“That year, 2020, Uğur told the crowd, would be the year BioNTech proved the doubters wrong.

There was no time to lose. Soon after he’d finished his talk, Uğur hopped on a plane to Seattle, where he met with a team at the Bill & Melinda Gates Foundation, which had recently signed a $100 million agreement with BioNTech to develop a slew of new drugs. Hours later, he moved on to Boston, to stop by a small cancer immunotherapy company that BioNTech was about to purchase in a $67 million deal. The purpose of the visit was to reassure staff that he, a fellow scientist, was interested in advancing their innovations and was not a vulture disguised in a lab coat who had come to gut the firm and slim down its workforce. At this point, Uğur was still fairly oblivious to events in Wuhan. He walked around the biotech firm’s foyer, introducing himself to dozens of soon-to-be employees, shaking each of them vigorously by the hand.”

Joe Miller is a journalist. He shares his story and discusses the book, The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic.

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Hosted by Kevin Pho, MD, The Podcast by KevinMD shares the stories of the many who intersect with our health care system but are rarely heard from.

Transcript

Kevin Pho: Hi, and welcome to the show, where we share the stories of the many who intersect with our health care system but are rarely heard from. My name is Kevin Pho, founder and editor of KevinMD. Rate and review the show at KevinMD.com/rate. Subscribe at KevinMD.com/follow. Today on the show we have Joe Miller. His book, “The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic,” is excerpted on KevinMD, and he is now joining us on the show. Joe, welcome to the show.

Joe Miller: Great to be with you, Kevin. Thank you.

Kevin Pho: So we’ll get into your book in a little bit, but first off, can you just briefly share your story and journey to where you are today?

Joe Miller: Sure. So I am the Frankfurt correspondent for the Financial Times. I’ve been here in Germany since 2019. Before that, I worked for the BBC around the world. My job here is to cover German industry, so mostly I cover German carmakers and steelmakers, etc. That’s why, at the beginning of 2020, I was slightly more alive to COVID-19 (it wasn’t called COVID-19 then yet, of course) than other people, because a lot of the companies that I cover have large plants in China that were suddenly being shut down by this mysterious virus. I was trying to find out a little bit more about this and what was going on, and someone in London at the FT pointed me toward these companies who were going to be developing, or trying to develop, a vaccine.

As I’m sure you remember, back then there were hundreds of companies trying to do this, but I stumbled across this one company and thought, “Hey, they sound kind of interesting.” And I have to say, I’d be lying if I said that I knew that this was going to be the company that ended up partnering with Pfizer and creating this vaccine, the first and now the most ubiquitous COVID-19 vaccine. I really thought that this guy who ran it, Uğur Şahin, was just an interesting guy, and I thought I would follow him for a few months and then write a story about how difficult it is to create a vaccine, and how they failed, and how most people would have failed at this, and the struggles that they went through.

It was really only in June or July, sometime in 2020, when Uğur called me, on one of the calls, and said, “Joe, it’s really as good as it gets.” He was referring to some of the early data that had come out of the clinical trials. And then I thought, “Oh my God, I’d better start looking into this in detail.” So I really upped my reporting on the company. I spoke to dozens and dozens of scientists, the regulators, and the politicians involved, and that’s how this book really came about.

Kevin Pho: So of course, now everyone knows BioNTech, but tell me about this company before COVID. What were they specializing in, and how prominent were they?

Joe Miller: Well, there’s a reason that I hadn’t heard of them before COVID, and that’s because, firstly, they’re based in Mainz, which is about 40 kilometers from where I’m sitting here in Frankfurt, and Mainz is not one of the big centers, as you’ll know, of biotechnology. It’s not Boston. It’s not Cambridge. It’s nothing like that. And this company was small. It had just listed on the Nasdaq a few months earlier, and it was mainly focused on cancer therapies. When I say mainly, they had 1,200 employees at the time, of which 15 were focused on infectious diseases. So it was really mainly a cancer immunology company, and it was sort of seen in the same group as CureVac and Moderna at the time. It had a pipeline of mRNA products that was nowhere close to even a phase 3 trial, never mind an approved or licensed pharmaceutical.

But they were extraordinary in that they had two very unique investors who were long term, and so they were operating on a different kind of time frame from many other biotechs around the world, in that they basically stuck with this technology and had been working at it for so long. In the book, that is one of the reasons why they got there first, because of this sort of long-term view that they had. But it’s really fair to say that they were probably among the most unlikely companies in the world, at least on paper, to have been the producer of the COVID-19 vaccine, the first and most successful one.

Kevin Pho: So with the mRNA technology before COVID, why were they studying that technology for so long? What conditions did they hope to treat with the mRNA technology?

