Speaker 1: Pushkin.
Speaker 2: There's this idea people have been waving their hands about
Speaker 2: for a while. Now, what if we're about to have
Speaker 2: a huge wave of technological progress in biology. On a
Speaker 2: few recent episodes of this show, we've talked about one
Speaker 2: obvious place we'd see that wave in medicine, with things
Speaker 2: like new drugs and human tissues grown in the lab.
Speaker 2: But the impact could be much broader than that. There's
Speaker 2: this whole nascent industry called synthetic biology. People are trying
Speaker 2: to genetically engineer yeast and bacteria to produce everything from
Speaker 2: fertilizer to fragrances. Take, for example, indigo colored dye, the
Speaker 2: dye used on billions of pairs of genes a year.
Speaker 2: That's j E, A N S, not ge nes, unfortunate
Speaker 2: hominem in this context today, that in goo colored dye
Speaker 2: typically comes from petrochemicals, and it's made in a process
Speaker 2: with lots of nasty byproducts. But what if you could
Speaker 2: use bacteria to make industrial quantities of that dye and
Speaker 2: get rid of all the nasty by products. I'm Jacob
Speaker 2: Goldstein and this is What's Your Problem the show where
Speaker 2: I talk to people who are trying to make technological progress.
Speaker 2: My guests today are Tammy Sue and Michelle Jude. They
Speaker 2: are the co founders of a company called Hugh hu
Speaker 2: u Me. Michelle is the CEO and Tammy is the
Speaker 2: CSO Chief Scientific Officer. Their problem is this, how can
Speaker 2: you get bacteria to produce indigo dye? And how can
Speaker 2: you do it cheaply and reliably enough to replace the
Speaker 2: dye made from petrochemicals.
Speaker 1: To start.
Speaker 2: I asked Michelle and Tammy how they arrived at their problem.
Speaker 2: As it turns out, they discovered the problem from very
Speaker 2: different directions.
Speaker 1: Shell answered first, So, my family, you know, we're immigrants
Speaker 1: from China, came here to you know, move to la
Speaker 1: when I was three years old, and that's when my
Speaker 1: parents actually started their own kind of traditional, you know,
Speaker 1: wholesale apparel business. So I really, I would say, I
Speaker 1: grew up in this like fashion and apparel business, but
Speaker 1: not in a very glamorous way. My experiences or or
Speaker 1: recollections of the fashion industry. Growing up in this family
Speaker 1: business was literally you know, traveling with my parents in
Speaker 1: family vacations back to China over the summers and visiting
Speaker 1: these mills or garment factories and really firsthand witnessing some
Speaker 1: of the the negative impacts right of apparel manufacturing and
Speaker 1: specifically you know, my parents their business was a they
Speaker 1: were doing streetwear right in the nineties, and so Denham
Speaker 1: was like a big part of that. And so you
Speaker 1: know it was specifically denim mills and and denim manufacturing.
Speaker 2: And so what did you see, like specifically when when
Speaker 2: you mentioned that you saw saw that side of the industry, Like,
Speaker 2: is there a particular trip or a particular thing that
Speaker 2: you saw that that stands out in your memory.
Speaker 1: Yeah, I mean I think about you know, going to
Speaker 1: the kind of literally like you know, textile manufacturing cities
Speaker 1: right in southern China where it's just like, you know,
Speaker 1: a bunch of kind of conglomertive factories all you know,
Speaker 1: all together. The air quality kind of outside isn't great.
Speaker 1: You go into the facility, it's even worse. Everybody has
Speaker 1: kind of masks on. There are basically like blue particles.
Speaker 3: In the air.
