Not Alone: Leaders in Conversation

In conversation with ... Robert Langer

• Rafael L Bras • Episode 2

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In this episode of Not Alone: Leaders in Conversation, hosted by Rafael Bras, Prof Robert Langer of MIT talks about his impressive career and contributions to medicine, including the co-founding of Moderna and the development of groundbreaking drug delivery systems.  

He shares his early influences, experiences with ADHD, the challenges he faced in academia, and his thoughts on leadership. 

Their conversation also delves into the evolution of biological sciences, the importance of entrepreneurship in higher education, and Langer’s dedication to teaching and innovation. Amid reflections on his significant achievements, including the rapid development of the Moderna COVID-19 vaccine, Langer emphasizes the critical balance between academic pursuit and real-world application. 

00:00:00 Introduction to Not Alone Podcast

00:00:52 Introducing Professor Robert Langer

00:02:19 Early Life and Influences

00:04:02 Challenges with ADD and Academic Journey

00:05:55 Personal Anecdotes and Religion

00:08:04 Collaborations and Family

00:10:22 MIT Career and Department Challenges

00:18:26 Leadership and Mentorship

00:23:21 Balancing Academia and Industry

00:26:22 Advancements in Biology and Health Sciences

00:30:39 Debating the Impact of CRISPR

00:31:42 Future Medical Treatments with CRISPR

00:32:39 Challenges in Treating Diseases

00:34:23 Public Perception of Higher Education

00:36:03 Free Speech and Campus Protests

00:40:11 Entrepreneurship in Academia

00:42:51 Balancing Academia and Entrepreneurship

00:48:07 The Story of Moderna

00:57:15 Reflections and Personal Insights

01:02:07 Closing Remarks and Gratitude

[00:00:00] Aileen: Welcome to Not Alone: Leaders in Conversation, a bimonthly podcast where we delve into the minds and experiences of academic leaders who are shaping the future of higher education. Your host is Rafael Bras, Professor at Georgia Institute of Technology and Editor of Elsevier's Not Alone newsletter.

[00:00:21] In each episode, he will explore the complex challenges, decisions and opportunities facing academic institutions today. Whether you're an academic leader, work in academia, or simply want to learn about the latest topics that are top of mind for academic leaders, this series is designed to provide valuable insights and inspiration.

[00:00:42] Please join us as we embark on this journey of conversation, discovery and leadership.

[00:00:51] Rafael: I'm thrilled to have Professor Robert Langer as our guest today. Describing Bob Langer is an exercise of [00:01:00] superlatives. A professor at MIT, Bob has been called the Edison of medicine, with around 1,500 patents, about 400 of them that have been licensed or sub-licensed. He is a cofounder of Moderna and has been involved in founding some other 40 companies.

[00:01:19] In his spare time, he finds the way to write 1,600 refereed publications. Bob is also the most cited engineer alive and arguably one of the most cited, if not the most cited, scientist or engineer ever. I cannot think of any major award he has not received. From the Draper Prize to the Kavli Prize, he's a member of all US National Academies of Engineering, Medicine, and Science. He has been elected to the Royal Academy of Engineering and the National Academy of Arts and Sciences. And he's one of the 14 individuals who have ever received both the US [00:02:00] Medal of Science and the National Medal of Technology and Innovation.

[00:02:05] But I better stop and leave time for conversation. Bob, thank you so much for participating. It is great to interact with you again.

[00:02:14] Bob Langer: Oh, it's my pleasure. Thank you.

[00:02:16] Rafael: More than welcome. It's really a pleasure. Let me begin a little bit with your personal history, which I know our audience is always interested. You were born in Albany, New York.

[00:02:26] Can you tell me about your early years? What influence did they have in your life?

[00:02:33] Bob Langer: Sure. So I was born in Albany, and I went to Public School 27, which is about three blocks away, up ‘til sixth grade. And then to what's called Milne High School — it's no longer there — also in Albany. I think I had a pretty normal childhood.

[00:02:51] I had a lot of friends. It was sort of a small street, though it didn't seem to be so small at the time, called Tudor Road. And I had a [00:03:00] number of friends, and we'd play like baseball, football and basketball. And for science and math kinds of things, I guess I was trying to think about what influenced me. You know, my dad and my grandfather, they'd play math games with me.

[00:03:17] And I think that I liked that when I was little. And then my dad and my mom, they got me these, what they had when I was young were these Gilbert sets. Like they had a Gilbert Erector Set where you could make a robot or a rocket launcher. A microscope set where you could watch shrimp eggs hatch, and the chemistry set, which I actually sort of set up …

[00:03:38] We had a little basement in our house, and so I set up like almost a little chemistry lab where I'd mix things together and watch things change color through reactions. So I liked those kinds of things, and I think that probably got me somewhat interested in science as I was a young kid.[00:04:00]

[00:04:02] Rafael: In prior interviews or writings, you have actually described yourself as ADD.

[00:04:08] You say I didn't know it then, but I think I probably do suffer a little bit of that. How did you overcome that problem, and is this still a factor?

[00:04:20] Bob Langer: Yeah, I never did overcome it. And I didn't realize so when I was in grammar school, I had it. I know my teacher felt like I was badly behaved.

[00:04:29] So some of the times she once had me, for maybe three weeks, having my desk next to her desk facing the rest of the class. But what was really hard for me was in high school, In high school, I just couldn't pay attention in

class. I just daydreamed and I didn't understand it. I wasn't trying to necessarily daydream, but I did.

[00:04:54] And I really like today, even now at 76, if I go to a lecture with a lot [00:05:00] of people, and I do go to lectures — it's hard to be in academics and not do that — I still daydream. I've never really ever been able to overcome it. I think from the standpoint of doing okay in school, the way I overcame it was just kind of teaching myself.

