WEBVTT - How to Start 40 Companies (and Counting) 0:00:15.356 --> 0:00:22.596 Pushkin. You want to start listing off the companies of 0:00:22.636 --> 0:00:24.436 which you're a founder and a co founder and stop 0:00:24.476 --> 0:00:25.436 wherever you get tired. 0:00:26.396 --> 0:00:28.076 I mean I can try to do that, but that 0:00:28.196 --> 0:00:29.476 might take some time. 0:00:30.116 --> 0:00:33.436 Give me a handful. Count count off five on your fingers, 0:00:33.476 --> 0:00:34.036 just for sure. 0:00:34.516 --> 0:00:42.116 Sure, well, Maderna Momenta PureTech Seer, living Proof. 0:00:42.676 --> 0:00:44.076 For a second thought, you were just going to do 0:00:44.116 --> 0:00:45.916 the MS, which might have been. 0:00:45.836 --> 0:00:48.156 A while I could, I could do with the aged. 0:00:50.036 --> 0:00:54.316 Robert Langer has founded or co founded something like forty companies. 0:00:54.756 --> 0:00:58.196 He is an institute professor at MIT. He holds over 0:00:58.276 --> 0:01:01.916 a thousand patents, and his research has been cited more 0:01:01.956 --> 0:01:06.556 than four hundred thousand times. But when he started his 0:01:06.636 --> 0:01:09.836 career in the nineteen seventies, he didn't see bound for 0:01:09.916 --> 0:01:13.196 professional glory. He had a hard time finding a job, 0:01:13.356 --> 0:01:16.156 he couldn't get funding for his research, and his patent 0:01:16.156 --> 0:01:20.516 applications kept getting rejected. And I think these two things, 0:01:21.076 --> 0:01:25.356 his early struggles and his later massive success are in 0:01:25.396 --> 0:01:29.396 fact closely connected. Langer was trying to do something that 0:01:29.556 --> 0:01:33.636 was deeply and profoundly different than what anybody had done before. 0:01:33.956 --> 0:01:37.276 Almost nobody understood it. Almost nobody knew what to do 0:01:37.356 --> 0:01:41.076 with him, and then when his work finally did succeed, 0:01:41.636 --> 0:01:44.956 it was such a new, powerful discovery that people are 0:01:45.036 --> 0:01:54.076 still building on it today half a century later. I'm 0:01:54.156 --> 0:01:56.916 Jacob Goldstein and this is What's Your Problem, the show 0:01:56.956 --> 0:01:59.076 where I talk to people who are trying to make 0:01:59.156 --> 0:02:04.156 technological progress. Robert Langer is still working, still doing research, 0:02:04.276 --> 0:02:06.956 still founding companies, and we talked about some of his 0:02:07.076 --> 0:02:10.076 current work in the later part of our conversation. But 0:02:10.236 --> 0:02:13.476 to start, we went back to the mid nineteen seventies 0:02:13.756 --> 0:02:17.316 when Langer got his doctorate in chemical engineering and he 0:02:17.396 --> 0:02:21.196 did something that at the time was really unusual. He 0:02:21.236 --> 0:02:24.676 did a postdoc with a medical school professor, a pediatric 0:02:24.756 --> 0:02:30.956 surgeon named Judah Folkman. Langer's field is bioengineering, basically bringing 0:02:30.996 --> 0:02:34.876 the tools of engineering to the fields of biology and medicine. 0:02:35.236 --> 0:02:39.276 And bioengineering is a huge field today, but it barely 0:02:39.316 --> 0:02:43.276 existed back when Langer started his postdoc with that doctor, 0:02:43.396 --> 0:02:48.956 Judah Folkman, and bioengineering was exactly what Judah Foalkman needed. 0:02:49.396 --> 0:02:52.116 Folkman had an idea for a new kind of drug, 0:02:52.636 --> 0:02:54.916 and this kind of drug was a molecule that was 0:02:54.996 --> 0:02:57.756 too big and complex to be given as a pill. 0:02:58.316 --> 0:03:01.756 So Folkman needed somebody who could figure out how to 0:03:01.876 --> 0:03:05.516 deliver this new kind of drug to patience. As you'll hear, 0:03:05.996 --> 0:03:10.676 that delivery problem was fundamentally an engineering problem, and when 0:03:10.796 --> 0:03:14.756 Langer solved that problem, he created an entirely new way 0:03:14.836 --> 0:03:18.716 to get medicine to patients, and it proved incredibly useful. 