How I Built This with Guy Raz - Moderna and Flagship Pioneering: Noubar Afeyan

Episode Date: October 11, 2021

In the field of bio-tech, it can take 10 years and millions of dollars to see if an experimental idea might turn into a life-saving treatment—if it ever does. Noubar Afeyan fully understood those risks when he co-founded Moderna in 2010. He and his colleagues were looking for a way to deploy the messenger RNA molecule to tackle life-threatening diseases. In January of 2020, an urgent opportunity presented itself in the form of a deadly virus that was spreading across the globe. At a breathtaking pace, Moderna produced a prototype for a COVID-19 vaccine, partnered with the NIH to test it, and produced millions of doses, becoming part of the most rapid vaccine roll-out in human history. While Moderna is the best known of Noubar's companies, he has launched many others in the bio-tech space as part of Flagship Pioneering, his multi-billion dollar venture studio. See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

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It had tall windows, beautiful old details, and plenty of space for all of us. And being in that home on Airbnb, right in the middle of Vienna, walking distance from so much of the city, made it feel less like a visit and more like we were actually living there. Plus, taking a trip is the perfect time to host your space on Airbnb. your place with all of its personal touches and its amazing location could make someone else's vacation even better. Your home might be worth more than you think. Find out how much at Airbnb.ca.ca. The reality is when you have a pandemic and you're a public company and you've got material data, our sense was that we at least needed to at a high level put that out there.

So in May, we indeed did come out and say at a very high level that we had some encouraging results. And people attacked us every which way for having said that because they basically said, well, that's doing science by press release. And so one of the things we learned, because none of us have been in this situation before, was that we were going to get criticized no matter what we did. From NPR, it's How I Built This, a show about innovators, entrepreneurs, idealists, and the stories behind the movements they built. I'm Guy Raz, and on the show today,

how Nubarafean's understanding of risk led to a life-saving vaccine and to the spectacular rise of Moderna, now one of the biggest biotech companies in the world. Innovation and risk are inextricably linked. You can't innovate without taking a risk. The calculation any entrepreneur has to make, of course, how much of a risk to take.

One of the greatest risk takers in American history was Thomas Edison. His team of engineers invented the light bulb, the phonograph, the motion picture camera, and Edison held more than a thousand patents. But to create these world-changing inventions, Edison's team had to fail more than it succeeded. Edison famously once said, I have not failed 10,000 times. I've successfully found 10,000 ways that will not work. It's why we don't talk about Edison's talking doll or his electric pen or the electrographic vote recorder

because despite massive investments of time and capital, those ideas failed. But the risk was necessary. And those failures often led Edison's engineers down paths that would lead to total different ideas. It's an approach that's helped to make flagship pioneering among the most successful biotech venture firms in the world. And let me just pause to explain all this for a moment because this episode is largely about the founding of Moderna and the man behind it, New Bar-A-Feyan. Moderna, as many of you know, created one of the major and most important COVID vaccines. But Moderna, the company, came out of the company.

that larger organization called Flagship. Nubara Fayan founded Flagship Pioneering back in 1999, and the idea was to do three things, all under one roof. The first, to raise lots of money to invest in innovative biotech and life sciences research. The second, to identify promising researchers and help to incubate new companies. And the third, to help manage and grow those companies. flagship pioneering has incubated more than 100 companies. Some of them are no longer operating, but many are thriving, including best known Moderna.

Moderna was founded in 2010, and it's already one of the largest biotech companies on Earth. Much of that success, of course, has to do with the breakthrough technology that led to the COVID vaccine. But Moderna didn't intend to become a vaccine maker. In fact, in December of 2020, it was not equipped to mass-produce vaccines. But the company had already spent billions of dollars on research around a new type of technology using MRNA molecules. And it just so happened that because of the research Moderna had been doing, it was perfectly placed to come up with a vaccine to fight the coronavirus. The story of how Nubar helped to build Moderna is also the story of how he co-founded it. dozens of other innovative biotech companies and the huge risks he took along the way.

Nubar was born in Beirut in Lebanon. Both of his parents are Armenian by descent. His father had a thriving business importing plastics in Beirut. His mother was a trained concert pianist. But by 1975, sectarian violence had broken out in Lebanon, and the country was soon to be engulfed in a long civil war. I remember a couple of events, among the most stunning one, was waking up at 5 o'clock in the morning with a gigantic explosion, which was a building, a rather large building, maybe a block away from us that was completely leveled. And, you know, with lots of dead people.

And it was just like for a 12-year-old at the time that was very shocking. But then when the war actually, the Civil War actually broke out, we stopped going to school. So from the beginning of 75 till probably May June, we were at home. home, we would have sirens going off, we would go into the basements, quite routinely. We had a ping pong table in the basement. So that was kind of a redeeming feature in that we could play ping pong while we were meant to stay in these kind of underground areas. You know, there was, we would watch from our vantage point, probably, you know, one or two kilometers from where we were, maybe one kilometer, lots of rocket fire back and forth, you know, buildings being blown up. And this was,

This went on for months and months. And of course, after we left, it went on for years. Yeah. And I know, I know, Noobar that your dad had this thriving business. He would import plastic products into Beirut. But I guess around this time in 1975, you were about 13. Your family left. You fled from Lebanon to Montreal and Canada.

That is a, you know, that was presumably a huge kind of risky decision for your, certainly for your dad. So what did he do when you got to Montreal? And what did the family leave behind? So we left the apartment we owned. We left all of the warehouses of inventory he had, just left it completely. Just left it in Lebanon. And actually he went back for the first time eight years later to actually liquidate what he could. But anyway, so when he came to Montreal, interestingly, he did not want to do the same thing.

So he really wanted to get into the production of something. He really wanted to make things. So he explored and explored finding some small production operation to invest in or buy a year and a half of trying later. He essentially decided he couldn't wait any longer. And he set up exactly the same business as he had done in Beirut and started all over again. That's amazing, because your dad must have been in his 40s by then. Yeah, my father was born in 29. So, yeah, we can do the math.

