Journalist and writer Brendan Borrell’s new book, The First Shots: The Epic Rivalries and Heroic Science Behind the Race to the Coronavirus Vaccine, has not only received considerable praise but has already been optioned for an HBO series.
In today’s Hub Dialogue, editor-at-large Sean Speer speaks with him about the book, its inside look into the race for a COVID-19 vaccine, and the individuals and investments that made success possible.
This conversation has been revised and edited for length and clarity.
SEAN SPEER: Thanks for joining us, Brendan.
BRENDAN BORRELL: Thanks for having me.
SEAN SPEER: Your fascinating book tells the story of an intense several months to test, prove, and develop the coronavirus vaccine. But the underlying science started in universities and government laboratories years prior. Who are the unsung heroes of this early work and how did it contribute to eventual vaccines?
BRENDAN BORRELL: The story of these emerging infectious diseases is a market failure situation where the pharmaceutical world doesn’t pay that much attention to them. All the action is happening in these university laboratories.
The coronavirus had been of concern to several groups, because of the previous SARS outbreak in 2002-2003, and then the Middle East Respiratory Syndrome which broke out in 2012. One person who was watching these outbreaks was Barney Graham at the National Institute of Health. He grew up on a farm in rural Kansas where, he told me, he was always fixing things. That was the best training for becoming a scientist because of course in science you’re always fixing your broken equipment or making your experiment work. He was toiling away for a long time on these very obscure viruses, including the coronavirus, and came up with the strategy for developing a vaccine to one of the challenges.
The coronavirus has the telltale spike protein, which we’ve all heard so much about. One of the challenges to making a vaccine against it was that the spike changes shape, and if your body produces antibodies to the wrong shape, it’s not going to be as effective. Barney came up with a way to stabilize that protein. He and his collaborators found a way to basically create a mould that the body can develop a good neutralizing antibody response to. The fact that he had done this work before the coronavirus broke out in 2020 prepared us for that response.
The other key innovation that we know is important was of course mRNA, which has been decades in the works and the dream of several scientists, including Katalin Karikó, the Hungarian chemist and molecular biologist. She grew up in communist Hungary, in a house with not even a flush toilet—she had a pit toilet in her backyard. She has a similar story as Dr. Graham in terms of being drawn to science in these rather rural environments. It’s interesting because everybody in the vaccine world either comes from the military or comes from a rural background, where you’re used to working with animals, dirt, and everything. So Karikó grew up there and because materials were always in scarce supply under the communist regime, she had to make her own chemicals in a way that we can’t even imagine over here in the West.
She also became very good at making mRNA, which she dreamed of using as a medicine. The idea with an mRNA medicine is, rather than producing the medicine in a factory, you give your body just the instructions to make that drug or vaccine. But the problem is it’s a very fragile, short-lived molecule and very hard to work with. Kariko was good at making it at the chemical side of things, and she eventually figured out a way to create mRNA and also get it to go into people without them having too strong of a negative immune reaction. This technology was on the verge of maturing when the virus broke out. These two innovations were critical to our ability to develop a vaccine in record time.
SEAN SPEER: One of the key insights from your research and journalism is how the competition between Moderna and Pfizer to produce the vaccines on such an expedited timeframe played into the whole episode. Can you explain how the two companies pushed one another and how the role of competition contributed to producing this vaccine at such a breakneck pace?
BRENDAN BORRELL: As I mentioned, vaccines against emerging infectious diseases are typically a market failure situation. By the time there’s a new emerging outbreak and you’re able to test a vaccine, there’s no market to sell it to. Most of the big pharma companies sat on the sidelines in the early days of the pandemic in January and February 2020. You didn’t see Merck or Sanofi moving very fast.
Instead it was the upstarts like Moderna, this untested biotech company out of Boston, that was banking on mRNA technology and had been in operation for 10 years without a product on the market. They were the guys that were racing fast. They got their vaccine into people by March 16, 2020—the first coronavirus vaccine tested in humans.
I describe in the book that the day after the first volunteers were dosed with the vaccine, Pfizer issued a press release saying, “Hey, we’re also in the game. We’re going to be competing against this virus.” From that point on, we have these two contenders: One is this 800-pound gorilla, and one is a substantial biotech, but much smaller company, that had never taken a vaccine to the phase-three clinical trials.
