Follow the Science
We talk with Dr. Lindsey R. Baden ’87, principal investigator for NIH-Moderna’s COVID-19 vaccine trials, about the historic development of vaccines during this pandemic, the renaissance it’s spurred, the role of media messaging, our social contract, and the intersection of science, philosophy, and ethics.
Are there key moments from the past year that really stand out to you personally?
Several. A key one is being a front-line health care worker and caring for patients with SARS-CoV-2 very early in the US epidemic over a year ago in Boston—I was struck, standing outside a patient room talking with a nurse as we were getting dressed in our PPE to go into the patient’s room, at how unsettled we all were—not knowing how this virus was spread. How do we protect ourselves, our families, and other patients? Were we going to become ill? And struck by the loneliness of our patients as we went into the room in full PPE (and I was glad we had PPE). Society was shut down or shutting down and we (health care workers) were running into the rooms of the sickest, most contagious persons. The seriousness, complexity, and lack of knowledge about basic aspects of this virus and how we care for patients permeated all that we were doing. How little we had to offer our patients in terms of targeted therapy was so frustrating.
Can you talk about the value of published research for the science community?
As a New England Journal of Medicine (NEJM) editor, I’m always on the lookout for the next infectious diseases threat, globally. In the nearly twenty years that I’ve been doing this, we had SARS-1, MERS, H1N1, H5N1, H7N9, Ebola, Marburg, Zika, and now SARS-CoV-2—we’ve had a major outbreak of concern every two or so years somewhere in the world. Even today, there are probably twenty of these going on. Do we need to pay attention to all of them? Absolutely. Should we be stopping society in its tracks for each other of them? We’ll never get anything done. As an infectious diseases person, I try to think, how does a bug work? Which of these organisms should we worry about? And how do we, at the NEJM, help to properly identify real threats in a timely manner and then share them with the global community in a scientifically rigorous manner?
Back in December , a pneumonia of unclear etiology was described. Many of us in the infectious diseases community were asking, “What does this curious cluster of cases in Wuhan, China, mean?” Soon, a clinical syndrome was characterized, there appeared to be person-to-person transmission, and a potential pathogen was identified and published in the NEJM [at the end of January 2020]. Shortly thereafter, we published a cluster of cases in Germany suggesting that asymptomatic/presymptomatic transmission may occur—a worrisome finding if it were common. At the time there was much skepticism about this observation—especially given the implications. Debate about this issue has not helped us in the response. High-quality scientific information, whether we like the answer or not, should be the basis upon which we determine how best to respond to an emerging pathogen.
Despite the prolonged debate about whether asymptomatic transmission happens, how can you not take into consideration the observation that there is substantial transmission of SARSCoV-2 across broad geographically distributed communities? It is overwhelming. Another challenging aspect of SARS-CoV-2 has been the politicization of the response. Why is face mask use viewed as a political issue? It’s a health issue. A respiratory virus spreads like a respiratory virus. I think that what we’ve learned in this last year is that infusing politics into science doesn’t serve us well as a community. It has been to all of our detriment. Politics and science have to work together, they have to inform each other, they have to be respectful of each other. But science should be science. Facts are facts. We need to decipher what the facts are and then respond to them with respect. Gravity is not going away. No matter how much I might argue about it, every day I will be responsive to gravity.
As you and your colleagues examine different pathogens and try to determine which one might be the next big thing, what is the red flag, where you say, “Now, we know. We have to do something.”
I’m going to reframe your question. What I hope we’ve learned from the different pathogens that have led to large outbreaks over the last twenty years is that we are a global community. We are all connected. SARS-CoV-2 reminds us that what happens anywhere in the world can affect us everywhere in the world. And, to be responsive, we have to be connected with scientists everywhere to start contributing to the identification of a problem and a response. We need to do it proportionately and thoughtfully so that we illuminate facts as quickly as possible, and then we need to decide what those facts mean.
It’s very hard to say what is the line that a pathogen can cross to create global concern. Zika, being mosquito-borne and teratogenic, creates a different set of issues than SARSCoV-2, which is a respiratory virus that is mild in most cases but severe in some. Ebola has a different set of parameters, being spread by physical contact and having a high associated lethality. There isn’t one red flag. One needs to look at the different features of each potential pathogen and ask, “At what point does the constellation of features raise enough concern that we as a community need to respond?”