Speaker 1: You know, it's just on people's skins, you know. And
Speaker 1: I was a child right at this time, but those
Speaker 1: are the kind of like images that are I think
Speaker 1: still ingrained in my mind. I Mean, the dye industry
Speaker 1: is a key kind of a fender, I would say
Speaker 1: in terms of, like, you know, jobs that pose threats
Speaker 1: to safety, both in terms of worker health as well
Speaker 1: as community health. You know, dying and the effluence from dying,
Speaker 1: you know, is a major source of water and kind
Speaker 1: of community pollution. Right. And by the way, you know,
Speaker 1: in the indigo process for example, right, specifically, you've got
Speaker 1: you know, not just analine, which is a benzene derivative,
Speaker 1: right that has true carcinogenic properties, but you've got you know,
Speaker 1: sodamide and formaldehyde and you know, these harsh chemicals that
Speaker 1: are going into the production process of these core dyes
Speaker 1: have done a lot of innovation in the fashion industry,
Speaker 1: but the kind of dye space itself hasn't seen a
Speaker 1: whole lot of innovation.
Speaker 2: Good. So that's your introduction to denim really early. The
Speaker 2: seed is planted, right, yeah, Tammy, how do how do
Speaker 2: you come into the story?
Speaker 4: So my story and background is very different from Michelle's.
Speaker 4: And so when I was in college, I was introduced
Speaker 4: to this field of synthetic biology, which is how do
Speaker 4: we take these microbes you know, e. Coli or yeast
Speaker 4: and actually program them to make them produce useful chemicals
Speaker 4: for for people.
Speaker 2: So you're in you go to grad school, you go
Speaker 2: to get a PhD in Berkeley, and you find yourself
Speaker 2: in a lab. What's what's the sort of generally what's
Speaker 2: the lab working on?
Speaker 4: Yeah, so the lab I was in was working on
Speaker 4: how do we develop tools for engineering E. Coli and
Speaker 4: yeast microbes to produce things like drug precursors or colors
Speaker 4: or kind of other biochemicals.
Speaker 2: Get microbes to make useful stuff for people exactly exactly?
Speaker 2: And how do you land on indigo?
Speaker 4: Yeah, there was there was this idea kind of floating
Speaker 4: around the lab right before I joined, about how do
Speaker 4: we produce indigo? Actually, I think it was because people
Speaker 4: wanted to be able to see what was going on
Speaker 4: inside the cells. Cells are really tiny, right, and often
Speaker 4: you make these changes and you try to get the
Speaker 4: enzymes to do different things, but you don't really know
Speaker 4: exactly what's going on without doing some complicated assay. So
Speaker 4: there was an idea that maybe we could use a
Speaker 4: color output, Like we change an enzyme and we get
Speaker 4: this color output, and indigo is kind of this natural
Speaker 4: diet's found and plants, so they were like, maybe we
Speaker 4: could use indigo to see what's kind of going on
Speaker 4: in the cell.
Speaker 2: So just to be clear. So just to be clear,
Speaker 2: the idea of getting a cell to express indigo this
Speaker 2: blue color. The idea wasn't oh, let's make clean or
Speaker 2: dye for blue jens. It's let's make a tool for
Speaker 2: scientists to use to understand what's going on inside the cell.
Speaker 4: Initially, yeah, and then as we were kind of looking
Speaker 4: into it, it actually seemed like indigo itself was a
Speaker 4: really big problem in the textile industry. Pretty much all
Speaker 4: indigos used for dnim genes and it we learned that
Speaker 4: all of it, the vast majority of it, is sourced
Speaker 4: from petrochemical sources right now, and so there was this
Speaker 4: need to actually make it in a biologically sourced manner.
Speaker 4: My advisor was on this fellowship and they published an
Speaker 4: article showing some very preliminary results that we were having
Speaker 4: in the lab on this project, and it was published
Speaker 4: on the UC Berkeley website, and then Dune and brands
Speaker 4: in the area actually started to reach out to him
Speaker 4: and say, oh, I heard you're working on other ways
Speaker 4: to make indigo. Can we talk what is it like?
Speaker 4: How much you know? Can we do a little trial, so.
Speaker 2: You decide to start the company. Tammy, you've done this research, Like,
Speaker 2: what exactly had you already done? What did you know
Speaker 2: how to do when you started the company.