What we saw here in the United States was that Pfizer ends up going it alone, sinking more than a billion dollars into its development and manufacturing of mRNA, whereas Moderna takes money from the U.S. government through Operation Warp Speed. One of the consequences of Moderna’s decision is that it was saddled with all of these government meddlers, telling it what to do and what it can do, making sure there were good reasons for its decisions throughout the process.
As an example, the government was not only reviewing Moderna’s clinical trials but it also wanted to access to all of the data that the company was collecting to help us get a vaccine. Pfizer by contrast could go as fast as possible. So, as I describe in the book, Operation Warp Speed was great, but it slowed the company down a little bit
This was particularly important when it came to adding greater diversity in clinical trials. Moderna was facing this problem when it started enrolling volunteers. There is a problem here in the U.S. where many clinical trials underrepresent people from communities of colour. As you know, the coronavirus disproportionately affected communities of colour, at least here in the U.S., and people in the government who are watching this were saying, “We can’t have a vaccine that’s only been tested on white people. This is going to be terrible for vaccine uptake.”
Moderna couldn’t figure out how to get more people from these communities enrolled quickly. And they’re looking at Pfizer who was not stuck or held back in that way. Ultimately, the trial was slowed down, but it was to the great advantage of Moderna and the country that we had a really good clinical trial. So, I tell that story in the book because it’s an important episode.
SEAN SPEER: The U.S. government had a pandemic planning capacity in place prior to COVID-19. What, if anything, did it say about vaccines including their development and production? And why were these plans ultimately insufficient to meet the nature of this particular pandemic?
BRENDAN BORRELL: There’s definitely this challenge with a pandemic threat. It’s like all those asteroids coming close to Earth’s orbit. It would be really bad if one of them slammed into our planet and ended civilization, but it’s also a very low likelihood event. So, how much money should you be spending on this? I think it’s an easy thing to kick the can down the road on. You can have some bureaucrats and scientists writing up plans and saying, “This is what we need, this is how much money it’s going to cost.” But whether that money actually gets invested is a big issue.
A second thing is there were certainly a lot of failings with the coronavirus response in the U.S. But we must also remember that the science was also holding us back because it was a new infectious disease, and we didn’t have any drugs or vaccine for it—even if we luckily had some of the pre-existing work that we talked about. We may have had a blueprint for what to do but we still needed the science to catch up.
I talked about Barney Graham earlier. He pointed out that there are 25 different families of viruses that are potentially threats to people. We have vaccines for 12 of those. His idea is that we should be preparing for the 13 other virus families that are potential threats, so that we kind of have something in the hopper, so to speak, and then you can pull it out and take it across the finish line relatively quickly. It’s not just a combination of being prepared. It’s a combination of getting the science up to speed.
We learned here there are these very old-fashioned measures that we can use to slow the spread of a respiratory virus. There’s masking and social distancing, and I think nobody anticipated quite how controversial that would become. This element of human behaviour is a tough thing to manage. I think going forward in future pandemics, it’s not just about what the government decides to do. It’s also about how society reacts to it.
Operation Warp Speed was created by people inside the administration who were not really fans of Trump.
SEAN SPEER: One thing I’ve always wondered is if the Trump administration’s lack of capacity and experience, which was obviously a major disadvantage on a number of files, may have counterintuitively been a bit of an advantage on Operation Warp Speed, on the grounds that a more experienced and technocratic administration may have been too consumed by convention and process to do something as novel and audacious as Operation Warp Speed. What do you think about that idea? And, more generally, how does the White House figure into the story that your book tells?
BRENDAN BORRELL: When Operation Warp Speed was announced in May 2020, we heard all of this pushback from the scientific peanut gallery, where people said, “There’s no way you’re going to get a vaccine across the finish line in 12 months. This is dangerous; you’re going to rush the process.” We even heard from insiders like Anthony Fauci who was working with Barney Graham on the vaccine that’s getting developed and knew how fast it’s already moving, and yet he was still saying it will take 18 months. He was talking about summer of 2021 when the Trump administration is saying “No, we’re going to have it by the end of the year.” So, I think there was, as you say, this question about what the insiders would do versus the outsiders.
Operation Warp Speed has been held up as part of Trump’s legacy. It was certainly one of the administration’s few successes during the coronavirus pandemic. But, in fact, Operation Warp Speed was created by people inside the administration who were not really fans of Trump.
