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Building a Company that Builds Companies · What's Your Problem?

• 0:15
  Speaker 1: Pushkin. One of the most interesting, most important companies in
• 0:23
  Speaker 1: the world right now is Maderna, this little biotech company
• 0:28
  Speaker 1: that almost nobody had ever heard of until a couple
• 0:30
  Speaker 1: of years ago. This company built on the wild idea
• 0:33
  Speaker 1: of making mRNA and putting it into people's cells. This
• 0:37
  Speaker 1: company has suddenly delivered COVID vaccines to hundreds of millions
• 0:41
  Speaker 1: of people, including full disclosure to me. And maybe the
• 0:46
  Speaker 1: most interesting thing about the story of Maderna is that
• 0:50
  Speaker 1: it doesn't start with the founding of the company back
• 0:52
  Speaker 1: in twenty ten. It starts ten years earlier with the
• 0:56
  Speaker 1: founding of another company, a company called Flagship Pioneering. Flagship
• 1:01
  Speaker 1: Pioneering is a company that makes companies. Flagship has created
• 1:05
  Speaker 1: dozens of companies, several of which have gone public. Pretty
• 1:09
  Speaker 1: much all of them have something to do with biology,
• 1:12
  Speaker 1: and they tend to be pretty out there. Companies using
• 1:16
  Speaker 1: bacteria as medicine, Companies trying to figure out how farms
• 1:20
  Speaker 1: can do more to pull carbon dioxide out of the atmosphere,
• 1:24
  Speaker 1: and of course, companies trying to figure out all the
• 1:26
  Speaker 1: things you can do with RNA, companies like Maderna. I'm
• 1:34
  Speaker 1: Jacob Goldstein and this is What's Your Problem, the show
• 1:37
  Speaker 1: where I talk to entrepreneurs and engineers about how they're
• 1:39
  Speaker 1: going to change the world once they've solved a few problems.
• 1:44
  Speaker 1: My guest today is Nubar Afaan. He is the founder
• 1:47
  Speaker 1: of Flagship Pioneering and the co founder of Maderna. And
• 1:51
  Speaker 1: the problem I wanted to talk with Nubar about is
• 1:54
  Speaker 1: the problem he started Flagship to solve. How do you
• 1:58
  Speaker 1: turn the unstructured, chaotic way that most entrepreneurs start companies
• 2:02
  Speaker 1: into a repeatable, systematic process and what can we learn
• 2:07
  Speaker 1: about that From the story of Maderna, the origins of
• 2:13
  Speaker 1: Flagship Pioneering new Bar's company, the company that started Maderna.
• 2:16
  Speaker 1: They go back to the beginning of his career as
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  Speaker 1: an entrepreneur. He saw at the time that venture capitalists
• 2:23
  Speaker 1: had a sort of unfair advantage over entrepreneurs like him
• 2:27
  Speaker 1: because they got to see into so many different companies
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  Speaker 1: all getting built at the same time. I was interested
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  Speaker 1: in the model that venture capitalists used, and what I
• 2:37
  Speaker 1: observed in the early phase of my career is just
• 2:40
  Speaker 1: how smart all these people seemed. And yet after a
• 2:44
  Speaker 1: while I realized, well, they're two they can't all be
• 2:46
  Speaker 1: that smart. And it occurred to me that they had
• 2:50
  Speaker 1: seen so many attempts at this, with so many different
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  Speaker 1: people of different backgrounds, compositions of teams that were only experienced,
• 2:58
  Speaker 1: only inexperienced the science the IP strategy in the markets.
• 3:02
  Speaker 1: So when you take it all together, they were learning
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  Speaker 1: at a massive, massive rate that which entrepreneur need to
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  Speaker 1: learn but never can learn in one go round. And
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  Speaker 1: so I thought, why can't the knowledge assembly practice, experimenting
• 3:20
  Speaker 1: and failing and learning be available to an entrepreneur. So
• 3:24
  Speaker 1: all of those things kind of combined in getting me
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  Speaker 1: interested in this notion that what if there was a
• 3:30
  Speaker 1: structure where entrepreneurs such as myself could take experience they
• 3:35
  Speaker 1: had gotten, let's say, in one in one instance, but
• 3:38
  Speaker 1: then started diversifying it and learning in parallel, and then
• 3:42
  Speaker 1: got really good at it. And those are the things
• 3:44
  Speaker 1: that led to the conception of Flagship in two thousand.
