is a highly sensationalized description of research to identify emerging pandemic risks, characterize them, and develop countermeasures that represented only a single component of a much larger, multi-faceted strategic response plan. The actual US pandemic preparedness and prevention strategy was much more complex and did not involve one specific type of virus research as outlined above. This included plans for public health responses, building out health care infrastructure, community-level guidelines for risk mitigation, stockpiling of vaccines, antiviral drugs, PPE, and medical equipment, etc. as well as doing virus research and developing new vaccines or other countermeasures.
The document that is actually called the US Pandemic Playbook details frameworks for risk assessment, rubrics for decision making, and assigns different responsibilities to different government departments including Health and Human Services (CDC, NIH, FDA, ASPR, BARDA, etc.), USDA, USAID, State, Labor, Defense, Transportation, and Homeland Security, as well as various intelligence agencies and the President.
“First, catalog every existing pathogen by sending scientists to every remote place (bat caves in China, and the like), take biological samples of wildlife there, and bring them back to labs, often located in city centers like Wuhan, China.”
Rasmussen: This first supposed step in the entire US pandemic preparedness playbook describes basic biological fieldwork that was carried out by a series of government-funded programs, including the USAID PREDICT program, the DARPA PREEMPT program, and various NIH grants issued through the National Institute of Allergy and Infectious Disease (NIAID) led by Director Anthony S. Fauci. These studies are not intended to “catalog every existing pathogen,” but to conduct surveillance and discovery for emerging threats. To do that for zoonotic viruses (viruses that can be transmitted from animal to human), you have to take samples from wild animals likely to be infected and test them to see what virus genomes are detected. Sometimes, you can also isolate live virus, depending on the type of sample and the animal. The purpose of these studies is to identify viruses that pose a risk to people or animals, but that is not their only scientific benefit. Understanding the diversity of viruses circulating in wildlife is critical to assessing risk, given the encroachment of humans on wild spaces and the impact of climate change on ecosystems because it is constantly changing. You also learn a lot of fundamental information about virus and host evolution, animal health, viral diversity, viral fitness, and genomic epidemiology from doing these types of surveillance or discovery studies, which can inform conservation and environmental policy as well. In order to carry out molecular testing, genomic sequencing, and (sometimes) virus isolation, you have to bring the samples you collect in the field back to a lab. Sometimes these labs are in big cities. Sometimes there may be a compelling scientific reason to functionally characterize a virus discovered in one of these studies further in the lab, such as by testing to see if it could infect human cells to assess its potential as a human pathogen. The reference to Wuhan, China, refers to the work of virologist Shi Zhengli at the Wuhan Institute of Virology, who carried out this type of work on bat coronaviruses related to SARS-CoV-1 and SARS-CoV-2. Because of Shi’s work, we learned a great deal about the diversity of these viruses, which have obvious pandemic potential. Some of these were a risk, so they did tests to assess the extent of the threat. A portion of this work was funded by NIAID subawards. There is no evidence that this work is connected to the origin of the SARS-CoV-2 pandemic.
“Second, evaluate the risk of each pathogen infecting humans by testing its ability to penetrate human cells—and sometimes even genetically modifying it to make this more likely.”
Rasmussen: The second supposed step in the entire US pandemic preparedness playbook according to Bhattacharya and Memoli is to take these viruses back to the lab and study them to see if they can infect people, or “ability to penetrate human cells.” (That’s not really how virologists usually refer to cell entry or host susceptibility studies). For a host to be susceptible to a virus, the virus has to be able to bind a receptor on a host cell to enter the cell so it can begin replicating. This process is not the virus penetrating the cell physically, but rather a protein on the surface of the virus particle binding a molecule on the surface of a potential host cell. That binding interaction triggers a process called endocytosis, which means the virus gets taken into the cell in a little membrane-bound compartment called an endosome. RNA viruses like SARS-CoV-2 have to get their genomes out of the endosome and into the cytoplasm to replicate, and this happens through a complex process called fusion. Entry and fusion determine host susceptibility, so studies to look at susceptibility described here are geared towards determining if the newly discovered virus can undergo those steps. After that, you would assess whether the virus can replicate in those cells. If it can, you assess if it can cause disease in an animal model and how it is transmitted. You can’t tell any of these things with sequence data alone. These viruses are completely unknown in terms of their ability to cause epidemics in humans. We can only see what these viruses are capable of by doing experiments in appropriate model systems. Here is an example of this type of characterization: two novel SARS-related coronaviruses were found in 2013. They were more similar to SARS-CoV-1 than any virus that had been seen before, so they tested them to see how similar they were and if they could infect humans and other animal cells. They did a lot of phylogenetic analysis and tested cell entry by infecting some human and animal cell lines genetically modified to express the receptor ACE2. They also showed that antibodies targeting SARS-CoV-1 could neutralize them. They confirmed these viruses were similar to SARS-CoV-1 and could replicate efficiently in human cells.
