Uncontrolled Spread: Why COVID-19 Crushed Us and How We Can Defeat the Next Pandemic

by Scott Gottlieb

This is another reason why it was important to have FDA oversight for these tests.

Didn’t the FDA have oversight of the CDCs test that turned out to be an epic failure?

Flus are named for the properties of two key proteins that appear on their surfaces, hemagglutinin (H) and neuraminidase (N). The two numbers used to describe a strain of flu correspond to which variant of these two proteins a virus harbors. There are eighteen different subtypes of hemagglutinin and eleven different subtypes of neuraminidase. So, H5N1 is named for the fact that it combines the fifth subtype of hemagglutinin with the first subtype of neuraminidase.

Making a vaccine can be hard. The development work might take years. Part of the challenge is the way that flu vaccines are manufactured, using chicken eggs to culture the virus and grow the critical proteins that are used as the stock for the vaccines. Under this process, a fertilized chicken egg is inoculated with a strain of influenza. The virus is allowed to replicate in the yolk, before it’s harvested, inactivated, and incorporated into vaccines. In this way, the eggs serve as incubators for the development of the viral proteins that are used for the vaccine.

“Perfection is the enemy of the good when it comes to emergency management,” he said. “Speed trumps perfection, and the problem in society we have at the moment is everyone is afraid of making a mistake, everyone is afraid of the consequence of error. But the greatest error is not to move. The greatest error is to be paralyzed by the fear of failure.”21

The CDC’s revised guidance would later declare that most of the transmission was through respiratory spread. However, it would take the CDC almost a year to fully revisit the risk from fomites.

It was probably the single most costly intervention the CDC recommended that was consistently applied throughout the pandemic, causing schools and businesses to have to forgo a lot of activity to create that much distance between students and patrons.35 It was another reflection of how the CDC’s focus on flu as a model for COVID spread ended up being a costly misjudgment.

“The origin of the six-foot distancing recommendation is something of a mystery,” wrote the New York Times in March 2021, a year after the pandemic started. “When the virus first emerged, many experts believed that it was transmitted primarily through large respiratory droplets, which are relatively heavy. Old scientific studies, some dating back more than a century, suggested that these droplets tend not to travel more than three to six feet.”37 One senior HHS official told me that the six-foot recommendation was a compromise reached between the CDC and officials in the Office of Management and Budget (OMB). Initially, in February 2020, the CDC had recommended eight to ten feet of distance. However, the acting head of OMB, Russ Vought, said that such a requirement would be inoperable, hard to follow, and as a practical matter, couldn’t be uniformly implemented. So, the CDC compromised with the White House and settled on six feet.

If we had more insight into where and how the virus was spreading, we would have been able to reserve the most stringent measures, like stay-at-home orders, only for cities where the virus was already epidemic. We would have been able to adopt mitigation tools that had the best opportunity to interrupt spread based on how the virus was being transmitted. That’s what happened with some success in 1918. That’s what the 2005 pandemic plan had prepped for. It envisioned that mitigation would be directed to places where there was active spread, with the strictest measures reserved for cities where the virus was already out of control.

Such targeting would have spared areas of the nation that were not yet at significant risk, where containment, by testing and tracing sick people and then isolating infected patients, was still possible. That would have reduced the national burden we incurred. It also would have preserved more credibility for public health officials to adopt these measures in places where stronger action was needed later, when the virus finally became epidemic in the South and Midwest. In July and August, when a heat wave struck the Sunbelt and people were driven inside for air-conditioning, the crowding fueled a dense epidemic.41 However, at that point, people in states like Arizona, Florida, and Texas were psychologically done with “lockdowns,” having shut down during the spring, when the virus wasn’t yet spreading widely in those regions. They resented having to close their businesses in the spring when their cities didn’t yet face significant risk from the virus. So, when that risk finally arrived in the late summer, and the epidemic spread to Houston, Phoenix, and Miami, governors were hesitant to reimpose tough measures. There was no popular support for more shutdowns. The people said: We already did this; we’re not going to do it again.

The application of public health requires public trust. When the tactics to confront a threat don’t line up with people’s perception of the risks, that trust is eroded. That’s what happened with COVID. We had adopted a model for mitigating a pandemic that would involve a flu and failed to see how COVID would spread through features that had some critical differences from flu, and in turn frustrate some of the tactics we’d use.

even after we developed more reliable ways to track its transmission, we had the chance to fine-tune our tactics, and mostly didn’t.

