Noubar Afeyan is the co-founder of Moderna and the founder of Flagship Pioneering. His problem: How do you turn the chaotic hero's journey of entrepreneurship into a repeatable, systematic process?
Noubar created Flagship Pioneering to solve the problems he saw with entrepreneurship. Flagship's mission: To create new companies in a systematic, repeatable way. On today's show, Noubar explains how that system led to the creation of Moderna, a company that developed a COVID vaccine and saved millions of lives.
If you’d like to keep up with the most recent news from this and other Pushkin podcasts, be sure to subscribe to our email list.
Learn more about your ad-choices at https://www.iheartpodcastnetwork.com
Pushkin. One of the most interesting, most important companies in the world right now is Maderna, this little biotech company that almost nobody had ever heard of until a couple of years ago. This company built on the wild idea of making mRNA and putting it into people's cells. This company has suddenly delivered COVID vaccines to hundreds of millions of people, including full disclosure to me. And maybe the most interesting thing about the story of Maderna is that it doesn't start with the founding of the company back in twenty ten. It starts ten years earlier with the founding of another company, a company called Flagship Pioneering. Flagship Pioneering is a company that makes companies. Flagship has created dozens of companies, several of which have gone public. Pretty much all of them have something to do with biology, and they tend to be pretty out there. Companies using bacteria as medicine, Companies trying to figure out how farms can do more to pull carbon dioxide out of the atmosphere, and of course, companies trying to figure out all the things you can do with RNA, companies like Maderna. I'm Jacob Goldstein and this is What's Your Problem, the show where I talk to entrepreneurs and engineers about how they're going to change the world once they've solved a few problems. My guest today is Nubar Afaan. He is the founder of Flagship Pioneering and the co founder of Maderna. And the problem I wanted to talk with Nubar about is the problem he started Flagship to solve. How do you turn the unstructured, chaotic way that most entrepreneurs start companies into a repeatable, systematic process and what can we learn about that From the story of Maderna, the origins of Flagship Pioneering new Bar's company, the company that started Maderna. They go back to the beginning of his career as an entrepreneur. He saw at the time that venture capitalists had a sort of unfair advantage over entrepreneurs like him because they got to see into so many different companies all getting built at the same time. I was interested in the model that venture capitalists used, and what I observed in the early phase of my career is just how smart all these people seemed. And yet after a while I realized, well, they're two they can't all be that smart. And it occurred to me that they had seen so many attempts at this, with so many different people of different backgrounds, compositions of teams that were only experienced, only inexperienced the science the IP strategy in the markets. So when you take it all together, they were learning at a massive, massive rate that which entrepreneur need to learn but never can learn in one go round. And so I thought, why can't the knowledge assembly practice, experimenting and failing and learning be available to an entrepreneur. So all of those things kind of combined in getting me interested in this notion that what if there was a structure where entrepreneurs such as myself could take experience they had gotten, let's say, in one in one instance, but then started diversifying it and learning in parallel, and then got really good at it. And those are the things that led to the conception of Flagship in two thousand. Starting a company that starts companies almost seems like cheating in a weird way, Like when you get the genie in the bottle and you get three wishes, it's like wishing for more wishes, right, you know, I've never seen a story which starts with you know, some Genie offered somebody three wishes, and the first wish was another Genie bottle. Yeah, it's a little poll have been a smart answer, Yeah, yeah, that would have been a smart answer. So it really is a kind of a curious thing as to why people don't do it. And I can trace it back, especially back in the twenty five years ago, to the fact that the field of entrepreneurship was a relatively young field. Early on, it was this kind of mystical activity, and you had certain personalities that kind of were able to raise money and govern, you know, create teams. There's a whole mythology, right, It's like the like Hero's journey, right where there's this one person who has a vision that nobody else believes in and only they can build the company. I mean, I feel like what you're building is sort of the antithesis of that. Well exactly, entrepreneurship as an activity today is today used to be and hasn't changed so much. Is very much improvisational. There's a lot of kind of almost a romantic side to it. There is chaos, and there is this struggle to survive. And while all of those things are really good, kind of spices in a meal. It is the meal in entrepreneurship. There is nothing else you don't point to, and we're developing products and we're solving on meth needs. Those things almost become kind of the boring part of the story that people want to fast forward through that part of the episode. So it did occur to me, in thinking of parallelyzing this, that actually all those parts can benefit from being more efficient, more effective, more predictable, and more planful. If there's this idea that you can build a system to create companies and that the system maybe ultimately can work better at least better in some settings, let's say, than the sort of visionary entrepreneur. What does that say about you in particular? Like can you build such a good system that you personally become replaceable? Oh? Yeah, that's my goal. So you are set up this company, Flagship Pioneering to solve the entrepreneurship problem. But how does it actually work and how did it lead to the creation of Maderna? That is