A subsequent study showed that these viruses didn’t infect mice very efficiently, so they made a chimeric virus, putting the spike protein from a bat virus called SHC014 into a mouse-adapted SARS-CoV-1 strain called MA15. This allowed the authors to test the SHC014 spike’s ability to cause disease in mice by isolating it within an established genetic backbone that is known to replicate and cause disease in mice. The SHC014-MA15 chimera replicated and spread in mice but wasn’t as pathogenic as regular MA15. They tested anti-SARS-CoV-1 antibodies and found they didn’t neutralize this virus very well. They also made a clone of full-length SHC014 that they tested for entry and spread in differentiated human airway cells and compared it to original SARS-CoV-1. Overall, this study provided a lot of valuable information about the risk of SHC014 or a similar virus being able to infect humans and cause disease using experimental model systems. The authors concluded by proposing models of emergence based on their findings that could inform pandemic preparedness efforts. This paper was an important contribution to our understanding of potential threats. In this case, it also could not have led to SARS-CoV-2.
There is no evidence that any of the above work or similar functional characterization research created SARS-CoV-2 or led to the pandemic through a laboratory or research accident.
“The latter practice is now called dangerous gain-of-function (dGOF) research.”
Faust: It’s undeniable that gain-of-function research has dangers. It’s also an extraordinarily important genetic tool. I’ve never heard it branded as “dGOF,” and it smacks of fear-mongering to me.
Rasmussen: The term “gain of function” has many meanings. In this context it usually refers to experiments designed to make a virus more pathogenic and/or more transmissible. However, this can be defined in very different ways. In 2017, NIH established the Potential Pandemic Pathogen Care and Oversight (P3CO) framework to govern pathogen research that poses extra risks. The P3CO addressed potential pandemic pathogens (PPP), defined as “likely highly transmissible and likely capable of wide and uncontrollable spread in human populations; and it is likely highly virulent and likely to cause significant morbidity and/or mortality in humans.” The NIH standard for a PPP was defined based on transmissibility and/or pathogenicity IN HUMANS. The P3CO defines gain of function (”an enhanced PPP”) as “a PPP resulting from the enhancement of the transmissibility and/or virulence of a pathogen. Enhanced PPPs do not include naturally occurring pathogens that are circulating in or have been recovered from nature, regardless of their pandemic potential.” In other words, a PPP that you’ve specifically juiced up with some new feature. The P3CO was how the NIH defined gain of function relevant to the pandemic’s origin prior to the pandemic.
With SARS-CoV-1 being an obvious exception, novel bat SARS-related coronaviruses prior to the pandemic did not usually meet P3CO criteria for PPP because you couldn’t say whether it was “likely” they would be transmissible or virulent in people without doing some experiments to find out whether they might even be able to infect people or not. Even experiments involving chimeric viruses that have been “genetically modified” did not usually meet P3CO criteria for being an enhanced PPP since we could not predict how modification impacts its transmissibility or pathogenicity without doing experiments. The only way to learn anything about novel viruses’ pathogenicity or transmissibility is to collect data using controlled experimental models like mouse models. Such experiments may have created more pathogenic or transmissible viruses that would have met the P3CO definition of an enhanced PPP, but that was not the intent and you wouldn’t know if you had an enhanced PPP until you did the experiment to find out. Then it would fall under P3CO oversight. Not many projects did. There is no evidence that any projects that were under P3CO oversight had any role in the origins of the COVID-19 pandemic. However, the P3CO is no more at NIH, and currently NIH-funded research is subject to their interpretation of the Presidential Executive Order on Improving the Safety and Security of Biological Research.
It is unclear how “dangerous gain-of-function (dGOF)” is defined. A standardized definition has never been provided, so by default it has become however the person implementing the policy interprets the Executive Order. Here, Bhattacharya and Memoli effectively define dGOF as NIH-funded bat coronavirus research that may have led to the pandemic according to them, despite providing no evidence to support this claim.
“This may seem crazy to the uninitiated, but it is a critical step in the playbook.”
Faust: It’s also an often critical step in knowledge acquisition that can lead to breakthroughs.
Rasmussen: It is not crazy to perform well-designed experiments that generate important knowledge on emerging viruses to assess the threat that they pose. It is a reasonable and scientific approach to accurately assessing a huge risk to public health, and it presents a low risk if done by properly trained experts in a biocontainment lab with proper mitigations in place for safety and security risks.
It is also not a “critical step in the playbook,” as the entire US Pandemic Preparedness Playbook only mentions coronaviruses (MERS-CoV and SARS-CoV-1) as “sample pathogens” that might cause a pandemic. There are components to the playbook that involve the intelligence community determining whether a pandemic was “deliberative” or not, but determining whether “dGOF” virology research was involved is not a critical step.
“The idea is to estimate the likelihood that the infectious pathogen will mutate in a way that could conceivably threaten humans.”
Rasmussen: The idea is partly to estimate the likelihood that a pathogen will mutate in the future, but also to assess the threat that the pathogen or other very similar pathogens present now. If we can accurately determine the current threat level, this allows us to reduce the risk of a novel virus causing a pandemic based on evidence, not guesswork. Bat coronaviruses don’t “conceivably” threaten humans. Some of them demonstrably DO threaten humans and cause pandemics! But we don’t know enough to distinguish a pandemic virus from one that can’t even enter a human host cell by just looking at the sequence. We don’t know what viruses will do in new hosts without doing an experiment to find out. Since we don’t test this in humans for what I hope are obvious reasons, we use molecular virology, cell culture systems, and animal models instead to generate data that helps assess this risk.
“Third, having identified which few of the countless pathogens studied pose the greatest risk, develop vaccines and therapeutics before they leap into human populations. Crucially, this step involves awarding large contracts to pharmaceutical manufacturers to develop and stockpile the countermeasures.”
