Janice Chen, Co-Founder and CTO, Mammoth Biosciences

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What’s it like being the first to develop a new way to detect COVID-19 using the CRISPR?

Janice Chen is the Co-Founder and Chief Technology Officer at Mammoth Biosciences, a biotechnology company based in the San Francisco Bay Area that is harnessing natural diversity to develop the next generation of CRISPR products across diagnostics and therapeutics.

CRISPR is the revolutionary gene-editing technology discovered in 2012 by Jennifer Doudna and Emmanuelle Charpentier. The pair earned the 2020 Nobel Prize in Chemistry for their work, and Dr. Doudna has since helped build a number of CRISPR-related businesses, including Mammoth, focused on developing real-world CRISPR applications for commercial use.

Janice studied and worked in the famous Doudna Lab at UC Berkeley before co-founding Mammoth with her partners Trevor Martin (CEO) and Lucas Harrington (CSO). In January 2022, Mammoth became the first company to receive FDA approval for a CRISPR-based test to detect COVID-19.

(Note: Sixth Street invested in Mammoth’s Series D in September 2021, and Dr. Doudna became Sixth Street’s Chief Science Advisor in February 2022.)

In this episode, we talk to Janice about how Mammoth’s focuses the excitement and potential of CRISPR into real-world applications, how to translate science for business people (and vice versa), and how she and her team consciously find ways to periodically step back from the microscope and see the bigger picture.

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Episode Transcript:

"It’s Not Magic" is a podcast from Sixth Street that brings to light insights and perspectives from founders and industry leaders on business building in plain English. Hosted by Sixth Street’s Co-Founder, Co-COO and Co-President, David Stiepleman, we ask guests what they do and how they do it – because building a business is a lot of things, but… It’s Not Magic.

On this episode, our host David Stiepleman sits down with Janice Chen, Co-Founder and Chief Technology Officer of Mammoth Biosciences.

DAVID STIEPLEMAN: Hello, welcome back to, "It’s Not Magic", a podcast from Sixth Street about business building that strips away the pretense and gets right to the useful stuff. We use this show to talk to founders and industry leaders and get them to explain in plain English what they set out to do, and specifically how they do it. I'm your host David Stiepleman. And I've been excited about every episode, but today it's especially true because we have a great guest. Janice Chen is a brilliant scientist and entrepreneur. She's the Co-Founder and Chief Technology Officer at Mammoth Biosciences. Janice and her co-founders are developing next generation diagnostics and therapeutics around the CRISPR gene editing technology.

JANICE CHEN: Jennifer and colleagues had done some of the foundational work in showing this was an extraordinary gene editing tool, but that was sort of where the conversation ended. What we had done, that I think was really exciting, was really focusing on the fundamental mechanisms of how these enzymes worked and what that had led to was this unexpected finding that you could use CRISPR not just to edit genes, but also detect DNA. So that was actually completely against dogma at the time.

DAVID STIEPLEMAN: Janice is, of course, referring to Jennifer Doudna, the Nobel Prize winner and co-discoverer of CRISPR, who is also Sixth Street's Chief Science Advisor. So, already you know you're in for an interesting and important discussion. But the other reason I'm so excited about today's conversation is that I was with one of my partners, Jeff Pootoolal, who, with our partner Vijay Mohan and a great team, runs Sixth Street's healthcare investing business. Jeff not coincidentally has a background in biochemistry and has been a life sciences and healthcare investor and business builder for a long time. And he is here now. Hey, Jeff.

JEFF POOTOOLAL: Hey, David. Thanks for having me.

DAVID STIEPLEMAN: Oh, it's a pleasure. So, let's frame this for everyone. What's CRISPR, and then what do Janice and the team at Mammoth Biosciences do?

JEFF POOTOOLAL: So, the easiest way to understand CRISPR is to start with your genes. Every living thing on earth has DNA, and everything has genes, which are segments of DNA. And those genes include a lot of information, including the information for a lot of what's makes us “us”, from the color of your hair to your predisposition for certain diseases.

What if there was a tool that could allow us to easily and accurately edit genes in a way that could help life on earth? And what if that tool occurred organically in nature, just waiting to be found. That's what CRISPR is. In 2020, Jennifer Doudna and her collaborator Emmanuelle Charpentier won the Nobel Prize for the discovery of CRISPR and how it can be used to edit genes, which dates back to their work in 2012, so 10 years ago now. A decade in, CRISPR is evolving from a highly valuable lab tool to having real world implications. CRISPR is being developed to help treat genetic diseases, diagnose infection, and even improve the nutrient profile of tomatoes.