Joe Miller: So what’s interesting about them is that, unlike many other biotech companies, Uğur Şahin and his wife and research partner, Özlem Türeci, who co-founded the company, are both clinicians. So they started off as doctors, and they started off as oncologists, and like many, they were really frustrated in their early days. They worked on a hematology ward and were just frustrated by the lack of options for treatment for their patients and how many of them were dying. And they came together on this quest to find a cure for cancer, a treatment for cancer.

They felt that mRNA, even though at the time, and this was the early ’90s when they were getting together, it was, as you probably know, a very ridiculed molecule in many ways. And I say ridiculed because people did say really nasty things about those who were interested in pursuing it. Because it’s so volatile, because it’s so difficult to protect, they thought that those people who were trying to create drugs using mRNA were essentially out of their minds. But they saw the potential of being able to harness mRNA to essentially, and they call themselves immune system whisperers, recruit the immune system and all the forces of the immune system to their cause, which was, at the time, to fight tumors. And so convinced were they of the benefits of this technology that they spent decades working on it.

But I must say that it’s not just them who spent decades on it. It’s lots of different people around the world, some of whom have now become quite familiar, like Katalin Karikó, who fled from communist Hungary and was at UPenn and was working on this with Drew Weissman, and people in pockets around the world. What’s quite interesting is that some of them didn’t even know of each other, but they all sort of built on each other’s work, and all of this sort of reached a crescendo around 2020. We really, really are very lucky that COVID-19 emerged at the beginning of 2020, because we had just gotten to a point where mRNA had been combined with lipid nanoparticles, and we got to just the right point where we could protect the molecule for long enough for it to reach the required cells, the dendritic cells, in order to create enough protein to have a successful vaccine. So what was unique is that they stuck with this, but also there’s a lot of serendipity involved in this story, much more than you’d think when you start off with it.

Kevin Pho: All right, let’s talk more about your book. It’s titled “The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic.” So Joe, what are some of the key points that you want readers to come away with after reading your book?

Joe Miller: Well, the first point really is just how unlikely this story is. Right from the beginning, I start with this tale about this guy, Uğur Şahin, who’s sitting at his computer on January 24th, reading the Lancet. He’s doing calculations based on this early report of some, what we now know to be COVID patients, but back then we didn’t know to be COVID patients, arriving at a hospital, and the early tests that were done. And he then goes on to predict, on January 24th, exactly what would happen in the pandemic. Exactly, and when I say exactly, I mean how quickly, which places it would spread to first, roughly how infectious the disease would be, etc., etc.

When I was writing this, I was so concerned people would think I was making this up, because it’s so prescient. But really, I know it’s true, because I’ve seen the contemporary emails. I only got in contact with Uğur a month later, but even in February, it wasn’t clear that this was all going to play out the way it would, and he was telling me, “This is how it’s going to happen.” I have those recordings, and he was saying to me, “It’s possible to do a vaccine in a year.”

But the main thrust of the book is also all of the other unlikely events that happened. As I’ve explained, this is not the company that you’d think would end up producing this, but also there’s the amount of hurdles that they had to overcome. No one had heard of them, so they weren’t prioritized in Germany for getting supplies. They couldn’t get the basics that they needed to run their labs in the early days. They were ignored by the European Commission for quite a long time, for several months. They couldn’t get the funding, neither from the capital markets in February 2020 nor from governments in the months afterwards, to essentially build the facilities that they would need to produce the vaccine.

And they had all sorts of other hindrances. For example, as a small company, they didn’t have the level of biosecure labs to be able to handle COVID, so they couldn’t test their own vaccine in-house, because they didn’t have the right labs. And the outside lab that they would have used, the contractor they would normally have used, was in northern Italy, which was closed down because of a COVID outbreak. So they had to come up with ingenious solutions. There’s a big story in the book about how they came up with a pseudovirus, etc., to be able to test it in the labs that they had. And all through this, it’s just a series of incredibly unlikely events.

I mentioned the investors earlier: two Bavarian billionaires, identical twins from Bavaria, who’d made their money in the ’80s and who wanted something else to back, and who basically gave them an open check and told them, “Go with it.” And there’s the fact that they had this ongoing flu collaboration with Pfizer and managed to get Pfizer on board, which wouldn’t have been possible with another company, because they already had a working relationship. It would have taken a lot longer to onboard Merck or someone like that. So all through this, it’s just a story of, as I say, serendipity and chance, and all of the mechanisms that you think might have been in place.