0:03:22.436 --> 0:03:24.916 Tell me about being an engineer and going off to 0:03:24.956 --> 0:03:28.356 work in the nineteen seventies in the lab of a physician. 0:03:29.396 --> 0:03:31.276 On the one hand, for me, it was very hard 0:03:31.356 --> 0:03:34.556 because I had to learn a lot about medical things 0:03:34.556 --> 0:03:39.236 and I didn't know very much biology, so that was 0:03:39.396 --> 0:03:43.836 that was difficult. But on the other hand, being an engineer, 0:03:43.876 --> 0:03:46.276 I guess I had a different perspective, you know that 0:03:46.396 --> 0:03:51.156 I didn't maybe think the same way as a clinician 0:03:51.276 --> 0:03:55.676 or surgeon or a biologist. You know, engineers they solve problems, 0:03:55.716 --> 0:03:58.836 and that Judah Falkman, who was my boss at the time, 0:03:58.956 --> 0:04:01.116 I mean, that's what he wanted. He wanted to see 0:04:01.116 --> 0:04:02.036 a problem solved. 0:04:02.836 --> 0:04:06.476 So let's talk specifically about that problem. What did you 0:04:06.796 --> 0:04:08.996 what did you go to doctor Falkman's lab to work on. 0:04:09.996 --> 0:04:12.636 Doctor Fokeland had this idea that if you could stop 0:04:12.676 --> 0:04:17.236 blood vessels, you could stop cancer. It wasn't most people 0:04:17.236 --> 0:04:20.476 didn't think he was right. In fact, he went further. 0:04:20.596 --> 0:04:24.956 He said that the reason blood vessels come to the 0:04:24.996 --> 0:04:29.036 tumor is that the tumor makes a chemical signal he 0:04:29.076 --> 0:04:32.916 called the tumor antigenesis factor, and he said that was 0:04:32.996 --> 0:04:36.996 chemically mediated. And also the idea that he thought about 0:04:37.116 --> 0:04:40.796 is if that was chemically mediated, maybe stopping it could 0:04:40.836 --> 0:04:45.236 also be chemically mediated. So my job really, in a 0:04:45.236 --> 0:04:47.876 way was to prove that he was right, because almost 0:04:47.916 --> 0:04:50.716 everybody told him he was wrong, and in so doing 0:04:50.836 --> 0:04:55.116 isolate the first you know, blood vessel or antiogenesis inhibitor, 0:04:55.756 --> 0:04:56.156 uh huh. 0:04:56.196 --> 0:04:59.436 And so it's basically that there is this theory that 0:04:59.476 --> 0:05:03.716 he had that tumors stimulate the growth of new blood vessels, 0:05:04.276 --> 0:05:07.596 and then if that's true, perhaps you could inhibit the 0:05:07.636 --> 0:05:11.356 growth of new blood vessels thereby inhibit the growth of tumors. Right, 0:05:13.116 --> 0:05:17.116 And so you get there, and I'm interested in that 0:05:17.236 --> 0:05:20.316 inhibition piece, right, because that seems like that's where you're really, 0:05:20.396 --> 0:05:24.996 in a very direct way, bringing your engineering skills to 0:05:25.076 --> 0:05:27.796 bear on this medical problem. So, like, talk about that 0:05:27.836 --> 0:05:29.556 side of it and how you approached it. 0:05:30.476 --> 0:05:32.836 So what we wanted to do was have a little 0:05:32.956 --> 0:05:37.876 nanoparticle or microparticle that could deliver different molecules I was isolating, 0:05:39.116 --> 0:05:42.196 and these were fairly large molecules, so that was really 0:05:42.236 --> 0:05:44.676 the idea, and then see could it stop the blood vessels? 0:05:45.036 --> 0:05:50.196 So this core idea of developing a nanoparticle to deliver 0:05:50.956 --> 0:05:56.156 a large molecule basically a complicated drug, is an engineering problem, right, 0:05:56.196 --> 0:05:59.516 this nanopart of It's like, we've got this this drug 0:05:59.676 --> 0:06:01.476 call it that we think might be able to stop 0:06:01.516 --> 0:06:04.316 tumor growth, but how do we get it to the tumor? Right? 