Janice is one of the co-founders of one such CRISPR company, Mammoth Biosciences, where she is CTO alongside co-founders Trevor Martin, CEO, and Lucas Harrington, CSO. As we will hear, this company is doing some of the coolest things with CRISPR, across therapeutics, diagnostics, and other CRISPR tools. One of the amazing things, which is what Janice focuses on and we'll get into today, is using CRISPR as a fast and effective way to detect diseases. Mammoth actually developed the first CRISPR-based test to detect COVID 19.

DAVID STIEPLEMAN: What's amazing is that this is all in the last four years or so. In any case, what's our connection?

JEFF POOTOOLAL: We're an investor at Mammoth, full disclosure. Sixth Street funds invested in their Series D, and as you mentioned, Jennifer Doudna is our Chief Science Advisor and is a Co-Founder of Mammoth. Janice worked in Jennifer's lab at Berkeley, the famous Doudna Lab, before starting Mammoth.

DAVID STIEPLEMAN: Awesome. That's helpful. And we'll add a bunch of other, not too technical, useful reading on CRISPR on the website. Let's get right to it.

DAVID STIEPLEMAN: Janice Chen, thank you for joining us. It's such a pleasure to have you.

JANICE CHEN: Thanks for having me, David

DAVID STIEPLEMAN: You're in the lab at Berkeley, with Jennifer Doudna, CRISPR is out there, it's a thing, and everyone's talking about interrupting the expression of diseases, or developing resistant crops, or making an incredibly juicy tomato, or whatever it is that people are talking about, and you're thinking about the engineering of it and diagnostics. Can you walk us through that, where you and your colleagues actually kind of happened on that moment?

JANICE CHEN: Yeah, absolutely. I had started in the lab of Jennifer Doudna. This was still early days of CRISPR, and frankly, a lot of the conversation was purely just how do you use CRISPR for gene editing. Jennifer and colleagues had done some of the foundational work in showing this was an extraordinary gene editing tool, but that was sort of where the conversation ended. What we had done that I think was really exciting was really focusing on the fundamental mechanisms of how these enzymes worked and what that had led to was this unexpected finding that you could use CRISPR not just to edit genes but also to detect DNA. So, that was actually completely against dogma at the time. I think no one had really thought about, “Oh, you could actually use this tool for detection,” but that actually just came through the process of really understanding the mechanisms behind how the protein worked, and sort of stumbled across this feature that continued to reproduce itself in the lab.

Once we had figured out that this was not just a fluke, this was actually a robust activity that we were observing in the protein, we said, “Okay, well, we have to then understand if we can actually leverage this as a potential diagnostic tool.” And that's where, with the help of Jennifer and my colleagues, [Mammoth Co-founder] Lucas [Harrington] and others in the lab, we said, “Why don't we go and reach out to physicians in the Bay Area and ask if they were ready to collaborate on using CRISPR as a potential diagnostic?” We had focused on looking at HPV as a proof of concept because it was a double stranded DNA virus, and we had shown that you could use CRISPR to detect double stranded DNA. So, we had the fortunate opportunity to work with one of the leading HPV researchers at UCSF, Dr. Joel Pulaski, and were able to basically create a diagnostic assay to detect specific HPV strains in patient samples.

And that was, for me, a major ‘aha’ moment because we were given essentially a panel of blinded clinical samples that we had no idea what they were infected with, and then basically used our CRISPR diagnostic, which essentially accurately detected the specific HPV strains. And I think that was a really exciting moment for me and one that actually allowed us to think really big about how we could then take this technology beyond the academic lab and make a big impact with it.

DAVID STIEPLEMAN: I'd love to unpack some of that. I've heard you talk about, and we've heard Jennifer Doudna talk about, creating an environment of curiosity-driven science in the lab. And I assume that's why you were picking your head up and scanning the universe of possible applications of this, but what is that environment? How do you create that environment?

