Moderna and Flagship Pioneering: Noubar Afeyan

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 And so

Was that we were gonna get criticized no matter what we did. From NPR, it's how I built this. about innovators, entrepreneurs, idealists.

No. I'm Guy Raz and on the show today, how Nubar of Fans 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, is 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 totally 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. You bar of fan. Moderna, as many of you know, is created one of the major and most important COVID vaccines.

But Moderna, the company, came out of that larger organization called Flagship. Nubara Faye 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 a hundred 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. Okay. The story of how Nubar helped to build Moderna is also the story of how he co-founded 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 nineteen seventy five, 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 five o'clock in the morning with a gigantic explosion, which was a a building, a rather large building, maybe a block away from us, that was completely leveled. And you know, with with lots of dead people and and just it was just like for a twelve year old at the time. That was very uh uh shocking. But then when the war actually the civil war actually broke out, we we stopped going to school, so

From the beginning of seventy five. Till probably May June we were at 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 uh kind of underground uh areas. Um you know, there was we would watch um

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. Um and I know I know Nubar that your dad had this thriving business. You he would import plastic products um into Beirut

But I guess around this time in nineteen seventy five, you were about thirteen the family your family left. You you fled. uh from Lebanon to to Montreal and Canada. Um that is a you know, that's a was a pr simply a huge kind of risky decision.

for your certainly for your dad. So what what did he do when you got to Montreal? Like and and what did the family leave behind? So we left the apartment we owned, we left all of the warehouses of equ of of uh inventory he had, just left it completely. Just left it in Lebanon. And he actually he went back for the first time eight years later. to actually liquidate what he could. But anyway, so so when he came to Montreal, interestingly Um 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.'Cause your dad must have been in his forties. By then.

Yeah, my father was born in twenty nine, so yeah, we could do the math probably definitely in his forties. When you got to Montreal I'm assuming you didn't you were not fluent in French. So you probably had to I mean,'cause you you went to school. Presumably it was school was taught in French?

No, so so Montreal in seventy five was still very much a bilingual place f in the full sense of the word, meaning that you could coexist uh 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 uh school, an all boys school, it was English, Loyola High School, but in the following three years in high school took advanced French and and learned the language alongside English, which was the main language of the school. Did you grow up, um, going to church every Sunday. Um obviously the Armenian Orthodox Church is a

Ancient. Church um goes back to I think Did you grow up going to Yeah.

Um I grew up going to church. Not only now you're making me reveal all sorts of stuff that I've never talked about. Uh I was I was a choir boy from probably seven, eight years old till till I came to Montreal and I continued in Montreal, as did my brothers. Um so we did go to church, I'd like to say every Sunday, but probably it was most Sundays uh throughout the year. So it's most most Armenians had a close interaction with the church and and we certainly did. Alright, so you are

In Montreal and Um I know that you went on to to study uh chemical engineering at McGill in Montreal. But then you went to graduate school in the US, you went to MIT in in Boston and From what I read, you 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 gotten in. But I must say I didn't know then. I I just wasn't Maybe this is I've learned since this is all kind of a

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, there may be 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. Um, and ultimately ended up uh joining a lab. And pursuing a a PhD. And everybody wanted to start doing this form of chemical engineering, biochemical engineering, because it was clear that a whole new industry

Without the necessary engineering, cadre of engineers and And principles. to apply to actually making the

the end product. So it was a Really fortunate time. to be entering the field. Took it took about four years. So yeah, I was I finished in the summer of Nineteen eighty seven. All right. So so you've got this

PhD in N 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, you know, 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 that you thought yeah let me Why don't I start my own my own business?