Faust: It’s true that the government has awarded large contracts for this kind of work. That public-private collaboration has led to America’s unmatched productivity and success in the scientific and medical arena. It’s always fair to reassess these, to make sure our investments are warranted and represent the best use of our tax dollars. But this kind of research pretty much requires public investment, because no for-profit company would be able to risk investing millions or even billions of dollars into research that has a relatively small probability of becoming highly useful anytime soon.
Rasmussen: The third supposed step in Bhattacharya and Memoli’s fantasy pandemic playbook is that big pharmaceutical manufacturers “cash in” on vaccines and antiviral drugs developed with the dGOF’d viruses made in the second step. They suggest that these countermeasures developed are then stockpiled. This is absurd.
Operation Warp Speed was successful in part because NIH-funded research on SARS-CoV-1 and mRNA vaccine technology had already created a clear path to developing a safe and effective vaccine in a short time frame. Moderna did establish numerous large contracts with the federal government, as did many other large corporations. That is necessary to carry out a national-scale immunization campaign as fast as possible. The government routinely contracts with vaccine and pharmaceutical corporations because they do not produce these highly regulated, lifesaving pharmaceuticals themselves. There are no US government vaccine factories. All drugs and vaccines are made by pharmaceutical companies and the government does business with them to ensure it can provide the public with essential drugs and immunizations. There is nothing weird, sinister, or corrupt about awarding large contracts to pharmaceutical manufacturers, especially when you are talking about buying vaccines from them at national scale.
Also, the idea that a bat coronavirus vaccine was ever manufactured and stockpiled is also absurd. Before any vaccine is stockpiled it has to undergo the same type of regulatory scrutiny from FDA as any other vaccine or drug. That involves extensive preclinical testing and clinical trials. It is not a small investment for any pharmaceutical company to put a new vaccine through this process and it is not worth it for vaccines that aren’t going to target large markets (unless there’s a pandemic). This has caused many promising vaccine candidates to stagnate in the development pipeline. Pharmaceutical manufacturers are generally not making crazy profits from vaccines for theoretical stockpiling.
“Every step of this agenda is fraught with risk and danger.”
Faust: This is true, but one-sided. Nuclear power is also dangerous. The key is to maintain and assure safety, not to shut down every nuclear power plant because there have been accidents. Bhattacharya and Memoli want us to join them in their cowering fear. Doing so surrenders the possibility of massive benefits, including tools that the public will demand we have if another pandemic occurs.
Rasmussen: Every step of this agenda according to them is doing virology experiments that have varying but high degrees of risk. Memoli, as a virologist who has worked on 1918 and bird flu, should know this is untrue if he is remotely competent at handling dangerous viruses like pandemic flu or highly pathogenic H5N1. He knows full well that “every step of this path”—using well-designed experiments to study emerging threats—is not “fraught with risk and danger. “ There are risks to doing work in high containment. Many of these can be mitigated. These viruses are dangerous. That’s why we study them—to figure out how to decrease the risk. Regulation itself demands evidence-driven risk-benefit analyses. If an experiment involves a dangerous virus and some risks that can be mitigated, but it will produce new knowledge that will improve our abilities to respond to or prevent a pandemic, then the benefits outweigh the risks of doing that experiment. What is needed is thoughtful advocacy for this type of approach, rather than proclaiming without support that every step of a process is fraught with danger.
“The very act of sending scientists into remote places to collect pathogens risks a spillover of a pathogen that might never have occurred otherwise.”
Faust: Finally, we get a sense of their strategy: The head-in-the-sand approach to pandemic prevention. This. Is. Unwise.
Rasmussen: Research-related infections, including some acquired in both the lab and the field, do occur. However, there is no reason to think that the risk of a spillover occurring in the field cannot be mitigated with established methods.
“The laboratory work, even if not classified as dGOF, is risky.”
Faust: Many worthwhile things are risky. I, for one, am glad that we have vaccines. Some life-saving vaccines came from genetic engineering that seems to make these two men tremble in fear. Bhattacharya has never done lab research (as far as I know). Memoli, however, has, and should know better than to use scare-tactic language to argue that we should not pursue research on infectious diseases.
Rasmussen: All laboratory research is inherently risky. Work with potential pathogens is risky. However, these risks can be effectively mitigated. The benefits of studying these pathogens vastly outweigh the risks.
“Even with precautions, there is always a risk that a lab will inadvertently leak a pathogen that poses a catastrophic threat.”
Rasmussen: Yes, lab leaks are a constant risk, and even the most rigorous mitigation measures don’t bring the risk to zero. Systems fail and people can screw up. But we can look at how well virology has done in this regard. As far as the history of labs inadvertently leaking “catastrophic threats”, zero have resulted in a lab leak pandemic. And yes, that includes the COVID-19 pandemic, because there is no evidence to support that it was a lab leak and a lot of evidence that supports that it was not.
“In fact, lab leaks are common, and biosafety oversight is not harmonized worldwide, meaning these pathogens are often manipulated in relatively low-security environments.”
Faust: I asked Dr. Rasmussen how common lab leaks are. Her reply is below. But I’ll just say that auto collisions are common. But most of them (example: while parallel parking, your bumper makes contact with the bumper of the car behind you) are not truly concerning. However, we do need to measure how often fatal collisions occur, and take steps to decrease their frequency.
