Mammoth Biosciences: Trevor Martin, CEO
“I've always found that where I can personally have the most impact is at the intersection of fields.”
The idea that human genetics will revolutionize healthcare is a pillar of 21st century biology and medicine. Recent advances in sequencing technologies and bioinformatic approaches to analyze big data have strengthened the promise of genomics to help patients. But the question remains: do we currently have the weapons to leverage this data to improve human health? Are we capable of correcting subtle genetic defects that drive disease, or quickly detecting viral variants during a pandemic? Mammoth Biosciences is building an armamentarium of tiny and powerful tools to address these questions. With a suite of CRISPR-based therapeutics and diagnostics, Mammoth strives to make the promise of precision medicine a clinical reality.
Based on science from co-founder Jennifer Doudna’s lab, Mammoth is pioneering novel CRISPR systems for therapeutic and diagnostic applications. These systems employ novel Cas14 or CasΦ nucleases, which are uniquely suited to translational application due to their ultra small size and editing flexibility. They made history in January of this year, by developing the DETECTR BOOST® SARS-CoV-2 assay, which is the first CRISPR-based high throughput test to be granted emergency use authorization by the FDA. Mammoth is currently leveraging its DETECTR platform to develop diagnostics for even single nucleotide polymorphisms (SNPs) linked to disease, bacterial and viral infections, as well as even cancer. By leveraging the favorable properties of their novel CRISPR systems (e.g. such as small size and efficiency), Mammoth also intends to make permanent cures for genetic disease —they have ongoing collaborations with Bayer and Vertex to develop CRISPR-based therapies. Mammoth was co-founded in 2017 by Jennifer Doudna (SAB chair), Janice Chen (CTO), Lucas Harrington (CSO) and Trevor Martin (CEO). In 2021 they raised $195M as part of a Series D financing led by Redmile Group, with participation from Foresite Capital, Senator Investment Group, Sixth Street, Greenspring Associates, Mayfield, Decheng Capital, NFX and Plum Alley, among others. It followed a $45 million Series C in late 2020, which was led by Redmile Group and Foresite Capital, and included participation from Amazon and many others as well.
Dr. Trevor Martin is co-founder and CEO of Mammoth. A statistician and biologist by training, he completed his undergraduate degree at Princeton. While there he participated in the Integrated Science Program—a course that tackles biology through the lens of physics, chemistry and computer science. He then earned a PhD in Biology from Stanford in 2017, where he used computational approaches to study gene expression in the Fraser lab. A deep appreciation for the emerging field of synthetic biology – and a cold email - connected Trevor with his co-founders, Jennifer Doudna, Janice Chen and Lucas Harrington. Trevor is passionate about making advances at the intersections of biology, engineering and statistics: “I've always sought out those types of intersections where you can have outsized impacts” (Q #3).
His vision places Mammoth at the cutting-edge of synthetic biology, computation and medicine: “the ambition has always been to pioneer this new way of thinking about CRISPR—as this kind of search engine rather than just a pair of scissors” (Q #4). Along with his co-founders and the rest of the Mammoth team, Trevor is working to build a therapeutics and diagnostics company that will fully realize the potential of CRISPR in precision medicine.
Below is an interview with Trevor Martin, CEO of Mammoth Biosciences from August 2022:
1. Tell us a bit about your background and what got you interested in science?
I grew up in Georgia, near Atlanta. But I don't have the Southern accent because I listened to a lot of NPR. I think a relic of that [growing up in Georgia] is that I use the word y'all a lot, just because it's very useful—both gender neutral and short.
I was interested in science in grade school and then in high school. I had this misimpression of the different fields; there were, I thought, physics and math where you could come up with these universal rules. And I always viewed biology as kind of like stamp collecting, which I now know is unfair.
