My guest on this week’s WhoWhatWhy podcast, award-winning Wall Street Journal reporter Gregory Zuckerman, calls the worldwide effort that produced the COVID-19 vaccines a science story for the ages.
In Zuckerman’s telling — A Shot To Save The World: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine — it took a unique collaboration of scientists, entrepreneurs, government officials, and market forces to bring the new vaccines to medical reality in time to save millions of lives.
Zuckerman shines a spotlight on the key figures in the story: scientists who were previously working on vaccines for cancer and AIDS, but who, with the aid of venture capital dollars, bet the ranch on mRNA (messenger RNA) technology.
One revelation that may surprise some readers (if not others): The business of creating and distributing vaccines has long been neglected by many pharmaceutical companies because it promised, at best, low profit margins.
Countering the claim that the vaccines were developed “too fast,” Zuckerman details the ground-breaking biotechnological work behind the mRNA vaccines that began as far back as the late 1980s.
While there is much to deplore in the global response to the pandemic, the race to develop safe, effective protection against the novel coronavirus, as told by Zuckerman, shows how a bracing mix of cooperation and competition can sometimes produce heartening results in record time.
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Jeff Schechtman: Welcome to the WhoWhatWhy Podcast. I’m your host, Jeff Schechtman. Amidst all the noise and debate about vaccine mandates, less than clear information from the CDC, and the broader context of healthcare and society, it’s easy to forget that these vaccines themselves are truly miracles of modern science and that the herculean effort to develop them in record time is a science story for the ages. But the story doesn’t exist without understanding the players: the global panoply of scientists, entrepreneurs, and government officials, and market forces that all came together in a war effort that saved millions of lives.
After all, imagine the debate we’d be having today, and what our society would look like if no vaccine had happened. We’re going to talk about that effort to create the vaccine today with my guest, Gregory Zuckerman. Greg Zuckerman is a special writer at The Wall Street Journal, where he writes about business, economics, and interesting topics. He’s a three-time winner of the Gerald Loeb Award, and regularly appears on numerous media outlets. It is my pleasure to welcome Greg Zuckerman here to talk about his new work, A Shot to Save the World: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine. Greg Zuckerman, thanks so much for joining us here on the WhoWhatWhy podcast.
Gregory Zuckerman: Great to be here, and thank you for pronouncing my last name accurately. Nine and a half times out of 10 people do not.
Jeff: [laughs] I appreciate that. Thank you.
One of the things that you talk about in the book early on is that the whole business of developing vaccines was not a particularly popular area of science or big pharma. It was a backwater in some respects.
Gregory: Yes, exactly right. It was a surprise to me. But when you talk to people in the pharmaceutical business, you realize that throughout history actually, vaccines are just not a sexy, very profitable business. If you think about it, you give a vaccine every so often — once a year, maybe more, infrequently once a lifetime — and it’s not like a drug, a pill, or statin kind of thing, where you take daily. So there’s just also so much you can charge for a vaccine, especially in other countries, not in the west, there’s pressure not to charge too much.
And they take years and years to develop. On average, the average vaccine historically has taken 10 years to develop. The fastest one until this past year was four years. So they take forever. Most of the time they don’t even work. They’re not successful. The efforts aren’t successful, not the vaccines themselves, but the efforts, and there’s just so much you can charge for it. So that’s why it takes outsider unlikely candidates to step up and develop some of these vaccines.
Jeff: What is it about vaccines inherently that takes so much longer to develop than say the normal drug?
Gregory: Well, partly it’s because viruses, these pathogens, sometimes go away. And we saw that with Zika. We saw it with MERS. We saw it with the first SARS where there were efforts, companies who set out to develop vaccines, effective vaccines, and they made headway. And I write about it in my book, and then these viruses went away. They evaporated, which is good for us, but bad for the vaccine makers. So that’s part of the problem as well. It’s also the case that a lot of drugs that are produced, they’re just incrementally better. They help you a little bit more than what’s on the market right now, whereas a vaccine, it’s a higher bar, and we aren’t just improving on what we have existing.
Jeff: And the technology, a lot of the technology that went into the COVID-19 vaccine was technology that was percolating along before January of 2020. Talk about that.
