How a new form of entrepreneurship led to the creation of Moderna : The Indicator from Planet Money The development of the Moderna vaccine was the culmination of decades of scientific research. This research was able to flourish thanks in large part to Flagship Pioneering and its founder, Noubar Afeyan. Today, the innovative way Flagship created one of the most successful COVID-19 vaccine makers in the world.

Replacing the cult of the entrepreneur

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SYLVIE DOUGLIS, BYLINE: NPR.

(SOUNDBITE OF DROP ELECTRIC’S "WAKING UP TO THE FIRE")

JACOB GOLDSTEIN, HOST:

When Noubar Afeyan got out of grad school in the 1980s, he started his first company. And before long, he realized that people thought about entrepreneurship in almost mythical terms.

NOUBAR AFEYAN: It was this kind of mystical activity, and you had certain personalities that kind of were able to raise money and create teams.

WAILIN WONG, HOST:

But over time, as he learned more about how businesses really work, he started to doubt the cult of the entrepreneur.

AFEYAN: There's a lot of kind of almost a romantic side to it. There is chaos, and there is this struggle to survive.

GOLDSTEIN: One thing you don't hear so much about in the entrepreneurship stories - actually making a thing, actually creating a product.

WONG: This kind of thinking made Noubar want to try something different. He imagined a company that would stand in direct opposition to the cult of the entrepreneur. So 20 years ago, he started a company that starts other companies.

GOLDSTEIN: The company he started is called Flagship Pioneering, and it has created dozens of companies, including, most famously, Moderna - the company that has made one of the most effective COVID vaccines in the world.

WONG: This is THE INDICATOR FROM PLANET MONEY. I'm Wailin Wong.

GOLDSTEIN: And I'm Jacob Goldstein. I used to host Planet Money, and now I host a new podcast called "What's Your Problem?" It's about entrepreneurs and engineers and the problems they're trying to solve. And I recently talked to Noubar for "What's Your Problem?" And I realized this story would be perfect for THE INDICATOR.

WONG: So today - why a single heroic entrepreneur battling the odds may not be the best model for starting a company and how the story of Moderna shows another way to do things.

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GOLDSTEIN: So Flagship Pioneering - this company that Noubar Afeyan started - has created this system for starting companies. These companies are mostly in the life sciences, but I should say Flagship is not a venture capital firm because venture capital, VC - they mostly just make investments, whereas Flagship actually starts and runs companies. And there are these very specific steps Flagship goes through to get from an idea to a full-fledged company.

WONG: So let's look at Moderna as an example of how the system works. We'll go through the key steps. The first step is what they call an exploration. In an exploration, Flagship has a few people on its team go out and talk to experts in the field, get a sense of what's new and exciting, the state of the art.

GOLDSTEIN: In the case of Moderna back in 2010, they were interested in the potential medical uses of mRNA - this molecule that tells cells in the body what proteins to make. And basically, what they wanted in the exploration step was for the experts to tell them all the ways that using RNA in the body could go wrong.

AFEYAN: So the way they react is to say, the RNA will be washed out of the body in 10 minutes. How are you going to make proteins for weeks? How are you going to get into the right cell types? By the way, the immune system inside the cell is one thing. There's all sorts of other immune reactions you're going to have to deal with. How are you going to make it? Nobody ever designed or made RNA.

WONG: They listen to all these objections, and then they think, OK, can we come up with a series of experiments to test whether we can solve all these problems that these experts are pointing to? If the answer is no, they give up. That's the end of the exploration.

GOLDSTEIN: But if the answer is yes, then they go on to step two, which I have to say is my favorite step. They create what they call a proto-company.

AFEYAN: So a proto-company is a prototype of a company. And a prototype 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.

GOLDSTEIN: So their exploration into mRNA clears that exploration phase, and they decide it is in fact promising enough to start a proto-company. They call this mRNA proto-company LS18. LS is for life science, and 18 because it's the 18th proto-company they started at Flagship. Noubar is adamant that proto-companies do not get names. They just get a number. This is a key part of that anti-cult of the entrepreneur system he's trying to build.

AFEYAN: One of the things that I knew literally on day one going into creating this whole thing in 2000 was that people hang on to their ideas and emotionally, almost romantically connect to them, and they never can kill them. And I wanted to create a safe zone during which the question was, what is the falsifying experiments 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, you know, Greek god's name, whatever - well, you try to kill it, right?

GOLDSTEIN: (Laughter) So you give it a number instead of a name to make it easier to kill.

AFEYAN: Disposable - exactly.

GOLDSTEIN: So Flagship gives this disposable proto-company a few million dollars to really test the hypothesis to see if it even deserves to become a full-blown company.

AFEYAN: We needed to convince ourselves that we can actually make things and try them in animals and have them make a protein. You know, this notion that now we go around saying, mRNA is the code of life, and we can put it in, and we can make any protein we want - yeah, $2 billion later, we could do that. But on the early days, nobody had shown that you could actually make the correct protein, fold it the correct way in animal models, not humans yet. And so we need to convince ourselves of that.

GOLDSTEIN: After a few months of experiments, Noubar and his colleagues are convinced. LS18 is promising enough to go on to the next step. It becomes a full-fledged company with its own name - Moderna.

WONG: And to be clear, Moderna didn't start out as a vaccine company. They had a long list of diseases they thought you might be able to treat with mRNA. But one of the things they decided would be relatively easy to test was making a flu vaccine, which they did in 2014.

AFEYAN: So we just took a very safe road, tried it, and sure enough, we showed in the first instance that that first attempt in humans could make neutralizing antibodies. And we felt like, OK, at least we know we can make proteins and that they do what we say they do.

WONG: This is proof of concept. You can use mRNA to do something useful in the body. And remember - to get here, Moderna started as an exploration, then graduated to a disposable proto-company, then proved itself worthy enough to become a fully fledged company. And by 2018, Moderna had an IPO. It became a publicly traded company. Most of Flagship's proto-companies don't make it this far, but some do. And when you make lots of longshot bets, only a few have to pay off for the whole model to work.

GOLDSTEIN: So because of all of this, because of the decade you had spent figuring out how to build a company that builds companies, and then the years after that, turning an idea into LS18 into Moderna into a company that makes vaccines - because of that whole 20-year arc, you're ready, essentially, when this new virus emerges at the end of 2019 to very quickly make a COVID vaccine.

AFEYAN: Exactly that. I mean, we worked for many, many years to put this platform into existence.

WONG: And I got the Moderna vaccine.

GOLDSTEIN: So did I. I interviewed Noubar for this new podcast that I host. It's called "What's Your Problem?" I've interviewed lots of other interesting people about drones and self-driving cars and ramps for wiener dogs. It's a fun show.

WONG: Especially the ramps for wiener dogs.

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WONG: Just a heads-up - there's no show tomorrow because the New York Stock Exchange is closed in observance of Good Friday. So have a great weekend, and we will see you on Monday for Tax Day.

This episode of THE INDICATOR was produced by Jess Kung and Nicky Ouellet with help from Isaac Rodrigues. It was fact-checked by Corey Bridges. Viet Le is the senior producer. Kate Concannon edits the show. And THE INDICATOR is a production of NPR.

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