Robert Langer: Edison of Medicine #105

Transcript

00:00:00 The following is a conversation with Bob Langer, professor at

00:00:03 MIT, and one of the most cited researchers in history,

00:00:07 specializing in biotechnology fields of drug delivery systems

00:00:11 and tissue engineering. He has bridged theory and practice by

00:00:15 being a key member and driving force in launching many

00:00:19 successful biotech companies out of MIT. This conversation was

00:00:23 recorded before the outbreak of the coronavirus pandemic. His

00:00:27 research and companies are at the forefront of developing

00:00:30 treatment for COVID 19, including a promising vaccine

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00:03:01 podcast. And now here’s my conversation with Bob Langer.

00:03:07 You have a bit of a love for magic. Do you see a connection

00:03:10 between magic and science?

00:03:12 I do. I think magic can surprise you. And, uh, you know, and I

00:03:17 think science can surprise you. And there’s something magical

00:03:20 about, about science. I mean, making discoveries and things

00:03:23 like that. Yeah. So on the, and then on the magic side, is

00:03:26 there some kind of engineering scientific process to the tricks

00:03:30 themselves? Do you see, cause there’s a duality to it. One is

00:03:34 you’re the, um, you’re, you’re sort of the person inside that

00:03:39 knows how the whole thing works, how the universe of the magic

00:03:42 trick works. And then from the outside observer, which is kind

00:03:45 of the role of the scientists, you, the people that observe

00:03:49 the magic trick don’t know at least initially anything that’s

00:03:52 going on. Do you see that kind of duality?

00:03:55 Well, I think the duality that I see is fascination. You know,

00:03:58 I think of it, you know, when I watch magic myself, I’m always

00:04:03 fascinated by it. Sometimes it’s a puzzle to think how it’s done,

00:04:06 but just the sheer fact that something that you never thought

00:04:09 could happen does happen. And I think about that in science too,

00:04:13 you know, sometimes you, it’s something that, that you might

00:04:17 dream about and hoping to discover, maybe you do in some

00:04:21 way or form.

00:04:22 What is the most amazing magic trick you’ve ever seen?

00:04:26 Well, there’s one I like, which is called the invisible pack.

00:04:30 And the way it works is you have this pack and you hold it up.

00:04:35 Well, first you say to somebody, this is invisible and this deck

00:04:40 and you say, well, shuffle it. They shuffle it, but you know,

00:04:43 they’re sort of make believe. And then you say, okay, I’d like

00:04:46 you to pick a card, any card and show it to me. And you show it

00:04:50 to me and I look at it. And let’s say it’s the three of

00:04:55 hearts. I said, we’ll put it back in the deck. But what I’d

00:04:57 like you to do is turn it up upside down from every other

00:05:00 card in the deck. So they do that imaginary. And I say,

00:05:04 do you want to shuffle it again? And they shuffle it. And I said,

00:05:07 well, so there’s still one card upside down from every other

00:05:10 card in the deck. I said, what is that? And they said, well,

00:05:12 three hearts. So what just so happens in my back pocket, I

00:05:15 have this deck, it’s, you know, it’s a real deck. I show it to

00:05:18 you and I just open it up. And there’s just one card upside

00:05:22 down. And it’s the three of hearts.

00:05:27 And, and you can do this trick.

00:05:30 I can, if I don’t, I would have probably brought it.

00:05:33 All right. Well, beautiful. Let’s get into the, into the

00:05:37 science. As of today, you have over 295,000 citations. An H

00:05:43 index of 269. You’re one of the most cited people in history and

00:05:47 the most cited engineer in history. And yet nothing great,

00:05:53 I think is ever achieved without failure. So the interesting

00:05:57 part, what rejected papers, ideas, efforts in your life or

00:06:01 most painful, or had the biggest impact on your life?

00:06:04 Well, it’s interesting. I mean, I’ve had plenty of rejection too,

00:06:07 you know, but I suppose one way I think about this is that when

00:06:11 I first started, and this certainly had an impact both

00:06:14 ways, you know, I first started, we made two big discoveries and

00:06:19 they were kind of interrelated. I mean, one was, I was trying to

00:06:22 isolate with my postdoctoral advisor, Judah Folkman,

00:06:25 substances that could stop blood vessels from growing and nobody

00:06:29 had done that before. And so that was part A, let’s say part B

00:06:35 is we had to develop a way to study that. And what was

00:06:38 critical to study that was to have a way to slowly release

00:06:42 those substances for, you know, more than a day, you know, maybe

00:06:47 months. And that had never been done before either. So we

00:06:50 published the first one we sent to Nature, the journal, and they

00:06:55 rejected it. And then we sent it, we revised it, we sent it to

00:06:59 Science and they accepted it. And the other, the opposite

00:07:04 happened, we sent it to Science and they rejected it. And then

00:07:06 we sent it to Nature and they accepted it. But I have to tell

00:07:10 you, when we got the rejections, it was really upsetting. I

00:07:12 thought, you know, I’d done some really good work. And Dr.