after the break. Now we're going back to the show. So in the first part of the conversation, Nubar and I were talking abstractly about this problem he set out to solve how do you shift entrepreneurship starting companies from this mythological hero's journey into a repeatable, systematic process. In the next part of the conversation, Nubar gave me an answer. He told me the story of Maderna as a case study for how flagship pioneering his company has started to solve this problem, has started to create a system for creating new companies. The story of Maderna starts in twenty ten when Nubar had a meeting with a Harvard scientist who was studying m RNA. mRNA, by the way, is a molecule that basically tells cells in the body what protein to make. I could researchers had been experimenting with mRNA for a while by this point, but they kept hitting problems when they tried to find clinical applications. And in the middle of this meeting with the Harvard scientist, Newbar thinks if we could make mRNA in the lab and inject it into the body, the results could be incredible. We could use mRNA to tele a patient cells what to make. So I come back from the meeting and I talked to some of the team here and we say, hey, let's launch an exploration, and it starts as an act of imagination. It is not an active reason. And in fact, one of my side i'd say, kind of, I won't call it ran. Yeah. A side rant would be the degree to which our education systematically discourages the use of imagination in creating the world we want to create, versus relying overly on analysis and reason as the only way to make progress. You want to try and be unreasonable to some extent. We need to be unreasonable in order to come up with leaps that eventually seem reasonable. So, in the case of what will become maderna, you have this unreasonable idea, let's use mRNA to get the body to make drugs inside the body. You start this first step, this thing you call an exploration, which means which means what you have this small team studying the state of the art, going out and talking to experts about this idea, and what kind of reactions are you getting from the experts. So the way that you react is to say, the RNA will be washed out of the body in ten minutes, How are you going to make proteins for weeks? How are you going to get into the right cell types by the way, there's all sorts of other immune reactions you're gonna have to deal with, how are you going to make it? Nobody ever designed and made Arnie, And so all those selection pressures causes you, causes us very specifically to go back and try to come up with ways to overcome those let's say, dogumatic objections to based on the present state of the art. And so because you might say, we why don't you just ignore them and just go into lab and do it. And the reason it turns out for us anyways, that we find that these initial hypotheses become refined and refined and refined before we want to go in and spend the money building a company. That's a really important thing. We don't build just any company. We build companies that have gone through a significant upfront set of iterative refinements. That's a process of a couple of months. It's a handful of people, three four people, and it's a couple of months, and we iterate, iterate, iterated internally until we get to a point by the fall where we say, you know what, we're going to make a go of this, because that we think we have a good sense of the range of things that have to be right for this to work. We can test for them, and we don't start the company. We actually start what we call a protocompany. Okay, that's the first phase. Okay, what is a proto company? So a product company is a prototype of a company, just like you make prototypes of every product that you make. But remarkably, there is no such thing as a prototype of a company. People just make companies. And a product type of a company is where, just like in a regular product, you get to beat it up and try to kill it. And that's exactly what we do. And so is it called Maderna Yet you have this idea and it's like proto Maderna. No, it's ls eighteen is the product company? Say it again. LSA teen is the name of the entity that got incorporated to become eventually if things went forward, Maderna. Why light, Oh, it's the eighteenth such thing we did. Okay, it's the eighteenth proto company you had ever made, exactly and today we're at number ninety as an example, why do you do that? Why do you give it just a number at that stage? Oh, you know, when you're trying to create an institution instead of behaviors. One of the things that I knew literally on day one going into creating this whole thing in two thousand was that people hang on to their ideas and emotionally almost romantically connected them and they never can kill them. And I wanted to create a safe zone during which the question was, what is the falsifying experiment that will kill the hypothesis so that we don't go forward. Well, guess what if you give something a name, worse yet, a name you really like, your pet, dog's name, some Greek god's name, whatever, Well you try to kill it. So you give it a number instead of a name to make it easier to kill. Disposable exactly. But anyway, I should say put our companies for us are like a one to two million dollars six months to twelve months plus minus process. It is not a license to hunt for the next three years and ten million dollars. That's a very important discipline. So a key part of doing that is to decide what are the key experiments that you want to do first in order to try to kill it. We needed to convince ourselves that we can actually make things and try them in animals and have them make a protein. There's notion that. Now we go around saying m RNA is the code of life, and we can put it in and we can make any protein we want. Yeah, two billion dollars later we could do that. But on the early days, nobody had shown that you can actually make the correct protein folded the correct way in animal models, not to humans yet, and so we need to convince ourselves of that. We did work on that in small animals mice, and then we had to believe is that we could actually somehow formulate these things so they can get into cells. A year or so nine months, a