Gregory: So that’s what a lot of what my book is about. It’s the revolutionary vaccines that were being developed without many of us being aware. And these are small incremental improvements, breakthroughs that are in labs around the world, and especially in America, that had been going on for years. And there was a lot of drama, a lot of competition, a lot of personalities, characters, fascinating scientists, quirky odd individuals. They’re often competitive, they’re envious, they’re ambitious, they’re innovative. And yet there was a lot of really interesting work that was going on that really wasn’t a focus for anyone until 2020.
Jeff: What was the nature of that work?
Gregory: They were developing primarily two innovative vaccine approaches, there’s messenger RNA, mRNA, which I think a lot of us are aware of now because that’s at the heart of the vaccines that were produced by Pfizer and BioNTech, as well as the Moderna ones, they’re the most effective ones for COVID-19. And messenger RNA is basically just a molecule. We have ’em inside of us, naturally, we do. They transport the instructions from our DNA to the part of the cell where proteins are created so that we really depend on mRNA every single day of the week.
DNA can’t do it themselves. It needs to be transported. And that’s what mRNA is. And for years, scientists said, “Well, what if we could create, synthesize mRNA in the lab?” In other words, create something and transport it into the body as part of a vaccine or even a drug, and tell the body to create any protein we wanted to create. And in effect, basically have the body itself be a vaccine manufacturer, be a vaccine factory, your own factory in your own body.
So it was always the dream, the holy grail for scientists. What if we could use mRNA at the heart, to be the heart, of a vaccine? And they spent years working on it, and people told ’em they were crazy. Don’t waste your time thinking about mRNA as it disappears really quickly. The enzyme chops it up and it disappears. So people said it’s too unstable to really depend on. Don’t waste your time. And yet some stubborn scientists who I write about in my book, they kept at it, they kept working on it. And it was very dramatic what they were doing.
Jeff: Among the scientists that kept at it. What did they think they could accomplish? Talk a little bit about their mindset, why they were so persistent, and what their vision was for being able to pull this forward.
Gregory: Originally, the scientists, and they include researchers, deep in the basement’s bowels of laboratories and places like Cambridge, Massachusetts, and Wisconsin, and Maryland, and elsewhere, in Germany as well, I write about, they really were hoping to create drugs using mRNA. In other words, you create the molecule in the laboratory, you stick it inside some encasement. It can’t go directly. It needs to be encased in this fatty substance so that it eases its way into the body, into the cells.
And we can tell, we can instruct the body to create anything, any protein you want to help our heart, to help fight cancer. Uğur Şahin, the CEO of BioNTech, was trying to insert using mRNA, using other kinds of methods, create proteins, let’s say a protein from cancer. So the idea being: we want to instruct the body’s immune system, we want to educate it. We want to teach it. That’s what a vaccine is. It’s an education, and you instruct, somehow you get the body to create a protein, or in the old school way, a traditional conventional way, you actually put a protein from the virus itself.
And somehow you tell the immune system, “Here’s what this protein looks like from a virus or from a cancer, and now go and fight it off. Next time you see it for real, when you experience the real thing, go and fight it off.” And that’s what they were trying to work on. It did not work for medicines, for drugs when it came to mRNA, but thankfully when it came to vaccines it was easier. And we didn’t know for sure it was going to work until last year, but these scientists on the eve of 2020, going into the pandemic, they were pretty confident. They had a method that would work.
Jeff: Were it not for all the testing and the FDA approvals, and all of the political and paperwork process that went into this, how quickly could this vaccine have been out there if everything else could have been done away with?
Gregory: I’m not sure why we would want to do away with testing. Frankly, you could have introduced vaccines, and what if they hadn’t worked, no one would want to take any nuance. They’d say, “I’m not taking a risk on this kind of thing.” They had to be really careful before introducing these vaccines. There already is so much vaccine hesitancy in this country. Can you imagine how much hesitancy there would be if these vaccines weren’t protective?
