How to Start 40 Companies (and Counting)

Published May 16, 2024, 4:30 AM

Robert Langer has co-founded dozens of companies, holds over a thousand patents, and is a pioneering figure in drug delivery and tissue engineering. Robert has solved a lot of problems, and is working on many more with his lab at MIT. But there is one big problem that has stuck with Robert his whole career: How do you get discoveries out of the lab and into the world?

Pushkin. You want to start listing off the companies of which you're a founder and a co founder and stop wherever you get tired.

I mean I can try to do that, but that might take some time.

Give me a handful. Count count off five on your fingers, just for sure.

Sure, well, Maderna Momenta PureTech Seer, living Proof.

For a second thought, you were just going to do the MS, which might have been.

A while I could, I could do with the aged.

Robert Langer has founded or co founded something like forty companies. He is an institute professor at MIT. He holds over a thousand patents, and his research has been cited more than four hundred thousand times. But when he started his career in the nineteen seventies, he didn't see bound for professional glory. He had a hard time finding a job, he couldn't get funding for his research, and his patent applications kept getting rejected. And I think these two things, his early struggles and his later massive success are in fact closely connected. Langer was trying to do something that was deeply and profoundly different than what anybody had done before. Almost nobody understood it. Almost nobody knew what to do with him, and then when his work finally did succeed, it was such a new, powerful discovery that people are still building on it today half a century later. I'm Jacob Goldstein and this is What's Your Problem, the show where I talk to people who are trying to make technological progress. Robert Langer is still working, still doing research, still founding companies, and we talked about some of his current work in the later part of our conversation. But to start, we went back to the mid nineteen seventies when Langer got his doctorate in chemical engineering and he did something that at the time was really unusual. He did a postdoc with a medical school professor, a pediatric surgeon named Judah Folkman. Langer's field is bioengineering, basically bringing the tools of engineering to the fields of biology and medicine. And bioengineering is a huge field today, but it barely existed back when Langer started his postdoc with that doctor, Judah Folkman, and bioengineering was exactly what Judah Foalkman needed. Folkman had an idea for a new kind of drug, and this kind of drug was a molecule that was too big and complex to be given as a pill. So Folkman needed somebody who could figure out how to deliver this new kind of drug to patience. As you'll hear, that delivery problem was fundamentally an engineering problem, and when Langer solved that problem, he created an entirely new way to get medicine to patients, and it proved incredibly useful. Tell me about being an engineer and going off to work in the nineteen seventies in the lab of a physician.

On the one hand, for me, it was very hard because I had to learn a lot about medical things and I didn't know very much biology, so that was that was difficult. But on the other hand, being an engineer, I guess I had a different perspective, you know that I didn't maybe think the same way as a clinician or surgeon or a biologist. You know, engineers they solve problems, and that Judah Falkman, who was my boss at the time, I mean, that's what he wanted. He wanted to see a problem solved.

So let's talk specifically about that problem. What did you what did you go to doctor Falkman's lab to work on.

Doctor Fokeland had this idea that if you could stop blood vessels, you could stop cancer. It wasn't most people didn't think he was right. In fact, he went further. He said that the reason blood vessels come to the tumor is that the tumor makes a chemical signal he called the tumor antigenesis factor, and he said that was chemically mediated. And also the idea that he thought about is if that was chemically mediated, maybe stopping it could also be chemically mediated. So my job really, in a way was to prove that he was right, because almost everybody told him he was wrong, and in so doing isolate the first you know, blood vessel or antiogenesis inhibitor, uh huh.

And so it's basically that there is this theory that he had that tumors stimulate the growth of new blood vessels, and then if that's true, perhaps you could inhibit the growth of new blood vessels thereby inhibit the growth of tumors. Right, And so you get there, and I'm interested in that inhibition piece, right, because that seems like that's where you're really, in a very direct way, bringing your engineering skills to bear on this medical problem. So, like, talk about that side of it and how you approached it.

So what we wanted to do was have a little nanoparticle or microparticle that could deliver different molecules I was isolating, and these were fairly large molecules, so that was really the idea, and then see could it stop the blood vessels?