I also find it hypocritical that the authors are arguing for “harmonized” global cooperation. One of the best ways to achieve this is collaboration. But the Trump administration has basically banned NIH funding for labs in places like China. The reality is that these types of collaborations are what *give us the ability to monitor and be involved in biosafety oversight*. So it’s pretty hypocritical for the administration to shun overseas collaboration, and then expect our former global partners to do what we tell them.
Rasmussen: Biosafety failures are common. This can mean anything from someone’s Tyvek suit tore to a full-on containment breach. These carry vastly different risks. They also happen at very different rates. Modern biosafety practices include built-in redundancies and virus- and facility-specific risk reduction measures to prevent any kind of exposure or containment breach of a high consequence pathogen. “Lab leaks” of a virus infecting a lab worker or getting out of a lab some other way and causing an epidemic have happened. They are a constant risk inherent to virus research, but the risk can be mitigated. They also are not “common,” especially relative to outbreaks caused by natural spillover. These are much more frequent, and a much higher risk to public health.
Lab leaks occur, but they are not common relative to the number of infectious disease outbreaks caused by naturally emergent pathogens. Biosafety oversight isn’t harmonized worldwide, but that doesn’t mean that virologists are studying pathogens or dGOFing them up in substandard biocontainment all over the place. This is an indirect reference to the idea that Shi cultured bat coronaviruses at biosafety level 2 (BSL2). Most coronavirologists (self-included) handle high-titer stocks of uncharacterized animal viruses at BSL3 since they pose an unknown risk. But they don’t always have to, including in the US. Bhattacharya and Memoli should familiarize themselves with the 6th (current) Edition of the Biosafety in Microbiological and Biomedical Laboratories (BMBL), which is a CDC publication on standard biosafety practices used for different pathogens at different biosafety levels. BSL2 is the minimum containment level for handling bat coronaviruses in the US according to the BMBL.
“President Trump’s executive order placing dangerous gain-of-function work under strict regulatory control helps address the problem, but achieving its goals will require the entire scientific community worldwide to embrace its principles.”
Faust: Again, the best way for us to improve the stated goal (lab safety), is for us to collaborate (and even fund) efforts around the world. But by canceling grants that did this, the Trump administration is encouraging the opposite to occur.
Rasmussen: Trump’s Executive Order is so vaguely written that it can include almost any type of research. Specifically, it bans the following types of dGOF research:
(a) enhancing the harmful consequences of the agent or toxin.
(b) disrupting beneficial immunological response or the effectiveness of an immunization against the agent or toxin.
(c) conferring to the agent or toxin resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitating their ability to evade detection methodologies.
(d) increasing the stability, transmissibility, or the ability to disseminate the agent or toxin.
(e) altering the host range or tropism of the agent or toxin.
(f) enhancing the susceptibility of a human host population to the agent or toxin.
(g) generating or reconstituting an eradicated or extinct agent or toxin.
For virologists, a very broad interpretation of these vaguely defined types of banned research effectively means no cloning, no serial passaging, no mouse-adapting, and no growing some viruses at all. Also we can’t de-extinct any more pandemic viruses, as Memoli’s long-time collaborator, Acting NIAID Director Jeffery Taubenberger, did with 1918. This means no research on transmission, pathogenesis, vaccines, or antiviral drugs. It means no more opportunities to learn what makes a pandemic virus capable of causing pandemics and leaves us less informed about how viruses jump across species, with sometimes devastating effect.
As a virologist who studies how emerging zoonotic viruses interact with their hosts and how this influences pathogenesis (the process by which viruses cause disease), I have an interest in virology and countermeasure research continuing because it is important. The unjustified restriction of essential virology, vaccine, and therapeutics research is profoundly damaging to pandemic preparedness and prevention. It will make us less prepared for emerging pathogens and put more people’s lives at risk. That is not a set of “scientific principles” I can embrace, at least not without abdicating my professional integrity.
“All scientists must embrace a culture of careful consideration of the benefits and risks of every experiment—regardless of whether it is classified as dGOF.”
Rasmussen: Pathogen researchers already do. All experiments in the US are under the direct oversight of an Institutional Biosafety Committee (IBC). IBCs manage and regulate all research for their institutions, including conducting risk-benefit analyses for every study. This is routine practice for administration and oversight of all research from a biosafety standpoint. Biosafety best practices already require a “culture of careful consideration,” and it is misleading and insulting to suggest this culture does not already exist.
“From a historical and evolutionary standpoint, the playbook makes little sense and needs to change.”
Rasmussen: No shit the playbook makes little sense, because what Memoli and Bhattacharya are calling the playbook is a lab leak fantasy they concocted with no evidence to back it up. This is not a playbook that needs to change because it’s not actually a real thing that exists and the claim that the US Pandemic Playbook was essentially to find dangerous viruses, make them more dangerous, then cash in making vaccines for them is demonstrably false. This is the actual US Pandemic Playbook.
“The measures developed to counter the threat will never have their efficacy tested in humans before an outbreak occurs.”
Rasmussen: This is deeply misleading. They are saying that vaccines and drugs can’t be tested on people before a novel pathogen emerges, so why bother doing any studies in mice or other models at all? Why bother collecting any experimental data? The fact is, we can test vaccine safety and immune responses in people without an outbreak occurring. We can test how safe drugs are and what side effects might be. We might not be able to test efficacy before an outbreak occurs, but we will have countermeasures that we know are safe and are far along the development pipeline. We can rapidly evaluate them and have them available in case of an outbreak.
