Janice Chen is very inspiring. At the age of 30, she has not only completed a PhD. with recent Nobel prize winner Jennifer Doudna at the University of California, Berkeley, but co-founded Mammoth Biosciences together, where she serves as its CTO.
Mammoth recently announced it had raised $195 million in financing, bringing its valuation up to more than $1 billion and allowing it to achieve ‘unicorn’ status, an impressive feat considering the young age of the company and the ongoing COVID-19 pandemic.
Chen spoke to Inside Precision Medicine’s Senior Editor, Helen Albert, at the recent Hello Tomorrow conference in Paris about her inspirations, challenges she has overcome and her hopes and plans for Mammoth and CRISPR gene editing in the future.
Q: What was it like to do a PhD. with Jennifer Doudna?
It was very cool. Jennifer is a really fantastic scientist and mentor. And I think she’s been able to attract some of the best scientists in her lab. So being not just in the forefront of CRISPR technology, but also working alongside some very talented people. As you know, the CRISPR field is very competitive. I think being able to have the opportunity to continue to push the field forward, that was really remarkable. The other great thing about working in Jennifer’s lab is that if you wanted to collaborate with anyone, you could simply send a cold email, and say, ‘Hey, I’m from Jennifer’s lab’, and they would always respond. So, things that I didn’t have expertise in, I could simply ask ‘is there someone else to collaborate with?’
Q: It’s very impressive that you went straight from doing that to co-founding a company with her. Can you tell me a little bit about that journey?
Early on in my PhD. Career, we had been working on more traditional Cas9 enzymes, and then I formed a really great collaboration with my lab mate, Lucas Harrington, who’s also a co-founder at Mammoth. We had been working very closely, he was focused on discovering a new enzyme, I was more focused on the mechanism and application of those. We’ve always been just amazed that how much there is to uncover with CRISPR. But I think what really sparked our imagination to start a company was the ability to use CRISPR, for detection or diagnostics. This was a new area for CRISPR, we felt there was just no better time to push this forward. So, with Jennifer’s support we decided to go all in, and we ended up partnering with our colleague from Stanford, Trevor Martin, who’s also the CEO. In the early stages, it’s sort of what you might imagine, we were just figuring things out.
Q: It must have been quite a big lead from being a Ph.D student to suddenly being CTO. How did you manage that?
You just have to accept that there’s so much that you don’t know and you have to constantly learn very quickly. I think part of what was absolutely critical is being able to adapt quickly, be flexible, but also bring in really, really good people. The best way to scale a company is to bring in people who are smarter than you, have done this before, and have much greater expertise in particular areas to help you take these new ideas, and bring them into the company. We also had really fantastic mentors and advisors, not just our investors and our board members, but also scientific advisors, general advisors on the business strategy who really helped us formulate where we could take Mammoth.
Q: How did you find the people management side?
It’s a challenge. Organizations are people and people are human. We all have our own aspirations and goals. The really fun part is building a team that is really aligned on a mission, but it also comes with challenges because especially as a new, young manager you’re learning all this in real time. You develop a skill in grad school, and you think ‘this is my expertise, I am in control’, but sometimes when you’re in an organization and managing people, sometimes there’s things outside of your control. There are other factors at play that you have just never experienced. So, it’s been a learning curve. But it’s also been rewarding to work with people that are just so talented and can move things forward.
Q: What are you trying to achieve at Mammoth?
When we founded the company, we were focused on diagnostics, because again, this was kind of opening up a new world of molecular detection. There are the incumbent technologies, PCR testing, antigen tests, but really, we felt like there wasn’t a good solution to take really high accurate testing into decentralized environments. And so CRISPR was able to make that possible. But as we’ve been developing the diagnostics piece, we also recognize a core competency of Mammoth was the fact that we had this ability to discover new CRISPR enzymes and that was kind of the heart of how this all came about. So, we said, ‘Okay, well, as part of building Mammoth into a really great company, we needed to leverage this whole discovery piece that can be the engine for new applications.’ Diagnostics is a key focus area. And then as we’ve grown the company, we also been really focused on the therapeutic space. That’s recently been announced as part of our series D, and also with a partnership with Vertex Pharma to actually develop new enzymes [eg. Cas14]. These are extraordinarily exciting for delivery, because of their size.
Q: Are we now moving on to the next generation of CRISPR gene editing?
I think for a lot of technology that is developed there’s a period where you’re just trying to understand how does this technology work? How can we use it? Cas9 has been extremely successful, but Cas9 was the first enzyme that the field discovered in development. Our approach is let’s see this funnel of enzymes and pick the best tool for the right job. Depending on the application, you can have different enzymes with different properties. It all comes down to making sure that your solution is not going to create more risk than benefit.