You're definitely in his 40s. When you got to Montreal, I'm assuming you were not fluent in French. So you probably had to, I mean, because you went to school. Presumably, school was taught in French? No, so Montreal in 75 was still very much a bilingual place in the full sense of the word, meaning that you could coexist without speaking both languages in either language was fine. So I ended up going to, and my brothers together, we ended up going to a Jesuit school, an all-boy school. It was English, Loyola High School. But in the following three years

in high school, took advanced French and learned the language alongside English, which was the main language of the school. Did you grow up going to church every Sunday? Obviously, that Armenian Orthodox Church is an ancient church. Goes back to, I think, Byzantine times. Did you grow up going to to church every Sunday? I grew up going to church. Not only, now you're making me reveal all sorts of stuff that I've never talked about. I was a choir boy from probably seven, eight years old, till I came to Montreal, and I continued in Montreal, as did my brothers.

So we did go to church, I'd like to say every Sunday, but probably it was most Sundays throughout the year. So most Armenians had a close interaction with the church, and we certainly did. All right, so you are in Montreal, and I know that you went on to study chemical engineering at McGill in Montreal, but then you went to graduate school in the U.S. You went to MIT in Boston. And from what I read, there is where you began to focus on biochemical engineering, right? Yeah, so as I was graduating from McGill, MIT was the only place I applied to.

And now I know in hindsight that it was very hard to get in, and I might not have. I've gotten in, but I must say I didn't know then. I just wasn't, maybe this is, I've learned since this is all kind of the comedy of being an immigrant in that you actually don't know a lot of things because people don't tell you, you're supposed to apply to five schools and, you know, maybe some in Canada, some in the states. So I just applied to one school. Thank God they took me.

And it was fascinating. It was just a completely transformative experience and ultimately ended up joining a lab. and pursuing a PhD, and everybody wanted to start doing this form of chemical engineering, biochemical engineering, because it was clear that a whole new industry was being born without the necessary engineering cadre of engineers and principles to apply to actually making the end product. So it was a really fortunate time to be entering the field. It took about four years. So, yeah, I finished in the summer of 1987.

All right. So you've got this PhD in biochemical engineering, and you can probably go work for a huge chemical company. I'm sure there was a lot of, there were a lot of offers out there. But you decided that you wanted to maybe start your own thing. And I have to assume that comes from your dad, who was an entrepreneur, right? I mean, that you thought, why don't I start my own business? It would have made for a good story if that was the case, but it turns out it wasn't. I did not. think of starting a company based on my upbringing. So in 1985, I had occasion to go to Washington, D.C., to a conference that had been put on by the National Science Foundation. And by chance, I sat next to a person at lunch and asked him what he did. And he started recounting this person was my father's age. And he started recounting how he and another friend of his, some maybe 30 years earlier,

had graduated from a brand new field of engineering, then called electronic engineering. And he said when he graduated, they realized that they didn't know what to do with what they had learned. And so he and his friend decided that rather than joining the fray of actually doing this type of engineering, they'd make instruments that their colleagues, their friends would use in doing what they did.

And they had invented the oscilloscope and decided to make some and provide it to their friends. And they started out in the garage, and over time they grew that business and I found this very interesting so I asked him who he was I just didn't know who he was at all and it was David Packard

from Hewlett Packard literally. Wow. And I had like it was really fascinating And this is 1985 85 so he must have been you know I think he died in the mid-90s he was an old guy older. He was he was

he was older certainly I mean I haven't thought back as to what his age was but I wouldn't miss fras if he was in his 70 maybe 70s at least that's how he looked to me, but very kind to spend the time and to make, and one of the things I also remember asking him is I said, you know, like, do I need to have a technology? Do I need to have an invention? Yeah. Because I didn't have the oscilloscope. And he said, you know, not really because

you're in such a new field, anything you do will be new and useful. So that, and that stuck with me because I kind of came back with this interest in learning what I could about innovation and technology management because I figured those are at least generic things I'd have to know. But also the very first business plan I ended up writing to try to claim that we were going to do this, didn't specify technology. It literally just said, we're going to develop instruments that kind of addressed needs in the biotechnology field. And I quickly learned that you can't raise money on that. You have to actually have something. So, but that's a long story. We're just going to start something in biotech and we'll kind of figure it out. But it is amazing

to me that meeting with David Packard, because he was, I mean, of course, everybody knows that name now, right? Eulet Packard and a name. But it really sounds like that encounter kind of started to get the gears in your head turning. Well, it definitely, I'll tell you one of the things that I've thought a lot about. And, you know, generally I realized these are fields that people don't talk about. And you only really, at least back then, used to hear about it glorified in some success story, which like Michael Jordan playing basketball, is completely unapproachable for somebody who doesn't have the physique.

and doesn't have, as I did. I grew up playing basketball. I still play some basketball. But Michael Jordan was never an inspiration to me because he was so aloof, if you will, physically, from I could not do what he did. Here was this guy who was completely grounded and normal and telling me about how he set out to do this.

And the way he said it actually made me feel like, and you can do it too. And it was fascinating. That probably singularly, his making it approachable, relatable was an important very, and that's why I've kind of tried to do the same to as many other people as I can. I mean, he started that business with like $550.50.

Well, it was 1939 or whatever, but still, it wasn't that much money. It was not that much money, indeed. So, yeah, what happened is that I came back, I started trying to learn about startups in general, not necessarily one that I would do, because I was not close to graduating yet when I was a couple of years out still. then I did in fact get approached by a West Coast San Diego based brand new startup company

which went on to be a very successful, very successful, well-known by a tech company called IDEC. They were just starting at the time and out of, I think, sure, desperation of not having anybody who knew engineering and they needed engineers to be able to make their product. They reached out to my professors and they said, look, who do you have graduating? And they said, well, this fellow is graduating. and literally they made me an offer to be vice president of process technology at this brand new startup, which you might have thought that would have been a golden thing because it was a startup. And you would have guaranteed riches and financial security, all those things, yeah.