“Inevitably, the version of the pathogen that ultimately causes an outbreak will differ significantly from those collected to develop countermeasures.”
Faust: This is saying we should not study influenza or coronaviruses that we know about because any new ones that could cause a pandemic would be too different to be useful. That’s demonstrably false. It was our knowledge of the spike protein of coronaviruses that enabled Operation Warp Speed to proceed is quickly and effectively as it did. These men are pretending like that did not happen, which is, frankly, just weird.
Rasmussen: These guys are so ridiculous. This is not how virology works. Just because viruses behave differently doesn’t mean we can’t learn really important things from them that still apply to other emerging pathogens in the future. Thanks to research on vaccines against SARS-CoV-1 spike, we knew how to make vaccines against SARS-CoV-2 quickly. Thanks to research on SARS-CoV-1 and MERS-CoV pathogenesis, we had a lot of knowledge about how SARS-CoV-2 might cause disease in people. We learn a lot from comparing different viruses. Memoli should know that, considering he’s done a number of comparative flu studies like this one where he used several flu viruses generated by dGOF including fully reconstructed 1918 to test a “universal” flu vaccine. According to Memoli’s own logic in this article, his own vaccine is pointless since any future flu it might need to fend off will be too different from the flu we know about now.
“Evolutionary processes are extremely hard to predict; indeed, the one thing we can say with confidence is that the pathogens with the capacity to cause outbreaks are unpredictable. We are left with well-prepared, expensive countermeasures that are unlikely to work.”
Faust: Operation Warp Speed explicitly proves this to be false. Knowledge from prior coronavirus research, combined with information gained in the early days of the Covid-19 pandemic is precisely what drove the success of the initiative, giving us life-saving vaccines in months, instead of years. I’d argue that we could have gotten the vaccines faster, had there been more of the kind of research that these authors are afraid of, not less of it. (I also think the clinical trials in 2020 could have been tweaked to get answers even sooner, but that’s another story.)
Rasmussen: It’s true that the government has awarded large contracts for this kind of work. That public-private collaboration has led to America’s unmatched productivity and success in the scientific and medical arena. It’s always fair to reassess these, to make sure our investments are warranted and represent the best use of our tax dollars. But this kind of research pretty much requires public investment, because no for-profit company would be able to risk investing millions or even billions of dollars into research that has a relatively small probability of becoming highly useful anytime soon.
“The stockpiled countermeasures developed under the old pandemic playbook offer a false sense of security and empower those who would impose lockdowns, mandates, and other such strategies.”
Faust: I agree that we have a false sense of security. For example, we have antivirals for influenza that many of my colleagues (including infectious diseases experts) have *way* too much confidence in. We need much better antivirals than the ones we have on hand. A great way to get these would be, again, to do the kind of research that these authors want us to fear.
Rasmussen: The idea that stockpiled countermeasures somehow empowered evil public health professionals to institute draconian and unnecessary “lockdowns” or “mandates” is absurd. Public health measures applied during the pandemic, including restrictions on gatherings, business and school closures, and mask and vaccine requirements were put into place with the goal of preventing new COVID cases and preventing people from dying. There were no stockpiled countermeasures available when SARS-CoV-2 emerged. Even for pathogens that do have stockpiled countermeasures, they are often insufficient to even provide a false sense of security. As Dr. Faust points out, the current influenza antivirals are underwhelming. They have to be given in a very short window of time after infection and, while they do work, their impact is modest and resistance can easily evolve. There are 10 million doses of inactivated H5N1 vaccine in the stockpile, but these are insufficient for the entire population and population-scale vaccine production will require nearly a year with current manufacturing capabilities. This does not give me a false sense of security that we are sufficiently prepared for a catastrophic pandemic, nor does it empower me to recommend lockdowns. It gives me a sense of concern that we have not done enough to prepare. It’s worth pointing out again that the “old pandemic playbook” did not only comprise virus discovery, characterization, and countermeasure research as Bhattacharya and Memoli claim. Their complaint of a “false sense of security” is actually an entirely false premise.
“The recent Covid pandemic is a case in point of how such an approach can dramatically fail, harm the population, and undermine confidence in public health.”
Faust: Do they believe in the vaccines or not? Also, Paxlovid was an antiviral that did not just appear out of thin air. (It’s far less useful today, but had we gotten it sooner, it could have saved many more lives.)
Rasmussen: At no point have Bhattacharya and Memoli provided evidence that the pandemic response to COVID-19 “undermined confidence in public health” more than their false claims about public health have. I would argue that being deliberately deceptive and misleading and in some cases outright lying about public health (the virus isn’t very dangerous, vaccines don’t prevent infection so they don’t work, restrictions didn’t have any effect except to hurt children, “natural” immunity is superior to vaccine-acquired immunity, and so on) has undermined confidence in it.
“Furthermore, the playbook creates vested interests with incentives to overreact to new threats. It creates a group of well-funded scientists who benefit from scaring the public beyond what the evidence warrants and at the same time falsely minimizing the risk of lab accidents.”
Faust: I agree that researchers often overstate the importance of the thing they study when, for example, writing grant proposals. In their defense, what are they supposed to write? “Hey, please give us funding to study something that is probably not a huge threat, but could someday be one?” In fact, basic science is *perfectly suited* to study low-probability but potentially high-impact threats. In a perfect world, science would be funded without researchers needing to overstate the risks. But that would only work if funders would recognize that low-probability problems are still worth funding. So, don’t hate the player, hate the game. And since these authors are literally in control of the game, they are actually in a position to change the rules in a positive way. Will they?