JANICE CHEN: Yeah, that's a great question. I think a lot of it, like you said, is driven by Jennifer's philosophy and her approach to science and how she's sort of been able to cultivate a culture where it's not about solving the easy problem, it's about looking at what's really difficult and actually challenging ourselves in terms of how we think about the current status of the way things work, so being comfortable with challenging dogma, and that's one thing I'm really proud of for myself and for my colleagues that were in Jennifer's lab. For instance, we talked about CRISPR diagnostics as one example where we challenged the belief that CRISPR was just a gene editing tool. Later on, in graduate school with my co-founder Lucas, we challenged this idea that CRISPR enzymes had to be a certain size to be able to work for gene editing, and through that unexpected direction, we learned that you could actually use these ultra-small enzymes that people thought, “Oh, there's no way these are going to work for gene editing.” But in fact, they were extremely robust and unlocked so many applications for therapeutics. Those are examples, I think, where going after the hard problems and being able to really focus on not just going after what's expected, but really going after the non-obvious is something that Jennifer really cultivated. And I think all of us in the lab really challenged each other to go after that.

JEFF POOTOOLAL: How much of that culture have you brought with you to Mammoth? And now that you're a leader, Janice, how do you make that culture stick?

JANICE CHEN: I think a tremendous amount of that is what we really value and bring to Mammoth. I mean, for us, it's all about driving the science forward and being at the forefront of that technology. Certainly being in the CRISPR field, one that is so incredibly competitive and so exciting, it's always about what's new, what's next, is something that we've brought very, very much to Mammoth. I think, throughout our graduate school years, we were actually kind of building the evidence and the thesis for this idea that you could actually be scientifically driven and use a scientific curiosity to help kind of drive the next generation of groundbreaking tools. And I think that's just a philosophy that we've been able to really bring to the company, and one that we hold very high in terms of the people that we bring in and how we are really mission driven towards that.

DAVID STIEPLEMAN: Can I ask, when you had that moment in the lab, and you started going around and you were mapping out the HPV virus, I feel like academics would ordinarily say, “Okay, let's stay in the lab and let's get grants and let's figure this out.” Why did you think about taking this to the commercial field?

JANICE CHEN: Yeah, I think as soon as we saw that this was reproducible, that it actually had the level of accuracy that matched the gold standard PCR for detecting these viruses, it became this sort of obsession, like, we're really onto something new, and I think it also made us recognize that there was more impact you could have by taking it outside of the academic lab. Throughout our training, it's sort of like, okay, you get to a proof of concept, you can publish impactful papers. But, sort of taking it to the next level of translation was something that I personally had never experienced, and I think one that I was really just eager to dive into. And I think through exploring this idea of, “Okay, maybe we should start a company based on this,” thesis that you could go from discovery of a new enzyme to understanding how it works to actually driving a new application, like, “Can we explore this a little bit more?” And I think it was just sort of a combination of being at the right time, being comfortable with taking new risks, frankly, being in a position where you're a graduate student making $30,000 a year, there's really nothing to lose. We're like, “Okay, we're all committed, so let's just go and do it.”

JEFF POOTOOLAL: How does your mindset change as you go from being an academic to an entrepreneur?

JANICE CHEN: Yeah, it's so different, right? As a graduate student, you're sort of like a mile deep and an inch wide. You become a deep expert in a particular area, and certainly for me, really understanding the atomic detail of these CRISPR enzymes. And then as you transition to an entrepreneur, it's the opposite, you become an inch deep, in a way, and a mile wide. I mean, I try to go further than an inch, but at some level, you're zooming out a lot more than you might as a graduate student. But for me personally, that's been one of the most exciting parts about entrepreneurship and being able to lead a company is to be able to zoom in and zoom out, go into the minutia but also then go really abstract, and being able to flex both sides of my thinking on that has been extremely exciting.

DAVID STIEPLEMAN: I want to talk about the company and the culture of the company. One is that you've got scientists who are coming in, and they're coming presumably out of the same kind of environment you came out of. My impression of scientists, let's challenge that if it's wrong, is that your work is siloed. You've got to be very, very focused on what you do. And now, you've had to come in and work to a company and work with other people and be able to present to investors. How do you help people make that transition? How did you make that transition?

JANICE CHEN: For sure. I think for us in particular, so there's four co-founders including Jennifer, Trevor Martin, who's our CEO (he actually came from Stanford, so we're a rare Berkeley-Stanford collaboration that so far seems to be working out!), and then of course my, lab mate Lucas as well. I think we sort of all came in with a level of shared life experience, shared vision, shared vision values, and really, I think we all have a similar, let's say, level of risk appetite, which is really great because we're not afraid to try new things.