All those things. And I would have been a very early person there, et cetera. But what was interesting about that was that that's the first time I started thinking about, you know, what would my contribution be as opposed to, what was my alternative thought, which was, should I try to figure out how to do the startup thing myself? So I remember talking and talking to lots of different people and getting advice. And the advice I got, which in hindsight was quite useful to me from some of my professors,

was, look, if you really want to be in a startup, be in a startup where what you do matters, you can score, you can actually make the contributions. And so that led me to ultimately decide to start a company. So the story I've read, and it's just a bare bones version, is that you decided to go seek funding for your venture. You didn't quite know what it was going to be, but it's going to be a biotech company. And you started to reach out to venture capitalists at the time in 87. And you didn't really know what that meant, but you knew that you had to raise some money. And how do those meetings go?

Well, yeah. So the very first meeting I had, and again, these things all kind of in hindsight seem, I'm only telling you the things that stand in my mind. The very first meeting I had was the Tuesday after Black Monday in 1987. When the market crashed. When the market crashed. And by that time, 25-year-old, having just got my PhD, I had no idea why market crashing would have anything to do with startup funding. So I went literally and pitched the very, very first time to a well-known educational. capitalist, Ginger Moore. And she gave me great advice. She said, look, this could be a good time in a way

to make sure you figure out what you want to do in the company because you're not going to have much competition. Everybody's going to run for the, run for the shore and not really venture out. And if you really conduct the time to figure out what's worth doing, go work on it, get some angel money if you can. And if you persist long enough, this will come back and end up, you know, and I talked to a couple of other people. I heard the same thing. And so that's what I ended up doing. So how did you find the money to start a business? Because biotech is cash intensive. Where did you get the capital?

Well, of course, you know, it's remarkable how, you know, every decade, the amount of money you need to do roughly the same thing goes up dramatically. But back then, late 80s, even early 90s, some of the more, you know, well-known biotech companies were started with $10 million, $15 million. In my case, I only ever raised $11 million over a three-year period from a very year. capitalist, but that was a lot of money. Yeah. So what I needed first was the first couple of hundred thousand.

And how did you get it? I could tell you it was very, very hard. There's no better way of describing it than persistent begging because at the end of the day, if you don't have something and you're proposing something that can't be shown to be either valuable or feasible, then I'm not sure what the difference is between that and begging. Ultimately, what happened is I talked to everybody and anybody I could meet, ended up getting connected to a gentleman named Gus Esselen, and he was interested in investing small amounts of

money, and I got introduced to him, and he said to me, my lawyers will reach out to you, and I'll give you $100,000, which was quite remarkable. It took probably more than a year to get to that point throughout this whole period. Wow. Yeah, and then in the meantime, I lived off of, you know, borrowing from my dad, and basically, I got a part-time job at MIT with my professor, helping him doing some things so I could at least stay afloat. This company you found it was called perceptive biosystems. Right. And I'm going to sort of butcher this, but I'm going to try and explain this in a way that hopefully most of us can understand.

But basically, you produced equipment that separated and identified proteins, which is the basis of most biotechnology drugs. This is what you need to separate these proteins and they need to be intact in order for the research to be engaged. No, you did a very good job, and I can put a finer point to what was the advance. The original advance was that chromatography, which was used to separate proteins, had been developed to work on chemicals, not proteins. Proteins are much, much larger in size than chemicals, and so they move around very slowly. As a result, what used to be a technique that was meant to run for 45 minutes to an hour, with proteins used to run for hours and hours, that limited the pace of advancement in research.

What we invented were particles that had this interesting characteristic where you could actually force liquid to flow through them. As a result, everything went faster so that you can actually separate proteins in 10 minutes, 15 minutes. And we showed that we could do this. We showed the actual theory behind how it was working. And then finally, that led many years later to another technology breakthrough,

which really made perceptive kind of much more known, which was a technology called mass spectrometry. So we worked on inventing a whole new way to cause proteins to be amenable to this type of technique. And that really opened up the protein research space significantly. And our revenues grew quite substantially as a result of that second technology. Newbar, I've interviewed lots of people from the creative arts world, from the scientific community, different spaces where they weren't sort of entrepreneurs or business people and had to really. kind of figure out how to structure a business. Sometimes they made mistakes. How did you know how to do

that? I mean, you had partners and people involved. I mean, even with your investors, you were 24, 25. If they were like, yeah, we'll give you, you know, $100,000 for 10% of the business. Like, how did you know what it was worth and how to structure it? And did you go to anybody for help? I did. I went to lots of people for help. And it's actually one of the more formative things that I've learned, which is that if you don't pretend you know a lot, people are much more prone to kind of advise you and help you. And it's not hard to pretend that when you're 25 years old. But that is the first time that helped me was back in those days. I clearly didn't know much about raising money, spending money, planning, budgeting. I did have a lot of people around me who were willing to

give advice, quickly realized that a lot of that advice was quite good. you know, kind of opposed to each other. So you had to figure out. It's like a ping pong match. Exactly. So what you have to do is you have to actually make some calculated bets. And then I also learned early on just about everything you assume may be wrong. You constantly have to figure out, okay, if I can't keep going down that path, where am I going to go next?

It's too late to think of that once you're stuck, you know, now being opposed by whatever elements you're up against. So there's plenty of people who gave advice. In fact, one of the things I remember very well is in the first instance raising money, I remember many investors by the time I had the story right telling me that they thought I'd be successful, but that they didn't think my first thing would be successful. And so a whole bunch of them told me that they would want to invest in my second company. And the other thing is a lot of people told me, listen, you're smart, you're capable, you got a lot to learn.

You should not be CEO. Yeah. And it was an interesting thing because I thought to myself, I couldn't tell whether what they're saying was good for me or good for them. It was indiscernible. So what I decided to do is I kept talking to people until I found a firm to invest with me as the initial CEO, which is what I had been for the whole time, the year and a half before. And the day after we closed a million dollars, I went to them and I said, I don't want to be CEO. Let's go hire a CEO. And they were like shocked.