Speaker 4: So at the end of my PhD, the last figure
Speaker 4: in the paper that we published was actually kind of
Speaker 4: unusual for a research paper. I had died one piece
Speaker 4: of fabric. It was a scarf with this indigo die.
Speaker 4: It was definitely died in a way that was not
Speaker 4: scalable and not industrially viable by any means.
Speaker 3: It smelled a little bit funky.
Speaker 2: How how was it died? Like, how did you how
Speaker 2: did you diet?
Speaker 4: I actually hung up a shoelace across across the hallway
Speaker 4: and just kind of flopped this piece of fabric over it,
Speaker 4: and I sprayed the dye against it and used the
Speaker 4: bucket to catch the remaining dye at the bottom. It
Speaker 4: was definitely an experience, but we at the end of
Speaker 4: the day we got this nice blue fabric and it
Speaker 4: was kind of our first proof of concept.
Speaker 2: So it worked. It worked at least for one scarf,
Speaker 2: one time in the hallway, at least once exactly good.
Speaker 1: I want to clarify that even though it turned blue
Speaker 1: that before. Right, we were literally telling the story yesterday
Speaker 1: to the company. It was like that was like, okay,
Speaker 1: blue is great. We had no idea you know, oh
Speaker 1: it's kind of blue greenish, or like you know what
Speaker 1: exactly all of that means. We had no capability to
Speaker 1: measure or understand any of that. So really getting it
Speaker 1: to those industrial specs, I would say, was probably the
Speaker 1: first major challenge that the company that we as a
Speaker 1: team had to tackle.
Speaker 2: So tell me about that, right, Like, blue isn't good enough? Right,
Speaker 2: you can't go to some genes manufacturer's going to make
Speaker 2: one hundred thousand pairs of genes be like yeah, it's blue.
Speaker 2: They're not gonna be like great, send it to us, right,
Speaker 2: so what do you have to do to get it
Speaker 2: to be the right kind of blue?
Speaker 4: So kind of where where we were at when at
Speaker 4: this first proof of concept was okay, so you have cells.
Speaker 4: They're making this indigo molecule. We know it's literally indigo molecule.
Speaker 4: The cells are growing in their own media. We just
Speaker 4: try to like you know, break open the cells and
Speaker 4: try to you know, get the blue onto the fabric.
Speaker 3: But that's not necessarily good enough, right, so you've.
Speaker 2: Got the right molecule, what do you have to what
Speaker 2: do you have to fix when you're you know, starting
Speaker 2: the company, leaving academia, going to make this industrial product.
Speaker 2: What do you have to fix on the kind of
Speaker 2: molecular level.
Speaker 4: I think the main thing is how do we separate
Speaker 4: out the indigo molecule away from all of the other things,
Speaker 4: all of the cells and all of the things that
Speaker 4: the cell is growing in. And so at the very beginning,
Speaker 4: a lot of our methods were very rudimentary, using you know,
Speaker 4: some off the shelf chemical engineering ways, and so that's
Speaker 4: why our first dye turned out a little bit green.
Speaker 4: And that's why kind of our first first hire was
Speaker 4: in a downstream processing engineer so that he could help
Speaker 4: us fix this problem.
Speaker 2: So the problem is, how do you get rid of
Speaker 2: everything that is not the indigo dye molecule, all the
Speaker 2: cells that made it, all the stuff that the cells
Speaker 2: were grown. You got to get rid of all that,
Speaker 2: but keep the dye. That's the first hard problem, exactly exactly.
Speaker 1: And then kind of pairing that, I think the other
Speaker 1: key unlock for us was also bringing in actual textile
Speaker 1: technical expertise, so no longer are we doing a visual
Speaker 1: test of is it blue or not? But now we
Speaker 1: can actually precisely quantify how green is it, how red
Speaker 1: is it relative to the amount of blue, and how
Speaker 1: close is that literally numerically compared to the synthetic standard
Speaker 1: that we want to be match up.