0:06:04.356 --> 0:06:07.196 That is a basic problem that you were coming up 0:06:07.196 --> 0:06:11.476 against early in your research, and that that problem winds 0:06:11.556 --> 0:06:13.116 up being a big deal, right, and the way you 0:06:13.156 --> 0:06:16.196 go about solving that problem winds up being a big deal. 0:06:16.276 --> 0:06:18.236 So tell me about that. 0:06:19.476 --> 0:06:27.276 Well, the nanoparticles and microparticles, really it's taking molecules drugs, encapsulating, 0:06:27.356 --> 0:06:32.076 surrounding them with a lipid or polymer, and delivering it 0:06:32.196 --> 0:06:35.556 to sells or a patient or an animal. 0:06:36.156 --> 0:06:38.436 And a lipid or a polymer is basically some fat 0:06:38.556 --> 0:06:39.356 or some plastic. 0:06:40.196 --> 0:06:43.516 Yeah, yeah, lipid is some fat and polymer some plastic. 0:06:43.636 --> 0:06:48.236 Generally speaking, So, yeah, if you escape the drug by 0:06:48.276 --> 0:06:51.356 itself and it wasn't packaged in those particles, it would 0:06:51.396 --> 0:06:55.996 just get destroyed. I mean, so the number one reason 0:06:56.036 --> 0:06:59.716 you do it is to protect it, you know, otherwise 0:06:59.756 --> 0:07:03.316 it won't you know, they'll just get destroyed, probably almost immediately. 0:07:03.916 --> 0:07:07.716 So you know, we ask people who are experts in 0:07:07.756 --> 0:07:10.316 that area, know about price winners and others who had 0:07:10.356 --> 0:07:15.996 done work or at least helped on delivery of small molecules, 0:07:16.276 --> 0:07:18.636 and we asked them about that, but they all told 0:07:18.716 --> 0:07:22.836 us it wasn't possible. So I spent years in the 0:07:22.916 --> 0:07:27.156 laboratory experimenting, finding hundreds of different ways, failing hundreds at 0:07:27.156 --> 0:07:32.636 different times, but finally I was successful. And you know, 0:07:32.676 --> 0:07:36.276 we published a paper in Nature in nineteen seventy six, 0:07:36.756 --> 0:07:40.276 the General Nature, and showed for the first time that 0:07:40.316 --> 0:07:43.476 you could deliver large molecules this way. And we published 0:07:43.516 --> 0:07:46.756 a paper in Science in nineteen seventy six showing for 0:07:46.836 --> 0:07:49.716 the first time that you could stop blood vessels by 0:07:49.796 --> 0:07:50.956 using approaches like this. 0:07:51.516 --> 0:07:54.996 And as I understand it, even after you published those papers, 0:07:55.596 --> 0:07:56.916 you met a lot of resistance. 0:07:57.916 --> 0:08:00.876 Yeah I did. I suppose I met a lot of 0:08:00.876 --> 0:08:04.756 resistance for a couple of ways. First, different people didn't 0:08:04.796 --> 0:08:06.636 agree with it or didn't believe it or didn't think 0:08:06.676 --> 0:08:11.076 it was possible. Secondly, my background really wasn't right. I 0:08:11.116 --> 0:08:15.756 suppose for the different review sections, I was an engineer, 0:08:15.796 --> 0:08:20.836 and when we sent the grants to the National Insituites 0:08:20.836 --> 0:08:23.156 of Health in places like that, you know, they had 0:08:23.196 --> 0:08:26.436 medical people or biological people reviewing it, and they said, well, 0:08:26.756 --> 0:08:28.916 what can an engineer, You know, he doesn't know anything 0:08:28.956 --> 0:08:33.276 about biology or oncology. Separately, I met a lot of 0:08:33.476 --> 0:08:36.676 resistance when I tried to do this get a job 0:08:36.716 --> 0:08:40.396 in an engineering department. They said, well, engineers a chemical 0:08:40.476 --> 0:08:44.836 engineering department, They said, engineers really don't do experimental biology. 0:08:44.876 --> 0:08:48.036 So I didn't get any faculty positions in a chemical 0:08:48.036 --> 0:08:51.116 engineering department for a very very long time. I ended 0:08:51.196 --> 0:08:52.476 up in an fishing department. 