Rasmussen: NIH funding is not awarded based on a Principal Investigator’s ability to scare the public. Researchers who are funded to study emerging threats have to convince a study section comprised of experts in the field that the research they propose is scientifically sound and will have a significant impact. Accurately assessing the threat through an evidence-based risk assessment is a critical part of developing a coherent preparedness plan and determining whether a research proposal is a good use of taxpayer dollars. Some of the emerging threats are, in fact, scary with no embellishment required. Rather than cowering in fear, the NIH has historically funded research that will reduce these risks. Researchers also have a strong incentive to accurately assess the risk of a lab accident: we don’t want to infect ourselves with the dangerous pathogens we study. We study these viruses because we want to prevent them from hurting and killing people, so we don’t want them to hurt or kill us either! Personally, I do not want to infect myself, my co-workers, my family, my friends, or anyone in my community with the viruses I study. Pathogen researchers have a strong personal incentive to conduct work with the highest biosafety standards possible: their own health and well-being. As an intramural NIAID researcher who studied highly pathogenic avian flu and 1918, Memoli should know that NIH also does not incentivize “falsely minimizing the risk of lab infections.” Every NIH grant that involves biohazards requires a detailed risk mitigation plan. All labs are inspected annually (sometimes more), with high containment labs singled out for extra scrutiny. Institutional, municipal, state, and federal regulators oversee lab operations, which includes inspecting training records, inventories, protocols and work practices, equipment, ethics approvals, facilities, and security. The inspectors specifically look for practices that increase the risk of an accident, a laboratory exposure, or a containment breach. Research involving Select Agents, like the viruses Memoli studies, requires the people working on them to obtain a security clearance from the FBI and undergo strict and continuous oversight from the government Federal Select Agent Program. It is a federal crime to mishandle a Select Agent, so the incentive to avoid minimizing that risk is staying out of prison. Memoli’s apparent lack of familiarity with standard biosafety practices and federal laws governing the use of the dangerous viruses that he studies makes me wonder if he has any incentives to falsely minimize the risks of an accident in his own lab.
“These scientists make a living doing research for the traditional pandemic preparedness playbook—an extreme conflict of interest.”
Faust: This takes a grim view of the scientific community, and one that is simply not accurate. If you believe this, you’d also believe that cancer researchers are intentionally sandbagging it, so that they don’t put themselves out of business. I remember a research group at my medical school that decided to change what it studied *because* HIV medications had gotten so good, that the problem they were studying was no longer major threat. They didn’t pretend that it was still a threat. Instead, they moved on to more interesting new questions. That’s how it works. The authors act as though research scientists are out there doing work they don’t believe in, just to stay in business--including academic ones. (The profit motive in some industry research can indeed sully things, but that’s not what’s under attack here.) In my experience, that pessimism is not warranted.
Rasmussen: Expertise is not a conflict of interest. I have spent two decades studying viruses and I know a lot about them, including about how they emerge and cause disease and how we can counter them. I also know that there’s still a lot we don’t know about viruses, and that filling these knowledge gaps is critical to reducing the risk they pose to our health and well-being. Viruses are also completely interesting and full of scientific surprises. I love being a virologist. But just because I have developed virology expertise over the years and I like my job, it doesn’t mean I will approach serious topics in pandemic preparedness with an insurmountable bias toward an NIH gravy train of unfettered reckless dGOF. Virologists are professional scientists and we get paid to do virology work. This is normal and it’s called “a job.” It is not accurate to imply that our expertise in our own scientific field can’t be trusted because we get a salary to do it in the course of being employed.
Memoli and Bhattacharya imply that “traditional” pandemic playbook scientists are personally incentivized by the financial allure of an R01 grant. It is illegal and impossible to just take money from an NIH grant for yourself because of the way federal grant money is administered. Grants are awarded to institutions, not individual people. When I get a grant, it goes to my university, who administers the funds for my research. I am the Principal Investigator (PI) of the grant, which means I’m responsible for doing the research and reporting the results. NIH grant funds are used to pay salaries, sometimes including the PI’s. However, the PI works for the institution, which provides their paycheck. The institution is legally obligated to ensure that grant funds go toward doing the research: paying people to do it, paying for supplies and services required to do the research, and paying to keep the lights on and manage the facilities where the work is being carried out. A PI cannot just tap their NIH grant to access funds for any purpose and there’s a lot of disincentive to doing so since it’s illegal.
Prior to becoming NIH Director, Bhattacharya served as the PI on NIH grants, so he is well aware of how grant funds are administered. I would love to ask Bhattacharya if he was ever so motivated by his Stanford health economist paycheck that he wrote grants proposing that he do more health economics research. Not because there’s anything wrong with that since it was his job, but I’m curious whether he thinks that’s a conflict of interest.
“The playbook also creates an industry of vaccine and drug manufacturers to whom the government awards vast sums of money to produce the pharmaceutical stockpile that, by design, has never been tested in human populations.”
Faust: I think the pharmaceutical industry needs reform. But the fact that Moderna made money off of their life-saving Covid-19 vaccine doesn’t bother me. It was a win-win for the American enterprise.