They’re historically among the greatest vaccines we’ve ever seen. They’re modern-day science’s greatest achievement, I would argue — vaccines that are 90-plus percent effective compared with the flu vaccine, which is 40 percent, 50 percent, 60 percent. So these are 90 percent-plus, but can you imagine if they had cut corners on the testing and they had introduced vaccine shots that weren’t effective or had side effects? No one would be taking this vaccine. And frankly, this pandemic would continue, and it would harm us all. So, luckily they didn’t cut corners in that regard.
Jeff: I guess the question is not so much about cutting corners, but about how close was what ultimately became the vaccine to what was originally there when January 2020 hit. How much further development of the technology had to take place?
Gregory: What’s interesting is that the technology was developed over years, even decades. Slowly sometimes, faster other times, small breakthroughs that people weren’t aware of. Lot of competition. It was almost like a relay race with a runner running fast, getting where you needed to go, but then stumbling maybe, and passing the baton to the next person, next researcher. And they moved a little forward, and a lot of egos along the way, a lot of controversy, a lot of competition, but they were making progress.
And then on the eve of 2020, they had the technology. They just didn’t know it was going to be effective as it was. They thought it would be, they weren’t sure. So had never really been tested like it was last year. They were waiting for some virus to challenge them, take on a new virus. They were hoping, in some ways, I wouldn’t say they were hoping for a pandemic, I wouldn’t say they were hoping for harm to be introduced to the world, but they were hoping to be able to test their approach. And they finally had that opportunity, they jumped on it.
Jeff: Where was the first effort that this developed? Where is the beginning of this process?
George: I would say the beginning of mRNA was in 1990 and in the late ’80s, really. In Wisconsin, there’s a gentleman named John Wolf, a researcher who worked with children with genetic abnormalities. And he was both a doctor, and a scientist, and researcher. And he treated his patients, and then in the evening went home to a lab and tried to figure out ways to help them. And he’s the first person who wrote a paper. He wrote with others. It wasn’t him alone. As with all scientific achievements, there are many people involved. But he’s the one who really kind of showed the world that actually this mRNA is worth working with.
Everyone had dismissed it, “It’s unstable, don’t touch it.” But he said, “No. I’m showing signs that mRNA injected into the body potentially can create proteins.” And now you say to yourself, “How does that help?” Proteins are the key to all medicines and drugs. And if you could instruct the body, that gets you a long way. Now, he didn’t make as much headway as he wanted to. And sadly, he passed away early in the COVID-19 pandemic, not from COVID-19, but he had cancer. But he showed the world, he sent a message. And then from there, there were some really pioneering researchers at Duke.
And they also made headway, and then stumbled and gave up. They said it wasn’t worth it. But then there were a couple of really interesting people, researchers at UPenn. So it went on and on. There was a group at MIT that eventually became Moderna. Moderna made headway. People dismissed them and thought they were exaggerating their possibility of mRNA, but they ignored the skeptics. So I find that the process and the evolution of this is really kind of fascinating and more dramatic than I had expected.
Jeff: And in the early days of trying to develop this vaccine, there were efforts that went away from the mRNA approach, some of the stuff at Oxford. Talk a little bit about that.
George: Sure. So there’s another approach, and that’s using something called an adenovirus, and that’s a harmless virus, like a cold virus, or with Oxford, a chimpanzee virus. And having that virus transport the genetic message to the body to create the spike protein. The spike protein we’re all familiar with, that sort of the characteristic — one of the characteristic aspects of this coronavirus. And just like mRNA sends a message to the body to create the spike protein, so does this adenovirus. It’s a virus that takes the genetic message and says, “Hey, immune system, we’re going to build this little spike protein in the body, teach the body’s immune system to fight it off next time.”
So the adenovirus approach, it’s a good one, it’s not a great one. It ended up leading to an effective vaccine for COVID-19, both the AstraZeneca Oxford one that’s in the UK and other parts of the country, but also in our country, the J&J, the Johnson & Johnson vaccine is based on this adenovirus approach, and a really pioneering vaccine researcher in Boston named Dan Barouch. It’s a good approach. It’s just not quite as effective as the mRNA one, but it’s cheaper. And it doesn’t have to be kept in the same cold storage. So that helps in other kinds of countries too.