Um it would have made for a Good story if that was the case, but it turns out it wasn't. I I did not think of starting a company Based on my upbringing. Okay. Uh so in nineteen eighty five. I had occasion to go to Washington, DC to a conference that had been put on by the National Science Foundation. And by chance I had a I sat next to a person at lunch and 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 uh some maybe thirty years earlier

had graduated from a brand new field of engineering, then called electronic engineering. And uh 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 that make instruments That their colleagues, their friends would use. in doing what they did. And they had invented the oscilloscope and and decided to make some and provide it to their friends. And they started out in a 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 he was David Packer. He was Packer. Uh literally. Wow. And and I had like it was really fascinating. Eighty five. So he must have been you know, gu I think he died in the in the mid nineties. He was an old guy, but older. He was a he was he was m yeah, he was older certainly. I mean I I I haven't thought back as to what his age was, but I wouldn't be surprised if he wasn't his

Seventy, maybe seventy, seven at least that's how he looked to me. But very kind to spend the time and to make and 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 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 I kinda 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 gonna do this. didn't specify technology. It literally just said, We're gonna develop instruments that kind of address needs in the biotechnology field and and I quickly learned that you can't Raise money on that. You have to actually have something to do with the that's a long story. We're just gonna start something in biotech and we'll f kinda figure it out. And but it is amazing to me that that meeting with David Packard because he was

I mean of course everybody knows that name now, right? You lett Packard in an A but it's really sounds like that encounter kind of started to get the gears in your head. Turning. Well, yeah, it definitely and 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've grew up playing basketball. I still play some basketball, but I in the Michael Jordan was never an inspiration to me because he was so So aloof, if you will, physically from I could not do what he did.

Here was this guy who was completely grounded 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 the His making it approachable um 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 five hundred and fifty bucks. Well, it was nineteen thirty nine or whatever, but still it wasn't 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. I mean I was I was a couple years out still Then I did in fact get approached by A West Coast San Diego based Br brand new startup company which went on to be a

very successful, very successful one known by a tech company called IDEC. Uh they We're just starting at the time and out of I think sheer desperation of not having anybody who knew engineering

uh and they needed engineers to be able to make their product. Yeah. They reached out to my professors and they said, look, who do you have graduating? And And they said, Well, this fellow's graduating And uh literally they made me an offer to be Vice President of Process Technology at this Brand new startup.

Which which you might have thought that would have been a golden thing, because it was a startup. And you would have been guaranteed riches and and financial security and all those things, yeah. All those things. 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 kind of I 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 and you can score. You can actually make the the the contributions. And so that led me to ultimately decide to start a company. So I the story I've read and and it's just a bare bones version is that you You decided to go seek funding for your Venture, you didn't quite know what it was going to be, but it's gonna be a biotech company. And you started to reach out to uh venture capitalists at at the time, in eighty-seven.

And you didn't really know what 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 out my mind. The very first meeting I had was the Tuesday after Black Monday in nineteen eighty seven. Well when the when the market crashed. And as a

By that time, twenty five year old having just gotten my PhD. I had no idea why market crashing would have anything to do with start up funding. So I went literally and pitched the very, very first time to a well-known venture capitalist, Ginger Moore. And uh 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 gonna have much competition. Everybody's gonna run for the run for the shore and and not really venture out. And if you really can take 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 and end it up, you know, and I talked to a couple of other people, heard the same thing, and so that's what I ended up doing. So how did you find the money to to start a a business? Because biotech is 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 um back then, late eighties, even early nineties, some of the more, you know, well known biotech companies were started with ten million, fifteen million dollars. In my case I only ever raised eleven million dollars. over a three year period from venture capitalists, but that was a lot of money. Yeah. So what I needed first was the first couple of hundred thousand and 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 Eslan. 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 a hundred thousand dollars. Which was quite remarkable. It took probably you know, more than a year to get to that point throughout this whole period. Wow. Um 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 stay afloat. Um this company he founded was called Perceptive Biosystems. Right. And um I'm gonna sort of butcher this, but I'm gonna 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 of of most biotechnology drugs. This is what what you need you need to separate

these proteins and they need to be intact in order for the research to be engaged. No, that you did a very good job, and 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 forty five minutes to an hour, with proteins used to run for hours and hours. That limited the pace of advancement and research. What we invented were particles That had this interesting characteristic where you can actually force liquid To flow through them. As a result, everything went faster.

