Podcast: Curiosity Unbounded, Episode 10 — Making medicine easier to swallow

Sally Kornbluth: Hello, I'm Sally Kornbluth, president of MIT, and I'm thrilled to welcome you to this MIT Community podcast, Curiosity Unbounded. One of the great pleasures of my job is the opportunity to talk with members of our faculty who recently earned tenure. Like their colleagues in every field here, they're pushing the boundaries of knowledge and possibility, their passion and brilliance, their boundless curiosity, or for a wonderful glimpse of the future of MIT. And this podcast is a way to share that inspiration with the world.

Today, my guest is Giovanni Traverso. Gio has a foot in two worlds. He's an associate professor of mechanical engineering at MIT, and he's a gastroenterologist at Boston's Brigham and Women's Hospital. His work focuses on innovative methods for drug delivery, diagnostics, and biological sensing. So Gio, welcome to the show.

Giovanni Traverso: Thank you. Thank you for having me.

Sally Kornbluth: Very happy to have you here. You moved around quite a bit when you were young, from England to Peru to Canada, then back to England. Can you tell us a little bit about these early moves, your early life and how this all led you to MIT?

Giovanni Traverso: Absolutely. So I was born in England. My dad is from Peru, and my mother's from Nicaragua, and they met in the UK. My dad had been sent to England to study economics, and then my mom was learning English. And, you know, they met and that's where they had me, that's where I was born. And then we left when I was just about to turn five, and we moved to Peru, and I lived there for just under 10 years. So I spent, uh, the better part of sort of my younger years there. And then we immigrated to Canada and we immigrated because of the instability in the country. And my parents really restarted their lives again, and, you know, found that Canada was very receptive really to hosting foreigners. And they built a new life there. And I went to school there. I spent six years there.

And then when my time came up for thinking about university, I had started and been exposed to science and had an opportunity to do research. And as part of that, I started to explore different opportunities and I applied back to the UK but also in Canada. But I had a wonderful opportunity to go back to England to study and specifically one of the areas of interest was medicine. And outside of North America and most countries in the world, most folks will start studying medicine right after high school. So I went directly into medicine and I moved to Cambridge, England, and studied there at the University of Cambridge.

Sally Kornbluth: You know, I did physiology part one B and-

Giovanni Traverso: Oh.

Sally Kornbluth: ... and Part 2 genetics at Cambridge.

Giovanni Traverso: So I was a Part 2 genetics, uh, student too.

Sally Kornbluth: Oh, interesting.

Giovanni Traverso: Yeah. Yeah.

Sally Kornbluth: Interesting. 

Giovanni Traverso: Yeah, so I did, uh, my Part 1 in medicine, and so I did physiology also, but Part 2 was in genetics. Yeah.

Sally Kornbluth: For our American listeners, this means in England, you really only do one single subject for the whole final undergraduate year. And it's very, very different from an American education where you're doing so many different subjects. And I have to say, I was kind of tripped up by the exam system in England because in America, you're doing continuous assessment where you're always taking exams all the time as our students at MIT do. In England, they save one exam till the end of the year. And that's not easy for an American person to adapt to.

Giovanni Traverso: No, absolutely. I would say it took me a couple of years to get used to the system because it is sort of 100% finals-

Sally Kornbluth: Yes, yes.

Giovanni Traverso: ... across all the subjects and-

Sally Kornbluth: And the temptation is to do nothing. (laughs)

Giovanni Traverso: Exactly. And there are many distractions.

Sally Kornbluth: Exactly, Exactly.

Giovanni Traverso: Yeah. Absolutely.

Sally Kornbluth: I understand that you had an early co-op working in a lab and how did you start, you know, getting interested in research? How did this sort of foster your love of research?

Giovanni Traverso: So in high school in Canada and Ontario at the time, the system essentially involved 13 years or grades. And so by grade 12 I had completed almost all of my requirements, and I had a wonderful chemistry teacher who really suggested I think about doing research in the lab and, and she connected me with someone that, someone's name is Steve Sheer, he's now the, runs essentially all of the research at the hospital for sick kids in Toronto. But at the time was a graduate student in the lab of Lap-Chee Tsui. Lap-Chee Tsui is known for essentially the linkage analysis and really identification of the gene for cystic fibrosis together with Francis Collins' Group.