Jeff: Who really was the greatest force in really pushing this whole mRNA approach to the COVID-19 vaccine? And where does that lie? Where does the real initial effort to bring this forward, lie?
George: I would say that Moderna, this company in Cambridge, they saw what was happening at UPenn, those earlier scientists I talk about, and they’re the first people that said, “We’ll just raise a lot of money. We’re talking billions of dollars, and focus on it as a company.” Moderna was the only one really focused on mRNA. This company, BioNTech in Germany, they were doing the mRNA work too, but they were doing other things as well. No one was as focused on it as Moderna, and no one did as many revolutionary advances as Moderna.
No one really was aware of them at the time. I think partly because Moderna was a pretty secretive company. They didn’t want competitors finding out what they were doing. I write in my book all about some science they were doing, some scientists who were really hard at work and came up with revolutionary advances. But again, they were very secretive and no one really knew about them. They didn’t want people to know about them because they didn’t want the big guys, the big pharmaceutical companies, to hear what they were up to.
Jeff: Why weren’t the big pharmaceutical companies more aggressive once there was the need?
George: I think some of them tried. Didn’t make that much headway. I write about Merck in my book. Merck is the vaccine giant. They developed the MMR vaccine that we’re all familiar with — mumps, measles, rubella — that we give our children. They’ve got a rich history of vaccine advancement. So early in the COVID-19 pandemic, there was a dispute within Merck I write about. Some scientists really wanted to focus on COVID-19. Others said, “This could peter out. We’re making such headway elsewhere. Things like cancer. We don’t want to be distracted.” And again, as we talked about earlier, vaccines are not the sexiest, most popular area of business for most pharmaceutical companies. So that explains it too.
Jeff: Where does Pfizer come into it?
George: So BioNTech needed a partner. BioNTech is a relatively small company in Germany. They had made advances with mRNA. They knew they couldn’t do it on their own. So they reached out to Pfizer. Pfizer’s not — as much as we all know them, a household name — they’re not a vaccine giant. They had closed down their infectious disease business.
So, it’s not like they were an obvious choice, but they were — it took them a little while — but they eventually were eager to work with BioNTech and they teamed up. What’s interesting is Moderna tried to find somebody too. Moderna reached out to Merck. They reached out to other people to find a partner, and no one wanted to work with Moderna. So they had to do it on their own, go up against Pfizer and BioNTech, which was a challenge.
Jeff: And talk a little bit about the impact this has had on Moderna as a company at this point.
George: So Moderna, it’s hard remember, but at the beginning of 2020 before the pandemic, people had a lot of skepticism about Moderna. The stock had been down and today they’re a huge company, $135 billion and they’re focusing on using mRNA for other kinds of things. I think in the next few years we are going to see advances potentially in both them and BioNTech in cancer, in malaria, in other kinds of neurological diseases — Lupus, MS maybe. So I’m excited about the future for both Moderna and other kinds of companies using these techniques.
Jeff: And talk a little bit about Moderna as a revolutionary startup. We can look at Moderna the way we look at startups in Silicon valley displacing some of the larger companies and really creating destruction in that regard. Is that really what Moderna is, and are there other companies like Moderna that are coming up?
George: Yes, it really is in the biotech world. We all know from historically companies like Amgen, but today Moderna is one of those kind of companies that has become a huge giant, almost overnight. It’s gone from about $3 billion in market value to $135 billion. And yes, they are like any kind of startup that has exploded in value. And the beauty of it is they’ve done it by helping people, by saving lives. And they are a really hard-charging, ambitious group. The CEO, Stefane Bancel, I write about a lot in my book, he’s an interesting, fascinating guy. He’s almost like a Steve Jobs in that he drives his people really hard. Early on, people were collapsing. They were fainting. They were literally being taken to the emergency rooms in Boston, in the area, because they were trying to keep up with this guy. And he had a vision and he kept pushing them. And he said, he literally said, “We’re going to be the ones to save lives during a crisis.” And people were skeptical about him. People thought he was exaggerating. People thought he was a little bit of an Elizabeth Holmes character. People compared him to Elizabeth Holmes from Theranos, Infamy, but in the end, he was right. He was accurate.