What I hope can happen from the current pandemic and the toughness, the sadness it’s caused for all of us, is for us to realize that we’re really in this together. When I say that, I mean globally. A new flu virus that emerges in country X affects all of us. A new coronavirus that arises in country Y affects all of us. We have to understand that and then position ourselves as a global community to be rapidly responsive. That’s one of the things that happened with SARS-CoV-2 in the last year—we’ve never responded as quickly as we did with any other pathogen, particularly with multiple vaccines that are highly efficacious being developed in under a year, but many would say we didn’t respond fast enough. I think there’s truth on all sides.
I hope that we as a community can look at it and say, “How do we do it better?” There are things that were clearly done wrong but, for the most part, a lot of things were done with good intentions, with the best of knowledge. We have to say, “Let’s learn from this so we can be more effective going forward.” I hope we can be more effective—not in the phase of the next pandemic but during the inter-pandemic period—and we as a community take the time and effort to ask, “What infrastructure, what structures do we need to put into place to be more responsive?”—from regulations, to countries talking to each other, to surveillance, to the science of identifying the problem, to the development of countermeasures. All of that has many different elements that need to be thought through, that can be thought through during the inter-pandemic period.
Regarding response time, these vaccines were developed quickly relative to the usual development for a vaccine. What is it about this situation and the science that made that different?
One, is the enormity of the tsunami. In early 2020, we were able to see the rapidity of spread and illness in other parts of the world. For example, the speed and severity of illness in Italy and then New York City in February 2020. In Boston, we were just watching the two-week delay as the virus spread up the East Coast. We had colleagues in Italy saying that patients were dying in the hallways because they didn’t have enough ventilators. As the weeks went by, it was sad confirmation in different cities as this virus rapidly spread. People realized that this was a big deal because it affected them directly. That was the galvanization of the societal response, that this really required immediate and large-scale action.
Another element that accelerated the response was the previous scientific work that had been done on the basic biology, structure, function, and vaccine development for other respiratory pathogens. Thus, once the genetic sequence of SARS-CoV-2 was known, it could be placed in context with what was known about other coronaviruses. That meant we could jump right into developing a vaccine, because the inferred biology, which of course was being confirmed at the same time, saved us months.
A large group of us, through collaborative mechanisms largely supported by NIAID [National Institute of Allergy and Infectious Diseases], have been working together. We were able to immediately pivot our collaborative clinical studies’ scientific infrastructure to mean we’d be able to do the clinical studies. There was a confluence of resources that was prepositioned scientifically that could respond immediately and didn’t require us to build a car from scratch, where we first have to spec out how to design the manufacturing plant.
Part of moving quickly was also ensuring that the efficacy trial (phase three) was inclusive of all at risk for infection. This is important not only for equity but also efficacy considerations. For this vaccine to be accepted, the person making the decision to get it or not is going to say, “Did you study me? Did you study my community?” If we didn’t study your community, then you are in a position to say, “How do I know if it works in my community?” Whether it’s a genetic background or social, socioeconomic, racial, ethnic considerations—it was important the studies engage the broad diversity of communities across the US and elsewhere. That was critical, especially given the increasing vaccine hesitancy in some communities. More work needs to be done on these issues.
An issue we’re facing across the nation is the question, “It was done too fast. Can I trust it?” That is a complicated tension because, on the one hand, there are some who think it was done too slowly because we have had more than 500,000 deaths, and climbing, in the US alone. [Ed: In the two-and-a-half months between this interview and press time, the US crossed the threshold of 600,000 deaths.] On the other hand, others are concerned that it was done too quickly. With the Pfizer and Moderna trials, we have had two independent phase-three, thirty- to forty-thousand-person studies, with the same findings and similar-based scientific technology. The efficacy looks uniform across all the different populations in these two trials. This reassures us that the key findings on efficacy are correct. We had all of the full processes of phase one, phase two, phase three, protocol safety review team, Data Safety Monitoring Board that was independent and paneled by the NIH, the FDA review, the CDC review, peer review publication, and scientific community discussion.
I’m harping on this because I do worry that across the nation there are those who are still asking, “Can I trust this?” That question has to be offset by the fact that we have thousands of deaths each day from wild-type SARS-CoV-2 infection and we don’t see a safety signal among hundreds of millions of individuals dosed with the mRNA vaccines to date with all of the different monitoring processes in place.