00:07:15 Folkman thought we’d done some really good work. And, and, but

00:07:19 it was very depressing to, you know, get rejected like that.

00:07:24 If you can linger on just the feeling or the thought process

00:07:27 when you get the rejection, especially early on in your

00:07:30 career, what, I mean, you don’t know, now people know you as a

00:07:39 brilliant scientist, but at the time, I’m sure you’re full of

00:07:42 self doubt. And did you believe that maybe this idea is actually

00:07:48 quite terrible, that it could have been done much better? Or

00:07:51 is there underlying confidence? What was the feelings?

00:07:54 Well, you feel depressed and I felt the same way when I got

00:07:58 grants rejected, which I did a lot in the beginning. I guess

00:08:02 part of me, you know, you have multiple emotions. One is being

00:08:07 sad and being upset and also being maybe a little bit angry

00:08:11 because you didn’t feel the reviewers didn’t get it. But

00:08:14 then as I thought about it more, I thought, well, maybe I just

00:08:17 didn’t explain it well enough. And you know, that, you know,

00:08:20 that you go through stages. And so you say, well, okay, I’ll

00:08:24 explain it better next time. And certainly you get reviews and

00:08:26 when you get the reviews, you see what they either didn’t like

00:08:29 or didn’t understand. And then you try to incorporate that into

00:08:32 your next versions.

00:08:34 You’ve given advice to students to do something big, do

00:08:37 something that really can change the world rather than something

00:08:40 incremental. How did you yourself seek out such ideas? Is

00:08:45 there a process? Is there a sort of a rigorous process? Or is it

00:08:49 more spontaneous?

00:08:51 It’s more spontaneous. I mean, part of its exposure to things,

00:08:55 part of its seeing other people, like I mentioned, Dr. Folkman,

00:08:58 he was my postdoctoral advisor, he was very good at that, you

00:09:02 could sort of see that he had big ideas. And I certainly met a

00:09:05 lot of people who didn’t. And I think you could spot an idea

00:09:08 that might have potential when you see it, you know, because it

00:09:11 could have very broad implications, whereas a lot of

00:09:14 people might just keep doing derivative stuff. And so I

00:09:19 don’t know. But it’s not something that I’ve ever done.

00:09:24 Systematically, I don’t think.

00:09:26 So in the space of ideas, how many are just when you see them?

00:09:31 It’s just magic. It’s something that you see that could be

00:09:34 impactful if you dig deeper.

00:09:38 Yeah, it’s sort of hard to say because there’s multiple levels

00:09:42 of ideas. One type of thing is like a new, you know, creation

00:09:49 that you could engineer tissues for the first time or make

00:09:51 dishes from scratch on the first time. But another thing is

00:09:54 really just deeply understanding something. And that’s important

00:09:58 too. So and that may lead to other things. So sometimes you

00:10:04 could think of a new technology, or I thought of a new

00:10:07 technology. But other times, things came from just the

00:10:11 process of trying to discover things. So it’s never and you

00:10:15 don’t necessarily know, like people talk about aha moments,

00:10:19 but I don’t know if I’ve, I mean, I certainly feel like I’ve

00:10:23 had some ideas that I really like. But it’s taken me a long

00:10:27 time to go from the thought process of starting it to all of

00:10:32 a sudden, knowing that it might work.

00:10:35 So if you take drug delivery, for example, is the notion is

00:10:39 the initial notion, kind of a very general one, that we should

00:10:43 be able to do something like this. And then you start to ask

00:10:48 the questions of Well, how would you do it and then and then

00:10:51 digging and digging and digging?

00:10:52 I think that’s right. I think it depends. I mean, there are

00:10:54 many different examples. The example I gave about delivering

00:10:58 large molecules, which we used to study these blood vessel

00:11:01 inhibitors. I mean, there, we had to invent something that

00:11:05 would do that. But other times, it’s, it’s, it’s different.

00:11:10 Sometimes it’s really understanding what goes on in

00:11:13 terms of understanding the mechanisms. And so it’s, it’s,

00:11:16 it’s not a single thing. And there are many different parts

00:11:19 to it, you know, over the years, we’ve invented different or

00:11:23 discovered different principles for aerosols for delivering,

00:11:27 you know, genetic therapy agents, you know, all kinds of

00:11:30 things.

00:11:31 So let’s explore some of the key ideas you’ve touched on in your

00:11:34 life. Let’s start with the basics. Okay. So first, let me

00:11:39 ask, how complicated is the biology and chemistry of the

00:11:42 human body from the perspective of trying to affect some parts

00:11:46 of it in a positive way? So that you know, for me, especially

00:11:50 coming from the field of computer science and computer

00:11:54 engineering and robotics, it seems that the human body is

00:11:57 exceptionally complicated, and how the heck you can figure out

00:12:00 anything is amazing.

00:12:02 I agree with you. I think it’s super complicated. I mean,

00:12:05 we’re still just scratching the surface in many ways. But I feel

00:12:08 like we have made progress in different ways. And some of its

00:12:12 by really understanding things like we were just talking about

00:12:16 other times, you know, you might, or somebody might we or

00:12:19 others might invent technologies that might be helpful on

00:12:23 exploring that. And I think over many years, we’ve understood

00:12:26 things better and better, but we still have such a long ways to

00:12:29 go.