• 3:48
  Speaker 1: Starting a company that starts companies almost seems like cheating
• 3:52
  Speaker 1: in a weird way, Like when you get the genie
• 3:54
  Speaker 1: in the bottle and you get three wishes, it's like
• 3:57
  Speaker 1: wishing for more wishes, right, you know, I've never seen
• 4:00
  Speaker 1: a story which starts with you know, some Genie offered
• 4:02
  Speaker 1: somebody three wishes, and the first wish was another Genie bottle. Yeah,
• 4:07
  Speaker 1: it's a little poll have been a smart answer, Yeah, yeah,
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  Speaker 1: that would have been a smart answer. So it really
• 4:13
  Speaker 1: is a kind of a curious thing as to why
• 4:16
  Speaker 1: people don't do it. And I can trace it back,
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  Speaker 1: especially back in the twenty five years ago, to the
• 4:22
  Speaker 1: fact that the field of entrepreneurship was a relatively young field.
• 4:26
  Speaker 1: Early on, it was this kind of mystical activity, and
• 4:30
  Speaker 1: you had certain personalities that kind of were able to
• 4:34
  Speaker 1: raise money and govern, you know, create teams. There's a
• 4:37
  Speaker 1: whole mythology, right, It's like the like Hero's journey, right
• 4:41
  Speaker 1: where there's this one person who has a vision that
• 4:44
  Speaker 1: nobody else believes in and only they can build the company.
• 4:47
  Speaker 1: I mean, I feel like what you're building is sort
• 4:48
  Speaker 1: of the antithesis of that. Well exactly, entrepreneurship as an
• 4:52
  Speaker 1: activity today is today used to be and hasn't changed
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  Speaker 1: so much. Is very much improvisational. There's a lot of
• 5:02
  Speaker 1: kind of almost a romantic side to it. There is chaos,
• 5:06
  Speaker 1: and there is this struggle to survive. And while all
• 5:11
  Speaker 1: of those things are really good, kind of spices in
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  Speaker 1: a meal. It is the meal in entrepreneurship. There is
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  Speaker 1: nothing else you don't point to, and we're developing products
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  Speaker 1: and we're solving on meth needs. Those things almost become
• 5:24
  Speaker 1: kind of the boring part of the story that people
• 5:26
  Speaker 1: want to fast forward through that part of the episode.
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  Speaker 1: So it did occur to me, in thinking of parallelyzing this,
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  Speaker 1: that actually all those parts can benefit from being more efficient,
• 5:38
  Speaker 1: more effective, more predictable, and more planful. If there's this
• 5:42
  Speaker 1: idea that you can build a system to create companies
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  Speaker 1: and that the system maybe ultimately can work better at
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  Speaker 1: least better in some settings, let's say, than the sort
• 5:53
  Speaker 1: of visionary entrepreneur. What does that say about you in particular?
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  Speaker 1: Like can you build such a good system that you
• 6:00
  Speaker 1: personally become replaceable? Oh? Yeah, that's my goal. So you
• 6:09
  Speaker 1: are set up this company, Flagship Pioneering to solve the
• 6:12
  Speaker 1: entrepreneurship problem. But how does it actually work and how
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  Speaker 1: did it lead to the creation of Maderna? That is
• 6:19
  Speaker 1: after the break. Now we're going back to the show.
• 6:28
  Speaker 1: So in the first part of the conversation, Nubar and
• 6:31
  Speaker 1: I were talking abstractly about this problem he set out
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  Speaker 1: to solve how do you shift entrepreneurship starting companies from
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  Speaker 1: this mythological hero's journey into a repeatable, systematic process. In
• 6:43
  Speaker 1: the next part of the conversation, Nubar gave me an answer.