How can we improve communication from scientists to the public?
We all need to communicate what has occurred and not in a propaganda way. There needs to be appropriate challenging and probing. Absolutely. And independent review and analysis. But, it needs to be from a scientifically based format, not a sensationalist-based format. That’s why I strongly welcome external review. That’s why saying the independence of the NIH Data Safety Monitoring Board, the independence of the FDA, the independence of the CDC, the independence of the peer review community [is important].
I think the media is very important in this arena to take hard looks at what has been done and then to ask, “Are you convinced or not? What’s the right way to have a responsible discussion?” Realizing, that if there is non-uptake of the vaccine, we should not be surprised that there is wild-type infection. This is not a stubbed toe. This is where a couple of percent of the people infected, which all 330 million of us in the US—I prefer to look at it as seven-and-a-half billion, world-wide—are at risk. So, a 1-2 percent severe illness; you do the math. That’s millions. Because we’re all susceptible.
A novel pathogen means all of us are at risk and all of us can be bioreactors who can amplify and spread it to others, particularly the most vulnerable among us, such as older individuals and those with weakened immune systems. I do think the media has a responsibility to affirm the veracity of findings, but the media also has a responsibility to not be sensationalistic when that can mislead the community in understanding the health concern. If they are, the consequences of that should not be a surprise, which is swaths of people who refuse to be vaccinated. Those communities will then suffer when the virus finds them and spreads.
The incentives for the media are in the short-term gain of a headline tonight versus the question, “What’s the right way to frame something so that we do the appropriate checks and balances and keep the health of the public in mind?” There’s some philosophy in there, but I think there is a lot to be gained by checks and balances. I hope that the goal of it is to help the community health and the community growth rather than a headline tonight, which sometimes gets a little warped in some of the media discussions about this.
Can you talk a little more about the intersection of philosophy, morality, and science?
It’s been front and center this past year; we’ve had to make lots of very difficult choices in our COVID response and our COVID management. We had to come up with plans for when our hospitals get overrun and we don’t have enough ventilators. Who gets the ventilator? Massachusetts came up with a plan for that because we expected to run out of ventilators, as New York did. And we witnessed this with the news stories about what was going on in New York with the freezer trucks as makeshift morgues. It’s been a very complicated year in terms of how to respond and how to respond as new information emerges. As I get new information and use the new information to inform action, it doesn’t mean I was an idiot yesterday. It means I used the best information yesterday—and, today, when there’s better information, I use the better information to inform what to do. In a pandemic, where we are learning as we go, it is important to continually recalibrate the response based on the latest, best observations.
What did we do with testing a year ago? Testing was based upon, “Did you travel to place x or y?” That made no sense to me. It’s a respiratory virus. Once it gets here then it doesn’t matter if you traveled to China or Iran. Once it is here then the question is, “Were you around somebody who is spreading it?” But, that was because we had limited testing. Because we had limited testing, we had to prioritize how we did testing, which had more to do with whether someone sick in the ICU had [the virus] or not and less to do with understanding community transmission and how to respond to that.
I think the challenge in front of us is the issue of how we have trust in the community so that the control measures are understood, respected, and applied. Physical distances, hand washing, mask wearing, testing, isolation and quarantine, and vaccines. And that the larger community understands how these fit in and uses them to their full potential to stop transmission. I think vaccines are phenomenally effective. The FDA said 50 percent effective would have been good. We set the bar at 60 percent with the pivotal phase three study, and it came out at 95 percent. That’s just phenomenal efficacy.
How long is the immunity to SARS-CoV-2? If you get wild-type infection, how long are you immune to it? We’ve only been studying SARS-CoV-2 for eighteen months. How can one comment on anything longer than what we’ve actually had on the planet? And then for the vaccine studies, they really had heavy enrollment in August and September, so the follow-up of six-month immunity will come out soon. One-year immunity has to wait until this fall. That doesn’t mean vaccination doesn’t have one-year immunity. It means we can’t measure it until we get there temporally. What we have to realize as a community and ask ourselves is, “Would we rather wait until we have all of the information perfectly? Wait until we have five-year follow-up, five-year durability, five-year everything?” Then nobody gets the vaccine until 2025, 2026. Yet, if we deploy now, as we are doing, then as new data emerge, we need to incorporate this knowledge as we go. It makes sense scientifically, but it is very difficult from a consumer perspective.