0:08:52.716 --> 0:08:57.476 And so, I mean, this idea of bioengineering that is 0:08:57.516 --> 0:09:00.116 a big deal now and was very novel. Then it 0:09:00.156 --> 0:09:02.636 feels like you're sort of coming up against this problem 0:09:02.716 --> 0:09:06.436 of creating a field that doesn't quite exist yet, or 0:09:06.476 --> 0:09:08.236 at least creating a part of a field that doesn't 0:09:08.276 --> 0:09:10.396 exist yet, which seems like, on the one hand, the 0:09:10.436 --> 0:09:13.476 opportunity to solve very large problems was clearly there. On 0:09:13.516 --> 0:09:16.676 the other hand, the kind of institutional structure to allow 0:09:16.716 --> 0:09:19.836 that to happen was was not on your side. 0:09:19.996 --> 0:09:22.796 Yeah, you're right. I mean, Ei there had been people 0:09:22.876 --> 0:09:27.236 in chemical engineering doing work on what i'd call mathematical modeling, 0:09:27.276 --> 0:09:31.716 you know, transport of molecules, but experimental stuff, inventing things. Yeah, 0:09:31.756 --> 0:09:36.596 that and discovering you know, new molecules that certainly had 0:09:36.836 --> 0:09:40.036 not been done, never been done in chemical engineering up 0:09:40.116 --> 0:09:45.836 till that time. So so that ended up being hard. 0:09:46.196 --> 0:09:48.836 Is it right that some of your early patent applications 0:09:48.836 --> 0:09:50.756 around this technology were also rejected? 0:09:51.436 --> 0:09:55.636 Yeah they were. I mean the first the main patent 0:09:55.676 --> 0:09:58.876 on it got rejected five times in a row. But 0:09:59.276 --> 0:10:03.156 you know, sometimes that happens. I'vet after that. I think 0:10:03.196 --> 0:10:05.276 I had one when we came up with the idea 0:10:05.276 --> 0:10:08.276 of tissue engineering. I think that got rejected even more. 0:10:08.396 --> 0:10:10.596 So those things happen. 0:10:10.676 --> 0:10:13.436 And so you get the patents and you end up 0:10:13.476 --> 0:10:18.476 licensing the technology initially to one or more big big companies, right, 0:10:18.516 --> 0:10:20.796 big pharmaceutical company. What happens with that? 0:10:21.436 --> 0:10:24.396 Yeah, well, actually the hospital did that the license because 0:10:24.556 --> 0:10:27.276 I mean, the past is my name, but they licensed it, 0:10:27.716 --> 0:10:30.396 you know. I well, I was very excited about that. 0:10:30.476 --> 0:10:34.236 There were two multi billion dollar companies won an animal 0:10:34.316 --> 0:10:37.916 health one in human health. You know, So they they 0:10:37.956 --> 0:10:40.236 gave me a consulting fee. They gave me actually a 0:10:40.316 --> 0:10:43.876 very large grant, which for young professors, you know, terrific. 0:10:44.196 --> 0:10:46.476 Most importantly, they were going to work on it, and 0:10:46.516 --> 0:10:48.996 they did work on it for maybe up to a year, 0:10:49.116 --> 0:10:52.076 but then they just gave up. So I got the 0:10:52.116 --> 0:10:54.956 grant and the consulting fee, but I didn't get what 0:10:54.996 --> 0:10:57.396 I wanted most, which was to see the work that 0:10:57.476 --> 0:10:59.076 we did make a difference in the world. 0:10:59.476 --> 0:11:01.596 Were you surprised when they gave up? What was your 0:11:01.636 --> 0:11:02.916 response when they gave up? 0:11:03.916 --> 0:11:05.876 I guess I was sad. I don't know that I 0:11:05.916 --> 0:11:09.596 was surprised. I certainly have seen plenty of places give 0:11:09.676 --> 0:11:12.436 up before, but it made me sad. I really thought 0:11:12.596 --> 0:11:16.636 that this was a way of moving things forward, was 0:11:17.196 --> 0:11:21.436 having companies, you know, take what you published and what 0:11:21.476 --> 0:11:25.436 you did and develop it. But I was mostly sad. 0:11:25.556 --> 0:11:27.596 So how do you get from there to starting your 0:11:27.636 --> 0:11:28.276 first company? 0:11:29.356 --> 0:11:31.876 Yeah? Well, a good friend of mine, Alex kleebman Off, 0:11:31.876 --> 0:11:35.036 he was a professor in that nutrition department lady. He 0:11:35.116 --> 0:11:39.076 was a professor in the chemistry department and mit he 0:11:39.196 --> 0:11:42.276 said to me one day after this happened, he said, well, Bob, 0:11:42.316 --> 0:11:45.596 we should start our own company. So I thought, yeah, 0:11:46.476 --> 0:11:48.716 if you're not your own champion, nobody else is going 0:11:48.756 --> 0:11:52.716 to be. So we did, and I got a number 0:11:52.716 --> 0:11:55.596 of my students to join that company, and they were 0:11:55.676 --> 0:11:59.556 very excited about it, so that that ended up. You know, 0:11:59.596 --> 0:12:01.356 they weren't going to give up very easily. 