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  Speaker 1: He told me the story of Maderna as a case
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  Speaker 1: study for how flagship pioneering his company has started to
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  Speaker 1: solve this problem, has started to create a system for
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  Speaker 1: creating new companies. The story of Maderna starts in twenty
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  Speaker 1: ten when Nubar had a meeting with a Harvard scientist
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  Speaker 1: who was studying m RNA. mRNA, by the way, is
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  Speaker 1: a molecule that basically tells cells in the body what
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  Speaker 1: protein to make. I could researchers had been experimenting with
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  Speaker 1: mRNA for a while by this point, but they kept
• 7:14
  Speaker 1: hitting problems when they tried to find clinical applications. And
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  Speaker 1: in the middle of this meeting with the Harvard scientist,
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  Speaker 1: Newbar thinks if we could make mRNA in the lab
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  Speaker 1: and inject it into the body, the results could be incredible.
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  Speaker 1: We could use mRNA to tele a patient cells what
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  Speaker 1: to make. So I come back from the meeting and
• 7:36
  Speaker 1: I talked to some of the team here and we say, hey,
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  Speaker 1: let's launch an exploration, and it starts as an act
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  Speaker 1: of imagination. It is not an active reason. And in fact,
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  Speaker 1: one of my side i'd say, kind of, I won't
• 7:50
  Speaker 1: call it ran. Yeah. A side rant would be the
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  Speaker 1: degree to which our education systematically discourages the use of
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  Speaker 1: imagination in creating the world we want to create, versus
• 8:04
  Speaker 1: relying overly on analysis and reason as the only way
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  Speaker 1: to make progress. You want to try and be unreasonable
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  Speaker 1: to some extent. We need to be unreasonable in order
• 8:16
  Speaker 1: to come up with leaps that eventually seem reasonable. So,
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  Speaker 1: in the case of what will become maderna, you have
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  Speaker 1: this unreasonable idea, let's use mRNA to get the body
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  Speaker 1: to make drugs inside the body. You start this first step,
• 8:32
  Speaker 1: this thing you call an exploration, which means which means
• 8:36
  Speaker 1: what you have this small team studying the state of
• 8:38
  Speaker 1: the art, going out and talking to experts about this idea,
• 8:41
  Speaker 1: and what kind of reactions are you getting from the experts.
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  Speaker 1: So the way that you react is to say, the
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  Speaker 1: RNA will be washed out of the body in ten minutes,
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  Speaker 1: How are you going to make proteins for weeks? How
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  Speaker 1: are you going to get into the right cell types
• 8:53
  Speaker 1: by the way, there's all sorts of other immune reactions
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  Speaker 1: you're gonna have to deal with, how are you going
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  Speaker 1: to make it? Nobody ever designed and made Arnie, And
• 9:00
  Speaker 1: so all those selection pressures causes you, causes us very
• 9:04
  Speaker 1: specifically to go back and try to come up with
• 9:06
  Speaker 1: ways to overcome those let's say, dogumatic objections to based
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  Speaker 1: on the present state of the art. And so because
• 9:14
  Speaker 1: you might say, we why don't you just ignore them
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  Speaker 1: and just go into lab and do it. And the
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  Speaker 1: reason it turns out for us anyways, that we find
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  Speaker 1: that these initial hypotheses become refined and refined and refined
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  Speaker 1: before we want to go in and spend the money
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  Speaker 1: building a company. That's a really important thing. We don't
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  Speaker 1: build just any company. We build companies that have gone
• 9:33
  Speaker 1: through a significant upfront set of iterative refinements. That's a
• 9:40
  Speaker 1: process of a couple of months. It's a handful of people,
• 9:43
  Speaker 1: three four people, and it's a couple of months, and
• 9:46
  Speaker 1: we iterate, iterate, iterated internally until we get to a
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  Speaker 1: point by the fall where we say, you know what,
• 9:51
  Speaker 1: we're going to make a go of this, because that
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  Speaker 1: we think we have a good sense of the range
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  Speaker 1: of things that have to be right for this to work.
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  Speaker 1: We can test for them, and we don't start the company.
• 10:00
  Speaker 1: We actually start what we call a protocompany. Okay, that's
• 10:03
  Speaker 1: the first phase. Okay, what is a proto company? So
• 10:06
  Speaker 1: a product company is a prototype of a company, just
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  Speaker 1: like you make prototypes of every product that you make.