And the only reason I felt that way was because I wanted to make sure they weren't investing in not me. but at the same time, I thought if they really think that we should really bring in somebody for a period of time who can help work with me, then let's do that. And so we found a very, very good, late in his career, senior executive. I became chairman and chief technical officer. He became CEO. And for a year, we worked really closely together. He taught me a lot.

He helped greatly. And as you were developing more products for perceptive biosystems, who were your customers? I mean, obviously, most of the people I talk to are making consumer products. So they're like, today it's social media marketing going on Instagram to find influencers. But this is not what you do or did then, obviously. Who were you selling your equipment to? In the first instance, there were a handful of biotechnology companies at the time who were noteworthy, biogen, genentech, MGen, Genzyme. And then there was a whole bunch of pharmaceutical companies, the household brands of, you know, roche and of all.

artists in GSK, Pfizer, etc. And they all had research labs. They had huge research labs. And every one of them used to do what it is we were selling a new technology to do. And so, you know, early adopters were not a concept back then, but clearly early adopters is how you get anything to be taken up. And they become your best salespeople because either they change jobs or they tell their colleagues, hey, I'm doing this thing really cool.

You should look into it. And so eventually we started getting kind of slowly, slowly growing. We're going hired our first salespeople. And eventually when the company grew up in 1997, at the end, we were about 900 people. As the company grew, because I think within 10 years, it was acquired, right? I think it was acquired for a stock swap. It was a $360 million stock acquisition. And oftentimes an acquisition means that the founders who are acquired joined the parent company now.

And you did. I think the company was called Applera. this was the late 90s. And if people remember, this was a time when there was an obsessive race to map the human genome. And you were right there

at kind of ground zero of that. Yes. So A Plera actually was a made-up name that came after the fact. The initial company that bought Perceptive was called Pricanelmer. Ultimately, the thing we decided to do was to become a content delivery company

modeled after Bloomberg, with the Bloomberg terminals, as you may remember. So Bloomberg takes public information, at least dated back then, annotates it, interconnects, it, adds some proprietary layers on it, and then sells it as a subscription, essentially, through terminals. And we thought we could do the same thing with biology, and the Human Genome Project was kind of the actual sequence became our way of actually trying to get people to come to our site

in order to receive all these higher-level connectivities from that baseline information. So this would be like a Bloomberg terminal for biotech companies. Absolutely. That was absolutely the vision. The idea would be like every finance firm had a Bloomberg terminal. Every biotech company would have these terminals and you could access this proprietary information.

That's what we set out to build. We needed to sequence the genome first. And we at first thought maybe the government's effort at the time would suffice, but it was going fairly slowly. And so we launched a what became a. a competitive effort, although it wasn't fully intended to be competitive in the first instance. With the Human Genome Project, you start to compete with them because they weren't moving, it wasn't moving fast enough. It wasn't moving fast enough. We weren't going to wait two,

three more years before this information could be available, but it definitely at the time allowed both sides to do something quite spectacular, which was to complete the sequencing of the genome. In our case, as a prelude to delivering this content business, in their case, as the basis for much of research going forward. It's amazing because you are now, you now spent a year being involved in one of most groundbreaking projects in, I think in the 20th century, mapping the human genome, which clearly you knew was going to have a huge impact on medicine.

Did that experience kind of once again, kind of get the gears turning in your head thinking, there's an opportunity from this for me to pursue? Yes, very much so. But in a different context than just a market opportunity, it was actually a foray into entrepreneurship, which is when a company creates a company. And I'd never thought of that as an activity before, where you literally can have a parent entity conceive of one thing and really develop it internally and then spin it out, which is

what we did. That actually was equally interesting. Of course, being in the middle of this whole kind of public storm, if you will, in many ways, positive-sensitive word and excitement, also pointed out to the fact that we were entering a new era in molecular biology. So that was exciting, definitely. When we come back in just a moment, how the new era of molecular biology just happened to match up with Newbar's idea for an entirely new type of biotech company. Stay with us. And you're listening to How I Built This from NPR.

Hey, welcome back to How I Built This. I'm Guy Raz. So it's the late 1990s and New Bar-A-Fa-N is working at a biotech company called Ablera. And he's involved in lots of different projects. But over time, Newbar is getting more and more interested in promoting a whole range of new promising molecular biology, research that doesn't necessarily have immediate commercial value. And so eventually he leaves up Lera to try to reimagine the way biotech companies are created. The idea was, you know, everybody was all fascinated with serial entrepreneurs and you go from one to the other. But the question that I got intrigued by, I'm not exactly sure why, is could you actually do this at the same time?

Could you have multiple of these things? And I was always curious about the venture capital community, which while they weren't starting these companies, they were investing in them. And they had this parallelism down. They could be involved in therapeutic companies, some in cardiovascular, some in cancer. One didn't seem to interfere with the other. And I thought, well, why can't you do that as an entrepreneur? Why can't you do that as an innovator? And so we started an otherwise unusual entity, which was called Nukogen, and it stood for

new company generation, new co-gen. That business, Nucogen is the entity that later became called flagship ventures and the flagship pioneering. we put up about $60 million. It was a company that would create companies. And that's how we started. The initial four or five projects, we already had some ideas what to pursue.

But it was definitely buoyed by the excitement around the genome. All right. So flagship ventures, now called Flagship Pioneering. This is what you kind of really launch in 2000. And this was, to be clear, I mean, this was very different from, and still is very different from what incubators Usually incubators are incubators and venture capital is venture capital.

And this idea was different. I mean, the idea was that everything would happen under one roof. Exactly. The research, the development, the teams, the businesses, almost like an MIT Media Lab, but that was a private business. Well, it's an interesting way of putting it. I'll tell you that what we set out to do is to combine the typically three separate inputs into a successful startup, that is the scientific ideas, usually comes from academia, the entrepreneurial talent,

and then capital, which is always multiple sources, venture capital, early stage, and then eventually some later stage. They all come from different places, they have different interests, and so you could imagine there's a lot of friction between all these different components. What we thought is, what if all three of those things pre-existent in the, you the same entity. Yeah. Because if you want to propose doing something that is way out there, if you will,

if you're doing it a traditional way, you have to convince other people to join you. And in any case, you have to convince investors to fund you. And all they care about is to minimize the risk. And so that's where we really found our footing is to say, can we take that advantage of having all three under one roof and apply it to propel ourselves beyond where people are comfortable going. Newbar, obviously by this point, when you started flagship, you were a known entity.