So that you can actually separate proteins in Ten minutes, fifteen minutes. And we showed that we could do this. We showed the 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 the protein research space.

significantly, and our revenues grew quite substantially as a result of that second technology. You are um I've interviewed lots of people from from the creative arts world, from the scientific community, different spaces where they they didn't They weren't sort of

entrepreneurs or or business people and had to really kind of figure out how to structure a business and sometimes They made mistakes. Um How did you know How to do that. I mean you had

Partners and people involved and I mean Even with your investors. You're twenty-four-twenty five. If they were like, Yeah, we'll give you, you know hundred thousand dollars for ten percent of the business. Like how did you know

what it was worth and how to structure it and did you Did you go to anybody for help? I did. I went to lots of people for help and 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 twenty five years old. But that is the first time

that helped me was 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 are willing to give advice. quickly realized that a lot of that advice was quite, you know, kind of opposed to each other. So you had to that's the challenge, right? 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 And then I you know, 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 gonna go next? Yeah 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

Th there's plenty of people who gave advice. I had 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 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. Yeah. It was indiscernible. Yeah. 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 the million dollars, I went to them and I said I don't wanna 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, you know, 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 he up greatly. And as you were developing more products for perceptive biosystems. Who are your customers? I mean I mean m obviously most of the people I talk to are are making consumer products, so they're like, today it's social media marketing and going on Instagram to find influencers, but this is not what you do or did then, obviously. Who are you selling your Your equipment too. Um, in the first instance, there were a handful of biotechnology companies at the time who were noteworthy, biogen, genentec, amgen, genzyme, and then there was a whole bunch of pharmaceutical companies, the household brands of you know Rotion, Novartis and GSK, Pfizer, etcetera. 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 in U Technology to do. And so, you know, early adopters were not a concept back then, but clearly early adopters is how you how you get anything to be taken up and 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 s slowly, slowly growing higher for salespeople. Yeah. And eventually when the company

Grew up in nineteen ninety seven, at the end we were about nine hundred people. As the company grew, because I think within ten years it was acquired, right? It was I think it was acquired for as a stock swap. It was a three hundred sixty million dollar Stock acquisition. And oftentimes an acquisition means that um the founders, uh who are acquired, join the parent company now, and you did.

Um I think the company was called Applera. This was the late nineties and and if pe people remember, this was a time when There was an obsessive race. To map the human genome. And uh you were right there at kind of ground zero of that.

Yeah, so so a player actually was a made up name that came after the fact. The initial company that bought Perceptive was called Brick and Elmer. 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 they did 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 uh kind of the 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 uh connectivities from that baseline information. So this would be like a Bloomberg terminal for biotech companies. Absolutely. That was the 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. Um we needed to sequence the genome first, and we at first thought maybe the government can the government's effort at the time would suffice, but it was going fairly slowly. And so we launched a what

became 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 gonna 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 you are now you've now spent a year being involved in One of the most groundbreaking projects in I w I think in the twentieth century, mapping the human genome, which is Clearly you knew.

was going to have a huge impact. On medicine. Did that experience kind of Once again, kinda get the gears turning in your head. thinking there's an opportunity

from this for me to pursue? Um yes, very much so, but in in a different context than just the market opportunity. It was actually a foray into intrapreneurship, which is when a company creates a company. Right. And I'd never thought of that as a 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. Middle of this whole kind of uh Public

Storm, if you will, in the in many ways positive sense of the word, and excitement. Also pointed out the fact that this 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 Nubar's idea for an entirely new type of Biotech Company. Stay with us, I'm Guy Raz and you're listening to How I Built This.