But certainly, coming in as first-time founders, first time entrepreneurs has been really great doing it as a team, and that's one thing, actually, going back to the culture of Jennifer's lab, is cultivating this idea and this culture of collaboration, frankly. I think in a lot of other PhD experiences, you might be completely siloed and really kind of heads down and working on a problem. But Jennifer's lab in particular, really, I do think challenged that idea that your science was really in your own world. I think that was the other learning experience that I had being in her lab was being able to essentially cold email anyone, like I talked about reaching out to physicians at UCSF, I had done that with other projects that I was working on, where I was like, “Oh, I want to be able to leverage this single molecule technology. Let me just cold email an expert in the field and say, ‘Hey, can we collaborate?’” And of course, being in Jennifer's lab, you could just be like, “Hey, I'm from the Doudna Lab, let's work together,” and everyone would be like, let's do it, right? So, I had that opportunity that a lot of people might not have, but I've really been able to leverage that. And then I've noticed that you can just do so much more by collaborating with others, especially people from diverse backgrounds and disciplines, in terms of being able to kind of unlock and uncover things that you might not be able to if you only looked at it from one direction.

DAVID STIEPLEMAN: So that's cool. You had that calling card and you realized, gee, if we all work together, it's terrific. You saw the benefits of it. How do you practice that model? How do you and your co-founders show the team that this is the way to be?

JANICE CHEN: Yeah, a lot of it is leading by example. Lucas and I have developed a really great working relationship. We've almost been working together for 10 years now, so we have a level of trust with each other where we can say, “Hey, I know you're really good at a certain thing, but I'm also going to challenge you, and I'm going to make sure that we're actually driving after the most important problems.” With Trevor as well, he also has a really long-term vision in terms of how do we want to build this company? We don't want to take things from a traditional approach. Even the fact that we are young, first-time founders has sort of changed the perception of the company, right? People don't see us as gray-haired management that's come in to drive for this biotech company, but really, we are a group of founders that are willing to rethink how we might be able to tackle some of the biggest challenges in healthcare today.

A lot of it is just leading by example, it's also really encouraging our teams to think outside of the box. Creativity, for example, is one of our core company values, and I think that's one thing that's really stood out as we interview candidates for roles, and what people are attracted to as well, in terms of, “Oh wow, Mammoth is just kind of doing things a little bit differently.” I think over the years, we've been able to really validate that. One thing we've noticed too is that we are certainly leading the way in terms of how we think about building this new CRISPR platform, and a feature of that is that we have many people trying to, frankly, copy our narrative or say that they're doing the same things that we are. So, there's a lot of noise there, but I'm really proud of our ability to create a momentum around the work that we're doing at Mammoth.

JEFF POOTOOLAL: Were there any initial challenges you thought you had to overcome, being young entrepreneurs specifically?

JANICE CHEN: Yeah. I mean, there are just so many challenges that we had to overcome. I think for me in particular, I've always had to manage my own imposter syndrome throughout even graduate school. And I think over the years, I've been able to be in control of that rather than having the imposter syndrome be in control of me. I've been able to manage through just active coaching and practice. But in general, I think, part of it is mindset and realizing that we're all coming in and trying to do something new, which means that even though we have maybe different years of experience or different perspectives, at the end of the day, we're all coming to this at the starting line, right, and how do we build that together? And I think that's been really important because then we can kind of see everyone as equal colleagues who have a lot to contribute to bring forward the vision that we’d like to accomplish. But in general, I think again, having a co-founding team that has not done this before is actually a feature and not a bug in this case, because it allows us to not just go down what people might traditionally want and believe is what the path towards success might be.

JEFF POOTOOLAL: Yeah, how do you think about that? I know at Mammoth you have some great, experienced folks around the table who I imagine you rely on for their advice. How do you kind of balance not leaning too heavily on them and being able to chart your own course, but still taking in some of their experience?

JANICE CHEN: Yeah, that's a great question. It's actually probably one of the more difficult things that I've had to learn myself, because on the one hand, yes, we have an incredible team, and one that I feel honored every day to be able to work with them. On the other hand, it's sort of like, you don't want to just fall into a comfort zone where you say, “Okay, you know this, and so let's just go to the simplest or the most comfortable thing to go forward with,” but really making sure that we hold each other accountable and really challenge each other to say, “Okay, actually, is this the right way to go about it?” Again, going back to this idea of challenging dogma and not just going the path of least resistance. But it is a really delicate balance. In a lot of ways, it's more of an art than a science, it's about really understanding why people are trying to go after things a certain way, understanding why you yourself feel strongly about a particular point of view, but making sure that's all being expressed, and then having a clear process for saying, “Okay, well there's a path forward that maybe we don't know, we have no idea if it's actually going to work, but we are going to be committed to it and move forward.”