And when I went to college, I thought I would be a physics major. But I took this program at Princeton that was started by David Botstein, who previously was at Stanford, and is the chief scientific officer at Calico. He had this program called Integrated Science, which was where they kind of ‘tricked’ undergrads who are interested in computer science, math or physics into becoming biologists. And I signed up for it on a whim thinking it would be a cool way to knock out some early requirements. But the whole point of the program is to really open your eyes to how biology can leverage insights from these different fields [like statistics and physics]. It can be like a science where you're not just stamp collecting, but are actually predicting the future and engineering. I really fell in love with those [Integrated Science] concepts. I ended up doing the integrated science program, all four years of my undergrad, and then went to do a PhD in Biology at Stanford right after
2. What is one book that has influenced the way you think, which you would recommend to fellow scientists or entrepreneurs?
In high school, I was most obsessed with Emerson in terms of literature—this idea that you can be self-reliant, and also go into your backyard and learn about the world and yourself. Another book, which touches on concepts of self-reliance, is Walt Whitman’s Song of Myself. Maybe it has some loose relation to biology—of just messiness in life and embracing that messiness. These books [by Emerson and Whitman] were definitely formative for me growing up.
3. What was the moment you realized you had to leave academia to start Mammoth?
I didn't go into my PhD thinking I would found a company. I think it’s always a tricky piece of advice, because everyone always asks: ‘should I do a PhD to [eventually] launch a startup?’ I think the answer is definitely not. A PhD is a really hard thing with a huge amount of opportunity cost. Honestly, you probably just won't finish it if your whole point is to do something else [i.e. start a company]. That being said, it is undeniable that doing a PhD can be a great jumping off point for building a startup.
So I went into my PhD, just loving research, and just wanting to work on interesting problems. I think what I learned during the PhD, especially towards the end, was that I was seeking something where there could be a higher impact. Citations are cool, and papers are interesting, but for me, personally, that wasn't something that I necessarily wanted the impact of my life to be. Not that it can't be [incredibly fulfilling], just for me, personally, it wasn't. So, the obvious place that was really exciting [to me], is more translational types of work. And in my PhD, my work was just at the very start of something that could eventually have an impact on patients. So, I was really interested in moving closer [to patients]—and an area where I thought this could happen is synthetic biology. In my career, I've always found that where I can personally have the most impact is at the intersection of fields.
For example, you know, the intersection of statistics and biology. But the way I see synthetic biology is that it is the intersection of engineering and biology—like programming biology. So, I think those are the areas where I can thrive and hopefully have something unique to offer. During college, I realized I would never be the best biologist or be the best statistician, even if I
worked 1000 hours a week. But I could be a really good biologist and a really good statistician.
And it turns out, that was a unique combination—going across fields can be unique in general. So, I've always sought out those types of intersections where you can have outsized impacts.
And then of course, during my PhD, [the discovery of] CRISPR was going on. And that was super exciting to see. And it really felt like what computation in biology felt like 10 years ago—in terms of this ultra-low hanging fruit. As an added bonus, it [synthetic biology/CRISPR] is ultra-translational, and you can have a direct impact on patients. So that made it going into this area a no brainer. And I definitely knew toward the end of my PhD, I didn't want to go down a postdoc route. At Stanford, of course, there's also something in the water. You're aware of startups and the potential opportunity there. So, I did a cold outreach [email] to Jennifer Doudna, and got connected with Janice Chen and Lucas Harrington in Jennifer's lab, who were the inventors of many of these technologies. We really hit it off and shared the same vision around translational impact. [We felt] that this is one of those rare opportunities to build the next great biotech company. And that is a very rare thing.
[On starting a company in a field outside of his PhD work]
I think it's a common misperception that if you're doing a startup, especially out of your PhD, it has to be based on your PhD work. And I think that's definitely a trap a lot of people fall into, because then you end up trying to shoehorn your PhD work into something that resembles a startup. I would say, if your work has potential to be the foundation of your startup, that’s amazing, great, go after it; but I don't think it has to be that way. So, I think you need something to start with, but it doesn't necessarily have to be the thing that you invented, right? You need to have a really close relationship with, hopefully, the people that did invent it, and they're going to be absolutely critical to building any startup.
I think there's lots of amazing technologies out there. And there's lots of big problems. It's really more of a matching problem to match technology to a big problem. So in general, I think the core thing that does matter, though, is that you share the same vision [with co-founders]. Whether it's your work or someone else's [scientific discovery], just make sure you are working with people where you’re vision aligned.