00:12:29 Are there? I mean, if you just look at the other things that

00:12:35 are there knobs that are reliably controllable about the

00:12:39 human body, if you consider is there is it? So if you start to

00:12:46 think about controlling various aspects of when we talk about

00:12:49 drug delivery a little bit, but controlling various aspects

00:12:54 chemically of the human body, is there a solid understanding

00:12:57 across the populations of humans that are solid, reliable knobs

00:13:02 that can be controlled?

00:13:03 I think that’s hard to do. But on the other hand, whenever we

00:13:06 make a new drug or medical device, to a certain extent,

00:13:09 we’re doing that, you know, in a small way, what you just said,

00:13:12 but I don’t know that there are great knobs. I mean, and we’re

00:13:16 learning about those knobs all the time. But if there’s a

00:13:20 biological pathway or something that you can affect, or

00:13:23 understand, I mean, then that might be such a knob.

00:13:27 So what is a pharmaceutical drug? How do you do? How do you

00:13:31 discover a specific one? How do you test it? How do you

00:13:34 understand it? How do you ship it?

00:13:36 Yeah, well, I’ll give an example, which goes back to

00:13:40 what I said before. So when I was doing my postdoctoral work

00:13:43 with Judah Folkman, we wanted to come up with drugs that would

00:13:46 stop blood vessels from growing or alternatively make them grow.

00:13:50 And actually, people didn’t even believe that, that those things

00:13:54 could happen. But

00:13:56 could we pause on that for a second? Sure. What is a blood

00:13:58 vessel? What does it mean for a blood vessel to grow and shrink?

00:14:01 And why is that important?

00:14:03 Sure. So a blood vessel is could be an artery or vein or a

00:14:08 capillary. And it, you know, provides oxygen, it provides

00:14:14 nutrients gets rid of waste. So, you know, to different parts of

00:14:19 your body if you so so the blood vessels end up being very, very

00:14:23 important. And, you know, if you have cancer, blood vessels grow

00:14:29 into the tumor. And that’s part of what enables the tumor to get

00:14:32 bigger. And that’s also part of what enables the tumor to

00:14:36 metastasize and which means spread throughout the body and

00:14:39 ultimately kill somebody. So that was part of what we were

00:14:42 trying to do. We tried what we wanted to see if we could find

00:14:45 substances that could stop that from happening. So first, I

00:14:49 mean, there are many steps. First, we had to develop a bio

00:14:51 assay to study blood vessel growth. Again, there wasn’t

00:14:54 one. That’s where we needed the polymer systems because the

00:14:57 blood vessels grew slowly took months. That so after we had the

00:15:03 polymer system and we had the bio assay, then I isolated many

00:15:07 different molecules initially from cartilage. And almost all

00:15:12 of them didn’t work. But we were fortunate we found one it wasn’t

00:15:17 purified, but we found one that did work. And that paper that

00:15:21 was this paper I mentioned science in 1976. Those were

00:15:24 really the isolation of some of the very first angiogenesis and

00:15:27 blood vessel inhibitors.

00:15:29 So there’s a lot of words there. Yeah, let’s go. First of all,

00:15:34 polymer molecules, big, big molecules. So the what are

00:15:38 polymers? What’s bio assay? What is the process of trying to

00:15:45 isolate this whole thing simplified to where you can

00:15:46 control and experiment with it?

00:15:48 Polymers are like plastics or like plastics or rubber. What

00:15:54 were some of the other questions?

00:15:55 Sorry, so a polymer, some plastics and rubber, and that

00:15:59 means something that has structure and that could be

00:16:01 useful for what?

00:16:03 Well, in this case, it would be something that could be useful

00:16:05 for delivering a molecule for a long time. So it could slowly

00:16:10 diffuse out of that at a controlled rate to where you

00:16:13 wanted it to go.

00:16:15 So then you would find the idea is that there would be a

00:16:17 particular blood vessels that you can target, say they’re

00:16:22 connected somehow to a tumor that you could target and over

00:16:27 a long period of time to be able to place the polymer there

00:16:31 and it’d be delivering a certain kind of chemical.

00:16:34 That’s correct. I think what you said is good. So so that it

00:16:37 would deliver the molecule or the chemical that would stop

00:16:41 the blood vessels from going over a long enough time so that

00:16:44 it really could happen. So that was sort of the what we call

00:16:47 the bio assay is the way that we would study that.

00:16:50 So, sorry, so what is a bio assay? Which part is the bio

00:16:53 assay?

00:16:54 All of it. In other words, the bio assay is the way you study

00:17:00 blood vessel growth.

00:17:01 The blood vessel growth and you can control that somehow with

00:17:05 is there an understanding what kind of chemicals could control

00:17:08 the growth of a blood vessel?