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  Speaker 1: But remarkably, there is no such thing as a prototype
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  Speaker 1: of a company. People just make companies. And a product
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  Speaker 1: type of a company is where, just like in a
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  Speaker 1: regular product, you get to beat it up and try
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  Speaker 1: to kill it. And that's exactly what we do. And
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  Speaker 1: so is it called Maderna Yet you have this idea
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  Speaker 1: and it's like proto Maderna. No, it's ls eighteen is
• 10:30
  Speaker 1: the product company? Say it again. LSA teen is the
• 10:34
  Speaker 1: name of the entity that got incorporated to become eventually
• 10:39
  Speaker 1: if things went forward, Maderna. Why light, Oh, it's the
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  Speaker 1: eighteenth such thing we did. Okay, it's the eighteenth proto
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  Speaker 1: company you had ever made, exactly and today we're at
• 10:49
  Speaker 1: number ninety as an example, why do you do that?
• 10:52
  Speaker 1: Why do you give it just a number at that stage? Oh,
• 10:56
  Speaker 1: you know, when you're trying to create an institution instead
• 10:59
  Speaker 1: of behaviors. One of the things that I knew literally
• 11:02
  Speaker 1: on day one going into creating this whole thing in
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  Speaker 1: two thousand was that people hang on to their ideas
• 11:09
  Speaker 1: and emotionally almost romantically connected them and they never can
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  Speaker 1: kill them. And I wanted to create a safe zone
• 11:15
  Speaker 1: during which the question was, what is the falsifying experiment
• 11:20
  Speaker 1: that will kill the hypothesis so that we don't go forward. Well,
• 11:22
  Speaker 1: guess what if you give something a name, worse yet,
• 11:26
  Speaker 1: a name you really like, your pet, dog's name, some
• 11:29
  Speaker 1: Greek god's name, whatever, Well you try to kill it.
• 11:32
  Speaker 1: So you give it a number instead of a name
• 11:33
  Speaker 1: to make it easier to kill. Disposable exactly. But anyway,
• 11:37
  Speaker 1: I should say put our companies for us are like
• 11:39
  Speaker 1: a one to two million dollars six months to twelve
• 11:43
  Speaker 1: months plus minus process. It is not a license to
• 11:48
  Speaker 1: hunt for the next three years and ten million dollars.
• 11:51
  Speaker 1: That's a very important discipline. So a key part of
• 11:54
  Speaker 1: doing that is to decide what are the key experiments
• 11:58
  Speaker 1: that you want to do first in order to try
• 12:00
  Speaker 1: to kill it. We needed to convince ourselves that we
• 12:02
  Speaker 1: can actually make things and try them in animals and
• 12:06
  Speaker 1: have them make a protein. There's notion that. Now we
• 12:09
  Speaker 1: go around saying m RNA is the code of life,
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  Speaker 1: and we can put it in and we can make
• 12:13
  Speaker 1: any protein we want. Yeah, two billion dollars later we
• 12:16
  Speaker 1: could do that. But on the early days, nobody had
• 12:20
  Speaker 1: shown that you can actually make the correct protein folded
• 12:23
  Speaker 1: the correct way in animal models, not to humans yet,
• 12:26
  Speaker 1: and so we need to convince ourselves of that. We
• 12:28
  Speaker 1: did work on that in small animals mice, and then
• 12:31
  Speaker 1: we had to believe is that we could actually somehow
• 12:34
  Speaker 1: formulate these things so they can get into cells. A
• 12:37
  Speaker 1: year or so nine months, a year of experimental work