Speaker 2: So there's figuring it out at that level, and then
Speaker 2: there's figuring out how to make thousands of pounds of
Speaker 2: this die, right, which seems like a related but distinct
Speaker 2: problem that you've got to be solving sort of at
Speaker 2: the same time.
Speaker 3: Yeah, exactly.
Speaker 4: So you know, like when Dunham Brands came a knocking,
Speaker 4: They're like, can you make a kilogram?
Speaker 3: I was like, absolutely not.
Speaker 4: And so one of the big limitations thus far in
Speaker 4: this field of synthetic biology is, Okay, so you can
Speaker 4: grow your microbe, you can grow it at larger scale,
Speaker 4: but how do we actually get the space to produce
Speaker 4: this at a large industrial scale over and over in
Speaker 4: a really repeatable way.
Speaker 3: And so for that you need really large scale equipment.
Speaker 2: How do you truly industrialized how do you make lots
Speaker 2: and lots of dye every day in a factory? For us?
Speaker 3: Exactly?
Speaker 4: And I think even that we with the growth of
Speaker 4: the synthetic biology industry, there's been a lot more demand
Speaker 4: and building out of these contract manufacturers where we can
Speaker 4: we don't have to build our own facility. We can
Speaker 4: kind of drop into an outsource facility and be able
Speaker 4: to make use of that infrastructure.
Speaker 2: Tammy and our team have now reached the point where
Speaker 2: they can in fact make not just one kilogram of dye,
Speaker 2: but hundreds of kilograms. Progress after the break, what they
Speaker 2: still have to figure out to get their die out
Speaker 2: into the real world. That's the end of the ads.
Speaker 1: Now we're going back to the show.
Speaker 2: So maybe for Michelle, Michelle, can you tell me just
Speaker 2: where's the company now? What are you making now? And
Speaker 2: like what can you not do yet that you need
Speaker 2: to do?
Speaker 1: M So, so maybe just taking a step back, I
Speaker 1: would say, you know, from back then when Tammy thought
Speaker 1: one killogram was too much, you know, I think we've
Speaker 1: really been able to step up in production every year
Speaker 1: as we've also refined and iterated on the process and
Speaker 1: the product. So you know, have gone from making just
Speaker 1: a couple of grams to a couple killograms to now,
Speaker 1: you know, hundreds of kilograms, and we have an eye
Speaker 1: towards you know, metric tons, so thousands of kilograms, so
Speaker 1: that we can actually meet the industry in these needs, right,
Speaker 1: which is the tens of thousands of metric tons kind
Speaker 1: of level.
Speaker 2: And so when do you think you'll be able to
Speaker 2: make at a big enough scale that you can actually
Speaker 2: sell it to somebody who's going to make g means
Speaker 2: for me and the world.
Speaker 1: Yeah, well, so we are. We have been testing and
Speaker 1: trialing our product to make sure that we're approving kind
Speaker 1: of the iterations of the product and designing something that
Speaker 1: is truly drop in and usable for the denim industry.
Speaker 1: We are already working with brands that you know, I
Speaker 1: think listeners, you know and love.
Speaker 2: Can you say the name? Can you say one name
Speaker 2: of one brand?
Speaker 1: We cannot share the name uncorriginately.
Speaker 2: Okay, when do you think I can buy a pair
Speaker 2: of genes? Died with your die?
Speaker 1: So I'm not going to make any promises, but I
Speaker 1: would say, you know, in the next couple years.
Speaker 2: For sure, you just made a promise. I'll take it.
Speaker 1: You're right, that's true? Cut out the foresure. Yeah, No,
Speaker 1: I mean just to say, I think you know we
Speaker 1: are in you know, we're working collaboratively with the brands,
Speaker 1: and it's really a matter of our own capacity and
Speaker 1: scaling and then kind of bringing the cost down over
Speaker 1: time too, so that it can be something that continues
Speaker 1: to be more and more accessible to the broader fashion industry.