[00:05:18] One of the nice things about being an engineer if you're taking classes and getting judged is really what's key is problem sets. So what I would keep doing when I was in college is I'd keep doing problem sets. And if you keep doing problem sets on physics, on mechanical engineering things, on all kinds of things, if you get good at that, when the test comes, you'll do well on the test too.

[00:05:45] So I did okay, but it was really by hard work and just really focusing in on those problem sets.

[00:05:54] Rafael: Yeah, but talking about getting in trouble, I understand your father used to have a liquor [00:06:00] store. Did you ever sneak out a drink and got in trouble?

[00:06:03] Bob Langer: No, no, you know, I never did though it is funny. When I was … Later, I remember getting bottles of wine and liquor from there.

[00:06:15] But no, I wasn't like … that kind of trouble I didn't really get in. If we had bad behavior I'd get in, but I don't think I ever did too much early drinking.

[00:06:28] Rafael: Has your religion played a role in your professional development? You're a Jewish man. Have you experienced discrimination, anti-Semitism?

[00:06:42] And how do you cope if you have?

[00:06:44] Bob Langer: Yeah, I don't know that I've ever experienced any of it directly. You never know indirectly what people say about you for anything, whether it's religion or other things. I'd certainly have had my share of rejection. [00:07:00] in all kinds of different things I've done personally and professionally.

[00:07:04] But I don't know whether it was because I was Jewish or because of other things. I certainly, I do remember once, though I didn't consider it anti-Semitism exactly, I remember I got invited to give a lecture at, I won't say which Midwestern university, by a group of students, and I know when they were having lunch, they said, ‘Gee, the Ku Klux Klan was here last week.’

[00:07:28] And they said, ‘But we've never met a Jewish person.’ It's just interesting to see what different parts of the country people thought about different things. But I have really, at least to my face, not other than somebody saying, maybe, you look Jewish or so.

[00:07:47] I haven't really had too much that at least know for sure was anti-Semitism.

[00:07:54] Rafael: That's an amazing statement, though, about in the Midwest, never have met a [00:08:00] Jewish man. That's interesting. Your wife has a PhD in neuroscience from MIT also. Have you ever worked together?

[00:08:11] When we first started going out, or maybe while we were even married, we wrote some papers. I think we wrote a paper for Technology Review with Henry Brem, who was a neurosurgeon, a friend of ours, and I think we wrote another paper in some neuroscience journal too. So we've done a little bit of work together.

[00:08:31] Of course, the big work we've done together is raising three children.

[00:08:35] Rafael: That’s right. Yeah, she works in issues of the brain as a neuroscientist. I don't think you have done too much in issues of the brain, which nowadays and probably into the future is a big frontier. Have you ever been tempted to go into get into that?

[00:08:55] Bob Langer: Yeah, well we actually have done some things, and the brain not that much, but [00:09:00] just a couple of examples. One of the things that we developed was a new family of polymers called polyanhydrides. And we worked with Henry Brem — I had mentioned that he was a neurosurgeon at Johns Hopkins — and we created what's called the GLIADEL Wafer.

[00:09:18] And that's actually been used for the last pretty much 30 years as a treatment for brain cancer. It’s used in over 30 countries. Also, more recently, we've collaborated with Anne Graybiel, who's a very famous professor at MIT — she's an Institute Professor — and Mike Cima, who's one of my friends and colleagues, on creating certain devices that could deliver drugs at precise locations in the brain.

[00:09:47] And most recently, which we haven't really even published yet, Li-Huei Tsai, who's head of the Picower Institute at MIT, and myself, we've had this postdoc, Alice Stanton, and [00:10:00] we've have had an NIH grant, and we've been creating what I'll call a tissue-engineered brain in vitro on a chip where you could hopefully observe brain function better and maybe even issues like crossing the blood-brain barrier and so forth.

[00:10:16] So we have worked on some things in the brain.

[00:10:22] Rafael: Talking a little bit about your MIT career, you were hired to Nutrition and Food Science that later became the Applied Biological Sciences at MIT. You've narrated in the past that you found yourself facing the situation where the department head that hired you left and somebody else came that wasn't particularly sympathetic.

[00:10:52] How did you navigate that difficult situation? I'm sure there will be plenty of young faculty listening to this [00:11:00] and would love to learn from that.

[00:11:02] Bob Langer: Yeah, I don't know that I navigated it that well. And it wasn't like the new department head was against me. It's just maybe I think the whole department was, but part of it was, so just to take a step back …

[00:11:16] So when I went there, actually, as a first-time a chemical engineer, no chemical engineering department would hire me. And I did get this job in nutrition. Nevin Scrimshaw, who was also an institute professor but what I always think of as a benevolent dictator kind of department head, he hired me. Why I say benevolent dictator, he was a visionary guy, and if he wanted to hire somebody, he'd hire them. But he didn't ask anybody else in the department what they thought. And so he hired me

[00:11:48] and then he left the next year. So a number of the senior faculty decided to tell, give me advice, and their advice is, I should leave too. How you [00:12:00] navigated, boy I kept trying, I kept trying to do a good job. I should point out that one of the things I did do, which maybe is advice for young people, I don't know that it necessarily helped, but what I did is when I came to that department, even before he left, I made a point of going to each of the senior faculty and saying, ‘What advice would you give me as a young faculty?’

[00:12:29] And I asked them that because they weren't involved even in interviewing me. But I asked them that, and I hope that made me a little bit less alien to them. But really, in the end, I think, I often think why did I finally get promoted or get promoted? And I actually think maybe for the right reasons.