• 12:41
  Speaker 1: that we engaged with within the context of LSA teen,
• 12:44
  Speaker 1: which was renamed a couple of months later Maderna. As
• 12:48
  Speaker 1: we started getting ourselves up and running, I just want
• 12:51
  Speaker 1: to I just want to pause. So ls eighteen, I
• 12:53
  Speaker 1: have the number, right, remember number, that's the point, right,
• 12:56
  Speaker 1: LSA teen becomes maderna. But at that time you're not
• 13:00
  Speaker 1: even thinking of vaccines yet, is that right? Well, let
• 13:03
  Speaker 1: me say this thing. We thought of every possible use
• 13:05
  Speaker 1: you could make of every kind of molecule, so vaccines
• 13:08
  Speaker 1: was definitely on tables of things we could do. But
• 13:12
  Speaker 1: by no means did our preliminary analysis suggest that we
• 13:15
  Speaker 1: should do vaccines, let alone only vaccines. And the reason
• 13:19
  Speaker 1: was because our dream, our imagination had us making any
• 13:23
  Speaker 1: protein in the body, and a relatively small subset of
• 13:27
  Speaker 1: the proteins that are made in the body is actually
• 13:30
  Speaker 1: for vaccines, and so we were working on cancer and
• 13:33
  Speaker 1: we were dreaming of cardiovascular disease. So the vaccine part
• 13:37
  Speaker 1: was a transition that started happening three to four years
• 13:41
  Speaker 1: into the development of the company, A long time. A
• 13:43
  Speaker 1: long time into the company, oh for sure, and probably
• 13:47
  Speaker 1: a good billion dollars of capital having gone into it
• 13:50
  Speaker 1: before now. Back in twenty fourteen thirteen, when we started
• 13:54
  Speaker 1: going down this path, of course, it was a pretty crappy,
• 13:57
  Speaker 1: for lack of a better word, marketplace because vaccines were
• 14:00
  Speaker 1: the domain of two or three pharma companies that had
• 14:03
  Speaker 1: a complete monopoly over the space. The development and regulatory
• 14:07
  Speaker 1: approval of them was extremely slow, very very costly, and
• 14:11
  Speaker 1: at the end you couldn't charge much for them. So
• 14:14
  Speaker 1: the reason the biotech industry, I think it'd be hard
• 14:16
  Speaker 1: pressed to find biotech companies that worked on vaccines was that,
• 14:20
  Speaker 1: And so investors, capital providers simply didn't want to go
• 14:24
  Speaker 1: there because it was generally written off as an area
• 14:27
  Speaker 1: for major innovation, but we weren't. We didn't really care
• 14:31
  Speaker 1: as much about that because all we wanted was the
• 14:33
  Speaker 1: proof of principle in humans that this could even be done.
• 14:37
  Speaker 1: You wanted that would work, yeah, in humans, yea. And
• 14:40
  Speaker 1: so in twenty fourteen, going into fifteen, we entered our
• 14:44
  Speaker 1: first clinical trial with two quite ironic people haven't quite
• 14:48
  Speaker 1: realized this yet, ironic in what I would say, two
• 14:51
  Speaker 1: strains of influenza that had not previously been in humans,
• 14:55
  Speaker 1: for which we wanted to make a prophylactic vaccine in
• 14:59
  Speaker 1: case someday they jump from birds or swine into humans. Basically, yeah, exactly.
• 15:09
  Speaker 1: So we just took a very safe road, tried it,
• 15:11
  Speaker 1: and sure enough we showed in the first instance that
• 15:14
  Speaker 1: that first attempt to humans could make neutralizing anybody's to
• 15:18
  Speaker 1: both of those trains, and we felt like, Okay, at
• 15:20
  Speaker 1: least we know we can make proteins and that they
• 15:22
  Speaker 1: do what we say, David, that's five years into it. Great. So,
• 15:26
  Speaker 1: because of all of this, because of the decade you'd
• 15:31
  Speaker 1: spent figuring out how to build a company that builds companies,
• 15:34
  Speaker 1: and then the years after that turning an idea into
• 15:38
  Speaker 1: LS eighteen, into Maderna into a company that makes vaccines.