And I worked in Lap-Chee's lab as a high school student together with Steve Scherer. You know, to me this was unbelievable that this was an actual job. This was sort of in the high school student perspective and, and I really enjoyed it, and really I would say, steered me in this direction, I mean to this day.

Sally Kornbluth: Very interesting. So you work on ingestible devices that have medical function known as electroceuticals. Can you explain a little bit about this? How do these work?

Giovanni Traverso: Absolutely. So we do many things, uh, across sort of a range of areas. As you mentioned earlier, I'm a gastroenterologist, so I tend to think about how we can interact and engage with our bodies and the bodies obviously of patients to really help them through the gastrointestinal tract. And one of the areas that we've started to really understand to a much greater degree is essentially our capacity to stimulate the GI tract to modulate different hormones. And so, let me give you an example. What we've shown is that we have the ability to either stimulate hunger or stimulate a sense of fullness depending on where and how we're stimulating the GI tract.

And so essentially, these are capsules that one would swallow and they can stimulate either the stomach or the small intestine. And depending on the stimulation, whether it's an electrical stimulus or whether it's a mechanical stimulus, it will induce these different patterns.

Sally Kornbluth: So presumably, you're stimulating some nerve that is then feeding back to what's going on in the central nervous system. And so how would you compare this to what's happening with the use of GLP-1 agonists, which clearly are affecting appetite? So there are neural gut pathways that must be modulating all this. So in a sense, you're activating this potentially similar pathways?

Giovanni Traverso: Exactly. You know, just as for example, if someone has a big bowl of oatmeal and they feel full in the morning, that feeling of fullness is really transmitted through nerves directly into the brain to really signal essentially that feeling of fullness or satiety. And so what we're able to do, and this is part of what we're doing right now, is characterizing how that signaling is taking place, and how we can encapsulate or capture that signal inside of an ingestible form factor to really facilitate patients to have control essentially over their nutrition sort of needs and modulate their own intake. You know, and I would say similar to the effects of many of the drugs including GLP-1 receptor agonists as well as others that start to modulate that sensation or the need or drive for intake.

Sally Kornbluth: That's interesting. And presumably, this could be done with fewer side effects than, you know, the one thing about the GLP-1 drugs is they seem to be now having just a huge array of effects that are at least heretofore inexplicable. So presumably, they're doing lots of other things either directly on organs or in the brain, which hopefully these sort of things would be more precisely stimulating the gut, I don't know, the gut brain access, I don't know ...

Giovanni Traverso: Yeah, that's... I mean that, I think that's our hypothesis also, is that by really tuning and working with, uh, essentially the endogenous systems that we're maximizing our own capacity to modulate intake-

Sally Kornbluth: Yes.

Giovanni Traverso: ... and rather than add an exogenous substance as such. That being said, I also wanna recognize that GLP-1 receptor agonists are transforming sort of how we can look after patients. That there was just another paper in the New England Journal that I just saw looking at how these drugs are helping people, for example, with sleep apnea.

Sally Kornbluth: Yes. 

Giovanni Traverso: But we've seen, like-

Sally Kornbluth: Yes.

Giovanni Traverso: ... you know, their-

Sally Kornbluth: It's, it's kind of crazy.

Giovanni Traverso: Yeah, it's a really exciting time right now.

Sally Kornbluth: So what other type of health issues do your devices address? What other disease areas are you working in?

Giovanni Traverso: So we have a lot of development on, and really the core challenges of taking medication. And you know, several years ago, one of the things that we started with the Gates Foundation involved addressing a fundamental aspect of essentially interacting with medication. And that is, when medications are administered on a frequent basis, in general, if a patient has an option of taking something more infrequently, they're likely to continue to take that medication. So this is the adherence or the compliance problem. Although, you know, I think adherence is a better term.

Sally Kornbluth: So like HIV regimens are notorious in sense?