4. What was Mammoth’s founding vision and has this evolved over time?
I think part of the vision we aligned on is this idea of moving beyond Cas9. There's this whole universe of CRISPR technologies. And I think now people have started to recognize this, but especially when we started the company, it was a very radical idea. And we had these ideas that novel systems can be used for diagnostics, and that there were ultra-small systems that could be used for in vivo therapeutics for permanent cures. So, this [vision] has always been there since the beginning. As you show success, you can be more public about your full vision and things like that. But definitely the ambition has always been to really pioneer this new way of thinking about CRISPR—as this kind of search engine rather than just a gene editing tool. So, I think in general, that's definitely what we were interested in since day one. I think, when you're doing any startup, it is key to hit the right milestones on the journey to that grand vision to make sure that you can realize that ultimate goal.
5. What was most difficult during the early months of being a founding CEO, coming from academia? What was the most enjoyable part about making this transition?
So, I think in general, there are some things in graduate school that do carry over in terms of founding a startup. I think a big one that is underappreciated maybe is dealing with uncertainty and navigating the unknown. I think a good PhD means doing something that no one's done before. And there's no textbook way of doing it. And you know, that's why you hear a lot about PhD struggles. It's a really arduous journey, with no defined path.
I think startups carry a lot of that same mental burden, maybe even times 10, because a PhD is just about you. But a startup that's [responsibility] you and a team, right? So, I think that grit is actually really important for startups—PhD programs can definitely provide that mental resilience.
I think many other things don't carry over at all—PhD programs often really don't prepare you for managing people, or, any of the nuts and bolts of the job. But yeah, I think there's definitely huge areas where you have to grow quickly. So I think a lot of it just comes down to how much do you want to embrace it [this growth]. I think the honest truth is that no job really prepares you for doing a startup. So, if you go in with a determined mindset, you really want something where you are being challenged and forced to grow, then you'll lean into it. And, then if that's not what you're looking for, you'll quickly realize that it is a grind. I think one of the big things I was looking for coming out of my PhD was to grow as an individual and person. And I was really craving that. So that was a feature of starting a company for me, not a bug.
6. Now, at the helm of a more established company, what is the most difficult aspect about your role as CEO? Most rewarding?
The learning never stops no matter what stage. It's just new things all the time. So, you know, that has to be something that you want and lean into. The most rewarding part is that as the company grows, you have this whole team that's working on what was maybe just on a napkin in the early days. Now, when you’re starting to see that become reality and starting to see products get closer and closer to the clinic, it's pretty crazy. And I think that going back to: ‘why do a startup?’ The reward is that you get to actually bring something into the world that has a huge impact. That's by far the most fun part. And if you have a really great team that you're working with on that, then it is great. Obviously there are the cliches about it ‘not feeling like work.’ No, it feels ‘like work’ often, but it's also extremely rewarding. And it only gets more rewarding.
7. What are you currently working hardest on at Mammoth as CEO? What are the upcoming milestones you are using to keep your team motivated?
I see the CEOs having three primary jobs and you kind of rotate your time. And obviously, there's a million other little things, but three core things—at any given moment you might be doing more or less of one or the other. But it's [1] making sure you're pointing in the right direction, and [2] strategically making sure you're hiring the best people in the world. Then [3] making sure you don't run out of money while you're doing that. Mammoth’s in a great place financially, so that’s good, but you always want to make sure that's the case. We are also doing some executive hiring right now, which we are spending a lot of time on. And especially as we continue to hit technical milestones and technical success, now we have new exciting things to work on that we need to bring executives in for. We definitely are doing a lot of thinking about strategy and how we're getting from point A to point B. You know, the broader biotech markets have been going through this dislocation recently. That means you want to really make sure you understand what's changed and what hasn't changed. So we’re doing a lot of thinking about that.