There’s an advisor in Britain, a political advisor called Dominic Cummings, who was a very controversial political advisor to the prime minister. He said in one of his committee hearings about COVID that when you join government, you think that somewhere there’s a door, and behind that door there’s a bunch of ninjas, and these ninjas know exactly what to do when a situation like this happens. And he said the lesson of the pandemic is that there is no door, and there are no ninjas. I think the lesson of this book is that it took extraordinary individuals, not least Uğur Şahin and Özlem, but also several other extraordinary individuals acting alone around the world, to bring us this vaccine. It wasn’t the sort of adults in the room, so to speak, who are all in action and brought us this vaccine.

Kevin Pho: So what are some of the special things about the founders and the company itself that caused them to overcome this myriad of challenges, obstacles, and hurdles that you articulated? If you could narrow it down or distill something about the founders and the company that got them to the point where they are now, what would those characteristics be?

Joe Miller: I would say Uğur and Özlem are steadfast believers in the scientific method, and when I say that, I’ll start with an example: It extends even to their personal lives. I was with Uğur one afternoon, sitting next to him, and I looked across at his computer monitor and realized that the font was tiny. I really couldn’t read it; the resolution was tiny. I said to him, “How is it possible? How can you possibly read that?” And he said, nonchalantly, “Oh, I’ve been training my eyes for decades.” What happened is he’d read an academic paper that said that if you strain your eyes for a certain period of time every day, then you can either prevent or postpone the degradation of your vision. And so he’d been sitting for years with one contact lens out, alternately, of one eye, enduring enormous headaches, and his vision is still pretty much perfect as a result.

And that extends to every area of his professional life as well. People won’t believe it when I say these people said, at the beginning of the year, that there would be a vaccine in a year. They believed that targeting the spike protein in the way that they did would work. They believed this technology would work, and they believed it 30 years in advance of when the rest of the world believed it. But I can tell you it’s true, because I sat with them, and I sat with them right at the beginning, when they were making these predictions, and all the way through, they were proven correct. Even when the variants came out, after the vaccine was out and everyone was panicking, they said, “Listen, this is exactly how it’s going to work. The antibody response is going to be weakened, but the T cells will be all right, and then we’ll have a booster,” etc. And they said all of this way before everyone else got to this point, and they’ve been proven right again and again and again.

And again, one of the issues I had was that I was worried that people wouldn’t believe this. People always used to ask me, “When you were following them throughout this extraordinary year, when were the big hiccups? When did they think they were failing?” And to be honest, there weren’t really any, because they were always so unbelievably confident that this would work. I think possibly for other people, and for most of us, that amount of self-belief could be damaging. You need to allow some room for doubt and for self-doubt. But in their case, because it’s based on science, and based on facts, and based on empirical data, once they are convinced that the data shows X, there is nothing in their fiber that stops them from believing it. And that’s what’s really extraordinary about them.

Kevin Pho: So I can imagine, and you probably know better than I do, that a lot of biotechnology companies have that steadfast belief in the science. Was their belief in the scientific method, was their belief in the technology, so much greater than other biotechnology companies’? And was that a reason why they succeeded when so many others have failed?

Joe Miller: Actually, I think that the reason why they succeeded when so many others have failed is because of what makes them different from other biotechnology companies. Yes, they were committed to this technology, but they were also committed to loads of other technologies. Unlike most biotech companies, which have one proprietary piece of tech that they would insist on until the end of days, they picked, firstly within mRNA, various different platforms, some of which they developed themselves, some of which they bought in through the expertise of, for example, Katalin Karikó and Drew Weissman, whom I mentioned earlier, but many others as well. And they ran them all in parallel. But they were also dealing with, and they still are as a company, loads of other technologies. So they were, in effect, hedging their bets.

The confidence that I mentioned isn’t the confidence that what we have will work for everything. It was a confidence that if they have an open enough culture and are open to ideas wherever they may come from, and it really is wherever they come from, I think there are people from 60 different countries in the company and from all different disciplines, then eventually they will hit on a winner.

And what made their vaccine so different from the others, some of which were extraordinarily successful as well, but some of which failed, was that they started with 20 candidates. They started with the most complexity you could possibly have. They started with candidates using all of their different mRNA platforms, and alternately targeting the spike protein and the receptor-binding domain, which is the bit right at the top of the spike protein. So they were trying it all from the beginning. They put loads of horses into the race and took four into their phase 1 trial, so they waited until the very last minute to make a decision, instead of saying, “This is the technology we have, and this is the only horse we’re going to enter into this race.” So while I say they have steadfast belief in their technology, that’s true, but it’s based on a realistic expectation of what the technology can do and a realistic process of evaluating how well various different technologies will work against SARS-CoV-2. They knew that one of them would be successful, but they put loads into the race just to make sure.