So this core idea of developing a nanoparticle to deliver a large molecule basically a complicated drug, is an engineering problem, right, this nanopart of It's like, we've got this this drug call it that we think might be able to stop tumor growth, but how do we get it to the tumor? Right? That is a basic problem that you were coming up against early in your research, and that that problem winds up being a big deal, right, and the way you go about solving that problem winds up being a big deal. So tell me about that.

Well, the nanoparticles and microparticles, really it's taking molecules drugs, encapsulating, surrounding them with a lipid or polymer, and delivering it to sells or a patient or an animal.

And a lipid or a polymer is basically some fat or some plastic.

Yeah, yeah, lipid is some fat and polymer some plastic. Generally speaking, So, yeah, if you escape the drug by itself and it wasn't packaged in those particles, it would just get destroyed. I mean, so the number one reason you do it is to protect it, you know, otherwise it won't you know, they'll just get destroyed, probably almost immediately. So you know, we ask people who are experts in that area, know about price winners and others who had done work or at least helped on delivery of small molecules, and we asked them about that, but they all told us it wasn't possible. So I spent years in the laboratory experimenting, finding hundreds of different ways, failing hundreds at different times, but finally I was successful. And you know, we published a paper in Nature in nineteen seventy six, the General Nature, and showed for the first time that you could deliver large molecules this way. And we published a paper in Science in nineteen seventy six showing for the first time that you could stop blood vessels by using approaches like this.

And as I understand it, even after you published those papers, you met a lot of resistance.

Yeah I did. I suppose I met a lot of resistance for a couple of ways. First, different people didn't agree with it or didn't believe it or didn't think it was possible. Secondly, my background really wasn't right. I suppose for the different review sections, I was an engineer, and when we sent the grants to the National Insituites of Health in places like that, you know, they had medical people or biological people reviewing it, and they said, well, what can an engineer, You know, he doesn't know anything about biology or oncology. Separately, I met a lot of resistance when I tried to do this get a job in an engineering department. They said, well, engineers a chemical engineering department, They said, engineers really don't do experimental biology. So I didn't get any faculty positions in a chemical engineering department for a very very long time. I ended up in an fishing department.

And so, I mean, this idea of bioengineering that is a big deal now and was very novel. Then it feels like you're sort of coming up against this problem of creating a field that doesn't quite exist yet, or at least creating a part of a field that doesn't exist yet, which seems like, on the one hand, the opportunity to solve very large problems was clearly there. On the other hand, the kind of institutional structure to allow that to happen was was not on your side.

Yeah, you're right. I mean, Ei there had been people in chemical engineering doing work on what i'd call mathematical modeling, you know, transport of molecules, but experimental stuff, inventing things. Yeah, that and discovering you know, new molecules that certainly had not been done, never been done in chemical engineering up till that time. So so that ended up being hard.

Is it right that some of your early patent applications around this technology were also rejected?

Yeah they were. I mean the first the main patent on it got rejected five times in a row. But you know, sometimes that happens. I'vet after that. I think I had one when we came up with the idea of tissue engineering. I think that got rejected even more. So those things happen.

And so you get the patents and you end up licensing the technology initially to one or more big big companies, right, big pharmaceutical company. What happens with that?

Yeah, well, actually the hospital did that the license because I mean, the past is my name, but they licensed it, you know. I well, I was very excited about that. There were two multi billion dollar companies won an animal health one in human health. You know, So they they gave me a consulting fee. They gave me actually a very large grant, which for young professors, you know, terrific. Most importantly, they were going to work on it, and they did work on it for maybe up to a year, but then they just gave up. So I got the grant and the consulting fee, but I didn't get what I wanted most, which was to see the work that we did make a difference in the world.

Were you surprised when they gave up? What was your response when they gave up?

I guess I was sad. I don't know that I was surprised. I certainly have seen plenty of places give up before, but it made me sad. I really thought that this was a way of moving things forward, was having companies, you know, take what you published and what you did and develop it. But I was mostly sad.