year of experimental work that we engaged with within the context of LSA teen, which was renamed a couple of months later Maderna. As we started getting ourselves up and running, I just want to I just want to pause. So ls eighteen, I have the number, right, remember number, that's the point, right, LSA teen becomes maderna. But at that time you're not even thinking of vaccines yet, is that right? Well, let me say this thing. We thought of every possible use you could make of every kind of molecule, so vaccines was definitely on tables of things we could do. But by no means did our preliminary analysis suggest that we should do vaccines, let alone only vaccines. And the reason was because our dream, our imagination had us making any protein in the body, and a relatively small subset of the proteins that are made in the body is actually for vaccines, and so we were working on cancer and we were dreaming of cardiovascular disease. So the vaccine part was a transition that started happening three to four years into the development of the company, A long time. A long time into the company, oh for sure, and probably a good billion dollars of capital having gone into it before now. Back in twenty fourteen thirteen, when we started going down this path, of course, it was a pretty crappy, for lack of a better word, marketplace because vaccines were the domain of two or three pharma companies that had a complete monopoly over the space. The development and regulatory approval of them was extremely slow, very very costly, and at the end you couldn't charge much for them. So the reason the biotech industry, I think it'd be hard pressed to find biotech companies that worked on vaccines was that, And so investors, capital providers simply didn't want to go there because it was generally written off as an area for major innovation, but we weren't. We didn't really care as much about that because all we wanted was the proof of principle in humans that this could even be done. You wanted that would work, yeah, in humans, yea. And so in twenty fourteen, going into fifteen, we entered our first clinical trial with two quite ironic people haven't quite realized this yet, ironic in what I would say, two strains of influenza that had not previously been in humans, for which we wanted to make a prophylactic vaccine in case someday they jump from birds or swine into humans. Basically, yeah, exactly. So we just took a very safe road, tried it, and sure enough we showed in the first instance that that first attempt to humans could make neutralizing anybody's to both of those trains, and we felt like, Okay, at least we know we can make proteins and that they do what we say, David, that's five years into it. Great. So, because of all of this, because of the decade you'd spent figuring out how to build a company that builds companies, and then the years after that turning an idea into LS eighteen, into Maderna into a company that makes vaccines. Because of that whole twenty year arc, you're ready, essentially when this new virus emerges at the end of twenty nineteen to very quickly make a COVID vaccine exactly that we worked for many, many years to put this platform into existence. In a minute, the Lightning Round, including new bars, tips for solving hard problems, and one weird trick for knowing when to shut down a company or a proto company. Okay, let's get back to the show. We're going to close with the Lightning Round. What's one piece of advice you'd give to someone who's working on a hard problem. Work both from the present forward, that is, from what you know to solve something, and also work future backwards, which is, imagine the problem already solved and see if you can back trace how you got there. Good. Okay, Two more, do you have any rules of thumb for knowing when to shut down a project? Not uniform rules, but I think that you have to keep the resistance up resistance meaning pressure in order for the team to conclude that they're going through more and more complicated rationalizations using longer and longer sentence is to justify whether its state life sentence length is a good is a good heuristic? I like that. And by the way, that's one of the biggest misunderstood things in the startup world is that more money leads to better companies. Lower money can just as easily lead to worst companies because it causes persistence of companies that don't feel that pressure. And so I think one of the key things is the pressure that comes from raising capital, the pressure that comes from being challenging. I think these are all really really important to produce the end result of deciding not to go forward. I got to add one question, because you talked about money being a problem. You just raised billions of dollars, which, on the one hand, congratulations. On the other hand, is that going to make it harder to do what you do? I mean, there's scale, there's As you've said, having more money can make it harder to keep the pressure on. Is that hard having all that money? Because it took us a long long time to get too larger pools of capital. The process and the discipline and the culture proceeds the capital and all of those are ways to find the capital availability and keep the pressure on. Okay, last one, if everything goes well, what problem will you be working on in say ten years? Honestly unfathomable. I could tell you what problem would be working on today ten years ago. Let me answer it in this way. We don't start with either problem or solution. We try to invent both, make them up, and then we try to match them in that regard. What problems will be visible even at the horizon and what solutions will be imaginable will dictate what we work on. So really the answer to the what problem are you going to be working on in ten years question is like you don't even know the problem yet, And that's sort of the point, Like, on some level your job is to add and discover problems, both problems and imaginable solutions. Number of Fan is founder and CEO of Flagship Pioneering and co founder of Maderna. Today's show was produced by Edith Russelo, edited by Robert Smith, and engine neared by Amanda ka Wong. I'm Jacob Goldstein. We'll be back next week with another episode of What's Your Problem