[00:12:54] I think that I did publish papers that [00:13:00] I thought were, that I think people felt were important, and I got research grants. One of the things I also did was ask several of those professors to be co-principal investigators on the research grants so they would get money and we'd collaborate, and I think that was helpful too.

[00:13:16] But ultimately, I think the reason I got promoted was, and this is to MIT's credit, that part of their decision was, what do people on the outside think? So they'd write letters and they wrote letters to different people. And including I remember one of them they wrote to apparently was Roy Vagelos, who was president of Merck at that time.

[00:13:40] And apparently the letters were good. They'd say the work I was doing in drug delivery would be very important someday. And I think it was because outside people wrote good things that that helped convince the people at MIT that maybe I wasn't so [00:14:00] bad.

[00:14:01] Rafael: Well, they certainly made the right decision.

[00:14:04] But your advice to young faculty about going on meeting your senior members and interacting with them is indeed right on target. That department ultimately — I was there at the time — was disbanded in a very controversial decision during that period. and then I believe you went directly to chemical engineering from there.

[00:14:33] Tell me about that time. What was the boss, how you felt about that? At MIT, it was a big deal.

[00:14:44] Bob Langer: Yeah. For me, it was very upsetting. I really, by this time, this was 1988, I liked the department. I felt by this time, I was full professor and I had a lot of friends there [00:15:00] and I thought it was doing important things.

[00:15:02] And I remember actually being away on a Christmas vacation and one of my friends, Alex Klibanov, had called me up and said, you know, Bob, they just got rid of the department, and I was shocked. And I think MIT handled it very badly. They basically decided to get rid of the department, and they had no plan on what to do with everybody.

[00:15:26] It wasn't like I went to Chemical Engineering directly. I think places, in fact, I think what some of the people told me was that they were trying to get people … I'm sure they were afraid of lawsuits from different people. Maybe they got some, I don't know. It was, like I say, handled so badly.

[00:15:47] In my case, I keep getting offers from all kinds of places and interviews from all kinds of places. I wasn't trying, but they could see [00:16:00] that what was happening. So you'd get these interviews from Stanford, Cornell, lots of good schools, but I still, I really liked being in Boston,

[00:16:10] I liked being in MIT. My wife had grown up around here. At any rate, what happened finally, as I remember Bob Brown, who was the associate head of chemi, came to see me and he was terrific. He, I think, wanted me to come. One of the things he said, he said, ‘Bob, a lot of people I think maybe don't want you to come because they're worried that you'll take all the students who want to work with you.

[00:16:43] And he gave me this example that one of the students who worked with me was Dave Mooney. And he said part of his job as associate department head was to talk people out of working … if they want to work with somebody not in the department, that he [00:17:00] would try to talk him out of it. And he said he had a number of talks with Dave Mooney, and Dave Mooney, who is a super nice guy —

[00:17:06] he's now associate dean and a very famous professor at Harvard —David Mooney kept saying, ‘It doesn't matter what you say, I want to work with Bob Langer.’ So Bob Brown, that made quite an impression on him. And so they ended up asking me to join that department. But it didn't come so easy because a lot of people apparently …

[00:17:31] well I guess at a faculty meeting said if I came, too many students would want to work with me. Actually, they're partly right. I think the first year, you're supposed to give choices, and I think 13 people put me down as either their first or second choice, and you're only supposed to get two students.

[00:17:49] But it's not that I was so great, I think. It's just that the projects they were doing, they were not only scientific but they were things that would end up — I think people felt would help people someday. [00:18:00] And of course, they have.

[00:18:01] Rafael: Yeah, that was an exciting time in the Institute, I must say, with a lot of discussions about governance, and you described very well the difficult transitions that many of you found yourself in

[00:18:18] that, for the most part, ended up well. You're clearly an extraordinary leader. What is your definition of leadership? Are there some characteristics that you would attribute to yourself and other leaders that you want to share?

[00:18:38] Bob Langer: Well, you know, I think leaders are in different ways …

[00:18:40] Bob Langer: For me, I never thought of myself as a leader, but I think that the students who work with me, I think they know I care about them. I think that means a lot. With some advisors, I don't know that they do feel that they care about them. To me, it's like my [00:19:00] students and my postdocs — they're not quite my children, but they're not that far away.

[00:19:04] You really feel pain if something bad happens to them, and you feel elated if something good happens to them. I've been very fortunate that a lot of them have had wonderful lives and careers. I think a second thing on leadership is the example you set. I think I work hard. I try to think about problems that I hope will be important science, important engineering

[00:19:30] but also make a, hopefully, a big impact on the world. And I think that example probably helps. I mean, I think it's more respect maybe then that I have some great ability to lead. And I think it really depends on the forum you're in in terms of leadership. I think those kinds of things are going to be important

[00:19:55] anyhow. I think other skills that may be important for some leaders could be communication. [00:20:00] Skills could be being wise. I don't know that I'm great at either of those, and I don't know that that's really what helps me in terms of, say, being a leader — I mean, our lab has probably over a hundred people

[00:20:15] so you kind of have to be a leader. But anyhow, those would be some of the things.

[00:20:23] Rafael: But Somebody defined leadership that if you're walking and you look back and nobody's following, you're not a leader. There's a lot of people that follow you, so it fits the definition very well.

[00:20:36] You're definitely a leader.

[00:20:41] Bob Langer: Well, thank you.

[00:20:44] Rafael: You have mentioned in the past, also your work as a, your first postdoc, if I recall, with Judah Folkman, and you speak about him clearly with a lot of appreciation [00:21:00] about him, of him. He clearly served as a mentor. Tell us, how did he impact the directions you went? What type of relationship you had with him.