People knew the story of your previous businesses. But how did you recruit talent to come to flagship and to take that leap that you guys would have their back? Well, I would say it took quite a while. So the first battle was hiring leadership into our companies because our own team size didn't have to grow very much, but the companies we were forming needed to attract leadership. And that was where we started really thinking more systematically,

what kind of people could make the transition, unlike the software field, and for that matter these days, internet-based companies or apps, there's a lot of people who've done multiple companies. In biotech, these companies have a half-life or a life cycle of, say, 10 years, 15 years. So people don't do one company after another, after another, after another. If they do one company after 10, 15 years and they succeed, they stop doing it. So you had to create the talent.

You had to create and cross-fertilize. And so the early leadership of our companies is all flagship the universe. And what that does is it doesn't mean that they're any better. It just means that they're more experienced and we're more familiar with them. You had a huge advantage in that you were in one of the biotech capitals, of the world, which is the Boston area. But I imagine you were recruiting, probably promising graduate students and scientists. Do I have this right that you would basically pair them up with people who could help to navigate their businesses? So presumably people with science backgrounds,

but who could do the business side of it? In the earlier days, it was a more of experimental, if you will. I did a lot of that just because I had quite a bit of experience by this time. You would just go from little company to company and kind of help them out guide them. There was a time back a decade ago when I would have been on 15 different boards and literally was kind of running around trying. I had a colleague, Doc Cole, who was with us now as a manager partner. So it was just early days in 2000, 2007, 8. We were figuring out what can be systematized and what cannot and what is a team sport and

what is not. You know, there's a lot of folklore in the startup world, which I'd say emphasizes the role of the individual. There's a hero kind of notion that's created, you know, against all odds. And here we were claiming that conceiving, creating, growing companies could be the object of a company. Very methodical, very learning-oriented, responsible to certain goals or accountable, let's say, versus kind of improvisational, romantic, chaotic, all the things that come to mind when you think of startups. I've spent the last 20 years together with my colleagues here

trying to show that most of that is unneeded. Some of that may be needed. Some of that may be how people decide to do it, but that's not like that's the only way you can do it. And just to be clear, most of these companies that you were hatching and forming, they were focused on biomedical research mainly? They were focused on biomedical research

or applications of life science in sustainability. Got it. So there are a lot of stories, like origin stories around MRNA research that go back to the 70s and the 80s. And Bob Langer, who is, he's one of the best biotechnologists in the world. And he would go on to become a Moderna co-founder. He was doing all kinds of research. And in the early 2000s, I read a story about some researchers from University of Pennsylvania. Pennsylvania, who were doing some pretty groundbreaking work around MRNA.

They went to a scientific conference, and almost nobody, this is 20 years ago, almost nobody in the scientific community was taking this seriously. When did you first, what did MRNA research first come onto your radar? Let me answer that by first pointing out to you that five years ago, nobody was taking R&A research seriously. That's kind of an interesting thing. But back in 2010, May of 2010, got a call from Bob Langer one day, and he said to me, hey, look, I just met with a junior faculty member at Harvard who approached me.

And so I went over and met with him and met with the faculty member, Derek Rossi. And he showed some of the scientific work that this lab had done. Essentially, what they had done is they'd taken MRNA and used the codes for the four what's called Yamanaka factors. Yamanaka factors are transcription factors. Think of these as proteins that interact with the human genome and control what genes get made and what genes don't get made. And that's what he was presenting and he was interested in that as potentially the basis of something useful in the biomedical research field. I got interested in the spot.

What if we could do this to introduce it into the body and have our own cells make. drugs at it. And so I asked that question in the meeting with Bob. He said, look, I don't, I don't know why we couldn't try. And so what ended up happening is we agreed that I would go back and initiate a project within flagship to start exploring whether that could be something of interest and use without any regard to whether we could technically do it or how we could do it, but rather more just explore, could we think about a molecule that when introduced to the body could cause the body to make any protein we wanted. And that's how the journey started for us.

That's what became a dana. It's amazing. I mean, the idea was that you had was, could we basically, you know, could you make medicines where you would inject them in order for the body to develop the proteins, right? To combat the ailment or whatever it is. That was the question that was being asked at the time?

That was the question that we asked as the, impetus for an exploration. And the answer to that question in general was, no, that's ridiculous. Is that, is that right, more or less? Well, the premonition was that it was ridiculous because it had never really been shown to be viable. And we, you know, by asking the question, we gave ourselves the permission to go find out why it is that either nobody had done it or nobody believed it could be done. And we quickly found out that people had tried it in the 80s and they had caused pretty significant immune response in cells. So people had this idea earlier. But it turns out it's not just the mRNA and the immunology. You then have to figure out which cells are going to take these up.

How much do they have to take up to make therapeutic doses available in your circulation? How do you know if the protein is actually the right protein, meaning will it fold correctly, will it secrete correctly? I mean, you're basically going in and introducing a tiny new piece of software, not hardware. You're not messing with the hardware, the genomes, but the software, to make a particular protein in a sea of thousands of other proteins being made every nanosecond of the day. So you got to get in precisely, make the protein you want, have the effect you want. So there was a lot of, as an engineer, there was a lot of unknowns, but we could list them and we could start asking a lot of people out there, what makes you

think it can't be done, what are the impediments, what has been tried. That's how, we do much of our innovations, that we kind of work backwards from an asserted destination, we want to be able to do this and then try to tie it to the present. I wanted to ask you about doubt. I mean, I understand that Flagship was really designed to do exactly this kind of work, to take on something risky and kind of weird and maybe the scientific consensus was kind of not. There was no consensus. The community was skeptical of this research. I understand that flagship was designed for this very reason in order to to take some risks that might fail. But I'm curious, I mean, this was going to require a lot of money, a lot of time, and a lot of uncertainty.