N PR. Hey, welcome back to how I built this. I'm Guy Raj. So it's the late 1990s and Nubora Fayin is working at a biotech company called Aplera. And he's involved in lots of different projects. But over time, Nubar 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 Uplara to try to reimagine the way biotech companies are created. The idea was You know, everybody was all fascinated with serial entrepreneurs and

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 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 you know cancer. Didn't 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 Nucogen. And it stood for new company generation, new cogen. That business, nucogen is the entity that Later became called flagship. Ventures and the flagship pioneering.

We put up about sixty million dollars. It was a company that would create companies, and and that's how we started. The initial four five projects we already had some ideas what to pursue. But it was definitely buoyed by the Excitement around the genome. Alright, so this was so flagship ventures, now called flagship pioneering.

This is what you kind of really launch in two thousand. And this was uh to be clear, I mean this was very different. From And still is very different from what

incubators are usually incubators are incubators And venture capital is venture capital. And the 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, like almost like a like an MIT media lab, but that was a private business. Well, it's an interesting way of putting it. I'll tell you, you know, that what we set out to do is to combine The typically three separate

Inputs. into a successful Start up. 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 different components. What we thought is what if all three of those things Pre existent. In 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 the traditional way. You have to convince Other people To join you. And in any case we have to convince investors

To fund you. Yeah. 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 y people are comfortable going. Nubar, obviously by this point, when you started Flagship, you were a known entity. People knew the story of your previouses, but how did you recruit? Talent to come. to come to flagship and to

Take that leap that you guys would would have their back. Well, I would say it took quite a while. Um 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 saying. Ten years, fifteen years.

So people don't do one company after another after another after another. If they do one company after ten, fifteen years and they succeed. They stop doing it. So you have to create the talent. You have to create and and cross fertilize And so the early leadership of our companies is all flagship developers and You know, that 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 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 you 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 it was a more experimental, if you will. I I did a lot of that. Just because I had quite a bit of experience by just a little bit. You would just go from little company to company and kinda help them absolutely. There was a time back a decade ago when I'm when I would have been on fifteen different boards and literal literally was was kind of running around trying. I had a colleague, Doug Cole, who's was was with us now as a manager partner. Uh so it was just early days in two thousand, two thousand seven, eight. We were figuring out what can be systematized and what cannot. And what is a team sport and what is not. Uh uh you know, there's a lot of folklore in the

Start up world. Which I'd say emphasizes the role of the individual, there's a hero kind of a notion that's created, you know, against all odds and And here we were. Claiming that

Conceiving, creating growing companies could be the object of a company. Uh very methodical, very uh 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 twenty 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 forming They were focused on biomedical research. Mainly. They were focused on biomedical research or applications of life science in sustainability.

Got it. So so there's a there are a lot of stories, um origin stories around MRNA research that that go back to the seventies and and the eighties and um a Bob Langer who is um Uh, he's one of the best biotechnologists in the world. Um and he would go on to become a a Moderna co founder. Um, he was doing all kinds of research and um

In the early two thousands, um I read a story about some researchers from from University of Pennsylvania who were uh doing some pretty groundbreaking work around MRA, they went to a a scientific conference and almost nobody This is twenty years ago. Almost nobody in the scientific community was taking this seriously. When did you first what did MRNA research first?

Come out of your radar. Let me answer that. By first pointing out to you that five years ago nobody was taking MRNA resource seriously. That's kind of an interesting thing. Back in two thousand ten, May of two thousand ten, 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 uh 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 M R 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 jeans 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 at the on the spot. Well, what if We could do this. to introduce it into the body and have our own cells Make drugs out of it.

So I asked that question. In the meeting with Bob. We kind of 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 Moderna.

It's amazing. I mean Th the idea was that you had was could we Basically, um, you know Could you could you make medicines? Where you inject them.

in order for the body to develop the proteins, right, to um To combat the The ailment or whatever it is. That 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, p by asking the question We gave ourselves the permission to go find out why it is that either nobody had

And we quickly found out that People had tried it in the eighties. And they had caused pretty significant immune response. Includes. So people had this idea earlier.