Certainly, I would say we've had so many incredible advisors, both inside, outside of the company that have helped us create and craft and refine the path forward. And I think our job as founders is to try to listen to all of that, synthesize it, but then at the end of the day, make sure that the decisions that we make are aligned with our core mission and values and that we are able to then direct things in the way that is going to lead to realizing the potential of the company,

DAVID STIEPLEMAN: Just staying on that theme of the team advisors and professionals there that may not be PhDs, and who are not doing the core work, but you need them to understand what it is that you're doing and to have some level of familiarity and subject matter expertise so they can filter their advice through the values of the company and what you're trying to accomplish. How do you do that? How do you overcome what may be translation issues?

JANICE CHEN: Yeah, it's a great question. The flip side is true, right? I might be a deep expert in some area of the technology, but then I'll have essentially no understanding of a different function or very surface level understanding, so there is this translational piece where I've learned that you can absolutely overcome that. A lot of it comes down to really breaking things down to first principles and saying, “Okay, what is the goal that we are trying to accomplish? How do we communicate that in a way that can be translatable?” So, instead of going into the minutia, what's most important? I think a lot of it at the end of the day comes down to having people who at least are not completely isolated from the different functions. As an example, our head of IP has a scientific background and also is just incredibly strategic on the IP side. I think having that mixture of different disciplines actually becomes a powerhouse. Those are the kind of people that we like to hire at Mammoth so that it's sort of a synergy, it's more than the sum of its parts because you have people that have this ability to translate. It's not always true, and it's not always necessary, but I think that's one thing that really brings the team to the next level.

DAVID STIEPLEMAN: In thinking about this conversation, I was thinking about the possible parallels between our business and Mammoth, and one of them is, and you said it actually, you're always focused on what's new, what's next. It's sort of like this relentless focus, the product is innovation. You have to continually evolve. Some other companies, maybe it's a conceit, but some other companies, you have to innovate, but you also do a thing. The thing you're doing is innovating and you grew four times since 2019 or whatever, right? That's exhausting. How do you not have everybody just running at full RPMs all the time?

JANICE CHEN: Yeah, it's something that we have to always watch out for, right? But like you said, the innovation is just so core to the longevity of a company depending on what your goals are. But for us, it's really about building. It's building a company, it's building a platform, it's really taking new technologies to patients. And with those big goals in mind, we have to innovate, otherwise we're going to become obsolete. Either we have to out-innovate ourselves, or some other company will. And I think that's one thing that keeps us really focused on making sure that we're not driving into obsolescence and that we are continuing to push the boundaries.

As far as making sure that you can continue to move forward without petering out, that's a conversation that we're all navigating together, right? I mean, it's incredibly motivating to go after [these problems]. I think that's where having really difficult problems is, at least for me, a way to manage that because you know that the effort that you put in is going to take you one step closer to being able to detect and cure all genetic diseases. Fundamentally being able to eradicate disease is something that is extremely far out there, but one that I think everyone is like, “I can get behind that, and I know that everything that we do is going to help us get closer to that reality.”

DAVID STIEPLEMAN: It's very motivating, I can imagine that.

JEFF POOTOOLAL: I was just going to ask: the growth has been tremendous, and there's three of you as founders. How do you manage dividing and conquering, but then understanding when you need to come together again for certain issues? How does that dynamic work?

JANICE CHEN: There are a couple rituals that us as founders have maintained throughout the growth of the company since we were just a tiny team to where we are today, and that is making sure that we have dedicated time with each other every single week to just talk about where things are, what's going on, what do we need, what help do we need? So, that's been a consistent drumbeat that's persisted throughout the years. From a roles and responsibility standpoint, that's always evolving, right? I think that's one thing your listeners are aware of, or may not be aware of, is that as founders, you have to acknowledge that your role is going to change over time, and that's a good thing, because that means the company is scaling. You're bringing in people with new expertise that can help drive things in ways that you can never do yourself, and in a lot of ways it becomes a relief sometimes to the founders, because all of a sudden, you're no longer burdened by something that maybe you just don't know that well, but you have to pull together to move things forward.