Q: What do you think have been the key findings in the field of CRISPR, since CRISPR-Cas9 was first discovered?
First of all, I think the clinical trials and the data that’s coming out from things like treating sickle cell disease in patients, I think that’s been remarkable. That’s really what the field is moving towards. And that’s where all these new systems will help enable the other areas since Cas9, which are new iterations of using CRISPR. Some of the technologies like CRISPRi or CRISPRa, the ability to transiently turn on and off genes, for certain cases is going to be more critical than permanently cutting or editing that locus. And then there’s also new ways of doing editing like base editing and prime editing, different ways you can modify the genome.
Q: What are the benefits of the smaller enzymes you have developed compared with cas9?
The smaller enzymes, most critically, are going to help in delivery of the [therapeutic] molecule to specific organs. Right now, there’s two major classes of delivery. Lipid nanoparticles (LNPs) and adeno-associated viral vectors (AAVs). LNPs are pretty nonspecific. When you deliver them to a patient, typically they just congregate in the liver. Then you have AAVs. There are different ‘flavors’ of AAVs that can be programmed to target different organs. The way people deliver it is mostly by directly injecting into organs, but it is not really optimal, because it’s pretty invasive. With these smaller enzymes, we’re not limited to just the liver because we fit into AAVs, we can also now tune the AAVs to target the specific organ of interest and maintain the same level of activity as Cas9. When you really shrink down that CRISPR piece, you can add all these different modules on top of that in a vector, and that essentially opens up the opportunity to use it in a therapeutic.
Q: Do you think we need a public dialogue about CRISPR-related gene editing and how it can be used to make next generation therapeutics?
I think we’re really in a critical time. Right now, we have the wave of Cas9 based therapeutics that are showing real progress in patients, but I think that will pave the way not just for the technology, but will also give us more knowledge about how this technology actually functions in patients. With new technologies there’s always fear of how anyone’s going to use that. A couple of years ago, we saw that with the gene editing of the Chinese twins. I think that has kind of sparked the reality that there are going to be people that are going to make decisions about how to use this technology for things that are ethically questionable. CRISPR is going to transform the way we think about genetic medicine. That’s going to happen. And so, all of a sudden, that opens up a Pandora’s box. Once we understand different specific targets and can modify that, anything becomes possible… You’re going to need to engage policymakers, you’re going to have to engage people who may one day use the technology, not just as a researcher, but who might also be on the receiving end, and help them get educated and understand what the technology is and what it can do. There are some boundaries that we don’t want to cross. Clearly, people will still make decisions that are quite shocking. But having a dialogue about the topic and expectations, I think we can all do that at a grassroots level.
Q: We can’t really talk today without mentioning COVID-19. Maybe you could talk a bit about how it impacted the company and how you responded to it?
I went to a conference in late December and heard government representatives saying there’s this strange virus in China, we were still figuring out what was going to happen, while we were all in DC. And then, I came back to San Francisco and it became clear this was a serious situation. I remember the phone call that I had with Charles Chiu at UCSF. He said, look, this is a growing situation, Charles had some of the first clinical samples from patients infected with COVID. And we said, ‘okay, we need to be able to demonstrate that there’s a different way we can detect, SARS-CoV-2 in samples’, and we felt that our platform was in a really great position to be quickly reconfigured to do that. So, it was just 10 days from designing the assays to getting the reagents and testing samples, and it was just such a whirlwind at the time. This was before the shutdown. People were still in the lab, I remember we said, okay, let’s focus this part of the company on COVID. You know, there’s still the other piece of the company on the therapeutic side, we just have to stay the course. It was it was extremely motivating, I think, for us to be able to help.
Q: What achievement are you most proud of since you started this journey?
I would say the first discovery of using CRISPR for detecting DNA was just one of those once in a lifetime moments. As a scientist, there’s nothing more fulfilling than to say we have this hypothesis, we followed up on it, and then we saw this is a really robust method and tool. That was extraordinarily exciting. And the other thing, too, is navigating all the challenges throughout the pandemic, and being part of a team that’s just so committed to taking these technologies forward. I think that’s been a very proud moment, for me, leading up that part of it.
Q: If you had to give someone who was in your position a couple of years ago some advice, or tips, what would you say?
I would say don’t be afraid to take risks. That was such an important mindset for me. It’s OK to think big, you’ve got to be outside your comfort zone, that I think that’s the kind of message that I think young entrepreneurs should take home.
Helen Albert is Senior Editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was Editor-in-Chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was Editor of The Biochemist magazine and blog, but also worked as a Senior Reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.