By the end of January 2021, the CDC had recorded only 1,316 positive flu cases in its surveillance network, compared to 129,997 they had recorded over the same time frame in 2019.55 The mitigation we put into place was designed to deal with a pandemic flu, not COVID, and it worked much better against its intended viral target.

Studies show that people will generally follow public health directives for about two weeks, and then compliance will break down. Without better ways to focus our interventions on regions where there was the greatest spread, we eroded public trust and squandered the social and political capital needed to maintain consent.

As sociologist Dr. Zeynep Tufekci noted in The Atlantic, “None of this made any practical sense. What happened at minute 16? Was five feet okay? Faux precision isn’t more informative; it’s misleading.”

The White House wanted schools to be reopened in fall 2020. But political officials feared that more information about transmission in schools and the conditions that led to outbreaks could frighten additional schools into staying shut. So these same political officials stymied efforts at the CDC to put out more prescriptive guidance to schools outlining the steps that schools could take to reduce the likelihood of outbreaks.

learned at the FDA that people are often willing to confront risks that they can adequately measure for themselves, but balk when forced to embrace risks that seem open-ended, ambiguous, or hard to measure.

“This information can provide insights into how combinations of public health mandates—masks, social distancing and school closures, for instance—can keep the virus spread in check. But the government, inexplicably, is not sharing all of its data. Researchers have asked federal officials many times for the missing information but have been told it won’t be shared outside the government.”14

The challenges played out in how the CDC reported on COVID hospitalizations. It turned out that the CDC wasn’t actually providing data that was being reported to the agency on real hospitalizations, but was instead posting an estimate derived from a predictive model. In other words, the number of hospitalizations that the CDC was reporting each day weren’t people who were actually being admitted to the hospital but were hypothetical patients being modeled off a small sample that the CDC was collecting.

The shortcomings with the way the CDC would collect its data, and then use these samples to try to render a national estimate through modeling, showed itself in other settings, including how the agency reported data on seasonal flu, where the CDC also uses models to try to make estimates of the annual number of hospitalizations. This is why, when the CDC reports flu data each year, its estimates have such a wide range, why they have a big “confidence interval.” For example, in the 2018–19 flu season, the CDC estimated that there were 97,967 people between the ages of fifty and sixty-four who were hospitalized for flu.18 That number sounds fairly precise, right down to the last sixty-seven people. However, it turns out that the confidence interval for that data, the range of potential estimates, was actually between 69,808 and 167,123 hospitalizations. So that means it might have been 70,000 patients. Or 100,000. Or 150,000. Or perhaps 143,294.

However, the CDC didn’t have actual data on who was currently hospitalized for COVID, just estimates built off a model. They couldn’t tell HHS where real patients were, only hypothetical patients that were being extrapolated from an algorithm.

Under the new reporting system, 95 percent of US hospitals soon provided 100 percent of their daily hospital admission data. In an unfortunate twist, the CDC declined to work with the new data, worrying that since it wasn’t their data, they couldn’t assure its provenance and couldn’t fully trust its reliability. As one senior HHS official put it to me, the CDC “took their ball and went home.”

The CDC’s orientation was always that its information defined the policy, through its findings and recommendations, rather than feeding into the decisions that would need to be made by others. The CDC was the final word, so it didn’t need to tailor its data to feed into someone else’s analysis.

Worse still, in the absence of definitive evidence on what worked, it left a void where critics were able to put forward their own cherry-picked evidence, or try to discredit the value of certain mitigation steps that they rejected and there wasn’t enough definitive data to fully contest these intrigues.

In Italy, hospitals ended up being a major source of spread.

The South Koreans employed a workforce of hundreds of epidemiological intelligence officers to track down those who were infected and get them into isolation, or find those who might have been exposed to place them in quarantine while they waited out the incubation period. To support these efforts, South Korea records almost every credit card and bank transaction on government databases. Health agencies were able to legally access this information and combine it with closed-circuit television footage and data from mobile phones to track people’s movements.21 South Korea’s response relied on a high level of public trust and a willingness to yield elements of privacy that would have never flown in the US.22

In Washington, one lesson I had learned by watching others be subject to political forces, and by coming under such pressure myself, is that once you show you can be influenced or controlled, it invites more people to try to push you around. Bend your principles a little, and you get pressured later to bend them a lot.