00:17:09 Sure. Well, now there is, but then when I started, there

00:17:11 wasn’t and that that gets to your original question. So you

00:17:14 go through various steps. We did the first steps. We showed

00:17:17 that a such molecules existed and then we developed

00:17:20 techniques for studying them. And we even isolated fractions,

00:17:24 you know, groups of substances that would do it. But what

00:17:28 would happen over the next, we did that in 1976, we published

00:17:33 that what would happen over the next 28 years is other people

00:17:37 would follow in our footsteps. I mean, we tried to do some

00:17:39 stuff too, but ultimately to make a new drug takes billions

00:17:43 of dollars. So what happened was there were different growth

00:17:47 factors that people would isolate, sometimes using the

00:17:50 techniques that we developed. And then they would figure out

00:17:55 using some of those techniques, ways to stop those growth

00:17:58 factors and ways to stop the blood vessels from growing. That

00:18:02 like I say, it took 28 years, it took billions of dollars and

00:18:05 work by many companies like Genetec. But in 2004, 28 years

00:18:11 after we started, the first one of those Avastin got approved

00:18:15 by the FDA. And that’s become, you know, one of the top

00:18:20 biotech selling drugs in history. And it’s been approved

00:18:23 for all kinds of cancers and actually for many eye diseases

00:18:27 too, where you have abnormal blood vessel growth, macular.

00:18:30 So in general, one of the key ways you can alleviate, what’s

00:18:38 the hope in terms of tumors associated with cancerous

00:18:41 tumors? What can you help by being able to control the

00:18:46 growth of vessels?

00:18:47 So if you cut off the blood supply, you cut off the, it’s

00:18:52 kind of like a war almost, right? If the nutrition is going

00:18:56 to the tumor and you can cut it off, I mean, you starve the

00:19:01 tumor and it becomes very small, it may disappear or it’s going

00:19:05 to be much more amenable to other therapies because it is

00:19:08 tiny, you know, like, you know, chemotherapy or immunotherapy

00:19:12 is going to be, have a much easier time against a small

00:19:15 tumor than a big one.

00:19:16 Is that an obvious idea? I mean, it seems like a very clever

00:19:20 strategy in this war against cancer.

00:19:23 Well, you know, in retrospect, it’s an obvious idea, but when

00:19:27 Dr. Folkman, my boss first proposed it, it wasn’t, a lot of

00:19:31 people didn’t thought he was pretty crazy.

00:19:33 And so in what sense, if you can sort of linger on it, when

00:19:39 you’re thinking about these ideas at the time, were you

00:19:42 feeling you’re out in the dark?

00:19:43 So how much mystery is there about the whole thing?

00:19:46 How much just blind experimentation, if you can put

00:19:50 yourself in that mindset from years ago?

00:19:52 Yeah.

00:19:52 Well, there was, I mean, for me, actually, it wasn’t just

00:19:56 the idea.

00:19:56 It was that I didn’t know a lot of biology or biochemistry.

00:19:59 So I certainly felt I was in the dark, but I kept trying and

00:20:03 I kept trying to learn and I kept plugging.

00:20:06 But I mean, a lot of it was being in the dark.

00:20:08 So the human body is complicated, right?

00:20:11 We’ll establish this.

00:20:12 Quantum mechanics in physics is a theory that works incredibly

00:20:16 well, but we don’t really necessarily understand the underlying

00:20:19 nature of it.

00:20:20 So are drugs the same in that you’re ultimately trying to

00:20:25 show that the thing works to do something that you try to do,

00:20:29 but you don’t necessarily understand the fundamental

00:20:33 mechanisms by which it’s doing it?

00:20:35 It really varies.

00:20:36 I think sometimes people do know them because they’ve figured

00:20:40 out pathways and ways to interfere with them.

00:20:42 Other times it is shooting in the dark.

00:20:45 It really has varied.

00:20:46 Okay.

00:20:47 And sometimes people make serendipitous discoveries and

00:20:49 they don’t even realize what they did.

00:20:51 So what is the discovery process for a drug?

00:20:55 You said a bunch of people trying to work with this.

00:20:59 Is it a kind of a mix of serendipitous discovery and art,

00:21:08 or is there a systematic science to trying different chemical

00:21:12 reactions and how they affect whatever you’re trying to do,

00:21:16 like shrink blood vessels?

00:21:18 Yeah, I don’t think there’s a single way to go about

00:21:22 something in terms of characterizing the entire drug

00:21:25 discovery process.

00:21:26 If I look at the blood vessel one,

00:21:28 yeah, there the first step was to have the kinds of theories

00:21:34 that Dr. Folkman had.

00:21:35 The second step was to have the techniques where you could

00:21:38 study blood vessel growth for the first time and at least

00:21:40 quantitate or semi quantitate it.

00:21:44 Third step was to find substances that would stop blood

00:21:48 vessels from growing.

00:21:49 Fourth step was to maybe purify those substances.

00:21:54 There are many other steps too.

00:21:55 I mean, before you have an effective drug,

00:21:57 you have to show that it’s safe.

00:21:58 You have to show that it’s effective.