Speaker 2: So let's talk about the cost. Yeah, tell me about
Speaker 2: the economics of it.
Speaker 1: I mean, it's it's one of the big goals of
Speaker 1: the business to make it write a success. You know,
Speaker 1: I would say, we're definitely not there yet right to
Speaker 1: your point, you know, probably and you know, order of
Speaker 1: magnitude of productivity away. In order to get there, you.
Speaker 2: Think it needs to be the same price as petrochemical dies.
Speaker 1: So what I would say on the kind of price
Speaker 1: side is I think we're making a bet that brands
Speaker 1: in the greater supply chain understand the big picture here
Speaker 1: and the opportunity is that, you know, luckily dies they
Speaker 1: can make this huge visual impact, but again they're only
Speaker 1: actually a very tiny fraction of what makes the garment itself.
Speaker 1: And so we believe there's a path to commercializing early
Speaker 1: even before we are cost neutral with the petrochemicals. But
Speaker 1: we can commercialize early to help build the business before
Speaker 1: we're there. At the cost side, because it just doesn't
Speaker 1: make a huge difference on the end price of the
Speaker 1: garment for example. Well as an example, it's like, are
Speaker 1: you willing to pay five dollars more for a pair
Speaker 1: of genes to help to facilitate that transition of the
Speaker 1: industry to better materials before it becomes cost neutral?
Speaker 2: And just to be clear, like five dollars more is
Speaker 2: when your die is how much more expensive that petrochemical
Speaker 2: based die.
Speaker 1: Five dollars more is like is like ten x more
Speaker 1: expensive chemical die.
Speaker 2: The die The die cost is a very small percentage
Speaker 2: of the overall cost of a paragenes exactly. Okay, So
Speaker 2: presumably there's like the sort of classic early adopter curve
Speaker 2: where there's a universe of people willing to pay more
Speaker 2: because they care or because they want to signal to
Speaker 2: people that they care whether they care or not. And
Speaker 2: those people will be your early adopters who will allow
Speaker 2: you to scale, and then you'll use that scale to
Speaker 2: become a cost neutral. That's the dream.
Speaker 1: Yeah, I think so, I think we think about, you know,
Speaker 1: the Tesla model for this right where you see.
Speaker 2: Everybody loves the Tesla. Everybody, everybody who's not making software
Speaker 2: everybody who's making a physical thing.
Speaker 1: It is.
Speaker 2: It is really remarkable how that metaphor is the It's
Speaker 2: like it used to the uber but for X, but
Speaker 2: now it's Tesla. But literally yesterday I was talking to
Speaker 2: a guy who's doing that with houses. He's building these
Speaker 2: little backyard houses. Cover. The companies called Cover and they're
Speaker 2: building like really nice little backyard studio apartments. But they
Speaker 2: want to build houses and they want them to be cheaper,
Speaker 2: and it's a Tesla metaphor.
Speaker 1: It's like you go to the premium and you go
Speaker 1: down and it worked.
Speaker 2: And it worked for them. They did it. Are you
Speaker 2: working on other colors?
Speaker 1: You know, there's a broader platform and kind of opportunity
Speaker 1: here right to not just you know, disrupt denim, but
Speaker 1: also the fashion industry and food and cosmetics in all
Speaker 1: of these areas where color is infused into our daily lives.
Speaker 1: And so we're actually now taking our learnings from you know,
Speaker 1: bioengineering our first color product and looking at the broader
Speaker 1: kind of platform that we've developed and saying, how can
Speaker 1: we also create a broader palette that isn't kind of
Speaker 1: one color at a time, knowing that there are tens
Speaker 1: of thousands of different colors in use in these variety
Speaker 1: of industries today.
Speaker 2: Uh huh. Build a system that is more easily customizable
Speaker 2: so that you can get the cells to make whatever
Speaker 2: is the color of the season.
Speaker 1: That's right.