The ability of a vaccine to stimulate the production of antibodies that are highly specific to a particular virus is one way vaccines protect against infection.5 Researchers measure the level of these neutralizing antibodies in determining whether a vaccine is triggering an adequate level of protection.6 But a good vaccine maximizes its ability to kindle all of our immune system’s machinery, not only stimulating the production of antibodies but also spurring the activity of T cells and B cells that have memory, and are able to churn out new antibodies and other mediators of our immune response after they come into contact with a virus months or years later.

In the early 1990s, as scientists were unraveling the genomes of different pathogens, they began to wonder if they could use this information to make vaccines directly from the sequence of a virus’s genomic material. What would happen if they produced pieces of a virus’s genetic material that coded for the production of its surface proteins and then injected these instruction sets directly into a person’s arm?

Moderna never had the actual coronavirus on its premises. It never needed a sample, just the computational sequence of the virus’s RNA. Once Moderna got the sequence, the entire process to construct a candidate vaccine took just two days.21 And in six weeks, Moderna went from having the sequence in their computers to beginning the manufacture of a vaccine to start human testing, in collaboration with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases and the team led by Dr. Barney Graham and Dr. Kizzmekia Corbett.

The first two constructs used a strand of mRNA that would code for the production of the entire spike protein, while the other two would use mRNA that coded for just a specific region on the spike, called the receptor-binding domain or RBD. It was believed that the RBD would make the most attractive target for human antibodies. It was the exact point on the spike where that protein latched onto the ACE2 receptors lining our tissues. There were a lot of these ACE2 receptors in our lower airways, explaining why COVID targeted its victims’ lungs. Antibodies that target the RBD interfere with the spike protein’s ability to bind to these receptors, effectively blocking its capacity to enter our cells, and neutralizing its ability to infect.29 Of all the different regions on the long spike protein, it was the receptor-binding domain where our most potent, neutralizing antibodies would attach. Measuring the sheer volume of antibodies that COVID patients produced against their SARS-CoV-2 infections after they recover, about 90 percent targeted the RBD. So, a lot of a vaccine’s effectiveness would be driven by its ability to induce antibodies to that very specific binding region on the virus’s surface. The idea of using mRNA had never before found its way into a commercially available vaccine.

The trial was blinded to the investigators and Pfizer. It’s standard practice in trials for patients to be randomly assigned to receive an experimental treatment or an alternative meant as an inert or predictable comparator (a placebo), to see if the novel agent is working, and for the investigators and the patients to be blind to who received what. Only the data safety monitoring board (DSMB) knew who was getting the vaccine and who was getting the placebo. A DSMB is an independent group of clinicians and scientists who monitor the safety of patients while a trial is ongoing. They also continuously evaluate how well an experimental drug or vaccine might be working. They can intervene to stop the trial early if they find that the product is especially effective and should be declared to work and be given to everyone, or if it’s judged to be ineffective and continued treatment with it is futile, or worse, it’s judged to be causing harm.32 The DSMB also reports the results when the trial reaches certain prespecified milestones.

Pfizer filed with the FDA on Friday, November 20, seeking authorization for emergency use of the vaccine.35 It was the first company to seek permission to offer a COVID vaccine to US patients. It was just 248 days since the company had first set out with BioNTech to develop the vaccine. No vaccine had ever been developed that fast. The process involved 150 different clinical trial sites, 43,661 patient volunteers, the work of thousands of Pfizer colleagues, and the hopes of a weary nation: it was one of the largest, fastest, and most important scientific endeavors of its kind in modern history.36

Pfizer initially committed $1 billion to the project, a sum that would soon double as the company ramped up manufacturing sites across the US and Europe and started to produce the vaccine. Much of that money would pay for facilities specially designed to manufacture the mRNA vaccines. The specially formulated mRNA used in the vaccine was produced by batteries of highly specialized mixing machines that Pfizer had custom-made for the purpose at a cost of $200 million each. I remember the board meeting when we voted to buy more of them. We initially purchased five of the batteries of machines in all, at a cost of $1 billion—before we even knew if the vaccine was going to work. We would end up purchasing many more. While other companies took grants from the federal government to offset the cost of development and to pay for the investments they would need to expand their manufacturing facilities, Pfizer made a decision to forgo federal money to support the venture. Pfizer agreed in advance to sell an initial allotment of 100 million doses of vaccine to the federal government at an agreed-upon price, but only if the vaccine was successful and won FDA authorization. The US government would pay Pfizer only if the vaccine worked, and only for the doses they were buying.37 Bourla wanted it that way. He was concerned that the strings attached with federal grant money could slow the process. He wanted his scientists unencumbered. He knew that speed to market would save lives.