That is where the media and science and communication have to work well together to say, “The data we have today are the best we can have given the temporal parameters we face. There are no markers of concern, but there is no way we can say what happens at a year until we get to a year.” How do you communicate that to the public without the public saying, “Should I trust it?” How do we communicate that transparently so people understand the strengths and the weaknesses of the available data and can make informed decisions?
A tricky part to this discussion is that if I make a bad decision—meaning I don’t get vaccinated or I don’t wear a mask—it can lead to me getting infected, and then I spread it in my community, and the eighty-year-olds then die. Do I have a responsibility or not? That is a complicated issue because of individual rights, freedoms, and consequences of restrictions. With a highly communicable infectious disease, I am infecting my community—my parents, my grandparents, my friends, people who worship with me, colleagues, my college friends. I feel strongly that we do have a social contract and we should think about, “Am I getting vaccinated for me or for you? Or is there a little bit of both?” Now that biomedical science has advanced so much, we have a lot of individuals who develop cancer get treated, beat it, or live with it for a long time. We have patients who get solid organ transplants or bone marrow transplants. We have patients who are on chronic immunosuppression for neurologic disease, inflammatory bowel disease, rheumatologic disease. The number of people around us who need immunosuppressant medication for one reason or another is quite large. It means that their immune system is a little sluggish, and therefore a little more vulnerable. I’m a believer in that social contract. I’m a believer in science. The issue, for those who are not vaccinated, is that they put the rest of us at risk. How do we think about that in terms of caring for each other?
It’s going to be a little strong: I think it's irresponsible of me to go to a public gathering, spreading virus, when some of those people in that public gathering may be very vulnerable because they're seventy years old or they're on an immune modulator for an underlying illness or they're a cancer survivor or cancer fighter. If they get these pathogens, they’d do much worse than I do. I worry that misinformation and disinformation has emerged as a substantial problem in this pandemic. A real challenge with vaccines is that those of us who did not get infected will not know that this bad thing did not happen to them. Thus, it is difficult to appreciate on an individual level the illness avoided.
The flip side of is not to accept what I say unquestioningly. We need to challenge each other. But I do hope that we will agree that the sun rises in the east and that there’s gravity and that the world is round. If we do not agree on those three things, it’s going to be very hard for you and I to discuss what time we should have a phone call. We may argue about if you like daylight savings or not. We may argue about whether it’s better to talk at 8:00 p.m. or 8:00 a.m. or Eastern time or Pacific time. That, to me, is all fair game. What I hope we agree with is the sun rises in the east and that we’ll pick a time in relation to how our lives are organized.
It’s very destructive to let nonfact-based information guide discussion. We can’t come to a common approach because we’re not dealing with facts. What it doesn’t mean, though, is that we have all the answers. The risks and benefits need to be carefully weighed as facts emerge to guide our discussion. I'm sure there are one in a million, one in 10 million, one in a hundred million safety issues that may or may not be real that have to be sussed out. There are side effects of the vaccines that we absolutely have to respect, we have to monitor for, we have to be responsive to. But, I look at that in reflection to one in a hundred, one in a thousand deaths from getting infected, and looking at the rate of spread just across this country, let alone globally.
It gets [back] to the issue about the responsibility of the media and how we communicate. I think that is very tricky. Because I’m all for freedom of speech, different ideas, and challenging each other. It just becomes very hard if I know the earth is round and you think it’s flat. I don’t know how we’d talk about air travel. It becomes a natural consequence that it cannot be a logical discussion if we don't agree that the virus replicates and spread person to person and that if I don’t spread it to you, that you are less likely to get it from me.
But, we also have to be respectful of the biology. This virus is not sitting on the sidelines doing nothing. This virus is saying, “My job is to replicate. My job is to replicate more efficiently.” The more people it’s replicating in, the better it human-adapts to be more efficient at transmitting. I’m sure you’re familiar with antibiotic resistance. If we use antibiotics, the bugs get resistant. Think of the immune system the same way. If we all develop the same immune response against the same part of the virus, might the virus eventually say, “How do I dodge that immune response?” So that the issue of the viral evolution to become resistant and to escape from immunologic selective pressure is something else.