Giovanni Traverso: HIV... Exactly. And the condition may, for example affect the ability for the individual take.

Sally Kornbluth: Yes, yes.

Giovanni Traverso: So neuropsychiatric conditions for example.

Sally Kornbluth: Yes, yes.

Giovanni Traverso: We've done some incredible work, again starting about 10 years ago also together with collaborators and now through a company that we started a few years ago where for example, we've been able to take a drug that's used for schizophrenia where a patient would've had to take it once or twice a day, but now they just take it once a week, and that can really give a stable dose to help maximize essentially the care of that person. So that's one example. But there's also examples, exactly like you said, an HIV, but also in substance abuse disorders where again, there's essentially the condition itself may impact the likelihood that the individual will continue to adhere.

Sally Kornbluth: Right.

Giovanni Traverso: And so again, it's more at the core of engaging with a therapeutic that exists and is known to have a positive impact. But the challenge that we're addressing is actually more of a behavioral one at the core of being a patient and engaging with that therapeutic.

Sally Kornbluth: To give our listeners a visual, I recall seeing one of your devices that-

Giovanni Traverso: Yes.

Sally Kornbluth: ... you swallow this pill and then it opens up in your stomach almost like a spider adheres to the wall and then gradually releases drug.

Giovanni Traverso: That's exactly right. Yeah. It opens up and because of the shape, because of the size and some of the mechanical properties, it can safely stay in the stomach and we can control exactly for how long it stays. And using those systems, we are applying it across a range of different areas. But schizophrenia is, I would say, the one that's most advanced and currently in phase three clinical trials.

Sally Kornbluth: That's really interesting. You're doing something in diabetes as well, I believe. Tell me a little bit about that.

Giovanni Traverso: Yeah, so we have several things that we've been collaborating with Novo Nordisk now for almost a decade, and we've worked with them in many different areas. So we started this collaboration back in 2015, really focused on developing systems that could enable the delivery of drugs like GLP-1 receptor agonists or insulin where the capsule could achieve levels comparable to a standard injection. And so, the technical term here is a bioavailability and essentially having bioavailability that are greater than 10%, the systems that are on the market, for example, and folks may be familiar with a drug called Respules, which is semaglutide in an oral format that has a oral bioavailability of about one to 2%. The systems that we're looking at are 10, 50 and and greater. So they actually achieve comparable levels to the injection. And we've actually demonstrated that. We've developed a whole array of systems that enable that.

Some that look like a little leopard tortoise and they can self orient, but certainly a whole array of systems. So that was sort of the initial body of work with using those systems, you can deliver several drugs like GLP-1 receptor agonists where now you can deliver a much lower amount than what is being included in the current capsules. So that starts to potentially address some of the challenges with the availability of these medications.

Sally Kornbluth: Yes.

Giovanni Traverso: That has been a major issue here in the US over the past few years. Now, about three years ago, we continued and really expanded that collaboration and have been working on cell therapies and really thinking about how we can develop curative interventions for patients, you know, suffering from diabetes. And that's certainly the very active area of research, really thinking about everything from the manufacturing to the administration to how do these systems sort of survive in the body-

Sally Kornbluth: Right.

Giovanni Traverso: And how do we monitor those-

Sally Kornbluth: Right.

Giovanni Traverso: ... and-

Sally Kornbluth: To have to not immunosuppressed people.

Giovanni Traverso: Exactly.

Sally Kornbluth: Right?

Giovanni Traverso: That's exactly right. So those are very active areas of, of research.

Sally Kornbluth: Oh, very interesting. So you're an associate professor in ME at MIT. You're a gastroenterologist at Brigham and Women's. This is a really perfect combination of skills for your work, but how do you manage to juggle both? Do you still see patients, and how does your clinical work inform how you're thinking about your laboratory work?