So how do you get from there to starting your first company?

Yeah? Well, a good friend of mine, Alex kleebman Off, he was a professor in that nutrition department lady. He was a professor in the chemistry department and mit he said to me one day after this happened, he said, well, Bob, we should start our own company. So I thought, yeah, if you're not your own champion, nobody else is going to be. So we did, and I got a number of my students to join that company, and they were very excited about it, so that that ended up. You know, they weren't going to give up very easily.

And so you keep working on this original idea of a particle that can deliver a drug, a large molecule drug basically, and when does it become clear to you that it's going to work.

Well, actually, for me, I was pretty clear it was going to work when we wrote that.

Early paper in Nature.

I mean I thought i'd see it with my own eyes. I put certain types of well I'm trying to think, I explained. I put certain enzymes. Those are all large molecules in these materials, and I had this test that would turn color if the enzymes are coming out, and I've got to see it not work many many, many times, hundreds of times. But finally I did see it work, and so I didn't see how this couldn't you know, so since I saw it with my own eyes, but that didn't mean that other people were going to necessarily believe it. But I did, and you know I had people still ten fifteen years later tell me couldn't possibly be right. I mean, very experienced people. But you know that's the world. I mean a lot of times they're skepticism.

And what was the first drug from that idea that made it to the market, that made it to patients.

You know, we had this collaboration with a company called Taketa as a Japanese company, and they had sent people to our lab every year and we got a grants from them, and they created what's called lupron depot and that was that ultimately did get approved and still versions of it are widely used today.

What kind of patients did that treat? What did that drug do?

It was a way to treat advanced prostate cancer and endometriosis.

And was it the anti angiogenesis? Was it inhibiting the formation of blood vessels or was it.

Something you no, No, it was it was affecting hormones. It was a different hormonal thing, the antiogenesis ones that there you know, other people used the essays we've developed and other things that we did and things that they did themselves, and they would ultimately get many drugs approved, but it took many, many years. That didn't take place till two thousand and four.

Can you just list off some of the conditions diseases that are treated with this, you know, technology, and the offshoots of this technology that you came.

Up with, well, prostate cancer and ametriosis. I mean, there are treatments for heart diseases, different eye diseases, schizophrenia, opioid addiction, osteoarthritis, diabetes. I mean, I'm sure I'm leaving all out a lot, but those are some.

Still to come on the show. How Robert Langer wound up creating forty companies also the research he's excited about today. So after you started that one initial company, you wound up starting or being a co founder of a lot of companies. I don't have the number in front of you. It's dozens, the right order of magnitude.

Yeah, forty forty forty one.

Yeah, Like, how's that happen? Like? What how'd that happen? Well, it's a lot of companies.

Yeah, but it's over it's over close to a forty year period.

Well a company a year seems like a lot time. I don't know.

Yeah, well, I mean I have a big lab, I have a lot of graduate students. Some of the graduate students would see what I did and bostocks and they wanted to start companies. So we did. I mean, you know, we may have done work in the lab for five or six years, and then when it got to a certain stage, we spun it out and some people with other people, colleagues of mine, would see that, you know, I had done this, and so they'd come to me and talked to me about companies. So I you know, so, yeah, we kept doing it. I mean, to me, it's it's been a great route for taking discoveries in the academic lab and getting them out to the world. You know. And as I mentioned, I had a hard time, maybe given the stage of the work, to get large companies that would do it. So we did it ourselves.

And when you started your first company, I feel like it was much less common for professors to start companies than it is now. I'm curious sort of culturally, you know, within MIT, within academia, how what was that like? Did you get pushback.

I think anytime money's involved, a lot of people will tell you and I think there's jealousy, you know, about it, and people feel you shouldn't be spending your time doing that, even at an MIT. So yeah, I had I ran into problems when people were thinking about me for promotion. You know, some one point I had a partial share and they took that away from me. So yeah, I was discouraging in the beginning. In fact, I'd say when I was in the nutrition department, a lot of people, some people told me that the drug delivery ideas they would never work and I should be looking for a new job.