Rasmussen: The government does not manufacture vaccines or drugs at all. If the government buys vaccines and drugs from manufacturers, they have to pay for them. Vaccines and drugs are essential for public health at national scale, so the government contracts with vaccine and drug manufacturers to acquire them. The “playbook” didn’t create the pharmaceutical industry or invent government contracts. And I call bullshit to the claim that “vast sums of money” have gone to produce a vaguely sinister-sounding stockpile of mystery junk countermeasures that have never been tested in people “by design.” This is only plausible in a parallel universe where regulatory standards, bioethics, and competence don’t exist. In reality, all drugs and vaccines are regulated by the FDA, including the ones in the stockpile. The FDA requires clinical trials for licensing vaccines and drugs. There are no massive stockpiles of useless vaccines and drugs that are untested in human populations. This is also an anti-vax dog whistle. The anti-vax movement loves to talk about supposedly untested or experimental vaccines. This conspiratorial “never been tested in human populations” line is a friendly MAHA hat tip.
“What, then, can be done in the face of the reality that another pandemic will eventually arise? We must stop wasting money on the traditional playbook.”
Rasmussen: Once again, Bhattacharya and Memoli are not accurately describing “the traditional playbook.” They are singling out one type of virology research and misrepresenting it as “the traditional playbook” in order to attack it with unsupported allegations. The fundamental premise of this article is dishonest and wrong.
“We do not need to find and create new pathogens that could cause future outbreaks.”
Faust: I’ll defer to Dr. Rasmussen on this, but it seems to me that our extraordinary progress in the biological sciences now equips us with the ability to safely study potential pathogens so that, if and when they occur, we have a head start that could save millions of lives *and* avoid the need for lengthy pandemic mitigation responses like we saw during Covid.
Rasmussen: If we want to better understand emerging zoonotic threats, we do need to continue doing virus discovery work, genomic surveillance, and experimental virology research. We also should continue to develop new antiviral drugs and vaccines. This work is scientifically beneficial across multiple fields. We can’t prevent pathogens from emerging if we don’t know anything about them. We can safely study these pathogens and we should, because I believe that we should do as much as we can to prevent and prepare for pandemics.
Bhattacharya and Memoli are arguing that the best approach to pandemic prevention is to do nothing besides pretend that the only pandemic risks are made in a lab. The risk of a naturally emergent pandemic is much, much higher. There are millions of novel viruses circulating in wildlife. Some of those could cause a pandemic as they evolve naturally with different hosts and there are new opportunities for cross-species transmission. The animal-human interface is growing. Opportunities for zoonotic transmission are increasing. Spillovers occur with increasing frequency. The many viruses continue to evolve and Mother Nature is the world’s most unregulated dGOF virologist. Bhattacharya and Memoli argue their playbook should address this risk by pretending it doesn’t exist. It is a short-sighted and dangerous proposal, given the current level of pandemic risk.
“Rather, we must improve our understanding of the pathogens that we know cause disease in humans now, without speculating about hypothetical risks.”
Faust: This is an oxymoron. Are they saying we should study H5N1 or Covid-19 in the lab, or not? The very presence of those pathogens in the lab could lead to spontaneous mutations that cause the next pandemic, the same as pathogens we understand far less well. So, should scientists study flu and Covid, or not?
Rasmussen: This is bullshit, considering Bhattacharya and Memoli have cut millions of dollars in funding for research on pathogens that we know cause disease in humans now. They are not committed to funding any pathogen research, except perhaps Memoli’s. It’s also pretty rich for them to fret over “speculating about hypothetical risks,” since the entire evidence base supporting this execrable piece is composed of speculative biosafety fantasies about hypothetical lab leaks.
“We should develop better prevention and treatment strategies for these existing pathogens.”
Faust: Finally, we all agree on something. I’m open to exploring this, but the best experts in this arena are, to the best of my knowledge, not being engaged or consulted by the new NIH.
Rasmussen: I had a brief moment of joy here, in which I thought I might find a sentence I didn’t object to. Alas. I do agree that we should develop better prevention and treatment strategies for pathogens that are current public health threats, but what will those prevention and treatment strategies be? Are we talking about new antibiotics and vaccines or are we talking about cod liver oil for measles? I fear it’s the latter.
“We should learn from recent example: a metabolically healthy population, physically active and eating nutritious food, will cope far better in the face of a novel pathogen than a population facing a severe chronic-disease crisis.”
Faust: A healthy population would indeed make the next pandemic less deadly. But it is not either-or!
Rasmussen: Yes, it’s good to be healthy. But viruses kill fit people with healthy diets, because all the nutritious food in the world won’t repel a virus from infecting a susceptible host. “Metabolically healthy” is also a weasel word that invokes the functional medicine wing of the MAHA movement led by Casey and Calley Means. They are always talking about ways to fix your broken metabolism, usually by buying wearables and other products and devices from their companies.
“Sweden, without lockdown or school closures, was the best in the world at protecting human life during the Covid pandemic. It had the lowest level of age-adjusted, all-cause excess deaths in the world between March 2020 and December 2024.”
Faust: This is unsupported. I don’t know where they are getting this claim from. There’s a paper by John Ioannidis that stratified excess death by age up through the end of 2023 (in which Sweden’s excess mortality looks to be good), but there are two problems with it that I’ll go into a bit here, but elsewhere in more detail in the future. First, the Ioannidis and colleagues seem to believe there was not excess mortality in Sweden during that period. But I just looked and it’s actually quite wrong. I wish I’d looked at this paper before because its methods are disqualifyingly incorrect. The main reason for the inaccurate conclusion that Sweden did not have ANY excess mortality is that they determined the number of deaths that “should” have occurred by taking the average of 2017-2019. The problem is that for many groups in Sweden, the death rate was on a long downward trend. If you don’t take that into account, you’re guaranteed to make the mistake of under-estimating excess mortality. I graphed this for all the age groups just now, and it’s perfectly obvious that there was in fact excess mortality in Sweden. (It’s amazing that this paper made it past peer review; it took me 10 minutes of looking at the raw data to debunk its central claim.)