0:12:02.236 --> 0:12:05.476 And so you keep working on this original idea of 0:12:06.396 --> 0:12:10.356 a particle that can deliver a drug, a large molecule 0:12:10.436 --> 0:12:15.196 drug basically, and when does it become clear to you 0:12:15.276 --> 0:12:16.356 that it's going to work. 0:12:17.516 --> 0:12:20.516 Well, actually, for me, I was pretty clear it was 0:12:20.556 --> 0:12:21.756 going to work when we wrote that. 0:12:21.756 --> 0:12:22.916 Early paper in Nature. 0:12:23.596 --> 0:12:25.876 I mean I thought i'd see it with my own eyes. 0:12:25.956 --> 0:12:28.596 I put certain types of well I'm trying to think, 0:12:28.636 --> 0:12:31.396 I explained. I put certain enzymes. Those are all large 0:12:31.396 --> 0:12:36.516 molecules in these materials, and I had this test that 0:12:36.596 --> 0:12:39.836 would turn color if the enzymes are coming out, and 0:12:40.356 --> 0:12:43.716 I've got to see it not work many many, many times, 0:12:43.836 --> 0:12:46.916 hundreds of times. But finally I did see it work, 0:12:46.956 --> 0:12:51.556 and so I didn't see how this couldn't you know, 0:12:51.596 --> 0:12:53.676 so since I saw it with my own eyes, but 0:12:53.756 --> 0:12:56.356 that didn't mean that other people were going to necessarily 0:12:56.396 --> 0:13:00.356 believe it. But I did, and you know I had 0:13:00.396 --> 0:13:04.436 people still ten fifteen years later tell me couldn't possibly 0:13:04.476 --> 0:13:08.436 be right. I mean, very experienced people. But you know 0:13:08.516 --> 0:13:11.476 that's the world. I mean a lot of times they're skepticism. 0:13:11.916 --> 0:13:14.836 And what was the first drug from that idea that 0:13:15.556 --> 0:13:18.916 made it to the market, that made it to patients. 0:13:19.436 --> 0:13:22.316 You know, we had this collaboration with a company called 0:13:22.356 --> 0:13:26.516 Taketa as a Japanese company, and they had sent people 0:13:26.556 --> 0:13:28.996 to our lab every year and we got a grants 0:13:28.996 --> 0:13:33.236 from them, and they created what's called lupron depot and 0:13:33.316 --> 0:13:39.076 that was that ultimately did get approved and still versions 0:13:39.116 --> 0:13:40.916 of it are widely used today. 0:13:41.356 --> 0:13:43.196 What kind of patients did that treat? What did that 0:13:43.276 --> 0:13:43.676 drug do? 0:13:44.676 --> 0:13:48.316 It was a way to treat advanced prostate cancer and endometriosis. 0:13:48.556 --> 0:13:51.836 And was it the anti angiogenesis? Was it inhibiting the 0:13:51.876 --> 0:13:53.916 formation of blood vessels or was it. 0:13:53.876 --> 0:13:56.676 Something you no, No, it was it was affecting hormones. 0:13:56.756 --> 0:14:01.316 It was a different hormonal thing, the antiogenesis ones that 0:14:01.436 --> 0:14:06.076 there you know, other people used the essays we've developed 0:14:06.076 --> 0:14:08.396 and other things that we did and things that they 0:14:08.436 --> 0:14:12.556 did themselves, and they would ultimately get many drugs approved, 0:14:13.516 --> 0:14:16.116 but it took many, many years. That didn't take place 0:14:16.236 --> 0:14:17.596 till two thousand and four. 0:14:18.236 --> 0:14:22.276 Can you just list off some of the conditions diseases 0:14:22.356 --> 0:14:25.436 that are treated with this, you know, technology, and the 0:14:25.436 --> 0:14:27.396 offshoots of this technology that you came. 0:14:27.316 --> 0:14:31.716 Up with, well, prostate cancer and ametriosis. I mean, there 0:14:31.716 --> 0:14:42.236 are treatments for heart diseases, different eye diseases, schizophrenia, opioid addiction, osteoarthritis, diabetes. 