Do you feel like you have have gained insight into what that moment is or particular elements of that moment when you take something that is basic research, academic research and decide, okay, this is the moment we're going to take the leap. We're going to start a company, We're going to try and commercialize it. How do you know?

Well, I don't think you ever know for sure, but the kinds of high level rules that I've used are generally you have what I'll call is a platform technology, meaning it's almost like a plug and play thing. Those drug delivery systems are a good example, right, you could use it for drug A, drug BA, DRUGSY. Then I think the next thing is that you've taken at a certain distance. Right, you have maybe animal data. You also have a paper and ideally a good journal like say Science or Nature. You have a patent or your high likelihood of getting a patent because you've advanced a certain distance. And usually there are people in my lab that want to be involved in it and that we're So those are the kinds of things that inform my thinking about about it.

So what is something right now on the basic research side that you're excited about. What is a big idea that is early that you think holds a lot of promise.

Well, I think the tissue engineering work we're doing holds a lot of promise. I mean an example that we're doing is we're working with the Leeway Si who's head of MIT's pick Hour Institute, and I have a wonderful post doc Alice Stanton. You know, we're actually creating a brain on a chip. It's not been published yet, but she's been able to convert you know, like say we could take your cells and convert it first ips cells and then convert each of those, depending on what we do, to a different brain cell type, six different cell types. She's found a matrix that she can put them on and that really makes them grow and function. And you know, so that's that's something I'm excited about.

And what when you say put it on a chip, what does that mean? And then what do you do with my brain on a chip?

Yeah? Well, what I mean by in a chip, it's in vitro. It's not in an animal, it's not in a person. What it means is that you could rather like you could think about if you were going to experiment on a person. I mean, of course there's a lot you wouldn't be able to find out anyhow because we'd have to take you apart, and we're obviously not going to do that.

I appreciate that.

Yeah, And with animals, you know, it's a little bit similar here. So what you do with it is you could literally test thousands and thousands of two thousands and thousands of experiments and get readouts on them. So it might someday reduce animal testing, hopefully also reduce human testing, and may greatly speed up drug discovery. I mean there's so many drugs that you'd like to be able to have for brain disease, right, like for Alzheimer's, for Luke Grigg's disease, als for Parkinson's. So I hope.

So brain disease has been famously difficult to treat with drugs, right. It's a very very hard set of diseases, right because.

We don't understand it well enough and the tests are very very hard to do. So something like this, if it truly ends up working well, you know, could change that someday. But that's an example of something I'm excited about as you.

As you said, it's like it's a platform, right, Presumably if you could do brain cells, you could do different kinds of cells. It could be a way to do lots of testing.

Well, we've done, yeah, we've put in this case we have six different brain cell types in vitro. We have our working on other cell types too. We have a guest or intestinal track on a chip. We've had a heart on a chip. And of course it's not just putting them on chip. Someday you could use it for repairing tissues, you know, you could maybe, I mean, in fact, Laura Nicholson, one of my former postdocs. She runs a company that's making new blood vessels that's been used on patients in the Ukraine. Others have used made artificial skin for burn victims or patients with diabetic skin ulcers, and people are trying to make new cartilage, all kinds of tissues. So yeah, so that is a big you know, that's an exciting area.

And that tissue engineering side. I mean, does that go back to a kind of similar origin story, right, I know there was sort of early tissue engineering work that you did as well. What was that work?

Yeah, well they are. One of the people I got to meet at Children's Hospital is Jay Vacanti. He was a pediatric surgeon is and he was treating patients with liver failure and one day he came to see me said, Bob, you know I do all these transplants, would it ever be possible to make a liver from scratch? And he and I brainstorm and came up with a way that we hope might do that with polymer scaffolds and cells. And so we've continued on working together and separately in different ways to make this happen. But that started probably over forty years ago, and that certainly was the basis for a lot of these things.

So we can't synthesize livers yet. But what are some of the clinical applications that have been found to some of the research you did there?