And most, I mean, you had great researchers and scientists. I mean, didn't anybody in flagship that you talked to say, this is not what we should pursue? Didn't anybody push back? Didn't you have doubts? I think I should try to put it in context. The important thing to realize is that we are set up to make innovation leaps that are beyond adjacencies. So the notion of adjacency, if you just simply on a piece of paper said in any given field, in any given endeavor of activity, I could draw a circle and let that circle, represent everything that's known or everything that exists.

And then I draw another ring around that circle that represents all sorts of things that have not yet been done, but are going to be done next. So imagine a sense of the arrow of time going outward from one circle to the next ring. And that's kind of, for me, a simplistic mental model of how innovation, science, products in the marketplace occur. Now, what defines the size of that adjacency? It's how far people are willing to go before they stop thinking that something is reasonable to work on. So the question is, when will we ever work beyond that adjacency? And in the ordinary course, you get there when you get there.

So you wait for a while, some new things happen. And then eventually you start working on what would have been too far out before, but now it's not so far out. So our job is to see if we could work beyond the adjacencies today. But what I'm trying to understand, Nubar, is this could have been a very different story, right? The story of Moderna could have been a story of folly of a bunch of, you know, well-funded scientists who just spent all of this money and it was a disaster. And we could have been telling that story at business schools, right? I mean, there's always a possibility that would have been this story. And by greenlighting moderna, you had to consider certain factors.

But if most of the scientific community was saying, this is not worth doing, why did you and your team think differently? So you're asking the question, again, in the context, it's a very valid question, but I want to say you're asking the question in isolation. Let me also just tell you that in the exact same year that we did the foundation laying for what became moderna, we also started four other projects that were each platforms in their own right going after different aspects of biomedical opportunity space, each with as big a leap, each with as much doubt, and we did that the year before, and we've done that for the 11 years since. So in fact, I've described this before, and I think it's really important to understand. We didn't conceive of moderna.

We conceived of 100 different modernas. Right. And what's happened is, and this is very much how I look at this, is that experiments and reality and execution have dictated which of those modernas got to live and which of those modernas got to die. How many of those other, quote, modernas didn't make it? You said we launched 100. A lot, a lot. We didn't launch 100. We imagined 100. And so the point I'm making is the accuracy with which you have to guess what's going to work is not at all important. Because we get into these brand new areas, it's wide open to find where value lies.

Imagine if we waited three, four years, as people did, or 10 years in the case of M RNA. Now all of a sudden, they'd go into the space and there's hundreds of patents and there's tons of different things that have already been done. That's a very different competitive approach. What we tend to do is say, you know what, we'll risk the possibility that there's absolutely no value to be had. So it's not that you have to get it dead right where you land. You just have to be in a rough space where you now start searching for where value, might be. Is it delivering it into the liver or skin? Is it delivering, you know, doing vaccines or cardiovascular drugs? So all of those variables, at least for me, represent alternative success

versions of which I don't need everyone to succeed. I just need one to succeed. When we come back in just a moment, one version of success that Newbar did not anticipate was how Moderna would develop a critical vaccine at a critical time and do it unbelievably fast. Stay with us, I'm Guy Raz, and you're listening to How I Built This from NPR. Hey, welcome back to How I Built This. I'm Guy Raz. So we're getting to the part of the story where Moderna will go from being a biotech company you probably never heard of to a household name for tens of millions of people. And it's easy to forget that when the company launched in 2010, the idea of was to find the best use for the new research around MRNA. And at that time, it wasn't at all clear that the best use would be a vaccine.

We worked from day one on any number of diseases, cardiovascular disease, cancer, and vaccines were a part of our thinking process. But indeed, what we did do is we went after everything. That's the 100 versions of Moderna that I'm referring to. We did not think for a minute that we were smart enough to anticipate what we should actually apply the platform to. And this is something else that probably is worth pointing out. We have over the years in our flagship labs kind of realized that rather than inventing technologies, we really ought to invent platforms. And a platform is a relatively rare thing in biotechnology, unlike in the tech sector, where we've seen phenomenal examples of platforms, whether it's.

the iOS, you know, Apple's platform or Amazon's, that whole idea of a technological suite upon which many, many products could be developed or attached. By 2010, before we even started Moderna, that is something that we had started many, many companies around that notion. And so, Moderna only ever was going to be a platform that enabled a code-based molecule to make proteins in the subjects, no matter what application it was. And a key discipline of that is to say, try many, many applications. And so we had, by the time this coronavirus came along, we had tested nine, maybe even 10 different human vaccines in every single case showing neutralizing

antibodies. And we had also another nine programs that were going after human therapeutics. So it was a fairly broad platform that had already been developed. About $2 billion of research had gone into developing the platform. Yeah. You went public in 2018. You still hadn't sold any products, really. You had an operating loss of almost $400 million. $2019 still, this is nine years in to Moderna. You had not, I believe you had not sold anything yet, and you had almost half a billion dollars in losses. But none of that seems like, like none of that seemed to phase you or the team at all. Like that was not even a concern. Yeah. So it's not. And in fact, guy, what I can tell you, having spent the last 34 years in the biotechnology field, is that there is no biotech company that was

started in 2010 with rare, rare exceptions, maybe one in a hundred, that had revenues by that time. Right. And so it's perfect. course in the sense that that's not because of the failing of the technology. That's because it takes five to ten years to actually develop a product in our field. So it's a little bit like saying, you know, I want to start a new airplane company. And then I'm surprised that I don't have an airplane on the market in the first 10 years. Well, it takes 14 years. Now, what would have been surprising is if we didn't have products in clinical testing. And that's something that was completely missed because before a single vacuum,