Giovanni Traverso: Absolutely, and I should add, I have three kids and I'm married, so you know, there's a lot and, but I think it's a team effort, right? And I think whether it's in the lab, whether it's in the clinic or at home, what we do is a team sport. And I think we have a wonderful team in all of these different venues. And so, I cut down my clinical time. I used to have a regular clinic endoscopy session, but once I started at MIT, I really removed my outpatient practice or stopped my outpatient practice. And so now I've transitioned to only doing inpatient time in between the semesters. So usually in January is when I'm on service, and I do that at the Brigham.

And I do that as part of a team. And so I work with fellows and trainees and also medical students, you know, which I think, I mean, is honestly a privilege to be able to interact with the trainees and of course patients. But, you know, I really... I think it gives me a unique perspective, and it's a very different, I would say, interaction than the one for example, that I would have in class like later today. You know, when I'm seeing someone at the bedside, it's a very different interaction and gives, I, I would say, gives me at least a different perspective and different level of motivation for everything that we do.

Sally Kornbluth: Right. It's interesting as a basic science, it always struck me that the clinical scientists also had laboratories could actually see coming down the road clinical needs that would really help direct where you are going with the basic science. Where, it's not that it's not fundamentally curiosity-driven research, it's just that it also has a, a trajectory upfront of a problem you, you know, would like to solve.

Giovanni Traverso: Absolutely. And I think our goal is to overall essentially have impact and really develop systems that will translate to patients, right? And so I would say, I mean, I love to read and certainly several of our scientists and students are investigating fundamental questions, but I also, I would say, have a tremendous amount of interest in ensuring that what we're doing and spending our time on will translate to help patients in the end.

Sally Kornbluth: Absolutely. Also, you, you mentioned your family life, your clinical work, your laboratory work, but you also hold 45 patents and have founded or co-founded a dozen companies that use your work. So how do you think about this? Is the entrepreneurial spirit something you... Where did you get that from, and do you aim that to instill that in your students?

Giovanni Traverso: To me, this is part of an arc where we start with a lot of the basic discoveries, developments and, you know, that arc continues beyond the academic realm. And in order to have those technologies essentially help people in the end beyond just the publication and beyond sort of the educational value involves basically generating products. And that often involves a startup or partnering or working and collaborating with other companies. And, you know, I was first exposed to this as a graduate student with Bert Vogelstein at Johns Hopkins. And Bert, you know, has spent his career as a cancer biologist but also as someone who's very focused on translating the work from his lab and, and the lab of Ken Kinsler, uh, his close collaborator, you know, for many decades. And one of the things that I did during my PhD was actually work very closely with a company, a small company at that time called Exact Sciences.

And it was really through those interactions that I would say my initial curiosity was really stimulated because I could see how the work that I was doing in the lab could eventually make it into a product. And eventually that work contributed to a test that is now on the market. I mean, it took many years, but, you know, that sort of really gave me a window. And then fast-forward, I would say about seven, eight years, I was a resident at the Brigham and I was looking into my fellowship or specialty training gastroenterology, a big component of which is actually the research aspect. And I had reached out to Bob Langer here at MIT, and I remember meeting with Bob and I said, "Look, I don't know anything about chemical engineering, material science, you know, these are some of the areas that I'm interested in really learning about." And he's like, you know, "Just come."

And he was extremely welcoming and, you know, and to this day, I mean he remains a, a mentor collaborator. And that also gave me that experience, gave me a window and an opportunity to learn more about that translational aspect with respect to-

Sally Kornbluth: Yes.

Giovanni Traverso: ... the intellectual property aspects, uh, the considerations that go into new company formation. And, you know, it's something that I try and pass on to the next generation. I do it through the classes that I teach. I do it in lab, and I continue to learn myself, I mean, from both the people that I work with as well as the students.

Sally Kornbluth: Yeah. I mean, it's actually so woven into the fabric at MIT in a way that I haven't seen a lot elsewhere. And, you know, Bob Langer is sort of the epitome of this, right? And also your story of coming and saying, "I don't know much about this, but I wanna do this," this echoes in my mind, you know, Bob's tales of his early career, of people being willing to take a chance on him. And we all know how that turned out very well.

You obviously don't have a lot of free time, given everything we followed, but, you know, when you do a free time, what do you like to do?