[00:21:17] Bob Langer: Yeah, he was a great man in my opinion, and certainly working at Children's Hospital with him changed my life. I think a couple things that he did. One is he asked big questions about that. And I could see immediately that they were big questions, that if he could solve them or I could help him solve them, they might have the ability to change cancer treatment and other treatments

[00:21:43] and actually they have. It was really important questions that he asked. But it was more than that. I think he thought that almost anything was possible and that's, as a young scientist, a very, very important thing to see. And he was [00:22:00] criticized for a lot of that, and it's never pleasant to be criticized.

[00:22:04] He was criticized not just by other scientists but by articles in science, articles in the newspaper. I think that was also important to see. That he would withstand that, and so I think all those things for me as a young person were important things to see. He was a great speaker too, and I would always pay attention to his talks or aspects of them.

[00:22:36] Like speaking loudly, he’d have some humor, and I tried to see what I could do when I gave talks that might mirror that in some way.

[00:22:46] So all of that.

[00:22:48] Rafael: Very good. Yeah, clearly he's had an incredible influence in your career, and it shows one of the things people who want to develop in [00:23:00] science and research must do, which is find somebody like Judah Folkman.

[00:23:04] You've led large laboratories. You have been a leader in research. You have served in innumerable boards, founded many companies. Why not go into the commercial world? Why academia? Why not simply jump the boat and go to business?

[00:23:36] Bob Langer: Yeah. Well, of course, the main reason I haven't done that is because I love

[00:23:40] being a teacher. I love working with students and postdocs. I've gotten enormous satisfaction out of that. But even beyond that, I've loved the freedom of academia, really coming up with all kinds of different ideas and seeing if [00:24:00] we can make them possible. And I don't think it's cost me. I've gotten involved, as you said, in terms of starting companies.

[00:24:10] But I'm probably better at starting a company. I hope if I was running a company, I'd do a good job, but I'd like this kind of early stage of a company, where you're creating something out of nothing, and I can help dream about what that company should be. I can help on the science. I can help them get some good people.

[00:24:30] I can help them think about good intellectual property. And so in a way, I feel I've been lucky. I can sort of have my cake and eat it too by being a professor and working with students and yet still starting companies and helping things get off the ground. And the beauty of it, in a way — I don't think I ever thought about this when I was very young — but the one complements the other.

[00:24:57] I think that to whatever [00:25:00] extent we've made an impact on the world, it's been because not only of the publications and the work we've done at MIT, but it's because the companies that I helped start have taken some of those principles and ideas and made products out of them that affect billions of people.

[00:25:17] Rafael: Wonderful. Yeah.

[00:25:19] You're clearly driven in everything you do. You have accomplished so much. How do you find that time? Is there a time when you're not working?

[00:25:30] Bob Langer: Well, yes. But a couple things I do: I work hard and I love it. I really do love the work. A couple things I'd say.

[00:25:43] One I've had a wonderful staff over the years, great people. I've gotten, I think, pretty good at delegating. I'm not … I would say I'm opposite of a control freak. I'd also think this is the privilege of being at an MIT, where you [00:26:00] get such great students and postdocs who, you can give them an idea and they'll run with it.

[00:26:06] And I've had wonderful collaborators. And also from a family standpoint, I'm lucky to have such a great wife who helps me on a lot of things.

[00:26:18] Rafael: Let me switch a little bit and talk about higher education. And let me begin by addressing the explosion of biological and health

[00:26:29] research as well as discoveries. For over 30 years, I think biology has been the topic of the moment. The human genome started in 1990, was decoded in 2003,

revolution. What do you see as the most important developments in biology and health sciences in the last 40 years?

[00:26:59] Bob Langer: [00:27:00] Well, that's a very good question. In the last 40 years, I think that certainly the human genome is one thing that's important. I think the, what I'll call things like genetic medicines, siRNA discovery, messenger RNA therapeutics, gene editing approaches. I think that these are some of the very important, things in in biology over the last 40 years. There's been probably new tools that have been developed: better

[00:27:35] spectrophotometers, better high throughput kinds of systems. But those are some of the things that come to my mind.

[00:27:43] Rafael: Yeah, as an outsider, I see what has happened and it's just mind boggling. But it reminds me a little bit that back in 2000 or so, I chaired the committee that ultimately [00:28:00] recommended the formation of the Department of Biological Engineering at MIT from the then Division of Biological Engineering.

[00:28:12] So I went around talking to people. I talked to you then, if I recall correctly, but one of the people I talked to was Phil Sharp, a Nobel Prize winner in biology. And I told Phil the following, in a very provocative fashion and on purpose: I said, ‘Phil, biology has always been and is a very descriptive science,

[00:28:39] and it rarely goes into the predictive, quantitative, prescriptive approaches that the biological engineers are doing.’ And in my mind, then, I told him I thought that the biological engineers were the [00:29:00] biology of the future. To my surprise, he didn't punch me but he actually agreed. What is your take on that?

[00:29:10] What is the merge that is occurring between science and engineering?

[00:29:16] Bob Langer: Yeah. Well, you talked to the right person by talking to Phil. He and I have written articles on what we call convergence, which kind of speaks to what you've talked about. And he's certainly a very visionary person in every way.

[00:29:29] I think that's right. I think that biological engineering, biolitical engineering — I think that's a giant area of the future. And I think that merge at many universities and companies, I think that's one of the big ways forward in terms of science and medicine. It's not the only way forward, but it’s playing an increasingly major role, and I expect will continue to do so.