for coronavirus that we tested, we had already 2,000 people who had received RNA from us. Yeah. And so we were far, far advanced in actually many, many different MRNAs for different activities, vaccines, non-vaccines. And that's what allowed us to have the conviction that what we would do in this space could be quite productive. Okay, let's go back to the timeline for a moment, because it's almost like, it plays out

like a movie, like a thriller. And from what I understand, I think it was like January 6th, 2020, Stefan Bancel, who's the CEO of Moderna, he found out about this virus in China and that it was probably a coronavirus. And I think a few days later, the first death was publicly announced in China. And at that point, I think that's January 11th, 2020. Almost no one in the U.S. was talking about this seriously or on a big world. way. I mean, probably a few people, but almost nobody. Do you remember this story of coming onto your radar around that time? Well, in the very early parts of January, we were exchanging emails and articles that were, you know, kind of appearing largely around the Wuhan situation. Initially,

it was not to be a flu-like thing, pneumonia. And it wasn't until January 23rd, which I remember quite clearly, partly because it was my daughters, one of my daughter's birthdays and so. And so, I was out at dinner with her in Cambridge, close to MIT. I actually got a call from Stefan, who was in Davos. The situation had increased in terms of intensity. It was not clear what this would become. It was not a pandemic. There was not at all viewed that way.

But that it could become a threat was beginning to at least appear. And our discussion, interestingly, was twofold. One, we probably didn't have any choice, but to at least do the first steps of this work, because if we didn't, then we'd be late reacting to it later on. But then second, it was an interesting opportunity for us to test the platform in one of its earliest, at least imagined advantages that we could never test in any other time,

which was that it would be a very rapid response technology. This technology had this innate advantage. We knew from day one that if you ever needed to go quickly, we could really go quickly, So it's just a code molecule. You just put the sequence in for the DNA. You make the RNA in one step. You put it in an LMP in a second step and you're done.

I mean, it's, I'm simplifying, but not by much. And so what was exciting to us was that we said we want to test our platform's ability to demonstrate very rapid capability to respond. And we did not know what an advantage that was. I mean, I think virtually overnight you and Stefan decided to pursue this, to try and do this, to manufacture the vaccine. Absolutely. It looked like the right thing to do and an incremental proof point for us that we were happy to jump into. Now, I must say, within days, probably a couple of weeks, the whole thing changed in its importance and significance. And we were quite happy that we had jumped in so early on because that's the only way that by already March we could enter the first humans and get data. How long before you had a prototype for the vaccine? Because from what I understand, the fastest time it took to get a vaccine from development to market was, I think the MMR, one of these childhood things. Measles. Yeah. It was like five years or something. So in this case, how quickly were you able to develop a prototype?

From the time we had the sequence to the time we had. The sequence of the coronavirus. Of the coronavirus. Which the Chinese published, I think, right? They made that available. That's right. And to the time when we had the computer-generated sequence of the RNA that is essentially today, MRNA 1273, was two days. Two days from the time that it was published, you basically had a computer model of a vaccine.

Basically a computer model of the sequence of MRNA that would essentially, when introduced into a human, would produce the S-protein. sufficient to generate an immune response. I mean, at the time, did you know that if it just got into clinical trials, it would quickly be shown to be effective? Like, did you know that from the computer models? Well, we knew that in every other protein that we had used in humans before, we could generate neutralizing antibodies. That much we knew. Whether we could make enough of it quickly enough, let alone to be able to do a 30,000, in a subject trial, which we'd never, ever done or dreamt of before, that was the unknown.

The unknown was, can you make enough of it? And we had some questions as to what dose we should choose. But essentially, there was a lot unknown, and we just had to kind of decide based on the best information what to try. We tried it. And by May of 2020, we had already the first human data that showed that we could generate robust antibody levels. In March of 2020, you began clinical trials with the NIH.

It was, I think, a nurse in Seattle. That same month, March of 2020, your father-in-law died of COVID. April. Yeah, April is when he passed away. In Sweden. Yeah, in Easter. I mean, this was affecting all of us. I mean, everybody knows somebody who was either severely ill or was killed by this.

I was devastating because his wife, a mother-in-law, also got quite sick, and we thought we were going to lose her as well. They were both in their early 90s. So it was very, very tough also because, you know, we were engaged in this day-to-day battle. And on the one hand, I was excited by what we were able to do. And on the other hand, when you see, you know, in his case, ultimately a life lost. You know, it's a... Anyway, it was quite personal to me.

Let me just say that I have not lost a family member during the time of iPhones. And I can tell you that being on a FaceTime with somebody close to you, when they're dying is a miserable, miserable experience. It was very tough. And it certainly made, brought into sharp focus what this was all about. Certainly many, many people lost lives and many more are suffering yet today with the downstream effects of this disease. New Bar, you knew already from that first clinical trial that the news was good, that the initial results from phase one were good. but you had to go through two more phases.

And we, the public, were not privy to that information for a variety of reasons, right? You could not come out and say, hey, phase one looks great. These are the results. There are rules against that, right? Well, we indeed, in May, we indeed did come out and say at a very high level that we had some encouraging results. And people attacked us every which way for having said that because they basically said, well, that's doing science by press release and many other things. And the reality is when you have a pandemic and you're a public company and you've got material data, our sense was that we at least

needed to at a high level put that out there. So one of the things we learned, because none of us have been in this situation before, and was that we were going to get criticized no matter what we did. And so we just had to do what we thought was right, make some calls, you know, explain ourselves. And so we did that. We ultimately published the data. The NIH came out. presented their data. We were quite surprised that people were questioning the NIH's own clinical clinical research. We didn't do the clinical work. They did. Yeah. By the end of the third trial, phase three end of November, and you announced that the preliminary data showed that the efficacy rate was 94%. Did that surprise you, even you? It did surprise me, and it didn't surprise me

scientifically, it's surprisingly me by that time I had lowered my expectations largely by having heard so much about how difficult all this would be. If you look at how vaccines are made, they either take bits and pieces of proteins and they make them artificially and they combine them and they put adjuvants that kind of get your immune system to get angry. There's nothing molecular about the current approaches. Here we were putting in a single protein, delivered a known way to specific cells. And so we were really priming the immune system. But still, there was no basis to believe that we could do 90 anything.