Speaker 2: In a minute, the lightning round with lots of questions
Speaker 2: about genes and genes as in denim. Now back to
Speaker 2: the show. Let's let's do a lightning round. Let me
Speaker 2: just ask you a bunch of questions before it's time
Speaker 2: to go. Oh gosh, Okay, they'll be different, they'll be
Speaker 2: simpler and more fun. Okay for either of you. Why
Speaker 2: are genes still almost always blue?
Speaker 4: Because I don't know if this is a very chicken
Speaker 4: and egg answer, but it's because it has to be
Speaker 4: made with indigo, and I think an indigo is blue.
Speaker 4: And indigo actually binds the yarns in such a way
Speaker 4: that you can kind of flake it off from the
Speaker 4: from the fabric, and you know, as you wear it,
Speaker 4: it takes the shape of you know, your body or
Speaker 4: you know, the wallet that you put in your back pocket.
Speaker 4: And it's really rare to have a dye that has
Speaker 4: these properties.
Speaker 2: I've seen numbers that seem wild for the number of
Speaker 2: jeans made in a year? Do you does either you
Speaker 2: know a true number for that?
Speaker 1: So our latest estimates are number of gens every year
Speaker 1: made is about two to four billion garments.
Speaker 2: Billion, Like that's billion. That's wild, right, Like yes, I
Speaker 2: mean what are we at for the world?
Speaker 1: Now?
Speaker 2: Eight billion people?
Speaker 1: Is that? Is that right?
Speaker 2: So it's like in a few years you have a
Speaker 2: pair of genes for every single man, woman, and child
Speaker 2: on earth.
Speaker 3: Yeah, exactly.
Speaker 2: Okay, here's one for both of you. And I want
Speaker 2: you to try and answer at the same time. So
Speaker 2: I'm gonna ask the question and then I'm gonna say one, two, three,
Speaker 2: and then when I get to three, I want you
Speaker 2: to just give a yes or no answer. Can you
Speaker 2: wear a jean jacket with jeans? Yes?
Speaker 4: Or no?
Speaker 1: One?
Speaker 2: Two three?
Speaker 1: Yes? Oh, it's coming back. It's a trend that is
Speaker 1: coming back. Now, I'm telling.
Speaker 3: You that may be true. That may be true.
Speaker 2: Michelle, you came to hear from the business world. What
Speaker 2: do you know about science now that you didn't know
Speaker 2: when you started the company?
Speaker 1: Ooh, too much? I know. I know so much about science.
Speaker 1: I know enough to be dangerous to talk about by
Speaker 1: engineering and chemical engineering. And you know the bio manufacturing
Speaker 1: to be to be really dangerous. So just to say,
Speaker 1: you know, I think there's a lot of great science,
Speaker 1: a lot of great ideas out there, but actually, you know,
Speaker 1: I have a lot of respect for the chemical engineers
Speaker 1: and the folks who actually go from R and D
Speaker 1: to actually turn it into something that has a commercial
Speaker 1: case around it. And you know, we need to make
Speaker 1: those tough decisions and work on those optimization problems to
Speaker 1: actually get it to be something that's adaptable for the industry.
Speaker 2: So I just want to shout out your dog, who's
Speaker 2: really doing amazing work back over your shoulder. What kind
Speaker 2: of dog is it?
Speaker 1: She's a Congress Spaniel. This is one of her better days.
Speaker 1: She really loves showing her just just all sides of her.
Speaker 1: Let's say to the camera whenever I am on.
Speaker 2: Camera, what's her name? Her name's Daisy, Daisy Classic. Michelle
Speaker 2: Zou and Tammy Sue are the co founders of Hugh.
Speaker 2: Today's show was produced by Edith Russello. It was edited
Speaker 2: by Sarah Nix and Robert Smith and engineered by Amanda
Speaker 2: k Wong. I'm Jacob Goldstein. You can find me on
Speaker 2: Twitter at Jacob Goldstein, or you can email us at
Speaker 2: problem at Cushkin dot fm. We'll be back next week
Speaker 2: with another episode of What's Your Problem.