[00:30:00] Rafael: You mentioned when I asked you about the discoveries of the last 40 years — things like gene editing, CRISPR obviously, mRNA technology, genomics, cloning, the use of nanoparticles for delivering of drugs that you have pioneered. These are the stuff of science fiction or what science fiction used to be written about in many ways.

[00:30:26] Many of these concepts literally control life. Can society handle it?

[00:30:35] Bob Langer: Well, I think so. I hope so. I mean it's always hard to know. I think there's often debate about these things. Certainly, there's misunderstandings about all these things as well. But I hope so. I think I'd say so far the answer is yes.

[00:30:57] Not to say that certain things, [00:31:00] not great things, have happened from time to time. But overall, I think all these things have moved. society forward and improved the health of many, many people and our understanding of many, many things.

[00:31:14] Rafael: Yeah, clearly technologies like CRISPR, the famous case of the gene editing of an embryo in China that created all sort of concerns, present quite a lot of challenges to society and to our way of living.

[00:31:36] So what's next for something like CRISPR?

[00:31:41] Bob Langer: Of course, actually I was thinking of what you said in terms of that baby when you asked about what's not good, and certainly that's an example. But what is good and I think what's next is new medical treatments that various groups are working [00:32:00] on already.

[00:32:01] There's been advances using CRISPR for treating sickle cell anemia. And I expect there'll be many other treatments as well from it. So I think it's certainly been a major advance in every way.

[00:32:17] Rafael: I've been reading about the use of that technology and others for mRNA deliveries of drugs and viruses to cure cancer, Alzheimer, et cetera.

[00:32:30] Are we going to see a cure to those things in our lifetime? Maybe not in our lifetime, but younger people …

[00:32:39] Bob Langer: Yeah I think you will see … I think in terms of cancer, I think you will see vast improvements using these approaches. I mean messenger RNA if you look at Moderna's work with Merck, if you look at BioNTech's work,

[00:32:58] you see what I'll call [00:33:00] individualized neoantigen therapies or it's also called personalized cancer vaccines. The results have been pretty amazing, and they're pretty advanced by now, I mean in phase three trials. So I think you will see better and better treatments.

[00:33:18] I don't know about cures. I think curing cancer is a different thing. Sometimes it is cured, but still, I think you'll see better and better treatments. I think with Alzheimer's, I don't think we know as much as we'd like to know. And I think you always need a target.

[00:33:39] And so, I think we need to understand more scientifically. There's a lot of good work going on, but I think we need to do more. And I think that what I just said is probably going to be true across the board. I think the beauty of things like CRISPR and messenger RNA and therapies like that, [00:34:00] siRNA, is that if you know enough about the disease, you can come up with a genetic therapy to deal with it.

[00:34:06] If you don't, then you obviously can't. And so there's still a tremendous amount of room, and it's important to do basic science to better understand all these diseases so that maybe someday there will be cures, or at a minimum, a lot better treatments.

[00:34:23] Rafael: One of the things that is happening in higher education, which is what you and I make our living in, is that the public at large has lost some of the respect that it has for higher education, even though the research that higher education produces saves lives at the very least and grow economies. Yet the trend of distrust is increasing.

[00:34:54] What do you think causes that? What's wrong? How can we change it?

[00:34:59] Bob Langer: [00:35:00] Yeah, it's a very, very good question, and I really don't know the answer to it. My wife has certainly made the observation that, and other people obviously have too, that something like over 30% of the people in the United States don't believe in evolution, which of course is well established scientifically.

[00:35:24] So obviously there's different people with different backgrounds that don't believe in different scientific things. So maybe it shouldn't be that surprising that they don't, about what you said. I think all you can hope to do is give people the best education, the best communication. I think, I believe you’ve got to keep free speech going in every way, but I do think the more we can do to really educate people across the board

[00:35:58] is [00:36:00] probably the most important thing we can do.

[00:36:03] Rafael: Let me pick up on that statement of free speech that you just made. You and I lived through the Vietnam era, with enormous campus protests. The country was in turmoil, and it showed. We have, all campuses around the country have been dealing with disruptions due to the war in Gaza.

[00:36:29] And it continues, and it's very controversial in the way that it may or may not be handled. Do you have any thoughts about that?

[00:36:42] Bob Langer: Well, I think it's a really, really tough problem. I'm hardly an expert on politics or policy. I mean, one hopes that one could get compromises, but I break it down into two parts.

[00:36:54] What should happen to Gaza and what should happen in the universities? I think in [00:37:00] Gaza, you see people trying to come up with ways of allowing a peaceful coexistence. I hope that they will come up with some ways to do that. At universities, Sally Kornbluth, who was our president at MIT, she made the point

[00:37:18] to me that the part of the issue is, where does one draw the line between free speech on the one hand and harassment on the other? It's probably not a simple question. And I don't know that … there's certainly not a simple answer to that. Obviously, if somebody does physical violence, that crosses the line.

[00:37:38] But the question is, where do you draw that line for sure? I think it's important to have rules, and I think it's important to enforce those rules if you have them. But those are some of the things that I would think about the question you asked.

[00:37:53] Rafael: Yeah. Let me take the opportunity.

[00:37:56] I did a similar interview with John [00:38:00] Hennessey, the former president of Stanford. I don't know if he you know John, but he's a wise, experienced person. And he made a distinction which really hit me, I had never thought of. He said the difference between what is happening now and what used to happen or what happened during the Vietnam era is that now,

[00:38:25] is student against student, faculty against faculty, students against faculty — is division within, not a unified division of academia against outsiders, which I thought changes the equation.