Jeff: And talk about the interaction between these companies and this whole broad effort and the government.
George: So what’s interesting is that on the one hand, Moderna was in competition with BioNTech and with Pfizer, and they were racing to be the first ones. And on the other hand, they also were rooting for their competitors. Was an interesting dynamic because let’s say BioNTech and Pfizer had come out with their vaccine and it didn’t work. People would be skeptical of all of the vaccines, especially mRNA. So Moderna didn’t want that to happen either. And it was also a fascinating dynamic because they were working with the government.
Moderna was working with the government. Others were too. Operation Warp Speed was helpful to all these companies. So for the first time I can remember, the government was working hand in hand with these companies. And listen, there were all kinds of bad things that the government did, missed the boat on a lot of things, took its eye off the ball, underplayed the pandemic and the virus, and the dangers. But when it comes to the vaccine effort, this is a story. My book is really a story of success, and a it’s a good story as opposed to all the things that went wrong. My book is about what went right.
Jeff: Talk about the efforts that the pharmaceutical companies were engaged in, Moderna, Pfizer, et cetera, and their interaction, their nexus with the regulatory agencies.
Gregory: So, and when it comes to the FDA, there was some concern among some people that perhaps things would be going too fast, they’d be cutting corners, et cetera. I was reassured in my research, I was reassured in a lot of ways. The average person hears about a new vaccine and gets worried, and for good reason. Historically, as I said, the average vaccine takes 10 years, and this took 300 days. So I understand the impulse to be concerned and wary.
But from my research for this book, I was so reassured that these vaccines took years to develop, not days, it just seemed that way. They tested them, they put them together quickly last year, but the research had taken years. And as you suggested, the regulatory aspects of things the FDA, et cetera, they were not cutting corners, the trials were tens of thousands of people. So in some ways, it was very reassuring to see everyone’s urgency that the regulators worked with the private industry was very reassuring to see.
Jeff: How important was it to the developers of the vaccine to understand or to think that they understood the source of the disease, because that debate seems to still be raging today?
Gregory: It is, it’s also an interesting one because it unites people on the left and on the right, far left and far right. There’s suspicion of China in both those groups. I find it interesting. The vaccine researchers didn’t spend that much time worrying about the origins. They were too focused on trying to stop this thing. Frankly, it takes years often to figure out the origin.
You look at HIV, for example, there were all kinds of suspicions about the Russians, the US government, or the CIA. What are the origins of HIV? Eventually, we found the origins of HIV. It was in an animal, and I think it’s likely to be the same thing here. But I think the researchers, the key ones that I talked to, they knew it could take years to find the origins of this virus, so they didn’t really focus on it so much.
Jeff: Talk a little bit about the potential future uses of this mRNA and where the research is taking itself right now.
Gregory: So the beauty of mRNA is it sends a message to the body, and you can send a message, any kind of message to the body. So there’s hope in all kinds of areas, I’m a tad cautious just because historically we haven’t made success when it comes to drugs, just this one vaccine so far. But the good thing is that all these hundreds of billions of dollars of profits that are going to accrue to the companies like Moderna, BioNTech, Pfizer, et cetera, they’re taking out a lot of that money, and they’re plowing it into new areas, and they’re just as focused on that.
And in some ways, they didn’t really expect to make headway on infectious disease. When it comes to BioNTech, they were a cancer company, they really still are in a lot of ways. So they’re going to take this money and plow it into cancer. Again, teaching the body through mRNA to fight off cancer and teaching the immune system, which I’m hopeful, I want to say I’m optimistic, but I’m hopeful others are using some of these techniques.
The adenovirus approach for malaria, for HIV. Just like we turn on the immune system now with these vaccines, maybe we can turn it off when we need to, for people that have rheumatoid arthritis, maybe lupus, things like that, MS that people are excited about. So in some ways, you could see this as the first chapter, and then maybe there are more successes ahead.
Jeff: Why has HIV been so resistant to any kind of a vaccine?