0:14:42.436 --> 0:14:45.156 I mean, I'm sure I'm leaving all out a lot, 0:14:45.916 --> 0:14:46.596 but those are some. 0:14:49.116 --> 0:14:51.796 Still to come on the show. How Robert Langer wound 0:14:51.836 --> 0:15:08.916 up creating forty companies also the research he's excited about today. 0:15:09.196 --> 0:15:13.116 So after you started that one initial company, you wound 0:15:13.156 --> 0:15:16.436 up starting or being a co founder of a lot 0:15:16.516 --> 0:15:18.036 of companies. I don't have the number in front of you. 0:15:18.076 --> 0:15:20.796 It's dozens, the right order of magnitude. 0:15:20.556 --> 0:15:22.756 Yeah, forty forty forty one. 0:15:22.876 --> 0:15:28.796 Yeah, Like, how's that happen? Like? What how'd that happen? Well, 0:15:28.796 --> 0:15:29.956 it's a lot of companies. 0:15:30.396 --> 0:15:32.916 Yeah, but it's over it's over close to a forty 0:15:32.956 --> 0:15:33.596 year period. 0:15:33.796 --> 0:15:36.116 Well a company a year seems like a lot time. 0:15:36.236 --> 0:15:36.596 I don't know. 0:15:36.796 --> 0:15:39.196 Yeah, well, I mean I have a big lab, I 0:15:39.196 --> 0:15:41.716 have a lot of graduate students. Some of the graduate 0:15:41.756 --> 0:15:45.236 students would see what I did and bostocks and they 0:15:45.276 --> 0:15:47.756 wanted to start companies. So we did. I mean, you know, 0:15:47.796 --> 0:15:49.716 we may have done work in the lab for five 0:15:49.796 --> 0:15:51.796 or six years, and then when it got to a 0:15:51.796 --> 0:15:54.636 certain stage, we spun it out and some people with 0:15:54.836 --> 0:16:00.316 other people, colleagues of mine, would see that, you know, 0:16:00.396 --> 0:16:01.956 I had done this, and so they'd come to me 0:16:01.996 --> 0:16:05.196 and talked to me about companies. So I you know, so, yeah, 0:16:05.236 --> 0:16:07.516 we kept doing it. I mean, to me, it's it's 0:16:07.556 --> 0:16:11.476 been a great route for taking discoveries in the academic 0:16:11.556 --> 0:16:15.596 lab and getting them out to the world. You know. 0:16:15.836 --> 0:16:19.996 And as I mentioned, I had a hard time, maybe 0:16:20.076 --> 0:16:23.116 given the stage of the work, to get large companies 0:16:23.956 --> 0:16:27.036 that would do it. So we did it ourselves. 0:16:27.676 --> 0:16:31.836 And when you started your first company, I feel like 0:16:31.876 --> 0:16:36.836 it was much less common for professors to start companies 0:16:36.876 --> 0:16:40.356 than it is now. I'm curious sort of culturally, you know, 0:16:40.676 --> 0:16:44.836 within MIT, within academia, how what was that like? Did 0:16:44.836 --> 0:16:45.556 you get pushback. 0:16:46.596 --> 0:16:49.836 I think anytime money's involved, a lot of people will 0:16:49.836 --> 0:16:53.676 tell you and I think there's jealousy, you know, about it, 0:16:53.716 --> 0:16:56.876 and people feel you shouldn't be spending your time doing that, 0:16:58.796 --> 0:17:02.396 even at an MIT. So yeah, I had I ran 0:17:02.436 --> 0:17:05.796 into problems when people were thinking about me for promotion. 0:17:07.516 --> 0:17:11.356 You know, some one point I had a partial share 0:17:11.476 --> 0:17:15.356 and they took that away from me. So yeah, I 0:17:15.396 --> 0:17:19.996 was discouraging in the beginning. In fact, I'd say when 0:17:20.036 --> 0:17:23.676 I was in the nutrition department, a lot of people, 0:17:23.716 --> 0:17:26.636 some people told me that the drug delivery ideas they 0:17:26.676 --> 0:17:28.556 would never work and I should be looking for a 0:17:28.556 --> 0:17:29.036 new job. 0:17:30.636 --> 0:17:35.796 Do you feel like you have have gained insight into 0:17:35.956 --> 0:17:39.636 what that moment is or particular elements of that moment 0:17:39.676 --> 0:17:44.596 when you take something that is basic research, academic research 0:17:44.596 --> 0:17:46.436 and decide, okay, this is the moment we're going to 0:17:46.476 --> 0:17:48.476 take the leap. We're going to start a company, We're 0:17:48.476 --> 0:17:50.796 going to try and