Kevin Pho: We’re talking to Joe Miller. His book is “The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic.” Joe, given the track record of the BioNTech founders, I’m certainly interested in any insight in terms of the future of the vaccine and the pandemic itself. Do they offer any insights in terms of what we can expect next, in the next six to 12 months?

Joe Miller: So I think they both expect, and again, I don’t speak on their behalf, but they both expect, as most of us do, the virus to become endemic, and for us to need regular boosters of the COVID vaccines, similar to flu. Their hope is that eventually we can have a multivalent vaccine, perhaps to include flu as well, by the way, so that we have one shot a year, one mRNA shot a year, in theory. There’s still a while to go from that, but given the sort of building-block system that mRNA vaccines allow you to work with, you could add a bunch of different viruses in there and get it all done in one go. That’s when it comes to COVID-19.

Now, of course, there’s a lot of interest in what mRNA technology can bring to other diseases, etc. As I mentioned before, there was already an ongoing flu collaboration with Pfizer. That’s carrying on, and that will probably yield some result in the near future. And the company’s looking at loads of other diseases, including malaria and even sclerosis, as possible targets for mRNA therapy. But I think that there’s been so much enthusiasm about mRNA that people will need to realize that COVID-19 was an almost unique disease, in that, and it sounds awful to say this, given that millions of people died, it was a relatively merciful disease. It could have been, A, a lot more deadly, but, B, a lot less susceptible to being targeted. With this virus, the spike protein is so pronounced and so easy to target. Many, many diseases, as you’ll know, don’t have a common target that’s as easy to pinpoint as COVID-19. So while the platform itself has been vindicated, I think people who are expecting that we now have a wave of mRNA pharmaceuticals overnight will have to be a little bit more patient.

Kevin Pho: Now, through all your reporting and the time that you spent with the founders and the company, what would you say is the single biggest surprise that you had from the story?

Joe Miller: Well, the single biggest surprise is that it was successful. As I say, I myself didn’t think it would be, and there was no reason, looking at the data, to believe that it would. But really, the single biggest surprise I had was that people who have a vision and who have a steadfast belief in, again, a data-based belief in their technology can actually, and I don’t know, this sounds trite, change the world. I didn’t really believe that the world worked in a way where, even if two very bright people in a small city in Germany had the cure to COVID-19, had the antibodies to COVID-19, they would be able to essentially move the world around them in order to really make everyone realize that this was the winner.

And the fact that they were able to do that, and that this was possible through really a load of chance encounters: They got to know Kathrin Jansen, who’s the head of infectious diseases at Pfizer, was also German originally, and they got on quite well and had a relationship that was in a good place when COVID came around. The investors I mentioned, completely bizarre investors really for a biotech to have attracted. And all of the various people who I mention in the book, who all deserve a book of their own, the brilliant scientists who worked on this. Most of them didn’t come from an mRNA background, certainly not, but some of them didn’t even work in immunology. They’d come from all sorts of disparate areas, and some of them had reached dead ends in their careers, and they all came together to create this incredible moment.

You couldn’t recreate that. You couldn’t sketch that. No think tank in the world could have brought together policies that would make that happen. There was something really just about the alchemy of extraordinary individuals coming into a room and sort of working night and day to push something out into the world and getting it done. And I just didn’t believe, and perhaps call me cynical, but I didn’t believe the world could work like that. And luckily for us, it did.

Kevin Pho: And my final question: What are some of your take-home messages that you want to leave with the KevinMD audience?

Joe Miller: The take-home message for people, and I know a lot of the audience is much more scientifically literate than me, but the take-home message behind this, I really think, is that so much of it is understandable. What I mean by that is there are all these questions about how we got a vaccine in a year when it took five years for the last one, for the Ebola vaccine, for example. How come an untested technology turned out to be ready just in time, in 2020? How come it happened in Germany and not in one of the big pharma companies, etc.? And I think these are legitimate questions, I really do, and some of them have not been given the best answers by public health communicators.

I think if you read this book, it kind of puts all of those pieces of the puzzle into place, and you can see how we got from Uğur sitting at a computer in January to that fateful day in November when we had an announcement of an efficacious vaccine. It wasn’t an easy route, and it wasn’t a risk-free route, and it wasn’t a smooth ride by any stretch of the imagination, but it does all make sense, if you get what I mean. There’s no magic potion or hoodoo involved or anything like that. It’s just an extraordinary story, almost too good to be true, but it is true.

Kevin Pho: The book is called “The Vaccine: Inside the Race to Conquer the COVID-19 Pandemic.” There’s a link to that book in the show notes. Joe, thank you so much for sharing your story, time, and insight.

Joe Miller: It’s been a pleasure, Kevin. Thank you.