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Speaker 1: Pushkin. One of the strange things about making a podcast

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Speaker 1: is you make the show, it goes out in the world.

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Speaker 1: Your mom tells you she likes it, but you don't

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Speaker 1: really know much about what people think of the show,

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Speaker 1: and in particular, you don't know how to make your

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Speaker 1: show better. And I really really want to make this

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Speaker 1: show better. I want this to be a show that

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Speaker 1: you look forward to every week, the show that you

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Speaker 1: tell your friends about. And so to that end, please

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Speaker 1: please please tell me how to do that. Tell me

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Speaker 1: how to make what's your problem a better show, a

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Speaker 1: show you like more. If there's some person you want

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Speaker 1: me to talk to, or some subject you want me

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Speaker 1: to cover, or something you want me to do differently, anything,

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Speaker 1: really let me know. You can email me at problem

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Speaker 1: at pushkin dot fm. That's problem at pushkin dot fm.

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Speaker 1: Or you can talk to me on Twitter. I'm at

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Speaker 1: Jacob Goldstein, just my name. To be honest, we don't

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Speaker 1: get that many email messages yet, not that many people

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Speaker 1: talk to me on Twitter. So I can guarantee you

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Speaker 1: I will personally read every email and Twitter message you

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Speaker 1: send with gratitude. Thank you. Now here's the show. Here's

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Speaker 1: a big, wild idea what if scientists and engineers could

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Speaker 1: turn yeast in bacteria into tiny factories that would manufacture

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Speaker 1: everything from perfume to food to fuel. This idea has

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Speaker 1: a name synthetic biology. People have been working on it

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Speaker 1: for more than a decade now, and it's really hard.

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Speaker 1: First you have to engineer DNA and then you stick

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Speaker 1: it into yeast or bacteria in order to make the

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Speaker 1: thing you want, the fragrance or the fuel or the food.

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Speaker 1: And then you have to figure out how to do

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Speaker 1: it at scale, how to make a lot of it,

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Speaker 1: and also you have to make it cheaper or better

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Speaker 1: than what's already out there. Really, the dream of synthetic

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Speaker 1: biology is like a whole new industrial revolution, but using

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Speaker 1: cells instead of machines. I'm Jacob Goldstein and this is

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Speaker 1: What's Your Problem, the show where entrepreneurs and engineers talk

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Speaker 1: about the world they're going to build once they solve

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Speaker 1: a few problems. My guest today is Reshma Shetty. She's

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Speaker 1: the co founder and chief operations officer of Ginko Bioworks.

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Speaker 1: It's one of the biggest synthetic biology companies in the world.

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Speaker 1: One big obvious problem that Ginko faces the company has

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Speaker 1: lost billions of dollars trying to turn synthetic biology into

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Speaker 1: a viable business. So the problem for today's show is this,

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Speaker 1: how do you try and do this big, hard thing

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Speaker 1: way out there on the scientific frontier and also eventually

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Speaker 1: make enough money to create a financially sustainable business. We

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Speaker 1: started our conversation talking about the original idea for Ginko,

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Speaker 1: which came to Reshma and her co founder when they

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Speaker 1: were grad students at MIT dreaming about the big things

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Speaker 1: they wanted to do with synthetic biology. So you start

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Speaker 1: a company. We did. We did. We started a company

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Speaker 1: because we worked at a place MT, like most academic institutions,

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Speaker 1: really focuses on doing new things. Right. Can you invent

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Speaker 1: something new? Can you discover something new so that you

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Speaker 1: can publish on it, Right, And that's what academia is

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Speaker 1: built to do. And that's a really great thing because

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Speaker 1: we should be discovering new things and we should be

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Speaker 1: inventing new things. Yeah, but with biology, what we really

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Speaker 1: felt was holding us back was not just doing something

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Speaker 1: new or inventing something new. It was could you make

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Speaker 1: the process of engineering biology faster, cheaper, easier. Yeah. And

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Speaker 1: what was interesting is that we started working on that

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Speaker 1: problem during grad school, but it just wasn't very celebrated.

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Speaker 1: People were like, why do you want to make it

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Speaker 1: easier for other people to do this? That seems like

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Speaker 1: a dumb thing. Work on it, right, You're just building tools.

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Speaker 1: You're not actually doing anything with the tools exactly right.

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Speaker 1: And so there's a sort of skepticism even at a

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Speaker 1: place like MT around spending your time tool building. Okay,

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Speaker 1: And so we decided to start a company, candidly, not

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Speaker 1: because I wanted to be a founder. I actually didn't

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Speaker 1: want to be a founder. You know, I had never

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Speaker 1: dreamt about starting a company before. But we felt that

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Speaker 1: starting a company was the best way to work on

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Speaker 1: this problem of how do you make biology easier to engineer?