commercialize it. How do you know? 0:17:51.876 --> 0:17:53.516 Well, I don't think you ever know for sure, but 0:17:53.676 --> 0:17:57.196 the kinds of high level rules that I've used are 0:17:57.596 --> 0:18:00.316 generally you have what I'll call is a platform technology, 0:18:00.356 --> 0:18:02.756 meaning it's almost like a plug and play thing. Those 0:18:02.796 --> 0:18:05.396 drug delivery systems are a good example, right, you could 0:18:05.476 --> 0:18:10.636 use it for drug A, drug BA, DRUGSY. Then I 0:18:10.676 --> 0:18:13.596 think the next thing is that you've taken at a 0:18:13.596 --> 0:18:19.236 certain distance. Right, you have maybe animal data. You also 0:18:19.316 --> 0:18:23.196 have a paper and ideally a good journal like say 0:18:23.236 --> 0:18:26.396 Science or Nature. You have a patent or your high 0:18:26.556 --> 0:18:29.956 likelihood of getting a patent because you've advanced a certain distance. 0:18:30.636 --> 0:18:33.356 And usually there are people in my lab that want 0:18:33.396 --> 0:18:37.116 to be involved in it and that we're So those 0:18:37.156 --> 0:18:42.756 are the kinds of things that inform my thinking about 0:18:42.876 --> 0:18:43.356 about it. 0:18:43.996 --> 0:18:49.116 So what is something right now on the basic research 0:18:49.156 --> 0:18:51.476 side that you're excited about. What is a big idea 0:18:51.556 --> 0:18:53.796 that is early that you think holds a lot of promise. 0:18:54.636 --> 0:18:57.796 Well, I think the tissue engineering work we're doing holds 0:18:57.796 --> 0:18:59.996 a lot of promise. I mean an example that we're 0:18:59.996 --> 0:19:03.716 doing is we're working with the Leeway Si who's head 0:19:03.716 --> 0:19:06.756 of MIT's pick Hour Institute, and I have a wonderful 0:19:06.836 --> 0:19:10.156 post doc Alice Stanton. You know, we're actually creating a 0:19:10.156 --> 0:19:13.676 brain on a chip. It's not been published yet, but 0:19:13.756 --> 0:19:18.476 she's been able to convert you know, like say we 0:19:18.516 --> 0:19:21.836 could take your cells and convert it first ips cells 0:19:21.876 --> 0:19:24.636 and then convert each of those, depending on what we do, 0:19:24.676 --> 0:19:27.436 to a different brain cell type, six different cell types. 0:19:27.476 --> 0:19:29.996 She's found a matrix that she can put them on 0:19:30.036 --> 0:19:35.036 and that really makes them grow and function. And you know, 0:19:35.396 --> 0:19:38.076 so that's that's something I'm excited about. 0:19:38.276 --> 0:19:41.556 And what when you say put it on a chip, 0:19:41.596 --> 0:19:43.036 what does that mean? And then what do you do 0:19:43.156 --> 0:19:44.436 with my brain on a chip? 0:19:44.836 --> 0:19:47.596 Yeah? Well, what I mean by in a chip, it's 0:19:47.676 --> 0:19:49.876 in vitro. It's not in an animal, it's not in 0:19:49.916 --> 0:19:53.716 a person. What it means is that you could rather 0:19:53.876 --> 0:19:55.196 like you could think about if you were going to 0:19:55.316 --> 0:19:57.796 experiment on a person. I mean, of course there's a 0:19:57.836 --> 0:20:00.076 lot you wouldn't be able to find out anyhow because 0:20:00.116 --> 0:20:02.516 we'd have to take you apart, and we're obviously not 0:20:02.556 --> 0:20:03.076 going to do that. 0:20:03.076 --> 0:20:03.836 I appreciate that. 0:20:03.996 --> 0:20:07.236 Yeah, And with animals, you know, it's a little bit 0:20:07.236 --> 0:20:11.876 similar here. So what you do with it is you 0:20:11.916 --> 0:20:16.716 could literally test thousands and thousands of two thousands and 0:20:16.756 --> 0:20:20.316 thousands of experiments and get readouts on them. So it 0:20:20.396 --> 0:20:25.316 might someday reduce animal testing, hopefully also reduce human testing, 0:20:25.876 --> 0:20:28.796 and may greatly speed up drug discovery. I mean there's 0:20:28.796 --> 0:20:31.196 so many drugs that you'd like to be able to 0:20:31.196 --> 0:20:34.076 have for brain disease, right, like for Alzheimer's, for Luke 0:20:34.076 --> 0:20:37.436 Grigg's disease, als for Parkinson's. So I hope. 0:20:37.516 --> 0:20:41.436 So brain disease has been famously difficult to treat with drugs, right. 