00:22:00 And you start with animals.

00:22:01 You ultimately go to patients.

00:22:03 And there are multiple kinds of clinical trials you have to do.

00:22:06 If you step back, is it amazing to you

00:22:08 that we descendants of great apes

00:22:11 are able to create drugs, chemicals that

00:22:18 are able to improve some aspects of our bodies?

00:22:22 Or is it quite natural that we’re

00:22:25 able to discover these kinds of things?

00:22:27 Well, at a high level, it is amazing.

00:22:29 I mean, evolution is amazing.

00:22:31 The way I look at your question, the fact

00:22:33 that we have evolved the way we’ve done,

00:22:36 I mean, it’s pretty remarkable.

00:22:38 So let’s talk about drug delivery.

00:22:41 What are the difficult problems in drug delivery?

00:22:43 What is drug delivery from starting

00:22:48 from your early seminal work in the field to today?

00:22:51 Well, drug delivery is getting a drug

00:22:55 to go where you want it, at the level you want it,

00:22:57 in a safe way.

00:22:59 Some of the big challenges, I mean, there are a lot.

00:23:02 I mean, I’d say one is, could you target the right cell?

00:23:06 Like, we talked about cancers or some way

00:23:08 to deliver a drug just to a cancer cell and no other cell.

00:23:11 Another challenge is to get drugs

00:23:14 across different barriers.

00:23:15 Like, could you ever give insulin orally?

00:23:17 Could you, or give it passively transdermally?

00:23:21 Can you get drugs across the blood brain barrier?

00:23:24 I mean, there are lots of big challenges.

00:23:26 Can you make smart drug delivery systems

00:23:29 that might respond to physiologic signals in the body?

00:23:32 Oh, interesting.

00:23:33 So smart, they have some kind of sense,

00:23:37 a chemical sensor, or is there something more

00:23:39 than a chemical sensor that’s able to respond

00:23:41 to something in the body?

00:23:43 Could be either one.

00:23:44 I mean, one example might be if you were diabetic,

00:23:48 if you got more glucose, could you get more insulin?

00:23:53 But that’s just an example.

00:23:57 Is there some way to control the actual mechanism

00:23:59 of delivery in response to what the body’s doing?

00:24:02 Yes, there is.

00:24:03 I mean, one of the things that we’ve done

00:24:05 is encapsulate what are called beta cells.

00:24:07 Those are insulin producing cells in a way

00:24:09 that they’re safe and protected.

00:24:11 And then what’ll happen is glucose will go in

00:24:15 and the cells will make insulin.

00:24:20 And so that’s an example.

00:24:23 So from an AI robotics perspective,

00:24:25 how close are these drug delivery systems

00:24:29 to something like a robot?

00:24:31 Or is it totally wrong to think about them

00:24:33 as intelligent agents?

00:24:35 And how much room is there to add that kind of intelligence

00:24:39 into these delivery systems, perhaps in the future?

00:24:42 Yeah, I think it depends on the particular delivery system.

00:24:45 Of course, one of the things people are concerned about

00:24:47 is cost, and if you add a lot of bells and whistles

00:24:49 to something, it’ll cost more.

00:24:51 But I mean, we, for example, have made

00:24:54 what I’ll call intelligent microchips

00:24:55 that can, where you can send a signal

00:24:58 and you’ll release drug in response to that signal.

00:25:01 And I think systems like that microchip someday

00:25:04 have the potential to do what you and I

00:25:06 were just talking about,

00:25:07 that there could be a signal like glucose

00:25:09 and it could have some instruction to say

00:25:11 when there’s more glucose, deliver more insulin.

00:25:14 So do you think it’s possible that there,

00:25:16 that could be robotic type systems roaming our body

00:25:19 sort of long term and be able to deliver

00:25:21 certain kinds of drugs in the future?

00:25:23 You see, do you see that kind of future?

00:25:26 Someday, I don’t think we’re very close to it yet,

00:25:29 but someday, you know that that’s nanotechnology

00:25:31 and that would mean even miniaturizing

00:25:33 some of the things that I just discussed.

00:25:35 And we’re certainly not at that point yet,

00:25:37 but someday I expect we will be.

00:25:40 So some of it is just the shrinking of the technology.

00:25:44 That’s a part of it, that’s one of the things.

00:25:47 In general, what role do you see AI sort of,

00:25:52 there’s a lot of work now with using data

00:25:55 to make intelligent, create systems

00:25:57 that make intelligent decisions.

00:25:59 Do you see any of that data driven kind of computing systems

00:26:04 having a role in any part of this,

00:26:09 into the delivery of drugs, the design of drugs

00:26:13 and any part of the chain?

00:26:15 I do, I think that AI can be useful

00:26:18 in a number of parts of the chain.