The virus is evolving but we’re able to make new vaccines. The vaccines are not hard to adapt to the new viral strains and the immune system has partial coverage to the new viral strain. It really is an immunologic dance between the immune system and the virus, to figure out how to coexist. The virus doesn’t want to kill us. If the virus kills me, it doesn’t replicate. The virus’ interest is to get me sick but not very sick. Very mildly sick, like the common cold. What did we do about the common cold three years ago? There are a bunch of coronaviruses that circulate among us, that have been circulating among us for decades—who cared about them? I had a cold for two days. That’s the goal of the virus. The goal of the virus isn’t to put me in intensive care. If I could use the goal of the virus as it wants to replicate and make more virus, because otherwise it extinguishes and then it goes away.
What we’re watching is an evolutionary dance between this new virus that has jumped species into a new host that the virus is figuring out how to adapt to replicate in us. Those of us who are vulnerable to it are getting sick and dying. Those of us who can tolerate it then develop an immune response. Then the virus is figuring out how to mutate so that it can continue to circulate usually in a more attenuated way, a less severe illness. We’re just witnessing that.
The problem that we have is if it’s a couple of percent of us who get really sick and die, then that's millions of people because we’re all naïve. It’s that newness of the virus to the population that makes it so dangerous. We have 50,000 deaths a year in the US from influenza, year in and year out for many years. I would argue, that’s a tragedy that should require the same response.
One shot is nothing compared to the amount of illness that these pathogens cause routinely. That’s why I love vaccines. It’s not a pill a day for the rest of your life, which means you have to have a supply chain and the resources for that supply chain. With vaccines, we eradicated smallpox, a disease that was truly devastating globally. We eradicated from everybody on the planet to nobody is suffering from it. I just think it’s way cool as an equalizer and a benefit for everybody.
Where are we with the study of the long-term effects of COVID-19?
I think that long COVID or PASC, post-acute sequelae COVID—different names for the same thing—is a really important issue. But we can only understand it when we follow it through time carefully. And then also make the proper attributions. One of my concerns is that if we don’t get the syndrome right—and I don’t think it’s one syndrome—it’s going to be very hard to get at the biology and then to improve it. Because some people may have a heart issue, some people may have a lung issue, some people may have fatigue.
For instance, let’s say I had COVID last September and I feel something today. How do I know it was related? Is COVID the only thing that happened to me in the last six months? What we need to do is very careful science to figure out what is background from other things in life to what is associated with this virus. And then the heart or lung syndromes may be different and therefore we may require different techniques to differentiate the pathogenesis of one organ getting injured versus another and how that is influenced by other factors in the individuals. A twenty-year-old who develops a heart issue may be different than an eight-year-old who had a heart issue who then gets COVID and has a worse heart issue. That must be differentiated.
Do vaccines and vaccine-induced immunity prevent COVID? Or if you had COVID, do they then ameliorate the consequences of COVID, like long COVID? These are important questions under active study. I don't think we’re at a position where we’re able to answer them yet because, again, it’s the time issue. How much time have we had with how many cases of each of these well characterized to be able to properly define? It’s a very active issue, but it means you have to go long enough to understand long COVID and then apply the scientific strategies to dissect out the kinds of issues that I just raised so we get it right. I don’t think it’s a one-size-fits-all.
The whole anti-vaxxer issue is something I do spend a lot of time on because things can be misconstrued intentionally or unintentionally. I’m very respectful of the fact that there’s so much we don’t know. Just because we don’t know doesn’t mean the vaccine makes no sense. I very much don’t want to give fuel to that way of thinking. I want to give fuel to questions.
We all need to say, "Does this make sense to me?" Poke at it, think about it, look at the pros and cons, the uncertainty, what we know, what we don't know. I very much want everyone to have the information to make an informed, thoughtful choice.
What I don't want to have is a community dead set on not allowing anyone to get vaccinated, to find ways to misconstrue the information so that it just confuses people without actually having meaningful, thoughtful discussion. That is something I’ve been dealing a lot with to try to minimize.
Another piece here is that some communities, particularly our Black and Latinx populations, have been poorly treated over the years—either scientifically or with access to health care and countermeasures. So, there’s a certain amount of distrust. We’ve spent a lot of time trying to build trust in these communities—to participate in research, and also to participate in the benefits of research. That’s been an ongoing struggle, and I can understand why certain communities don’t trust the establishment. The obligation is on us to build that trust.