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Speaker 1: I read that some of your earliest customers were in

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Speaker 1: the in the fragrance industry, and I thought going through

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Speaker 1: that work you did might be a case study to understand,

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Speaker 1: you know, what the company does and what kind of

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Speaker 1: problems come up and how you solve those problems. Can

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Speaker 1: you talk me through that work? Yeah? So when we

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Speaker 1: first started the company, you know, we didn't have a

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Speaker 1: particular technology, we didn't have a business model, we didn't

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Speaker 1: have a way of making money, right, it was a

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Speaker 1: great way to start a company. I highly recommend. But

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Speaker 1: what we did have was that we were kind of

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Speaker 1: voracious learners. We kept coming up with wrong hypotheses. Where

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Speaker 1: we finally got some traction was actually looking at the

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Speaker 1: flavor and fragrance industry. So it turned out that this

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Speaker 1: is a huge industry. It's a multibillion dollar industry that

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Speaker 1: almost no one's heard of. I certainly hadn't heard of

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Speaker 1: it when we started the company. But they make all

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Speaker 1: of the flavors and fragrances that go into household goods. Right,

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Speaker 1: So if you go browse the DETERSI denial, you know,

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Speaker 1: and you can probably smell some of the detergents and

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Speaker 1: soaps and shampoos and whatnot that are in your local supermarket,

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Speaker 1: you know, those fragrances are all concocted by the flavor

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Speaker 1: and fragrance industry. So it turned out that there was

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Speaker 1: this pain point in the flavor and fragrance industry where

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Speaker 1: they wanted to use biology to manufacture their ingredients, but

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Speaker 1: it just you know, it wasn't feasible at scale, and

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Speaker 1: so they were really interested in using fermentation. This idea

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Speaker 1: that you could grow yeast in a vat to produce

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Speaker 1: flavors and fragrances, much like you might brew beer. And

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Speaker 1: so cracking that nut was our first sort of realization, Hey,

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Speaker 1: there's actually really a market or engineeredsels that could produce

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Speaker 1: flavor and fragrance ingredients. Are you allowed to say specifically

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Speaker 1: what you did or is it like that? So some

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Speaker 1: of our earliest contracts were around things like peach flavor,

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Speaker 1: coconut flavor, and so, so what specifically do you do?

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Speaker 1: I mean, do you take some jeans from a peach

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Speaker 1: and stick them in a yeast and the yeast makes

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Speaker 1: peach smell? Is it like that? Yeah, basically, except you're

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Speaker 1: not just limited to beach, because it turns out that,

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Speaker 1: you know, biology has a lot of reuse and a

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Speaker 1: lot of commonality, and so it might be the actually

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Speaker 1: the best genes for making a peach flavor might not

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Speaker 1: come from a peach. They might come from another species,

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Speaker 1: which is kind of fascinating, right, And so you keep

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Speaker 1: tweaking it and iterating on it until you're making a

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Speaker 1: lot of your ingredient of interest. And so, right now,

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Speaker 1: somewhere in the world, is there like a vat full

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Speaker 1: of yeast, cranking out peach smell that's going to go

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Speaker 1: into like soap or shampoo or something. There absolutely is, yes,

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Speaker 1: So where is the company now? What's sort of what

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Speaker 1: is the state of Ginko now? The span of what

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Speaker 1: we work on is huge, right, everything from food to health,

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Speaker 1: to act culture, to flavors and fragrances. So we started

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Speaker 1: a joint venture with Buyer, the largest ad company in

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Speaker 1: the world, working on essentially a biofertilizer, So being able

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Speaker 1: to reduce the amount of fertilizer that we need to

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Speaker 1: grow crops like corn by essentially engineering microbes to provide

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Speaker 1: the fertilizer to provide the fixed nitrogen rather than fertilizer.

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Speaker 1: And if you actually look at it, fertilizer is incredibly

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Speaker 1: bad for the environment. The process by which we make

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Speaker 1: fertilizer in this world, I don't know, It's like something

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Speaker 1: like fertilizer is like six or seven percent greenhouse gas emissions.

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Speaker 1: I mean, it's something completely interesting. So it's the production

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Speaker 1: of fertilizer emits a lot of carbon dioxide into the atmosphere.

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Speaker 1: So if you can if you can reduce the need

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Speaker 1: to make fertilizer then that helps exactly solve the problem. Yeah,

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Speaker 1: so can you sort of give me a comparison of

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Speaker 1: the state of the world as it was when you

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Speaker 1: were in grad school versus the state of the world

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Speaker 1: that you have created now? In grad school, it probably

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Speaker 1: take me nine months or so to basically design, build,

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Speaker 1: and test twenty designs at a time, like twenty different Yeah,

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Speaker 1: twenty different genes or to many different pathways. Maybe at

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Speaker 1: a time that was like state of the art. How

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Speaker 1: long would it take Ginko now to try twenty designs. Well,

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Speaker 1: we wouldn't ever bother to try twenty designs. We only

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Speaker 1: try thousands of designs at a time. Okay, It still

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Speaker 1: takes a lot longer than i'd like. It still probably

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Speaker 1: takes three months to kind of go through the whole cycle,

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Speaker 1: maybe two months if we're lucky. So, if before it

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Speaker 1: was you could try twenty designs in nine months, how

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Speaker 1: many designs could you try now in two or three months.