when the CDC created the Epidemic Intelligence Service, the inclusion of the

once Russia had developed its own successful COVID vaccine, Sputnik V, its intelligence services mounted an elaborate campaign to undermine confidence in the COVID vaccine marketed by Pfizer.19 It was believed that Russia waged this derogatory operation as part of an effort to gain commercial advantage over Western vaccines as Russia tried to compete with US drug makers for the market primacy of its own vaccine, especially in middle-income nations where Russia was using its vaccine for diplomacy. At one point, a head of state from an Eastern European nation called Pfizer CEO Albert Bourla and implored Bourla to try and encourage the Biden administration to allow US COVID vaccines to be shipped to Eastern Europe because those nations were being flooded with Russian products. Bourla’s subsequent efforts helped instigate a broader action by the Biden administration to procure 500 million doses of Pfizer vaccine, at a not-for-profit price, and distribute it to low- and middle-income countries through COVAX. The actions of Russia, and the situation in Eastern Europe, had provided an added impetus to efforts by the US government to expand global distribution of the American products.

While the evidence for the benefits of border closures and travel controls was weak, so was proof for the counterargument.36 The case against travel restrictions is based on a small number of studies showing that closing borders will delay but not prevent spread and can do more harm than good by destabilizing regions where an outbreak is occurring, causing people to flee hot zones. However, there’s no firm data to support the notion that travel bans are bad. After they were used in COVID, there was a belief that they helped some and little convincing data to say they didn’t.

Magnifying these dangers, sometimes the highest-risk research gets exported to the countries with the weakest controls in place because those are the regions of the world where more dangerous experiments are still permitted.

During the Ebola epidemic in West Africa in 2014, the CDC signed a bilateral agreement with the government of Liberia to share information, but the CDC subsequently refused to give the data it gathered to the US Department of Defense, arguing that its agreement with Liberia prohibited the CDC from sharing the information with “third parties.” This was “unconscionable,” one former senior US government official involved in the Ebola response said to me. “They wouldn’t even share it across agencies of the U.S. government,” he said. The US military was already on the ground in Liberia, as part of a major mobilization to assist in the response to the Ebola outbreak, and the CDC wouldn’t share information that the Pentagon believed could help adjust and guide its response.

In 2007, the cost of sequencing a single human genome was about $10 million, according to the National Human Genome Research Institute; today it’s under $1,000, and most predict the cost will soon fall below $100.91

When it comes to new threats arising from nature, the pathogens that demand our greatest focus are respiratory RNA viruses. Not just influenza, not just coronaviruses, but the entire category of respiratory pathogens that derive their genetic instruction set from RNA. The fact that these viruses replicate through RNA means that the pathogens can undergo rapid mutation when they face selective pressure and can adapt to threaten us in unforeseen ways or evade our drugs and vaccines. Something that spreads through inhalation is also hard to isolate and contain.111

Friendly nations like Canada and Australia refused to ship to the US vaccine that had been purchased by our government and manufactured at our behest but made at facilities in those two nations. Only after Canada had satisfied the needs of its own citizens did it allow American products to flow to the US for American patients.20 With COVID, the same behaviors would reoccur. Italy exercised its export control regulations under European Union rules to block the shipment of 250,000 doses of the AstraZeneca vaccine that was bound for Australia, on the grounds that Australia had controlled its epidemic and was in less immediate need of the doses.21 It was the first time that these EU regulations had ever been invoked.22 A few weeks later, the EU implemented new emergency legislation that gave it broad powers to curb exports of COVID vaccines that were manufactured in facilities located in member nations. The rules hit Britain especially hard, since the country was far ahead of other European nations in vaccinating its population at the time and was dependent on shipments from other European countries to keep up its vaccination campaign.23 The European Union was putting its interests first. The same tenets influenced US policy. In May 2021, even as the US developed a surplus of COVID vaccine—stockpiling as many as 100 million vaccine doses by the beginning of the month—the Biden administration wouldn’t allow those doses to be shipped to Brazil, which was experiencing an uncontro...

“Life can only be understood backward; but it must be lived forwards,”