It's not at all typical in vaccines, let alone with a new technology, let alone out of the gates, that you start at 94. We thought if we were well above 50%, at least we will start putting up a fight and maybe we can make a better and better version. And in parallel to the testing, presumably you had to ramp up your ability to produce this vaccine. Yes, and that was really the massive heroism that I think of all the things that we could not imagine that we could make a billion doses, the first year of production, up from probably making a thousand doses the year before of anything. How did you do that? How did you go from the capacity to make a thousand or ten thousand to a billion in less than a year?

Well, first of all these things start with people. we had a great fortune of having a gentleman named Juan Andres, who as head of our whole technical operations, manufacturing, quality, the whole field previously held that role at Novartis, one of the largest pharmaceutical companies, had gone through previous flu epidemic kind of scale up of vaccines of that generation and just is a phenomenal leader of people. And he was really a godsend to us. And when it came to planning rapidly, responding, organizing, hiring people, and just not taking, that's not possible for an answer for just about anything that they did in terms of either timeframes or scale. And several months later, we started producing millions of doses and then eventually tens of millions and hundreds of doses. What does this mean now? I mean, what does it mean for the development of other vaccines or other treatments? I mean, has this, at least to the scientific community, proved that you can really maybe develop a long-lasting flu vaccine or a malaria vaccine or an HIV vaccine?

Like, is that within the realm of possibility? Well, you asked me two questions in one. One was, has it proved that? The answer is no. but does it suggest that that's possible and perhaps wise to work on? The answer is yes. That's a better question. And we are working on it.

No, no. And I'm only saying it because, look, I learned long ago Thomas Cune and all these guys who've written on these things that, you know, the scientific process is one of organized skepticism. Yeah. And that organized skepticism is a good thing because it keeps you constantly looking for proof. I would say that there's a slightly greater reason to believe that MRNs. could actually be a new drug modality.

But the other thing it does, just to come back more broadly to what it is that we've been doing in flagship is that it illustrates that yet again, completely transformative things could come out of unreasonable beginnings and that if all you do is look for reasonable beginnings, you're probably not going to find breakthroughs. It's probably remarkable to younger people today that everybody had their chicken pox. not that long ago. And kids don't get it anymore because there's a vaccine. Is there a potential future where there's no such thing as seasonal flu?

That I cannot say, although I never want to say no to that either. Right. Because more broadly, I raising an issue, which is important to me and I've worked for the last two years. And that is broadly what I would view as health security or practicing medicine in a preemptive way. And what I mean by that is we've learned so much about disease that we realize that disease isn't just a switch that goes on and all of a sudden now you have it and you have to fight it, but that there are long ramps, kind of on ramps towards disease,

that if we could intervene long before the disease is manifest and we can find it now with new techniques, then both to prevent it through vaccines, but also to delay it, slow it down, redirect it. There's many things we can do. And I think unless we do those, things. If all we do is wait for diseases to be good and advanced until we start treating them, the cost of that, the human loss, as a result of that, is just going to be prohibitive.

So in the same vein, I can't imagine a time when seasonal flu is mastered and basically kept up bay. Why? Because I think that we're learning enough about the immune system that if we intervene early enough and broadly enough, we may well create a shield, a protective shield. shield against these hyper-variable viruses like influenza, like corona, like rhinovirus that causes the common flu, like HIV. I mean, there's a lot of these threats that aren't just themselves threats, but they're hyper-proliferating threats. And for that, our immune system is the only answer. Newbar, when you think about the arc of your career and your life, you know, a chance meeting

with David Packard, who kind of inspires you to think about maybe starting your own thing, Taking a gamble on MRNA, which would lead to the fastest vaccine ever manufactured in history, to now, you know, Moderna was founded 10 years ago. I think it's market cap. The last I checked was almost $170 billion. And that's just one of the businesses you started. It's a pretty remarkable story. How much of your, of where you are today do you attribute to how hard you worked and how much. How much do you think has to do with just luck? How hard I work is a function of probably the orientation that I had that as an immigrant, you don't really take much for granted. You don't think much is owed to you, and everything is a possibility. And you have to go get it. In my case, the motivator has been truly trying to figure out if we could innovate a new way

to innovate. So hard work, yes. In terms of luck, you know, it's ironic that you ask me that because somebody had written to me something the other day that I wanted to respond to, but I didn't by saying better lucky and good, in the sense that I think that to some extent, counting on luck is not a strategy. But it is the case that no matter how hard you work, there's no guarantee that the opportunity will come up or that you will fail to fail long enough to succeed. These are all things that otherwise can only be explained by chance. But I don't know what to do with that because I can't count on it. I can't summon it. If I could summon it any time, that would be fun, but I can't.

And so therefore it doesn't play any role in my actions. And when it comes, it comes. That's Nubar a fan. He's co-founder and chairman of Moderna. And he's also the founder and CEO of flagship pioneering. Today, Moderna is probably the most famous biotech company Nubar has developed. But since it was founded over 20 years ago, flagship pioneering has helped launch more than 100 other companies. And of those, 30 are now publicly traded.

Thanks so much for listening to the show this week. If you're not yet a subscriber, please do subscribe wherever you get your podcasts. If you want to write to us, our email address is hibt at npr.org. And if you want to follow us on Twitter or at Guy Raz or at how I built this. You can also find us on Instagram. That's at How I Built This NPR or my personal account at guy.org. This episode was produced by Casey Herman with music composed by Rumtin Arablui. It was edited by Neva Grant with research help from Claire Murashima.

Our production staff includes J.C. Howard, James Delahousie, Rachel Falkner, Liz Metzger, Julia Carney, Faris Safari, Elaine Coates, Annalise Sober, and Harrison V.J. Choi. Jeff Rogers is our executive producer. I'm Guy Raz, and you've been listening to How I Built This. This is NPR.