But it turns out it's not just the MRA and the immunology. You then have to figure out which cells are gonna take these up. Yeah. How 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 genome, but the software to to make A particular protein. In a sea of Thousands of other proteins being made.

Every nanosecond of the day. So so you gotta get in Precisely Make the protein you want, have the effect you want. Yeah, so there was a lot of

As an engineer It 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 innovation is that we kind of work backwards.

From a An asserted destination We wanna be able to do this. And then try to tie it to the present. I wanted to ask you about um about doubt. I mean, I understand that flagship was really designed to do exactly

weird and maybe the 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. Um a lot of uncertainty. I mean you had great researchers and scientists I mean didn't anybody

In flagship that you talk to say This is not what we should pursue. Didn't Didn't anybody push back? Didn't you have doubts? Um I think we sh I should try to put it in context.

The important thing to realise is that We are set up. Two Uh make innovation leaps. That are beyond

adjacencies. So you know this The 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. Yeah 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 gonna be done next. So imagine a sense of the arrow of time. going kind of outward from one circle to the next ring. Sure. And that's kind of for me a simplistic mental model of how innovation science uh product 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, you some new things happen, and then eventually You start working on what would have been 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 r you know funded Scientists who just spent all of this money And it was a disaster. And we could have been telling this stor that story at business schools, right? I mean there's a always a possibility that would have been the story. And by green lighting Moderna. You had to

Consider certain factors. But if 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 in a in again in in a context it's a very valid question, but I wanna say you're asking the question in isolation. Yeah. 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.

Inch. With as big a leap. Each with as much doubt. And we did that the year before and we've done that for the eleven 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 a hundred different modernas. Right. And what's happened is, and this is very much how I look at this. Is that Experiments and reality and and execution have dictated which of those Modernas got to live and which of those Modernas got to die.

How how many of those Other than quote Modernas. Didn't make it. You said we launched a hundred.

A lot, a lot. We didn't launch a hundred, we ha imagined a hundred. Right. And so I the point I'm making is The accuracy with which you have to guess what's gonna work. Is not at all important. Because we get into these brand new areas. It's wide open.

To find where value lies. Right. Imagine if we waited three, four years as people did, or ten years In the case of M R and A. 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. Yeah. So it's not that you have to get it dead right.

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. Репрезент альтернатив. 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 Nubar 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.

how I built this. My TR. 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.

It's easy to forget that when the company launched in 2010, The idea 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've worked from day one.

On any number of diseases, uh cardiovascular disease, cancer. En and vaccines were a part of our Thinking process but indeed What we did do is we went after everything. Right. That's the hundred versions of Madonna that I'm referring to. We did not think for a minute. That we who 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. Realize that rather than inventing technologies, we really ought to invent platforms.

And that 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 technology suit. Upon which many many products could be Developed or attached. By twenty ten, 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. Yeah. And so we had by the time This coronavirus came along. We had tested

Nine. Maybe even ten. Different human vaccines. In every single case showing neutralizing antibodies. And we had also another nine programs that were going after human therapeutic. So it was a fairly broad

platform. that had already been developed, about two billion dollars of research had gone into developing the platform. Yeah. Yeah you

You went public in in twenty eighteen. You uh Still hadn't sold any products, really. Um you had an operating loss of Almost four hundred million dollars.

twenty nineteen. Still You 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. But None of that seems like like none of that seemed to to phase you or the team at all. Like that was not

Even a concern. Yeah, so um it's not and in fact Guy, what I can tell you having spent the last thirty four years in The biotechnology field. is that there is no biotech company that was started in two thousand ten.

With rare, rare exceptions, maybe one in a hundred. That had revenues. By that time. And so it's par for the 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 wanna start a new Airplane company. And then I'm surprised that I don't have an airplane on the market in the first ten years. Well it takes fourteen years. Yeah. Now what would have been surprising Is if we didn't have

Products in clinical Testing. And and that's something that was completely missed because Before a single vaccine for coronavirus that we tested. We had already two thousand people. Who had received MRA from us. Yeah.