I think a lot of the being able to work together also is understanding very clear swim lanes. You’re accountable and responsible for certain things, and then your counterparts are accountable and responsible for other things, and then making sure that we also are being able to pull our weight at the same kind of intensity as everyone else. So, a lot of it is of course built on just trust and communication, and also recognizing each other's strengths and weaknesses and being able to really create a cohesive group based on where we are as people and teammates, and I think that's how we've been able to pull through.

DAVID STIEPLEMAN: Do you review each other?

JANICE CHEN: We definitely do, yeah. I think one thing that I'm really grateful for with the team is that we are very frank. Our personalities are such that we're very much direct with each other. We also have our own executive coaches who help us, whether it's with each other or others on our team, give and receive feedback. I think that's something that, if you can't figure that out, it becomes incredibly difficult to course correct or just try to make ourselves better.

DAVID STIEPLEMAN: Can I ask you a question that's not particular to Mammoth or the field, but as a business leader and as a business leader who's out there talking to people about a variety of things? Do you get pressure or encouragement internally or externally to talk about the issues of the day? I feel like that's more of an issue for business leaders - we certainly see it. And if so, what's your framework for deciding what you're going to speak on and what you're going to not speak on?

JANICE CHEN: Yeah, it's a good question. I think both internally and externally, there is an expectation that as a leader, you are able to have clear position statements or at least a point of view around what's going on. And I think the way that we've been sort of managing that over the last couple years and, well before we even started Mammoth, there's always been new, unexpected world events that have happened. I think one thing that we've done is just to create a platform for being able to have that kind of open dialogue internally. A lot of times, what I've learned is that certain events may not impact me directly but have tremendous impact on someone else in the company, and so being able to have a safe space to talk about things and listen has been extremely important for us to build that trust and community, and recognizing that we all have very multidimensional lives and things that impact us day to day.

So that's more on the internal side. On the external side, I think in a lot of ways, there's not as much pressure I would say, but it's more about, well, how do you want to be known as a company, right? And I think as leaders, we all are representatives of the company, and so making sure that we are aligned as a team in terms of what are the things that we really feel like are most important, what are the things that may be distractions, those are not so straightforward. And a lot of times, it's not a single person necessarily that's saying, “Okay, this is what the company will stand for,” but I think it's a combination of understanding your culture and what your company ultimately values. I think that all kind of ties together.

DAVID STIEPLEMAN: I like how you're thinking about it, you have to identify who you are, what you want to be, and just be clear about it. Mammoth in five years, the field in five years, what do you think? What should we expect?

JANICE CHEN: Oh my gosh, five years is like, an eternity in CRISPR, right? I mean, if you just think about it, it's been 10 years, right - it's been like a decade since the original 2012 papers that Jennifer and Emmanuelle and colleagues received the Nobel prize for just a couple years ago. So, it's kind of incredible to think just in a decade what the field has been able to accomplish from understanding that you could reprogram these enzymes to edit DNA to now, reaching the clinic and showing a ton of promise in terms of being able to edit genetic disease. But then, of course, the next five years, I think it's really going to be about creating real cures for these diseases. It’s also being able to expand what's possible with CRISPR. Again, CRISPR started from basically being synonymous with this cast line protein to now recognizing that this is an incredible, rich, diverse toolbox of enzymes that have all these capabilities and so much power as new possibilities for genetic medicine.

And when I say medicine, I'm really talking about the continuum of healthcare, right? From all the way from the detection through the treatment. I think recognizing there's a full ecosystem and continuum of care is where CRISPR's going to play an incredible role throughout that whole process. So yeah, in five years we're absolutely going to see CRISPR diagnostics products in the market. We're going to see really exciting readouts in terms of the progress that we're making on in vivo gene editing with new CRISPR enzymes. I think these are all critical milestones for validating what the technology can do, but the ultimate vision is that you can show you are able to deliver on these kind of focused areas, but then it becomes a platform and a vehicle for us to then be able to apply that to so many diseases and being able to capture this entire space of what essentially has no really reliable, accessible diagnostic that is going to lead to a permanent cure. So, I think being able to capture that full spectrum is something that we're going to start to see in the next five years.