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Speaker 1: Now I'm trying thousands of designs in two or three months.

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Speaker 1: Thousands Okay, So it's thousands of times faster than it

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Speaker 1: was when you started. Yeah, and then I can learn

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Speaker 1: from which ones worked and which ones didn't and even

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Speaker 1: more intelligently do my next round of thousands of designs.

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Speaker 1: And so is what you have built sort of like

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Speaker 1: a factory for testing? Have you built like a factory lab? Yeah,

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Speaker 1: it's it's essentially a factory for cell programming. What's it

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Speaker 1: look like. It's a whole bunch of robots sort of

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Speaker 1: placed in rows across the lab with these essentially train

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Speaker 1: tracks that can move samples between the different robots, and

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Speaker 1: so it's pretty cool looking. So like the robots are

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Speaker 1: like robot arms, and what's going on the train tracks? Yeah,

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Speaker 1: these these big arms that can basically move plates from

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Speaker 1: one robot to another and train tracks to be able

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Speaker 1: to move samples between the robots. To do the processing

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Speaker 1: steps you need to either read the DNA or write

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Speaker 1: the DNA, or put the DNA into cells or test

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Speaker 1: how those cells are performing. So the robots are doing

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Speaker 1: all of those steps. Yes, that's a dream after the break,

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Speaker 1: a problem Ginko has not solved yet. How do you

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Speaker 1: build a company based on this wild, radically new technology

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Speaker 1: and also make a profit. That's the end of the ads.

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Speaker 1: Now we're going back to the show. Kinko went public

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Speaker 1: last year and the company is now worth billions of dollars,

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Speaker 1: but Reshma and our co founders still haven't made the

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Speaker 1: company work as a profitable business. They have revenue, but

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Speaker 1: it doesn't come close to covering their costs, and so

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Speaker 1: the problem of becoming a profitable company is what we

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Speaker 1: focused on in the second part of the interview. It's

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Speaker 1: impressive in a way that you know, it's continued to

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Speaker 1: get funded and you've grown so big, and you have

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Speaker 1: lost and continued to lose a lot of money. I

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Speaker 1: feel like in the long run, that's a problem that

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Speaker 1: you have to solve eventually, Like how do you solve

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Speaker 1: that problem? So in our business, the way our business

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Speaker 1: model works is when we collaborate with a customer on

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Speaker 1: a self program, we get two different kinds of value

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Speaker 1: out of the relationship. We get fees and milestone payments

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Speaker 1: from our customers to help offset our dcosts, and we

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Speaker 1: get what's called downstream value share. Downstream value share typically

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Speaker 1: comes in the form of either royalties on products made

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Speaker 1: using Ginko organisms or equity stakes in our customers. And

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Speaker 1: we've been expanding a lot in the number of cell

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Speaker 1: programs that we've taken on, but many of them are

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Speaker 1: still in the development stage, and so essentially the way

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Speaker 1: we ultimately become a sustainable business is as more and

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Speaker 1: more of our cell programs successfully complete and recognize that

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Speaker 1: downstream value share. That's where the rail like ultimate long

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Speaker 1: term value potential of Ginko is. So you're basically saying

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Speaker 1: when the investments you've already made payoff, that will do it.

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Speaker 1: I mean, I get the math of what you're saying

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Speaker 1: is that you've put a lot of money into things,

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Speaker 1: and if they make a lot of money in the future,

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Speaker 1: then you will be profitable. Is that right? Yeah? I

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Speaker 1: mean it's like, um, you know, think about it. If

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Speaker 1: your typical like pharma biotech company, they lose the hundreds

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Speaker 1: of millions of dollars, right, but if the drug works,

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Speaker 1: there's like a big, big enough path at the end

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Speaker 1: to justify that upfront risk. Basically, it's sort of all

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Speaker 1: long shots, right. The drug companies essentially make lots and

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Speaker 1: lots of long shot bets and most of them don't work,

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Speaker 1: and then once in a while they have a huge

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Speaker 1: winner that makes up for all the ones that don't. Exactly,

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Speaker 1: but in our case, we instead of a company that

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Speaker 1: is betting up like typically in pharma or in biopharma,

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Speaker 1: you know, the company might have one bet, right, one

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Speaker 1: long shot bet, or maybe a couple of long shot bets.