00:26:20 I mean, one, I think if you get a large amount

00:26:22 of information, you know, say you have some chemical data

00:26:26 because you’ve done high throughput screens

00:26:29 and let’s, I’ll just make this up,

00:26:30 but let’s say I have a, I’m trying to come up with a drug

00:26:33 to treat disease X, whatever that disease is

00:26:37 and I have a test for that and hopefully a fast test

00:26:43 and let’s say I test 10,000 chemical substances

00:26:47 and a couple work, most of them don’t work,

00:26:49 some maybe work a little, but if I had a,

00:26:52 with the right kind of artificial intelligence,

00:26:54 maybe you could look at the chemical structures

00:26:57 and look at what works and see

00:26:58 if there’s certain commonalities,

00:26:59 look at what doesn’t work and see what commonalities

00:27:02 there are and then maybe use that somehow

00:27:05 to predict the next generation of things

00:27:07 that you would test.

00:27:08 As a tangent, what are your thoughts

00:27:10 on our society’s relationship with pharmaceutical drugs?

00:27:14 Do we, and perhaps I apologize

00:27:17 if this is a philosophical broader question,

00:27:19 but do we over rely on them?

00:27:22 Do we improperly prescribe them?

00:27:24 In what ways is the system working well

00:27:26 and what way can it improve?

00:27:28 Well, I think pharmaceutical drugs are really important.

00:27:33 I mean, the life expectancy and life quality of people

00:27:37 over many, many years has increased tremendously

00:27:40 and I think that’s a really good thing.

00:27:42 I think one thing that would also be good

00:27:44 is if we could extend that more and more

00:27:45 to people in the developing world,

00:27:47 which is something that our lab has been doing

00:27:49 with the Gates Foundation or trying to do.

00:27:53 So I think ways in which it could improve,

00:27:55 I mean, if there was some way to reduce costs,

00:27:59 that’s certainly an issue people are concerned about.

00:28:01 If there was some way to help people in poor countries,

00:28:05 that would also be a good thing.

00:28:06 And then of course, we still need to make better drugs

00:28:10 for so many diseases.

00:28:12 I mean, cancer, diabetes.

00:28:14 I mean, there’s heart disease and rare diseases.

00:28:17 There are many, many situations where it’d be great

00:28:20 if we could do better and help more people.

00:28:22 Can we talk about another exciting space,

00:28:27 which is tissue engineering?

00:28:29 What is tissue engineering or regenerative medicine?

00:28:32 Yeah, so that tissue engineering or regenerative medicine

00:28:35 have to do with building an organ or tissue from scratch.

00:28:38 So someday maybe we can build a liver

00:28:43 or make new cartilage and also would enable you

00:28:47 to someday create organs on a chip,

00:28:49 which we and others are trying to do,

00:28:52 which might lead to better drug testing

00:28:54 and maybe less testing on animals or people.

00:28:57 Organs on a chip, that sounds fascinating.

00:29:01 So what are the various ways to generate tissue?

00:29:06 And how do, so is it, you know,

00:29:08 the one is of course from stem cells.

00:29:10 Is there other methods?

00:29:11 What are the different possible flavors here?

00:29:14 Yeah, well, I think, I mean, there’s multiple components.

00:29:17 One is having generally some type of scaffold.

00:29:19 That’s what Jay Vacanti and I started many, many years ago.

00:29:23 And then on that scaffold,

00:29:26 you might put different cell types,

00:29:28 which could be a cartilage cell, a bone cell,

00:29:30 could be a stem cell that might differentiate

00:29:32 into different things, could be more than one cell.

00:29:35 And the scaffold, sorry to interrupt,

00:29:37 is kind of like a canvas that’s a structure

00:29:39 that you can, on which the cells can grow?

00:29:43 I think that’s a good explanation what you just did.

00:29:44 I’ll have to use that, the canvas, that’s good.

00:29:47 Yeah, so I think that that’s fair.

00:29:49 You know, and the chip could be such a canvas.

00:29:52 Could be fibers that are made of plastics

00:29:55 that you’d put in the body someday.

00:29:57 And when you say chip, do you mean electronic chip?

00:29:59 Like a…

00:30:00 Not necessarily, it could be though.

00:30:02 But it doesn’t have to be, it could just be a structure

00:30:04 that’s not in vivo, so to speak,

00:30:08 that’s, you know, that’s outside the body.

00:30:10 So is there…

00:30:11 Canvas is not a bad word.

00:30:13 So is there a possibility to weave into this canvas

00:30:20 a computational component?

00:30:22 So if we talk about electronic chips,

00:30:23 some ability to sense, control,

00:30:28 some aspect of this growth process for the tissue.

00:30:31 I would say the answer to that is yes.

00:30:33 I think right now people are working mostly

00:30:36 on validating these kinds of chips for saying,

00:30:40 well, it does work as effectively,

00:30:43 or hopefully as just putting something in the body.

00:30:47 But I think someday what you suggested,

00:30:49 you certainly would be possible.

00:30:51 So what kind of tissues can we engineer today?

00:30:53 What would, yeah.

00:30:54 Yeah, well, so skin’s already been made

00:30:57 and approved by the FDA.

00:30:58 There are advanced clinical trials,

00:31:00 like what are called phase three trials,

00:31:03 that are at complete or near completion

00:31:05 for making new blood vessels.