“Sweden succeeded in part because its people are relatively metabolically healthy.”
Faust: Also, they stayed home during the pre-vaccine era. I graphed that (Google Mobility trends) just now and the Swedish people’s behavior in 2020 was perfectly rational. That is, they stayed home and did not gather in crowded settings. The idea that Sweden didn’t “do lockdowns” is often put forth as evidence that social distancing was not necessary. But the Swedish people were smart enough to alter their behaviors without official government-advised shutdowns. Also, Sweden has universal healthcare and mandatory sick leave. So, maybe we could try that too?
Rasmussen: How do they define “metabolically healthy”? This probably actually means “less obese.” While it’s true that obesity increases risk for severe COVID, so do many other conditions that have nothing to do with metabolism. I am not aware of any study showing that Sweden’s “success” (not actually so successful, as Dr. Faust points out) was related to “metabolic health.”
“By contrast, the U.S. chronic-disease crisis all but guaranteed that Americans would have one of the highest mortality rates in the world.”
Faust: I’ve written that one of the best ways to prepare for the next pandemic is to have a healthier population. So, yes, this is true. But, this is being used as an excuse to not do all the scientific research possible that could give us vaccines, therapeutics, and pursue other tools that could help us achieve the best possible outcome. As they say: ¿Por qué no los dos?
Rasmussen: Is there lots of chronic disease in the US? Yes. Should we do something to reduce that? Also yes. However, is it a “crisis”? Did we just learn about it and things are at a breaking point and action must occur now? Not really. Many chronic diseases were being studied. NIH-funded research has led to huge advances for a ton of chronic diseases: diabetes, cancer, HIV, obesity, neurodegenerative diseases, heart disease, autoimmune diseases, the list goes on and on. Chronic diseases remain a huge public health challenge, but progress was being made before the administration took a chainsaw to NIH’s research portfolio. Memoli and Bhattacharya didn’t hesitate to cut millions of dollars of research grants on these chronic diseases, though. You would think that if it’s truly a crisis, you’d want to sustain ongoing and demonstratively productive research efforts.
“Ultimately, public health agencies encouraging people to take whatever steps they can to improve their health will have a dramatic effect during the next pandemic. Whether simply by stopping smoking, controlling hypertension or diabetes, or getting up and walking more, anything that makes the population healthier will prepare us better for the next pandemic.”
Faust: All well and good. But, again, why are they using this to argue against everything else we can do to prevent a pandemic (or make it less painful if it happens)?
Rasmussen: If another pandemic occurs and the best advice America’s top health officials can give is “get up and walk more,” we are well and truly fucked.
Viruses are certainly capable of causing lethal disease in healthy hosts. You don’t prevent infections or contain outbreaks by taking hypertension medication and quitting smoking. You do it with vaccination (and antivirals). You cannot simply say “get healthier” and expect a future pandemic not to result in sky high mortality.
This is a morally depraved approach to pandemic preparedness. Memoli and Bhattacharya argue for aggressive inaction: stop pandemic research, stop studying countermeasures, stop manufacturing drugs and vaccines, stop doing anything that might be proven to work during pandemics. Instead, go for a walk. This is gross negligence. In a pandemic, people will die because of it.
“The best pandemic preparedness playbook for the United States is making America healthy again.”
Faust: I’ve noticed that a lot of HHS writing ends with obligatory RFK Jr. bootlicking like this. Also, this statement is false. The best playbook could include that sentiment, but also must do virtually everything Bhattacharya and Memoli have argued against.
Rasmussen: The MAHA pandemic preparedness playbook is making science more ignorant, public health more fractured, data more inaccessible, and Americans more vulnerable. It is also corrupting the entire American scientific and public health enterprise with outright lies about the health and security threats we face and the priorities of our government.
Congratulations, stalwart readers! You made it! If you’re here, you know how important this analysis and expertise is and that you won’t find elsewhere. If you value work of this nature, please support our newsletters. Thanks! —Dr. Jeremy Faust & Dr. Angela Rasmussen.
If you have information about any of the unfolding stories we are following, please email me or find me on Signal at InsideMedicine.88.
(City Journal is a publication of the Manhattan Institute, which many describe as conservative, although it describes itself as “free market think tank.)
 | A guest post by
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Hilariously, in my cross-post I called my co-author "Jeremy Fauci" & it's evidently not editable. 🤣 Welcome to the Fauci family, Jeremy!
My attention likely slipped while reflecting nostalgically on the glory days when the NIH had competent leadership that took pandemic preparedness seriously.
I spent decades doing infectious disease discovery; my work helped put five antiviral drugs on the market (for Hepatitis B, Hepatitis C, and HIV). I strongly opposed the nominations of RFK Jr and Dr. Bhattacharya for reasons the article being so thoroughly dissected here exemplifies.
To me the attacks on Infectious Disease Research feel like a desecration of what I hold most sacred: saving lives by learning the truth.