0:20:41.476 --> 0:20:45.716 It's a very very hard set of diseases, right because. 0:20:45.476 --> 0:20:47.956 We don't understand it well enough and the tests are 0:20:48.076 --> 0:20:51.676 very very hard to do. So something like this, if 0:20:51.716 --> 0:20:55.156 it truly ends up working well, you know, could change 0:20:55.156 --> 0:20:58.676 that someday. But that's an example of something I'm excited 0:20:58.716 --> 0:20:59.476 about as you. 0:20:59.636 --> 0:21:02.236 As you said, it's like it's a platform, right, Presumably 0:21:02.236 --> 0:21:04.316 if you could do brain cells, you could do different 0:21:04.396 --> 0:21:06.236 kinds of cells. It could be a way to do 0:21:06.316 --> 0:21:07.116 lots of testing. 0:21:07.636 --> 0:21:10.556 Well, we've done, yeah, we've put in this case we 0:21:10.596 --> 0:21:13.956 have six different brain cell types in vitro. We have 0:21:14.636 --> 0:21:16.996 our working on other cell types too. We have a 0:21:17.036 --> 0:21:19.596 guest or intestinal track on a chip. We've had a 0:21:19.596 --> 0:21:22.236 heart on a chip. And of course it's not just 0:21:22.276 --> 0:21:24.916 putting them on chip. Someday you could use it for 0:21:25.276 --> 0:21:28.716 repairing tissues, you know, you could maybe, I mean, in fact, 0:21:28.996 --> 0:21:31.996 Laura Nicholson, one of my former postdocs. She runs a 0:21:31.996 --> 0:21:35.436 company that's making new blood vessels that's been used on 0:21:35.796 --> 0:21:39.876 patients in the Ukraine. Others have used made artificial skin 0:21:39.996 --> 0:21:43.316 for burn victims or patients with diabetic skin ulcers, and 0:21:43.396 --> 0:21:46.316 people are trying to make new cartilage, all kinds of tissues. 0:21:46.596 --> 0:21:50.356 So yeah, so that is a big you know, that's 0:21:50.356 --> 0:21:51.556 an exciting area. 0:21:51.916 --> 0:21:54.396 And that tissue engineering side. I mean, does that go 0:21:54.556 --> 0:21:57.756 back to a kind of similar origin story, right, I 0:21:57.796 --> 0:22:00.316 know there was sort of early tissue engineering work that 0:22:00.356 --> 0:22:02.036 you did as well. What was that work? 0:22:02.516 --> 0:22:04.956 Yeah, well they are. One of the people I got 0:22:04.956 --> 0:22:07.476 to meet at Children's Hospital is Jay Vacanti. He was 0:22:07.516 --> 0:22:11.756 a pediatric surgeon is and he was treating patients with 0:22:11.836 --> 0:22:14.716 liver failure and one day he came to see me said, Bob, 0:22:15.276 --> 0:22:18.436 you know I do all these transplants, would it ever 0:22:18.516 --> 0:22:20.996 be possible to make a liver from scratch? And he 0:22:21.036 --> 0:22:24.836 and I brainstorm and came up with a way that 0:22:24.956 --> 0:22:30.516 we hope might do that with polymer scaffolds and cells. 0:22:31.116 --> 0:22:34.876 And so we've continued on working together and separately in 0:22:34.956 --> 0:22:40.716 different ways to make this happen. But that started probably 0:22:40.716 --> 0:22:44.196 over forty years ago, and that certainly was the basis 0:22:44.196 --> 0:22:45.236 for a lot of these things. 0:22:45.476 --> 0:22:48.876 So we can't synthesize livers yet. But what are some 0:22:48.956 --> 0:22:51.836 of the clinical applications that have been found to some 0:22:51.916 --> 0:22:53.196 of the research you did there? 0:22:53.436 --> 0:22:56.796 Well, you can make artificial skin for burn victims. You 0:22:57.276 --> 0:22:59.836 looks like we'll be able to make blood vessels. I 0:22:59.836 --> 0:23:02.756 mean there have been clinical trials on a variety of things, 0:23:02.916 --> 0:23:08.196 ranging from new spinal cord, repaired hearing loss, you know, 0:23:08.356 --> 0:23:11.996 a lot of different things. But I think ultimately it's unlimited. 0:23:12.316 --> 0:23:15.876