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Speaker 1: We're a platform company, so we actually have lots and

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Speaker 1: lots of long, long shot bets, and you know, and honestly,

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Speaker 1: some of them are not going to work, right. You know,

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Speaker 1: some cell programs won't work, or the cell program will work,

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Speaker 1: but it won't commercialize the way we think, or whatnot.

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Speaker 1: The question is will there be enough winners, and will

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Speaker 1: they be those winners be big enough to justify the

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Speaker 1: whole thing? And we're betting that they will. I recognize

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Speaker 1: that we're sort of at a time will tell ending

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Speaker 1: of the narrative, and it's valid. It's clearly true. Time

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Speaker 1: will indeed tell. I'm just trying to think of how

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Speaker 1: to parse it. I mean, I guess another way to

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Speaker 1: think about it is whether and to what extent these

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Speaker 1: various bets will pay off. Let me flip the question

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Speaker 1: on you, right, yeah, please please, Here's the way I

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Speaker 1: look at it. Right, the world has a lot of

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Speaker 1: serious things that it is facing, right, climate change, pandemics,

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Speaker 1: you know, supply chain issues, right, having enough food to

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Speaker 1: feed our planet having enough clean water to provide to

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Speaker 1: our planet. Right to me, the cost of not doing

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Speaker 1: something is unfathomable to me. So I would much rather

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Speaker 1: try and fail at this, which at least has gives

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Speaker 1: us a shot of solving some of these pressing world problems,

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Speaker 1: then not try at all. In a minute, the Lightning Round,

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Speaker 1: where we learned Rashma's favorite micro organism, her least favorite

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Speaker 1: trait in a coworker, and the one piece of advice

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Speaker 1: she'd give to somebody who is trying to solve a

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Speaker 1: hard problem. Now let's get back to what's your problem? Now,

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Speaker 1: it's just the lightning round. Can we do the lightning round? Absolutely?

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Speaker 1: What's your favorite micro organism? E coli? That's what I did.

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Speaker 1: My PhD on tell me why E Coli is great? So.

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Speaker 1: Equali is this little microbe. It's found in every person's gout,

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Speaker 1: smells awful, smells like pooh. Right, it's part of what

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Speaker 1: makes your poo smell like pooh. And we did a

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Speaker 1: project when we were at MIT mentoring a group of

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Speaker 1: undergraduates to change the smell of ecali to smell like

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Speaker 1: weren't a green and bananas. So while Eli gets a

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Speaker 1: bad rap for smelling bad, You can actually reprogramage to

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Speaker 1: smell pretty good. What's your favorite trade and a co worker?

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Speaker 1: Passion and curiosity? What's your least favorite trait in a

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Speaker 1: co worker? Self promotion? If you have a ten minute

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Speaker 1: break in the middle of the day, what do you

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Speaker 1: do to relax? Take a walk through the lapse? What

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Speaker 1: is one piece of advice you would give to somebody

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Speaker 1: who's trying to solve a hard problem? Better to try

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Speaker 1: and fail than not try at all. It sounds trite, right,

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Speaker 1: but you know, the way I could get myself to

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Speaker 1: a place where I felt comfortable, you know, making the

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Speaker 1: leap and starting a company is that, you know, starting

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Speaker 1: a company working on really hard problems, you may or

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Speaker 1: may not succeed, right. You just don't know. It's a crapshoot, right,

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Speaker 1: And so what you want to do is be able

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Speaker 1: to get to yourself to a place where you'll never

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Speaker 1: regret try, right. And the nice thing about hard problems

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Speaker 1: and important problems is that it's very hard to regret

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Speaker 1: working on them. Rash Machete is the co founder and

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Speaker 1: chief operations officer of ging Go Buy Awards. Today's show

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Speaker 1: was produced by Edith Russolo, edited by Robert Smith and

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Speaker 1: engineered by Amanda kay Waugh. Our theme music is by

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Speaker 1: Luis Gara. A huge team of people makes this show possible.

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Speaker 1: This team includes, but is not limited to, Jacob Weisberg, Milobell,

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Speaker 1: Leta Mulad, Justine Lang, Heather Fame, John Schnars, Kry Brody,

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Speaker 1: Carli Nigliori, Christina Sullivan, Jason Gambrel, Grant Hays, Eric Sandler,

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Speaker 1: Maggie Taylor, Morgan Rattner, Nicole Morano, Mary Beth Smith, Royston Baserve,

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Speaker 1: Maya Kanig, Daniella Lakhan, Kazeia Tan and David Clover. What's

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Speaker 1: Your Problem is a co production of Pushkin Industries and iHeartMedia.

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Speaker 1: To find more Pushkin podcasts, listen on the iHeartRadio app,

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Speaker 1: Apple Podcasts, or wherever. I'm Jacob Goldstein and I'll be

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Speaker 1: back next week with another episode of What's Your Problem