That’s why, in these kinds of things, I just want to make sure we don’t inadvertently play to the distrusters. We need to be transparent, we need to have good debate, but not give fuel to what I would call nonsense discussions from people who are not interested in having serious debate about the issues. There are a lot of issues we should be debating. I think that’s healthy. But again, it gets to the concept that if we don’t agree the world is round, I don’t know how we'd talk about air travel.
I remember the Sunday when we had our first DSMB [Data Safety Monitoring Review Board] meeting. That’s the group that oversees the safety of a study and reviews the data periodically to make sure we’re doing it correctly. The DSMB for the Operation Warp Speed vaccines, and all the major vaccines that are government funded, was empaneled by the NIH. The National Institute of Health had an overarching data safety monitoring board for the phase three trials. They are independent senior scientists who the data get presented to and they make sure it's being done safely and they then make judgements that are independent. We presented to them on Sunday, the 15th of November, on Zoom. We left and hours later they came back and said, “95 percent. The study needs to change because it worked.” I said, “Holy shit.” Because at that moment, we knew that we had something that worked at the 95-percent level. Again, science works. You have a process, the process is rigid. The process has scientific rules around it. You exceed the scientific rules. You now act on it. They could have said, “You’re in the gray zone. Do the study as designed.” It’s highly unusual at the first DSMB meeting to stop the study for efficacy. That was just way cool. It was one of those magic moments.
At that point, then, a real challenge, talking about philosophy and science. We have a thirty-thousand-person study. Fifteen thousand are getting the vaccine, fifteen thousand are getting placebo. These are people at high risk for COVID. Many of them are seniors, health care workers, or in communities of high transmission. What do you do with the placebo group?
By the time we got to the FDA presentation on Thursday, December 18, there was Thanksgiving, and we had Christmas and New Year’s coming. The VRBPAC [Vaccines and Related Biological Products Advisory Committee]—that's the FDA's independent advisory group—gave us thumbs up, that it should be approved. The following day, the FDA approves it. On Saturday, the CDC Advisory Committee reviews it and recommends it. Sunday, it gets shipped. Monday, the vaccine is being clinically deployed at health centers.
What do you do with the placebos in the vaccine study? We had thirty serious illnesses and a death in the placebo group, none in the vaccine group. What do we do with the placebo recipients? Talk about a very complicated discussion. Is that ethically appropriate, allowing the placebo group individuals to stay at risk? If we vaccinate the placebo recipients, then we no longer have a double-blind placebo-controlled study to continue that high-quality science to define the safety and efficacy that everybody wants.
The FDA was really struggling with this, and so was the scientific community. We know the vaccine works. Nobody was arguing over efficacy. We’re arguing over longer-term safety. But can you say to the placebo recipients, “You have a duty to get sick and get hospitalized with COVID so we can further demonstrate how well this works.” I couldn’t say that. I couldn’t.
There were also discussions about state rollouts, and we should follow the state rollout. The problem there was fifty states with fifty different chaotic rollout strategies. And the rollout strategies change every few weeks. We have the Institutional Review Board we have to answer to, the FDA. We can’t just do this study however I feel like. The study has a very, very rigid rule book called the protocol. I follow the protocol to the letter of the protocol. I don’t make it up. I can’t just say I feel like doing something different today. You have a protocol that’s scientifically carefully designed. And then you have ethics committees who make sure you follow the protocol you designed. If you thought it should be done differently, you should have designed it differently.
We wound up doing a crossover. We crossed over our volunteers to get vaccinated and crossed them over with those at highest risk first—an eighty-year-old before a forty-year-old. My argument, which we had vigorous discussion around—I had to testify before the FDA for this, and then with the scientific community debate—was if we did not crossover the volunteers... We proposed a scientifically better way to do it: a double-blind crossover that I helped design with some colleagues and we're in the process of publishing, where we could have kept everyone blinded and just revaccinated everyone. All the placebos get vaccine and all the vaccinees get a placebo. Therefore, we would continue to design and maximize the scientific value. But that takes two months to implement, and we had two days. We didn’t have time. Once the FDA approves it and it’s shipped to your hospital, either you get it or don’t. We didn’t have the luxury of two months for a scientific evolution because there are too many regulatory bodies that we had to interact with. We did the open label crossover because if we didn’t, in my view, and this eventually carried the day, was when people would just leave the study and get vaccinated clinically and not be part of the study. The majority of our volunteers were in the tier 1A, 1B risk groups, because those were the people who were in the study at highest risk for getting COVID and getting the complications of COVID.