DAVID STIEPLEMAN: At the risk of embarrassing Jeff, sorry, Jeff, because I'm going to ask a question that may be an incredibly stupid question - I heard you talking about, on someone else's podcast, you're out there in national parks, in thermal vents in the ocean, looking for enzyme, what does that mean? What are you doing?

JANICE CHEN: I think that's one really exciting part about the diversity of CRISPR, right? So, if we zoom all the way back to help us understand why it's important to go to nature for this stuff is remembering that CRISPR actually comes from this natural bacterial immune system. So, in the same way that humans have an adaptive immune system to fight against viruses, it turns out that these bacteria also have a process to fight against invading viruses. We all know that the microbiome is incredibly diverse around the globe in different environments. If you go and just take a soil sample, for instance, you're going to uncover so much diversity just within that sample. And now imagine going to a lake or forest or thermal vent, right? A lot of key molecular biology tools were discovered, frankly, from these extreme environments.

And that's an example of, again, uncovering the natural diversity that exists for these tools, and CRISPR is no exception, right? There are quite literally folks that go into these environments and collect these samples, sequence them, create these really rich data sets that we can then mine computationally for the next generation CRISPR enzymes. And then a lot of the magic actually then comes from having the know-how and expertise to translate those sequences into functional enzymes that will work at the lab and then will work into specific applications. So that's the secret sauce that Mammoth has really cultivated and been able to leverage in tremendous ways.

DAVID STIEPLEMAN: It's like these 19th century naturalists who are out there collecting the samples of whatever mollusk that had never been discovered. It's like the 21st century version. It's so cool.

JANICE CHEN: Exactly.

DAVID STIEPLEMAN: Sorry, Jeff, interrupted you.

JEFF POOTOOLAL: No, actually it's a good segue. Janice, you talked earlier about the breadth of CRISPR and that it can be applied across the healthcare spectrum. When I look at Mammoth, the one thing that I think really sets it apart is these three businesses actually. You've got this platform that you just talked about, then you're doing diagnostics, you're also doing therapeutics. How do you manage all of that at once, and how do you think about where you want to dial in and dial out your time and energy?

JANICE CHEN: Yeah, that's a question that we've had to ask and answer over and over and over again over the years, right? I think even in the early days, we were primarily really focusing on CRISPR diagnostics, but recognizing that we had this powerful engine that was driving forward the core competency of the company around this CRISPR platform and recognizing that there was this incredible opportunity that we could go after and then pursuing the therapeutics application. In a lot of ways, yes, we are a very multidimensional company, and I think that's been both a challenge but also a huge opportunity. Even in the early days, I think a lot of investors were having a hard time trying to understand and wrap their minds, like, are you a diagnostic company? Are you a therapeutics company? And I think we've had to be able to really refine that narrative and say, “Look, this is broader than just any one business, it's showing that you can have one technology that is able to address all of the unmet needs across the healthcare spectrum.” I think there's no other example that currently exists that we know of at least.

I think that's been the overarching reason of why we are cultivating all of this within Mammoth. But then as far as the execution, that's a different story, right? There's a narrative and then there's the extra execution piece, and I think a lot of that comes down to how you're structuring the different areas within the company, how are you making decisions around what are the highest priorities, but of course staying true to what you want to actually achieve? One way that we do that is to have really dedicated leaders and experts to help drive forward these different businesses that have gone through that product life cycle, they've been through the trenches, and they know how to take that all the way through. But then also making sure that we never lose our core, which is, again, this discovery engine that truly is going to unlock maybe new applications that we can't even think of today. I think being able to have that optionality is also really exciting and that's one thing that really draws people to Mammoth as well, because they realize, wow, there really is this fountain of opportunity. It's a question of: how do we then prioritize within that?

I think that's a process that we have a working framework we constantly do need to revise because there's new opportunities that come up, and then there are things that we say, look, we're going to stay super focused on making sure that we execute towards the goals here. But at the end of the day, it's constant discussion and strategy and negotiation and figuring out how do we look at this in totality, right? And so as far as my role, I sort of wore multiple hats, but again, the role's been evolving over time. As Chief Technology Officer at Mammoth, I have oversight over all the different technologies that we're developing and how we actually translate that into products, but also, I do have a role as the head of diagnostics and really thinking about how do we actually translate this new technology into transformative diagnostic products that are really going to change the landscape for diagnostic testing in the near term and the long term? So, it's a lot of contact switching at times, but I think overall, my primary role is a founder, right? I'm always thinking about how do we actually make sure that we deliver on what we intended to do when we started Mammoth?