8. What was the most exciting or fun part of working at Mammoth?
When we got the Emergency Use Authorization for the [COVID Diagnostic] tests, it was pretty exciting. Because that's obviously a huge milestone, not just for Mammoth, but for CRISPR, in general. And I think it's a sign of getting closer and closer to patients. And then also, just this idea, kind of accordingly, that we're pioneering things that maybe people don't expect—whether that's on the therapeutic or the diagnostic side. And this is a field that didn't exist before we pioneered it. And now it has an Emergency Use Authorization. So it's really an ultimate example of going from something that is in a research lab all the way through to something that can actually be used.
9. What is another biotech (public or private) that you think serves as a paragon of an impactful company? What are the key learnings from this case study?
Definitely a lot of examples, but the classic one is Genentech. Just fundamental technology, finding the right application, and then expanding your internal pipeline and your collaborations and building what became an amazing business—which helps countless people with disease. It was also started here, kicking off the San Francisco biotech hub. So yeah, Genentech is definitely a great guidepost for what's possible. And, you know, that company really pioneered the whole idea of biotech in general.
10. In today’s climate what is one short piece of advice you would give to prospective and first-time biotech entrepreneurs?
Regardless of the state of the markets, let others say ‘no’ to you—you don't have to say no to yourself. I think especially for PhD students, and postdocs there's a lot of self-limiting [thoughts]: “I guess I can't do that. Or, I shouldn't do that, especially if markets are bad.”
But it’s like the cliché saying: “You miss 100% of the shots you don't take.” This is especially true in what's still a nontraditional path, but definitely a quickly growing one for PhDs and postdocs. So, if you really are passionate about it, then it's a great time [to do a startup]. There's more time now for VCs to focus on companies, that regardless of conditions, are like: “well, I just take the jump.” And it's super scary, because you know, it's not a traditional path, but I think it could actually be a great positive signal [to investors], especially in a down market [that you are passionate]. If anything, I think it's harder in a bull market, because there's just so much stuff. And it's hard to separate the wheat from the chaff.
11. What has most impressed you about any experienced or thoughtful investors with which you have interacted? What is one piece of advice you would give to new biotech investors?
Having a lot of curiosity is a good thing. I mean, your firm can still say “no”, but even if you are disagreeing with someone, I think founders like thoughtful feedback, which is actually kind of rare. I think this can lead to very positive interactions with founders. If it's a very thoughtful comment: “look you might disagree with me, I may be right, I hope I'm wrong. X, Y and Z are what I see as the challenge here. Stay in touch.” I think the best founders, hopefully, really value that. And that can actually help build a relationship over time. So, you know, don't be scared to have a true conversation and back and forth. I think that can be very welcomed.
If you are really excited about something, and curious, I think it just naturally comes across. As opposed to if it's just running the meat grinder. And I'm sure some of that's unavoidable, but especially if you are really excited about something, don’t be afraid to show it, even if it doesn't end up resulting in a deal. I think that can really get both parties excited and having a real conversation.
12. What is an area of science, outside of what you are working on at Mammoth, which you are most excited about seeing develop in the next 5-10 years?
I think there's still a ton of work to be done in complex disease. We thought when we sequenced the human genome we could cure all diseases. And I guess this is related to Mammoth in terms of the more we understand disease, the better we can target the right parts of the genome. Don't get me wrong, there's like 4000 monogenic genetic diseases, and it'll take us many decades to get through this. But I think in general, just really starting to understand complex disease and interaction with the environment will be super helpful for us to either decrease the risk for it with tools like CRISPR, or to get rid of it entirely. And there's still so much left to do. My background is in statistics, and I hope that there are better statistical methods to solve it. Some think it's like a data problem, and we're not collecting enough data to do it—so maybe integrating our health records will help. I don't know what the right answer is. But I think that's just clearly this huge gap where there could be a huge benefit to patients.
[As an example of developing more advanced and sensitive statistical methods to detect complex polygenic disease, the author (DN) would like to highlight some recent papers: Weiner et al., 2022 from the labs of Elise Robinson and Steve McCarroll published in Nature Genetics & Hujoel et al., 2022 from Po-Ru Loh’s lab published in Cell]