• 15:42
  Speaker 1: Because of that whole twenty year arc, you're ready, essentially
• 15:47
  Speaker 1: when this new virus emerges at the end of twenty
• 15:52
  Speaker 1: nineteen to very quickly make a COVID vaccine exactly that
• 15:58
  Speaker 1: we worked for many, many years to put this platform
• 16:02
  Speaker 1: into existence. In a minute, the Lightning Round, including new bars,
• 16:07
  Speaker 1: tips for solving hard problems, and one weird trick for
• 16:11
  Speaker 1: knowing when to shut down a company or a proto company. Okay,
• 16:22
  Speaker 1: let's get back to the show. We're going to close
• 16:25
  Speaker 1: with the Lightning Round. What's one piece of advice you'd
• 16:27
  Speaker 1: give to someone who's working on a hard problem. Work
• 16:31
  Speaker 1: both from the present forward, that is, from what you
• 16:34
  Speaker 1: know to solve something, and also work future backwards, which is,
• 16:38
  Speaker 1: imagine the problem already solved and see if you can
• 16:41
  Speaker 1: back trace how you got there. Good. Okay, Two more,
• 16:45
  Speaker 1: do you have any rules of thumb for knowing when
• 16:49
  Speaker 1: to shut down a project? Not uniform rules, but I
• 16:54
  Speaker 1: think that you have to keep the resistance up resistance
• 16:58
  Speaker 1: meaning pressure in order for the team to conclude that
• 17:02
  Speaker 1: they're going through more and more complicated rationalizations using longer
• 17:08
  Speaker 1: and longer sentence is to justify whether its state life
• 17:11
  Speaker 1: sentence length is a good is a good heuristic? I
• 17:13
  Speaker 1: like that. And by the way, that's one of the
• 17:15
  Speaker 1: biggest misunderstood things in the startup world is that more
• 17:18
  Speaker 1: money leads to better companies. Lower money can just as
• 17:22
  Speaker 1: easily lead to worst companies because it causes persistence of
• 17:26
  Speaker 1: companies that don't feel that pressure. And so I think
• 17:30
  Speaker 1: one of the key things is the pressure that comes
• 17:32
  Speaker 1: from raising capital, the pressure that comes from being challenging.
• 17:36
  Speaker 1: I think these are all really really important to produce
• 17:39
  Speaker 1: the end result of deciding not to go forward. I
• 17:42
  Speaker 1: got to add one question, because you talked about money
• 17:44
  Speaker 1: being a problem. You just raised billions of dollars, which,
• 17:47
  Speaker 1: on the one hand, congratulations. On the other hand, is
• 17:50
  Speaker 1: that going to make it harder to do what you do?
• 17:52
  Speaker 1: I mean, there's scale, there's As you've said, having more
• 17:55
  Speaker 1: money can make it harder to keep the pressure on.
• 17:57
  Speaker 1: Is that hard having all that money? Because it took
• 18:00
  Speaker 1: us a long long time to get too larger pools
• 18:02
  Speaker 1: of capital. The process and the discipline and the culture
• 18:05
  Speaker 1: proceeds the capital and all of those are ways to
• 18:09
  Speaker 1: find the capital availability and keep the pressure on. Okay,
• 18:13
  Speaker 1: last one, if everything goes well, what problem will you
• 18:17
  Speaker 1: be working on in say ten years? Honestly unfathomable. I
• 18:21
  Speaker 1: could tell you what problem would be working on today
• 18:24
  Speaker 1: ten years ago. Let me answer it in this way.
• 18:26
  Speaker 1: We don't start with either problem or solution. We try
• 18:29
  Speaker 1: to invent both, make them up, and then we try
• 18:32
  Speaker 1: to match them in that regard. What problems will be
• 18:35
  Speaker 1: visible even at the horizon and what solutions will be
• 18:38
  Speaker 1: imaginable will dictate what we work on. So really the
• 18:42
  Speaker 1: answer to the what problem are you going to be
• 18:44
  Speaker 1: working on in ten years question is like you don't
• 18:46
  Speaker 1: even know the problem yet, And that's sort of the point, Like,
• 18:48
  Speaker 1: on some level your job is to add and discover problems,
• 18:52
  Speaker 1: both problems and imaginable solutions. Number of Fan is founder
• 18:59
  Speaker 1: and CEO of Flagship Pioneering and co founder of Maderna.
• 19:04
  Speaker 1: Today's show was produced by Edith Russelo, edited by Robert Smith,
• 19:08
  Speaker 1: and engine neared by Amanda ka Wong. I'm Jacob Goldstein.
• 19:12
  Speaker 1: We'll be back next week with another episode of What's
• 19:15
  Speaker 1: Your Problem