DAVID STIEPLEMAN: Well, really casting the sharp relief on what you were talking about before, your communication among you and your co-founders, that has to be super important to make sure that you're able to execute on all that.

JANICE CHEN: Exactly.

DAVID STIEPLEMAN: I have a last question for you and I'm going to disclose my bias. I'm hoping that you validate my sense that the liberal arts are a really great way to get into all kinds of things. And my question is, you went to Johns Hopkins, undergrad. You obviously did a lot of work, I’ve heard you talk about building the yeast genome in college, which sounds amazing. But what's the class outside of your discipline, is there a class - I guess I should ask it in a less leading way - that you think about now, you're like, gee whiz, I'm glad I took that, or I think about that all the time, or is there something like that in your academic past?

JANICE CHEN: I think that there's so much that you learn outside of class, actually. I think your academic training kind of helps you think about specific problems, but I feel like a lot of the learning, at least for me personally, came outside of the classroom. That’s through actually getting your hands dirty in the lab, it's talking with other really passionate people about what they're working on. I personally feel like I loved my time at Hopkins, I think I had an extraordinary opportunity to get into cutting edge science, but at the end of the day, having the opportunity to actually drive research in a laboratory probably was the most transformative thing. And then, the second I would say career defining moment for me was being able to join Jennifer's lab and having that experience of being in the forefront of the field. But as you point out, I think it's more than just science, right? I personally have an artistic side to me, I was really involved in dance and music. I really like to connect the non-obvious, and I have this deep appreciation for not just one focus area, but how does this all come together? Because at the end of the day, especially when you're building a company, you're working with people with all kinds of backgrounds, and you just have to have an appreciation for all of it.

DAVID STIEPLEMAN: What a great answer. I'm going to leave it there, cause that's fabulous, thank you for that. And thank you - on Jeff's behalf, on Sixth Street's behalf, on behalf of our listeners - thank you. It's been a great conversation and I really enjoyed spending time with you.

JANICE CHEN: Awesome. Thanks David, and thanks Jeff.

DAVID STIEPLEMAN: Janice Chen of Mammoth Biosciences joined us for an interview on May 25th, 2022. She and her colleagues are doing incredible things that will change how we live and have unbelievable opportunities and risks. But what struck me most from our conversation is how a deep expert like Janice very deliberately approaches leadership and managing a business. First, in particular, this reinforced for me how multiple disciplines coming together can be incredibly powerful, but you have to help people with different expertise get on the same page. I was actually struck by Janice's answer to the question on how she translates the technical to the non-technical staff. And she turned it around and insisted it's her responsibility to make sure she understood what experts outside her area are trying to accomplish, which I thought was a great example of ownership mentality and what being a leader means. Jeff, did you have any thoughts?

JEFF POOTOOLAL: Yeah, the idea that Mammoth’s product being innovation itself and how Janice said, they have to keep out innovating themselves or someone else is going to do it, and having the overall mission of changing the world, it's a very useful prod for continuing to push.

DAVID STIEPLEMAN: Yeah, I agree. And finally, I thought if you have to be able to see the field, and you have to set up your machine or your process or whatever you call it to make it more likely that you're picking your head up, it'd be very easy for someone like Janice to only focus on lab work, but she spoke very thoughtfully on how the leadership team tries to make sure the dots are connected, and being intentional about giving the company, but also herself personally, space to see the bigger picture, and how they do that with constant communication and straight talk. If you want to learn more about CRISPR, go to our website, we'll have educational resources up there to check out. And Jeff, thanks so much for doing this.

JEFF POOTOOLAL: Yeah, thanks David. This was fun.

DAVID STIEPLEMAN: It was. And thank you from both of us and all of Sixth Street to Janice Chen for her time and her insights

DAVID STIEPLEMAN: You've been listening to, It’s Not Magic, a Sixth Street podcast. You can sign up to receive an email when a new episode drops at sixthstreet.com or subscribe wherever you get your podcast. If you enjoy today's show, please share it and follow @SixthStreetNews for more on the show and our firm. Thanks to Sixth Street's production team, Patrick Clifford and Kate Hanick for putting this together with sound engineering by Steven Cologne. Our theme song is It's Not Magic, an original song from Patrick Dyer Wolf. Once again, I'm David Stiepleman. Thanks for listening.

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