Giovanni Traverso: I mean, I love to spend time with my family. You know, my kids are, are 8, 11, and 13.

Sally Kornbluth: Wow.

Giovanni Traverso: And, you know, they all play sports.

Sally Kornbluth: Okay, your weekend's done then

Giovanni Traverso: Well, absolutely. And so they all have tournaments every weekend or multiple games, but, you know, I think it's wonderful to see them grow and develop their own interests. And, you know, I love to be outside. I love to go biking. You know, we live in the northeast, so I, I do love and I've tried to, uh, support winter sports also with our kids.

Sally Kornbluth: Yes.

Giovanni Traverso: So I'm a snowboarder and all of our kids either ski or snowboard. So we try, as soon as the snow comes, we do try and get out.

Sally Kornbluth: Oh, that's great. That's great.

Giovanni Traverso: And I enjoy the outdoors. Yeah.

Sally Kornbluth: The snow has been a little bit-

Giovanni Traverso: I know.

Sally Kornbluth: ... limited in the line. I mean-

Giovanni Traverso: Yeah.

Sally Kornbluth: ... we, we could have a whole conversation about climate change.

Giovanni Traverso: Yeah.

Sally Kornbluth: In any event, one final question about the work, which is, you know, we think about drug delivery and bioinspiration and you mentioned cell and gene therapies. So how do you think about bio inspiration in your work? In other words, how do you think about the intrinsic ways biological systems operate, and how you leverage them, uh, for therapeutic and in, in your own work?

Giovanni Traverso: Great question. And we have this large grant that we received from the government earlier this year, and we just gave our six-month report. And as part of that I had convened an external advisory panel, and one of the members had asked me about bioinspiration, 'cause I could see that in several programs. And I would say we look at bio inspiration in generally two different ways. One is essentially when we map out a set of challenges for a project, we do look for adjacencies in nature to see has nature solved this challenge-

Sally Kornbluth: Yes, yes.

Giovanni Traverso: ... in a similar way. And that certainly does happen. And we have two projects right now. There's one that, uh, essentially looks at the evolutionary elements that underpin the behavior of a specific fish. And we've taken that learning and applied it now to a whole new family of devices. So that's certainly is something that we do. And we collaborated in that specific body of work with a scientist over at Boston College. But we also look at bioinspiration to help convey our work. And so, sometimes the complexity that is involved in developing these systems, I recognize, can be complex, but we also wanna be able to share and essentially help the audience quickly appreciate sort of the nuances of the work.

And so we also look at bioinspiration as a way of explaining or helping explain the work. So I would say those are the two ways that bio-inspiration really weaves into what we do and how we explain the work that we do.

Sally Kornbluth: I mean, it seems like there's an infinite array of possibilities with the approaches you take. So many disease states and indeed sort of health states that could be stimulated by the variety of devices. So we really look forward to seeing what happens in the coming years from having sat in and discussions of your promotion case that everyone was very excited. So now I'm extremely excited to see what comes next. So thank you for having this conversation.

Giovanni Traverso: Well, thank you so much for having me.

Sally Kornbluth: Absolutely. And to our audience, thank you for listening to Curiosity Unbounded. I very much hope you'll join us again. I'm Sally Kornbluth, stay curious.

Curiosity Unbounded is a production of MIT News and the Institute Office of Communications, in partnership with the Office of the President. This episode was researched, written, and produced by Christine Daniloff and Alexandra Steed. Our sound engineer is Dave Lashinsky. For show notes, transcripts and other episodes, please visit news.mit.edu/podcasts/curiosity-unbounded, and find us on YouTube, Spotify, Apple, or wherever you get your podcasts. To learn about the latest developments and updates from MIT, please visit news.mit.edu.

You can follow us on Facebook, Instagram, and LinkedIn at Curiosity Unbounded podcast. Thank you for joining us today. We hope you'll tune in next time when Sally will be speaking with political scientist, Ariel White. Ariel's work touches on voting, voter rights, the criminal legal system, and how ordinary people can make a difference. We hope you'll be there. And remember, stay curious.