And so we were far far advanced. In actually many, many different MRNAs for different activities, vaccines, nonvaccines, and that's what allowed us to have the conviction. That what we would do in this space could be quite productive.

Okay. Okay let's let's go back to to the timeline. For a moment'cause it's almost like um Please I like him. like a movie, like a thriller. Um and from what I understand

I think it was like January sixth, two thousand twenty, Stefan Bonsell, who's the CEO of Moderna. he found out about this virus in China and that it was probably A coronavirus. And I I think a few days later, the first death was publicly announced in China.

And Uh At that point I think that's january eleventh. twenty twenty. Um

Almost no one in the US was was talking. about this seriously or in a big I mean probably a few people, but almost nobody. Do you remember this Story um coming onto your radar around that time. Well, in the very early parts of January we were exchanging emails and and articles that were

you know, kind of appearing. Largely around the Wuhan. situation initially was thought to be a flu like thing, a pneumonia, and it wasn't until January twenty third, which I remember quite clearly, partly because it was my daughter's one of my daughters' birthdays and and and so I I was out

In Cambridge, close to MIT. I actually Stefan, who was in Davos.

Uh 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. View that way, but But that it could become a threat.

was beginning to at least appear. And um our discussion interestingly was twofold. One 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.

uh 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'cause we're so It's just a code molecule. You just sequence put the sequence in for the DNA, you make the RNA in one step, you put it in L M P 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 wanna test. Our platform's ability. to demonstrate very rapid capability to respond. And and we did not know how what a What an advantage that was. I mean, I think virtually overnight you and and Stefan uh 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 We're 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 a prototype for the vaccine? Because

Uh, from from what I understand, the fastest time it took to get A vaccine from development. to mark it was uh I think the MMR one one of these or one of these childhood things measles, yeah. It was like five years or something. So In this case, how can quickly were you able to

From the time we had the sequence To the time we had the sequence of the of the coronavirus. Of the coronavirus. Which the Chinese published, I think, right? They made that available. And and to the time when we had the computer generated sequence of the RNA That is essentially today MRA twelve seventy three was two days.

Two days from the time that it was published You basically had had a a computer model of a vaccine. A c 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 gotten to clinical trials it would be

It w 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 thirty thousand in a subject trial, which we've never ever done or dreamt of before. That was the unknown. The unknown was Can you make enough of it? Yeah. And we had some questions as to what those

We should choose. Um but essentially there was a lot unknown and we just had to kind of Decide on based on the best information. What to try, we tried it, and by May of two thousand twenty. We had already the first human data that showed that we could generate robust antibody levels. In in March of twenty twenty you began clinical trials with the NIH. Uh it was it was a I think a nurse in Seattle.

That same month. Mm. March of twenty twenty, your father in law. Died of Covid. April. Yeah. April is when he passed away, yeah. In Sweden. Yeah, in Easter.

This was affecting all of us. I mean everybody knows somebody who was either severely ill or or was killed by this. I was devastated because his wife My mother in law also got quite sick and we thought we were gonna lose her as well.

Uh they were both in their early nineties. So it was It was very, very tough also because Іноведж і де с дай та дай батл. And on the one hand I was excited by what we were able to do, and on the other hand

When you see uh you know in his case ultimately a life lost. Um, you know, it's uh Anyway, it's it was quite personal to me, let me just say that I have not lost a family member during the time of of iPhones and and I can Tell you that being on a FaceTime

With somebody close to you when they're dying is a Miserable, miserable uh experience. Uh it was very tough. And it 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. You but you knew

Already from that first clinical trial. That the news was good. that um the initial results from from phase one were good, but but you had to go through two more phases and We the public were not um uh privy to that information for a variety of reasons, right? You can't

You could not come out and say, Hey, phase one looks great. Th these are the results. Is that 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 t every which way. for having said that because they basically

said well that's doing science by press release and many other things. And 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 gonna get criticized no matter what we did. And so we just had to do what we thought was right. uh make some calls, you know, explain ourselves and And so we did that. We we ultimately published the data.