Well, you can make artificial skin for burn victims. You looks like we'll be able to make blood vessels. I mean there have been clinical trials on a variety of things, ranging from new spinal cord, repaired hearing loss, you know, a lot of different things. But I think ultimately it's unlimited. You know, you could theoretically use approaches like this if you understand the right cells, the right signals, the right biology, and the right engineering. I don't see that there's necessarily any limit to what you could use it for, but people, we need to understand it more.

We'll be back in a minute with the Lightning Round. M M. I want to finish. We're almost done. I appreciate your time. I want to finish with the Lightning Round, which is just some quicker, kind of more random show, maybe occasionally silly questions. Who is one engineer from history who you wish more people knew about?

Boy? Well, I suppose a lot of people don't realize maybe that Leonardo da Vinci was a very good engineer.

Good What are some of your favorite engineering work of Leonardo's?

Well, I mean he did all kinds of things. He looked at at hearts, he looked at at you know, you know, waterflow. I mean he did he did a lot, not just art.

Who is the best teacher you ever had?

Maybe George Sieli at Cornell?

What about him made him such a good teacher?

Well, first, he cared a lot and he explained things. Well, but I think caring a lot that that means a lot.

But you're also a magician, and I'm curious if there are any skills from close up magic that have been helpful to you in your day job.

You know, the one thing that does make a difference with magic is presentation. So you know, if you give if so what I learned in magic. If I make a mistake, sometimes of course you make it deliberately. But if I made an mistake, you know, it's part of the show. You don't get upset, You just you know, you just you just go with the flow. And what I'd say is if I made a mistake from the talk, same thing. You know, it's like you don't get flustered. You just say you just keep going, and that does make a difference.

So your research also helped to create, as I understand it, a line of hair care products called living Proof. Jennifer Aniston, who I will say had great hair before the company started, is involved in that company, And so I'm curious, what's your favorite living Proof product? And are you using it right now?

Well, so I would say, you know, one of the living Proof products is called PhD and stands for Perfect hair Day.

Oh, Perfect hair Day? Okay, are you using it right now? So?

I use a shampoos okay, but gee, my wife and my daughter and lots of people use lots of the products. But I basically use it in the shampoo every so often when my hair gets longer, I have, you know, just a spray that I put on that doesn't make it frize up so much.

Great. Is there anything else you think we should talk about?

Well, the only other thing I'd say that we've done that we really didn't touch on is you know, we're doing a lot of work with the Gates Foundation to help the developing world, you know, and I'm excited about that as well. I mean, they've been a big supporter of our lab and he's done a terrific job in terms of helping and it's I think the work is leading to new kinds of nutrition, new kinds of oral delivery that could last much longer than just a day can lead. It's also leading to what we call self boosting injections, so you wouldn't have to come back for a second shot. So I think it's leading to a lot of things that I hope will someday help a lot of people, whether you not only in the developing world, but everyone in the world period.

Of those technologies that you just listed, is any one of them, particularly you know, farther along in development.

Well, several of them are already. I mean the pills that you can swallow orally are in that lasts for a week or a month. They're in phase three clinical trials. There's a company Lindra that Geotraverso and I have start that's probably the most advanced.

Is that for anti malarials or what is the first application there?

The most advanced application of schizophrenias and phase three trial It is in clinical trials from malaria too. Okay, but that's like at phase one.

So Presumably that would be a big deal because drug adherence is always a problem. People very often don't take their drugs. Presumably people who are mentally ill might have more trouble with adherents. So if you could have a pill once a week instead of every day, that would be a very large.

Impress Yeah, and also once a month. You know, we've been working onto you know, like a once a mo on birth control pill and yeah, so all those things, do you know, things moving forward.

Robert Langer is an institute professor at MIT. Today's show was produced by Gabriel Hunter Chang. It was edited by Lyddy Jean Kott and engineered by Sarah Bruguer. You can email us at problem at Pushkin dot fm. I'm Jacob Goldstein and we'll be back next week with another episode of What's Your Problem.

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