[00:38:25] Bob Langer: Wow. Couple things. Absolutely. I do know John. John actually was on the committee of the Queen Elizabeth Prize when I received that award, and I think he's on that board now.

[00:38:54] I'm on that board too. But I obviously he's a [00:39:00] very wise man, president of Stanford. I completely agree with that. I mean, the way I've always looked at it is, when I was around in the 1960s as a student and basically the students, we were all on the same side. Everybody, people were against the Vietnam War.

[00:39:20] I don't remember anybody, I don't remember anybody being for it. Here, you're absolutely right: There's two sides, and that makes it far more difficult.

[00:39:29] Rafael: Yeah, that's the main difficulties. And as simple as it sounds, I don't know that too many people have crystallized that point. And it indeed, makes the whole problem very, very difficult.

[00:39:43] Bob Langer: I think people do. I think that at least when I look in Boston, people understand that there are two sides, whereas before there was one, but that doesn't change the fact that those two sides disagree tremendously. [00:40:00] And there and that there's lots and lots of protests, and the protests go against each other in contrast to just against

[00:40:08] government or something like that.

[00:40:11] Rafael: Let me talk about entrepreneurship, something close to your heart. These days, societal impact, economic impact are really part and parcel of what a top research university has to do — translation of ideas to improve the human condition. It's one of our, everybody's goal.

[00:40:35] You are the poster child of entrepreneurial faculty. What drives your entrepreneurial spirit? How did you become an entrepreneur?

[00:40:45] Bob Langer: Yeah, well I wasn't thinking about becoming an entrepreneur. What happened to me is I made some findings, some discoveries, some inventions. And I just thought naively, [00:41:00] this was the 1970s, that if I publish things, people would hopefully use them.

[00:41:05] And certainly academically, people have used them. I mean our papers are widely cited. But I really thought that maybe it would lead to new medicines that would help people. And that really wasn't happening. Finally after 10 years of doing this work — and we got a patent finally too — I'd get

calls from some major pharmaceutical companies, some multibillion dollar companies.

[00:41:30] And they said, gee, they'd like for me to consult for them and they wanted to license my patents and some things like that. I was very, very happy about that. I got a consulting fee. I got a big grant from both of them. Most important to me was that they were going to develop it. But they worked on it for maybe a year and then they just gave up.

[00:41:51] And then one day Alex Klebanoff, one of my friends, said to me, ‘Bob, we should start our own company.’ And we did. And I think that was overall a good [00:42:00] experience. And what I'd learned from all that is that if you're not your own champion, nobody else will be. So I kept doing it. I kept starting companies with my students

[00:42:11] to take things that I'd been involved in in the lab and try to bring them to the public. And I think that has — I mean not that I had any great vision when I started it that that’s what would happen, but it has happened. And I think those companies have made a tremendous difference in the world.

[00:42:34] And it's not just me — lots of people are doing that now. And I think some of these young companies, and some of them aren't so young anymore, they enable discoveries, often academic discoveries, to get out to the world and save and improve many, many lives.

[00:42:51] Rafael: Should everybody in academia be an entrepreneur? Should it be a metric of success?

[00:42:59] Bob Langer: I don't think [00:43:00] so. I think that's one thing you can do. I don't think that that should be a requirement at all. At the same time, I think if somebody does it, I think it can be important. But I think the important thing, overall, is to make a contribution. Somebody in academics can make a contribution by teaching, by writing books, by writing articles, by just doing good science or good engineering. They can also make it by being an entrepreneur.

[00:43:29] But I think as long as you make a contribution, as long as you do something good, that's what's important, and there are many ways to do something good.

[00:43:37] Rafael: Yeah, one of the things about involvement in business and translation is that it becomes quite hard, particularly in biological areas. To distinguish the university work from the private work, leading to all sort of

conflicts and [00:44:00] potential or perceived conflicts of interest. Is the model of a faculty member

[00:44:11] the correct one, because that conflicting messaging that we get as faculty and we give as faculty about being an entrepreneur and being in the university, that boundary gets very, very fuzzy, and it causes a lot of problems. And I must say this is particularly true in public universities.

[00:44:36] Bob Langer: No, I think you're right.

[00:44:38] I think it can do that. I think what's important, I mean the way I've always looked at it is, being at MIT, is MIT has different rules. Even if I don't like those rules, I'm going to follow them. So I end up writing a very large stack of forms that I filled out that I do. And it takes [00:45:00] time, but those are the rules, and I feel I'm going to follow those rules.

[00:45:04] And I wish sometimes that conflict of interest rules were easier, I said, but the thing is, what's happened in different cases is, sometimes people have abused those rules. And if those rules get abused and real problems get created, that's not good. So I think you have to have some rules, and different universities have different rules.

[00:45:30] I think it could be a good national effort to try to come up with collective rules if you could. But I have not seen that, or at least I've not seen any set of national or international rules on that. But from my standpoint, I guess what I look at is I've always viewed my number one job as to be a professor at MIT, to work with students, to write papers.

[00:45:55] We publish everything we do. Anybody can academically use [00:46:00] them. But I also feel it would be a mistake to not take those things and try to see if we can help the world by making products out of them. And if we didn't do that, if I didn't do that, who would? And especially, like I said, if you're not your own champion, I don't think you can expect other people to do that.

[00:46:22] So I feel as long as you obey whatever rules there are by the federal government, by your universities, you're doing all you can. And so that's what I've tried to do. And I think others too.

[00:46:37] Rafael: You have been an extraordinary, successful entrepreneur most recently as a founder of Moderna, which is now a household word, a name. That certainly has made you extraordinarily wealthy.

[00:46:55] How does that change your [00:47:00] attitude? How does it change what you do, if at all?