00:31:08 One of my former students, Laura Nicholson,

00:31:10 led a lot of that.

00:31:13 Oh, that’s amazing.

00:31:14 So human skin can be grown.

00:31:16 That’s already approved in the entire, the FDA process.

00:31:20 So that means what,

00:31:23 so one, that means you can grow that tissue

00:31:27 and do various kinds of experiments

00:31:30 in terms of drugs and so on.

00:31:34 But what does that, does that mean

00:31:35 that some kind of healing and treatment

00:31:38 of different conditions for unhuman beings?

00:31:41 Yes, I mean, they’ve been approved now for,

00:31:43 I mean, different groups have made them,

00:31:45 different companies and different professors,

00:31:47 but they’ve been approved for burn victims

00:31:50 and for patients with diabetic skin ulcers.

00:31:53 That’s amazing.

00:31:54 Okay, so skin, what else?

00:31:59 Well, at different stages,

00:32:01 people are, like skin, blood vessels,

00:32:05 there’s clinical trials going now for helping patients

00:32:08 hear better, for patients that might be paralyzed,

00:32:12 for patients that have different eye problems.

00:32:15 I mean, and different groups have worked on

00:32:18 just about everything, new liver, new kidneys.

00:32:20 I mean, there’ve been all kinds of work done in this area.

00:32:24 Some of it’s early, but there’s certainly

00:32:26 a lot of activity.

00:32:27 What about neural tissue?

00:32:30 Yeah.

00:32:31 The nervous system and even the brain.

00:32:34 Well, there’ve been people out of working on that too.

00:32:36 We’ve done a little bit with that,

00:32:37 but there are people who’ve done a lot on neural stem cells

00:32:40 and I know Evan Snyder, who’s been one of our collaborators

00:32:43 on some of our spinal cord works done work like that

00:32:46 and there’ve been other people as well.

00:32:48 Is there challenges for the,

00:32:51 when it is part of the human body,

00:32:52 is there challenges to getting the body to accept

00:32:55 this new tissue that’s being generated?

00:32:58 How do you solve that kind of challenge?

00:33:00 There can be problems with accepting it.

00:33:02 I think maybe in particular,

00:33:04 you might mean rejection by the body.

00:33:07 So there are multiple ways that people are trying

00:33:09 to deal with that.

00:33:10 One way is, which was what we’ve done with Dan Anderson,

00:33:14 who was one of my former postdocs

00:33:16 and I mentioned this a little bit before for a pancreas,

00:33:19 is encapsulating the cells.

00:33:20 So immune cells or antibodies can’t get in and attack them.

00:33:26 So that’s a way to protect them.

00:33:28 Other strategies could be making the cells non immunogenic,

00:33:34 which might be done by different either techniques

00:33:36 which might mask them or using some gene editing approaches.

00:33:40 So there are different ways that people

00:33:42 are trying to do that.

00:33:43 And of course, if you use the patient’s own cells

00:33:45 or cells from a close relative, that might be another way.

00:33:50 It increases the likelihood that it’ll get accepted

00:33:52 if you use the patient’s own cells.

00:33:54 Yes.

00:33:55 And then finally, there’s immunosuppressive drugs,

00:33:57 which will suppress the immune response.

00:34:00 That’s right now what’s done, say, for a liver transplant.

00:34:03 The fact that this whole thing works is fascinating,

00:34:06 at least from my outside perspective.

00:34:09 Will we one day be able to regenerate any organ

00:34:13 or part of the human body?

00:34:15 Any of you?

00:34:16 I mean, it’s exciting to think about future possibilities

00:34:19 of tissue engineering.

00:34:22 Do you see some tissues more difficult than others?

00:34:25 What are the possibilities here?

00:34:27 Yeah, well, of course, I’m an optimist.

00:34:29 And I also feel the timeframe,

00:34:30 if we’re talking about someday,

00:34:32 someday could be hundreds of years.

00:34:33 But I think that, yes, someday,

00:34:36 I think we will be able to regenerate many things.

00:34:39 And there are different strategies that one might use.

00:34:41 One might use some cells themselves.

00:34:44 One might use some molecules

00:34:47 that might help regenerate the cells.

00:34:49 And so I think there are different possibilities.

00:34:51 What do you think that means for longevity?

00:34:54 If we look maybe not someday, but 10, 20 years out,

00:35:00 the possibilities of tissue engineering,

00:35:01 the possibilities of the research that you’re doing,

00:35:04 does it have a significant impact

00:35:06 on the longevity of human life?

00:35:10 I don’t know that we’ll see

00:35:11 a radical increase in longevity,

00:35:12 but I think that in certain areas,

00:35:15 we’ll see people live better lives

00:35:19 and maybe somewhat longer lives.

00:35:21 What’s the most beautiful scientific idea

00:35:25 in bioengineering that you’ve come across

00:35:28 in your years of research?

00:35:30 I apologize for the romantic question.

00:35:33 No, that’s an interesting question.

00:35:35 I certainly think what’s happening right now

00:35:37 with CRISPR is a beautiful idea.