I highlight Bob Kadlec, for instance, who’d been in the biosecurity industry and business, and was a former Air Force doctor for around 20 years. Trump wanted to fire him. He was disliked by many people and was reviled in the media, but he was actually a pretty savvy guy.
He was working with Peter Marks at the FDA who oversees the office of vaccines. They were having conversations about how to roll out a vaccine as fast as possible. There had been some steps that were taken to see what sort of additional testing you would do with animals to make make sure that the vaccine would be safe for people if you couldn’t run the face of clinical trials. And they talked about why there are delays in the vaccine process, including the so-called “dead spaces.” Remember we had never faced a crisis like this. So, we didn’t know how fast the FDA could move. But Peter Marks was saying, “Yes, we can do it.” Well, that really changed the equation.
So, I think to your point, there was an iconoclastic view within this small group of people. Maybe if all these naysayers were part of government then it wouldn’t have happened.
SEAN SPEER: I’ve heard Francis Collins, the outgoing head of the NIH, say that he somewhat regrets describing the process as Operation Warp Speed, on the grounds that it may have caused some people to think that corners were cut in the name of expediency but at the expense of safety. How much thinking went into trying to establish confidence in the minds of Americans? Or was the overriding priority of those involved in Operation Warp Speed getting a vaccine as quickly as possible?
BRENDAN BORRELL: I would disagree with Francis Collins about the name Operation Warp Speed being the problem. The fundamental problem was, as we went into the election season here, the administration led by the president was attacking the FDA and the companies. Not only were they promising this thing on an accelerated timeline, which was possible, but I think that a lot of the doubt came from the way it was managed and rolled out at the top. The name Warp Speed was a little bit cheesy, but if we didn’t have all of this rigmarole around the election, it probably wouldn’t have been as much of a problem.
I think there were people who really thought that the educational aspects of it were important. There were various programs to combat vaccine hesitancy, but the way that this vaccine hesitancy issue has evolved so much has been interesting. In the beginning, before the vaccine was rolled out, we were very concerned about members of the Black community that tended to have a level of distrust of the medical establishment for historic reasons. And then with the change of the administration here in the US, we’ve had this incredible refusal of the vaccine by people on the more conservative side, along with the rejection of vaccine mandates because of this very libertarian perspective. I think there’s also the thought that people have that, “Oh, I’m going to be okay. I’m young, do I really need to take this vaccine?” It’s an incredibly multi-dimensional issue. I think the name only plays a small part in it.
I actually liked the name, and I think it’s funny because, people think “Oh, of course, Donald Trump has named it with this goofy, overblown name,” but it actually was created by Peter Marks, this career bureaucrat and oncologist. He was a Star Trek fan when he was younger, and he thought it was cool. I mean, come on. I like that.
SEAN SPEER: I just have one final question, and I think you’re uniquely placed to answer it because you’ve written on other scientific topics in the past. To what extent, based on your deep dive into Operation Warp Speed in recent months, do you think we can draw some lessons from the experience that may have broader applicability to cultivating breakthrough technologies to address other challenges like climate change or reaching Mars or some other audacious goal that we have as a society?
BRENDAN BORRELL: It tells you that some of these mental blocks we have about timelines are sometimes wrong. You could ask: what’s it going to take to get the entire world to go electric? It seems impossible on the face of it, but once you have a concerted push and a willingness to invest money into it, it can get accomplished.
I just want to go back to Operation Warp Speed again, because when it was first proposed, the idea that the government would spend $20 to 30 billion on getting these vaccines was unprecedented. Even here in the U.S., to give a vaccine maker a billion dollars was unconventional. But the return on investment is in the trillions. The country was shut down, and people were afraid to work. It was just horrific. Who wouldn’t make that investment in those circumstances?
So, it’s funny to look at some of these other big problems we’re facing. I think economists have done the work on climate change, and other types of goals that we as society should be aiming for. And it’s always like, “Wow, that return on investment is pretty good. How do we motivate society to look at the financial picture of this?” So, I would say that Operation Warp Speed is an inspiration in that way. How are we going to get the globe to create an Operation Warp Speed for climate change? That’s a pretty big challenge.
SEAN SPEER: Well, maybe that’s your next book. This one is called The First Shots: The Epic Rivalries and Heroic Science Behind the Race to the Coronavirus Vaccine. Brendan, congratulations on producing a book with such depth on a warp speed-like trajectory. Thanks for taking the time to share your insights with us today.
BRENDAN BORRELL: Thanks so much for chatting with me.