Gregory: HIV makes COVID-19 look like kids play. It’s such a challenging, awful virus for so many people. It’s different from one patient to the next. It’s not the same virus, which makes it really difficult for a vaccine company or a drug company as well. It’s always changing. It commandeers the immune system, so the immune system actually has no chance against HIV often, or frequently, and actually the virus can make use of the immune system.
So it’s really just the biggest challenge modern science has ever seen. And we’ve made a lot of headway in terms of drugs, thank God, but not so much on a vaccine. But the same people I write about are going right back into that lab, and they’re using some of these techniques they’ve developed for COVID-19 and working on HIV. So I’m optimistic, I’m hopeful.
Jeff: When those that have put so much effort and time, and research, and resources into the vaccine see the hesitancy that’s out there, the resistance in some places even beyond the hesitancy, talk a little bit about what you understand their reaction to be to all of that.
Gregory: They’re frustrated, they’re perplexed, they’re saddened. I would say I share those sentiments. To work as hard as they did, to save lives, and to have such an effective vaccine. The flu vaccine is what, 50, 60 percent effective? And here we have much more effective and protective vaccines that they worked hard to develop, and to have people question their motives, and people resist taking them when the side effects are relatively few. These are relatively very safe vaccines.
It’s just perplexing also, because I don’t know, you step on a nail, and right away, you go to your doctor’s and you get a tetanus shot. No one’s asking, where is it from? How is it developed? How long did it take? You just trust the science, you trust the experts when it comes to medicine. But now people, everyone’s an expert, and they go on YouTube, and they heard a friend say something. And there’s a lot of junk science out there. So I think it frustrates them, it frustrates me as well.
Jeff: And do any of them feel that it really impacts the work, that whatever the next breakthrough is, that it will be met with resistance and fear, and this kind of junk science that you’re talking about?
Gregory: That’s a good question. I don’t think they have that fear. I think in the back of the mind, maybe, but it’s all relatively new. We didn’t have this resistance a few years ago. So we are in a new world, sadly, where people defer to somebody who says something on Facebook as opposed to their own internist who they’ve been going to for years. So I have not heard researchers say, “Jeez, why am I wasting my time on HIV or something like this, curing and finding this new discovery if people are going to ignore it?” But I bet you in the back of their minds, it’s a concern.
Jeff: Do you think that it has to do with other societal forces that we certainly won’t get into? Or do you think that there’s an element of the resistance, is because this is so new, so different, so cutting edge?
Gregory: I think among reasonable people who are resistant, yes, there’s that initial concern that this vaccine has been done so quickly. During an election cycle maybe that’s the hesitancy, but I think your earlier point, I think there’s so much in society that splits us and it’s politicized. I did a book earlier in my career called The Frackers, about the energy revolution and all the oil and gas we’ve discovered in this country.
And I traveled the country, little towns in Oklahoma, North Dakota, and Pennsylvania, and Texas, and got to meet people. It was a privilege for me, I don’t think we all have a chance to meet others, people that don’t agree with us, people from different parties, and support different types of efforts. And, sadly, I think we’re just split as a nation, and we don’t get a chance to interact with people that think differently than we do. And I wish we had more of an opportunity.
Jeff: The irony is that one would think that it would be a crisis like COVID-19 and the potential for a cure or a vaccine, in this case, that would bring people together, that it would have exactly the opposite impact.
Gregory: Yes, 9/11 I lived through and that brought us together, all political stripes of people. This one I think initially did, but it didn’t take long for the divide to become clear and become even worse. So yes, you would have thought that, but sadly, that’s not the case.
Jeff: Gregory Zuckerman. The book is A Shot To Save The World: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine. Greg, I thank you so much for spending time with us here at WhoWhatWhy.
Gregory: Thank you. It was a sad way to end things, but I want people to know that it’s about what went right, not what went wrong.
Jeff: Thank you so much.
Gregory: Have a great day.
Jeff: Thanks. And thank you for listening and joining us here on the WhoWhatWhy podcast. I hope you join us next week for another radio WhoWhatWhy podcast. I’m Jeff Schechtman. If you like this podcast, please feel free to share and help others find it by rating and reviewing it on iTunes. You can also support this podcast and all the work we do by going to whowhatwhy.org/donate.