[00:47:03] Bob Langer: Yeah, I don't think it's changed what I do. I haven't sold any shares and its paper. I’m glad that that Moderna has done so well, not necessarily because of that, but because it's helped so many people.

[00:47:19] And that was really my intent when I started every company — that it would help people, it would create jobs and … But the way I look at it, nothing's really changed. I still spend a lot of time at MIT and work with students, and I don't have to, I'm 76 years old, I could retire, but I love what I do, so I keep doing it.

[00:47:45] And it's not about money or anything else, it's about … You know, I keep always asking myself, how can I spend my time doing whatever I hope will have the greatest positive impact on the world? [00:48:00] So probably if I played golf, I don't know that would have a major positive impact on the world.

[00:48:07] Rafael: Let me ask you about Moderna. Tell me a little bit about or tell us a little bit about the history of Moderna — how it came about. How did it gear up to be so successful in the middle of a crisis?

[00:48:21] Bob Langer: Yeah, so maybe even a little bit on the history. So other people before us in the United States tried to start mRNA companies.

[00:48:37] The terrific work out of Penn by Drew Weissman and Katalin Kariko in 2005 modifying messenger RNA, for which they won the Nobel Prize, was a very major discovery. They tried to start a company and had patents, and nobody would give up funding. Derrick Rossi, five years [00:49:00] later, really modified or applied their techniques to developing messenger RNA to change a stem cell into, or to change cells into what are called IPS cells.

[00:49:16] And he also, he was named to Time Magazine's 100 Most Influential People, and he tried to get venture companies like Third Rock to fund him and start a company, but they weren't willing to do that. Tim Springer told him he should come to see me, and a lot of people would say one of the biggest issues of trying to create a messenger RNA therapeutics company was delivery systems.

[00:49:43] That's actually when you mentioned Phil Sharp, he's always said that the delivery is like the big problem with a lot of these RNA therapeutics. Well, I've certainly felt that was a problem that we could certainly hopefully address for maybe five or six reasons. [00:50:00] Starting back to the 70s when we

published the earliest paper in Nature showing that you could deliver nucleic acids from little particles.

[00:50:08] But we did further work, Ruxandra Gref in our lab and Vladimir Torchilin and others. We published papers on how you could design nanoparticles with polyethylene glycol on them so that they wouldn't aggregate and they'd circulate for long enough times. And that would become a major component.

[00:50:30] A couple years later, Dan Pack and David Putnam on our lab came up with this idea of an ionizable molecule that you could put on, which could help endosomal escape, which was important in getting a cargo out. Dan Anderson, who was in our lab, he came up with this idea of using combinatorial ideas so that you could generate lots of these ionizable molecules.

[00:50:57] And then finally [00:51:00] Robert Carnick, who was in our lab, along with Omid Farokhzad, actually published ways that we could use microfluidics to create lots and lots of nanoparticles, which seemed to me like a scalable method. So I felt that we could probably, enough was there certainly that we could solve these problems.

[00:51:21] We then talked to Noubar Afeyan, who was a MIT graduate and then founded Flagship, an incredibly successful venture company, and he's a visionary guy. And Ken Chien, was an outstanding cardiologist. So the four of us decided we’d try to form Moderna. We were very, very fortunate a couple of years later … that in the next year, Noubar knew Stéphane Bancel, who was really an outstanding scientist and businessman who was

[00:51:50] president or CEO of BioMérieux, and he agreed to be our CEO, giving up a [00:52:00] tremendously high paying job to do this. And then we got other great people like Stephen Hoge, Melissa Moore — all kinds of really great people. And we kept building it. We kept trying to solve problems, building on the delivery that I mentioned.

[00:52:17] They got deals with different people. So we made a big gamble on building a manufacturing plant spending over a hundred million dollars on this, which I think a lot of people thought was nuts, but very important to the question that you asked. So by the end of 2019, we had 13 products in clinical trials, and then of course COVID hit, but we were in a position scientifically and even manufacturing-wise where we could hopefully address that.

[00:52:47] Even though nothing had been approved yet, we tackled that problem and the people at Moderna, they just worked unbelievably hard.

They're [00:53:00] just such an outstanding group of people, a number of whom are students at MIT and elsewhere, and they just did an amazing job.

[00:53:07] And so in less than a year, I mean less than two days, the Moderna vaccine was made and then put in nanoparticles. The clinical trial started in two months. Of course, lots and lots of people said it would never work. Criticized me. But by November, when the code was broken, it was over 94% effective.

[00:53:30] And of course, the only other one that really worked was also a vaccine mRNA vaccine and nanoparticles done by a German company, BioNTech. And fortunately, Pfizer was working with them, and so those two vaccines have been really the key to trying to address that problem, and I think it really is just the tip of the iceberg.

[00:53:56] Rafael: The story about the creation [00:54:00] of the vaccine is truly mind boggling. Just to repeat a little bit of what I've heard, and you just alluded to the, basically, the genetic code of the virus is released, and within a couple of days, Moderna had a vaccine, and then immediately went into trials in a matter of we're talking January in a matter of a couple of months or three months in March, the vaccine is out.

[00:54:28] It is like the speed of light. It's really amazing. Now, you compare that to the normal way that medicines are approved and clearly for that to happen, we were in a crisis. A lot of corners were caught. Regulations had to be abrogated, if I can put it that way. Why not do that all the time?

[00:54:57] Were you at all concerned during [00:55:00] that period that something would go wrong and people would be hurt?

[00:55:05] Bob Langer: Absolutely. I think everybody was concerned about safety. I think the goal always in these things is first do no harm. But I think in any case, you always have to look at a risk-reward ratio.