If we didn’t keep them in the study, then they would get it clinically and they’d be upset with us and not want to come back. All you have to do is to put yourself in the position of the volunteers in the study saying, “What the hell are you guys doing? You said you cared about me, but you’re telling me I can’t get vaccinated when I have access to it? And you’ve already told me it’s 95 percent effective and it’s approved and my hospital is giving it out?” It was an incredibly interesting philosophical, scientific, ethical debate as to what is correct.
What I try to remind people is our phase three vaccine trials are not over. They showed efficacy, but we still have two years of follow up. There’s a lot more science to be learned, even though the product has been FDA approved or emergency-use authorized (EUA), and is being deployed broadly. We still have people in our vaccine studies who are six months ahead of the rest of us. Because I’m with you, I got vaccinated after it was approved and available in my hospital. The vanguard of individuals in the studies are going to give information six months before the rest of us. Does the immunity wane? Do we need to boost? Are there other aspects of the immuno response that we want to enhance or monitor?
My argument was, if we lose this vanguard of volunteers, we lose a whole chunk of science that we need. Let alone all of the goodwill that they brought to us by volunteering. Talk about heroism. For us not to take seriously the people in August of last year who said, “I’m willing to go first with this new stuff because given everything we know, it makes sense.” They are really heroes. We shouldn’t forget the sacrifices they made by allowing us to advance knowledge.
What does the successful generation of COVID-19 vaccines mean going forward?
Dr. Fauci said, “Follow the science.” Science works—if we bring rigor, if we bring the right approaches, built upon many different groups debating about how to do the best science. But if we follow the science, it works. On the one hand, the variants are scary. On the other hand, we have a road map. We made a vaccine in a year. We can order our primers. We already have the new vaccines designed and in testing. The manufacturing of the vaccines; we built the manufacturing plants. The ability to go to scale quickly with an altered vaccine is already well underway if we were to need them. Hopefully we won’t need them. But if we continue to do the science, we’ll determine if we do. And if we do, we already have them in advance development.
This experience in 2020 may change vaccinology going forward for many other pathogens for which we want vaccines. We now have a playbook on how to make vaccines rapidly that are highly potent as long as we understand the key biology of the virus. I think we are in a renaissance of changing how vaccinology and vaccine development occur, and hopefully can extend this to a lot more pathogens. If we can get the immune system to do its job through a vaccine versus through natural infection, avoiding the associated illness, isn’t that amazing? And it’s exportable to the whole world. You don’t have to be a rich person, or in a rich country. I just think it is so cool.
The fact that the scientific community was able to pivot and move quickly, with the same scientific principles that we’ve been working on for decades—using the latest technology, and again, at the speed that was proportionate to the problem—was, to me, a bright spot in this past year of darkness. And, it’s a bright spot now, as we sit here on the precipice of what we can and should do next.
What do you do to unwind, to relax?
This last year or fifteen months has been a marathon. It has been a global catastrophe. I’m married, I have two kids. I do have hobbies. I had lots of things I [used to] do for fun but I’ve been in the hospital every day for the last fifteen months, working on different aspects of this, because it is such a problem and there’s no time to spare. All you have to do is watch the numbers of new infections and deaths that we know about. If we’re able to shave off a day, a week, a month, that’s huge. Many in the scientific community have been working nonstop.
There’s a lot that we don’t know so we’re always, on the scientific side, poking each other to make sure we get it right. It's fun to think about, “Do we understand the problem well enough to do something about it?” That’s where there are communities on the science and clinical side where we've just spent a lot of time talking and interacting with each other. In that sense, there is fun in unraveling the science here and then translating that into meaningful action.
Lindsey R. Baden ’87 is director of the Center for Clinical Investigation at Brigham and Women’s Hospital, director of infectious diseases at Dana-Farber Cancer Institute, a deputy editor at the New England Journal of Medicine, chair of the antimicrobial Drug Advisory Committee for the US FDA, and an associate professor of medicine at Harvard Medical School.
This story first appeared in the Spring/Summer 2021 issue of Bowdoin Magazine. Manage your subscription and see other stories from the magazine on the Bowdoin Magazine website.