NIH came out and 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. Bye. Um the end of the third trial.

Phase three end of November. And you announced That's the same. The preliminary data showed that the efficacy rate was 94%. Did that e that

Surprise you, even you? It did surprise me. And it didn't surprise me scientifically, it surprised 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 you know, 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 in 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 and that was really the the massive heroism that I think of all the things that We could not imagine that we could make I know a billion.

The first year of production. Up from probably making, you know, a thousand doses the year before of anything. How did you do that? How did you go from uh the capacity to make a thousand or ten thousand to a billion in less than a year? We had the 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 uh uh 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

that they did in terms of either time frames or scale. And uh several months later We started producing Millions of doses and then and then eventually Tens of millions and hundreds of millions of doses.

What does this mean now? I mean what what does What does it mean for the development of other vaccines or other um 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 is that within the realm of possibility? Well you asked me to

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 and and I'm only saying it because look, I learned long ago Thomas Kuhn and all these guys who've Written on on these things that You know, the scientific process is one of organized skepticism. Yeah. And that organized scepticism is a good thing.

Because it keeps you constantly looking for proof. I would say that there's there's a slightly greater reason to believe that MRA Could actually be a new drug modality. And um 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 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 gonna find breakthroughs. Um

It's uh probably remarkable to um young younger people today that that everybody had their chicken pox not that long ago. And no kids don't get it anymore'cause there's a vaccine. Is there a potential future where the There's no such thing as f seasonal flu. That I can not say alvo

I never want to say no to that either. Right. Um, because more broadly, uh you're raising an issue which which is important to me and I've I've worked for the last two years. And that is probably 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. But if we could intervene. long before the diseases manifest, and we can find it now with 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 you know as a result of that. is just gonna be prohibitive. So In the same vein. I can imagine a time when seasonal fluid Is mastered and basically kept at 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 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. Umar, when you think about the arc of your career in your life, you know, a chance meeting with David Packard who kind of Inspires you to think about Maybe you starting your own thing.

Taking a gamble on M RNA Which would lead to the fastest Vaccine ever. manufactured in history.

to now, you know, Moderna was founded ten years ago. I think its market cap uh the last I checked was almost a hundred and seventy billion dollars. And that's just one of the businesses you you started. Um it's a pretty remarkable story. Um How much of of your of where you are today? do you attribute to how hard you worked and how much do you think has to do with just luck?

Um How hard I work is a function of probably the orientation that I had Then as an immigrant you don't really take much for granted.

Uh, 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. Yeah. So Hard work, yes. In terms of luck, you know, it's it's ironic that you're that that you asked me that'cause 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 sens 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.

But the opportunity will come up. Or that you will fail to fail long enough to succeed. And 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 roll doesn't play any role in in my actions and But when it comes, it comes. It's new bar 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 one hundred other companies. And of those Thirty.

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, we're at GuyRoz or at How I Built This. You can also find us on Instagram, that's at HowIBiltThisNPR, my personal account. At guy got Raj. This episode was produced by Casey Herman with music composed by Ramteen Arevlui. It was edited by Neba Grant with research help from Claire Murishima.

Our production staff includes JC Howard, James Delahouse, Rachel Faulkner, Liz Metzger, Julia Carney, Faris Safari, Elaine Coates, Annalee Sober, and Harrison BJ Choi. Jeff Rogers is our executive producer. I'm Guy Raz and you've been listening. to how I built this. This

is NPR.

What you see above is a preview of the first minutes. One unlock costs 3 credits and covers this episode forever: full segment and word-level timestamps on this page, plus .txt, .srt, .vtt and word-level JSON downloads, as many times as you like.