[00:55:21] And in this case the risk was very, very high. So I think it's ultimately, it's not me or Moderna, it's the FDA and the CDC in the United States and regulatory authorities all over the world, the World Health Organization and so forth, really trying to make an assessment of how long … what do you need to see?

[00:55:45] And I think they tried to get the best experts on those places to see, what do you need to see to feel reasonably confident that it would be safe and effective? And t

was 30,000 patients, the Pfizer BioNTech trial was 42,000 patients, so there were many, many people who they studied and looked at.

[00:56:13] Now I think the other thing that's really important when you look at this is, not only was it very effective. For reference, the flu vaccine, which lots and lots of people get, is 40% effective or 50% at best. Here, you're talking about 94–95% percent, so it's much more effective.

[00:56:34] And actually, when you look at publications, it's safer, too, than flu. No vaccine, no drug, of course, it’s very important to realize, is perfectly safe. I think the misconception sometimes people have, because there are side effects, it would be absolutely a mistake to say that the vaccine couldn't cause some harm or that any drug you take can't cause some harm.

[00:56:56] But I would say when you look at published work, [00:57:00] that the mRNA vaccines have caused less side effects than the flu vaccine. And of course, they've saved millions of lives by really any standards.

[00:57:15] Rafael: It must be an incredible satisfaction. Let me ask you one last question relative to this, which is: If Bob Langer could go back to childhood

[00:57:26] and start all over again, do you think you could have done or you could do what you have done? Is it repeatable?

[00:57:37] Bob Langer: Well, you know, I think whatever I've done, I feel very lucky, and I don't think anything would be exactly repeatable. There's a funny thing, Judah Folkman had an interesting sense of humor when I told him, and he knew this,

[00:57:53] that really, I applied to 20 oil companies, or I got jobs from 20 oil [00:58:00] companies, which all paid me very high amounts at the time, 1974. And yet I chose to take the lowest paying job, which was his, at Children's Hospital. And he'd always make the comment when, he said, you know, if — because I developed all these long-acting drug delivery systems — he always made the comment that, ‘Gee, if Bob had gone into the oil industry, you'd end up getting your car filled up with gas once a year.’

[00:58:26] Rafael: Yeah. In those accidents of history, those decisions change the trajectory of everybody. Let me end by saying, one thing that has always impressed me about you is enormous curiosity about everything and anything. And I don't know, you probably don't recall, you don't have to answer it, but the first time I met you.

[00:58:52] I recall you came to my office with a young PhD and you were talking [00:59:00] about preventing evaporation from surfaces of water supply reservoirs which, I don't know if you have that memory, but that conversation really …

[00:59:14] Bob Langer: I do. Moshe Alamaro.

[00:59:17] Rafael: That conversation really, one, told me, wow this person is incredibly curious about all sorts of things.

[00:59:29] And second, I must say, I wasn't great and supportive. So I apologize for that at the time, but anyway I do recall that I think that was the first time I met you. To end up, one very important question. I know you're a baseball fan. We spent together an enjoyable afternoon the other day watching baseball.

[00:59:58] Are you a New York [01:00:00] Yankees fan or a Red Sox fan?

[01:00:03] Bob Langer: Well, first of all, I do remember going to your office with Moshe Alamaro, and you're an expert at this area. You know, I dabble and try to do different kinds of things. So I appreciated your taking the time to see us. On baseball,

[01:00:19] I am absolutely not a Yankees fan. I guess I'd say I'm a Red Sox fan, but they're having a five, but I've always been I grew up in Albany, New York, and my dad actually was a Brooklyn Dodger fan, so I was a Brooklyn Dodger fan, and if you were a Brooklyn Dodger fan, you didn't like the Yankees. So moving to Boston, you're, I'm in the same boat. You like the Red Sox and you don't like the Yankees. But of course the Yankees have done very, very well. They did very well against the Dodgers, and they do very well against the Red Sox.

[01:00:54] But, that's okay.

[01:00:56] Rafael: They're the common enemy. So you care to [01:01:00] predict? The Red Sox have not won since 2018. The Yankees since 2009. Will they make it anytime soon?

[01:01:12] Bob Langer: Well, the Yankees look pretty good. Again, I think the Red Sox are having a hard time. The Yankees, they look pretty good. I hope they don't, but I would not be surprised if they do.

[01:01:23] They have some pretty good players, like Aaron Judd and so forth. By the way, the way I look at what you said, when the Red Sox won in 2018, I

have a very good memory that when I lived in Boston for many years, they had won I think in 2018, I'm sorry, 1918, or something like that, or 1916, and then they did not win ‘til 2004.

[01:01:49] So they went a long time, over 80 years, without winning the World Series. So the fact that we have only waited six years since 2018, I [01:02:00] think I can tolerate that.

[01:02:01] Rafael: Yeah. Say famous curse of the Bambino. Anyway, Bob, I really want to thank you for spending this hour with us. It's been great to have the opportunity to talk again like this

[01:02:18] and freely. In the name of all the audience and certainly personally, thank you so much.

[01:02:25] Bob Langer: Well, it's an honor for me to be a part of it. I thought you, boy, you did a lot of great research on me, and it's wonderful to see you again, Rafael. Thank you.

[01:02:36] Rafael: Thank you.

[01:02:40] Aileen: Thank you for tuning in to this episode of Not Alone: Leaders in Conversation. We hope this discussion today sparked new ideas and left you with plenty to think about as you continue to lead in your own institution. If you found this conversation interesting, insightful or thought provoking, please share this episode with your colleagues, [01:03:00] peers and friends.

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