00:35:39 That certainly wasn’t my idea.

00:35:42 I mean, but I think it’s very interesting here

00:35:45 what people have capitalized on

00:35:48 is that there’s a mechanism by which bacteria

00:35:52 are able to destroy viruses.

00:35:54 And that understanding that leads to machinery

00:35:58 to sort of cut and paste genes and fix a cell.

00:36:06 So that kind of, do you see a promise

00:36:09 for that kind of ability to copy and paste?

00:36:13 I mean, like we said, the human body is complicated.

00:36:16 Is that, that seems exceptionally difficult to do.

00:36:23 I think it is exceptionally difficult to do,

00:36:25 but that doesn’t mean that it won’t be done.

00:36:27 There’s a lot of companies and people trying to do it.

00:36:30 And I think in some areas it will be done.

00:36:32 Some of the ways that you might lower the bar

00:36:36 are not, are just taking,

00:36:39 like not necessarily doing it directly,

00:36:40 but you could take a cell that might be useful,

00:36:45 but you want to give it some cancer killing capabilities,

00:36:48 something like what’s called a CAR T cell.

00:36:50 And that might be a different way

00:36:52 of somehow making a CAR T cell and maybe making it better.

00:36:56 So there might be sort of easier things

00:36:58 and rather than just fixing the whole body.

00:37:01 So the way a lot of things have moved with medicine

00:37:04 over time is stepwise.

00:37:06 So I can see things that might be easier to do

00:37:10 than say, fix a brain.

00:37:11 That would be very hard to do,

00:37:13 but maybe someday that’ll happen too.

00:37:16 So in terms of stepwise, that’s an interesting notion.

00:37:19 Do you see that if you look at medicine or bioengineering,

00:37:25 do you see that there is these big leaps

00:37:29 that happen every decade or so, or some distant period,

00:37:33 or is it a lot of incremental work?

00:37:36 Not, I don’t mean to reduce its impact

00:37:39 by saying it’s incremental,

00:37:40 but is there sort of phase shifts in the science,

00:37:46 big leaps?

00:37:48 I think there’s both.

00:37:49 Every so often a new technique or a new technology comes out.

00:37:54 I mean, genetic engineering was an example.

00:37:56 I mentioned CRISPR.

00:37:58 I think every so often things happen

00:38:01 that make a big difference,

00:38:03 but still there’s to try to really make progress,

00:38:07 make a new drug, make a new device.

00:38:09 There’s a lot of things.

00:38:11 I don’t know if I’d call them incremental,

00:38:12 but there’s a lot, a lot of work that needs to be done.

00:38:15 Absolutely.

00:38:16 So you have over, numbers could be off,

00:38:20 but it’s a big amount.

00:38:22 You have over 1,100 current or pending patents

00:38:25 that have been licensed, sublicensed

00:38:27 to over 300 companies.

00:38:29 What’s your view, what in your view are the strengths

00:38:33 and what are the drawbacks of the patenting process?

00:38:36 Well, I think for the most part, there’s strengths.

00:38:39 I think that if you didn’t have patents,

00:38:42 especially in medicine,

00:38:43 you’d never get the funding that it takes

00:38:45 to make a new drug or a new device.

00:38:47 I mean, which according to Tufts,

00:38:49 to make a new drug costs over $2 billion right now.

00:38:52 And nobody would even come close to giving you that money,

00:38:55 any of that money, if it weren’t for the patent system,

00:39:00 because then anybody else could do it.

00:39:03 That then leads to the negative though.

00:39:08 Sometimes somebody does have a very successful drug

00:39:11 and you certainly wanna try to make it available

00:39:14 to everybody.

00:39:15 And so the patent system allowed it to happen

00:39:21 in the first place, but maybe it’ll impede it

00:39:23 after a little bit, or certainly to some people

00:39:26 or to some companies, once it is out there.

00:39:31 What’s the, on the point of the cost,

00:39:34 what would you say is the most expensive part

00:39:37 of the $2 billion of making a drug?

00:39:40 Human clinical trials.

00:39:42 That is by far the most expensive.

00:39:44 In terms of money or pain or both?

00:39:47 Well, money, but pain goes, it’s hard to know.

00:39:50 I mean, but usually proving things that are,

00:39:54 proving that something new is safe and effective in people

00:39:57 is almost always the biggest expense.

00:40:00 Could you linger on that for just a little longer

00:40:02 and describe what it takes to prove,

00:40:06 for people that don’t know, in general,

00:40:09 what it takes to prove that something is effective on humans?

00:40:12 Well, you’d have to take a particular disease,

00:40:17 but the process is you start out with,

00:40:20 usually you start out with cells,

00:40:21 then you’d go to animal models.

00:40:23 Usually you have to do a couple animal models.

00:40:25 And of course the animal models aren’t perfect for humans.

00:40:28 And then you have to do three sets of clinical trials

00:40:31 at a minimum, a phase one trial to show that it’s safe

00:40:34 in small number of patients, a phase two trial

00:40:36 to show that it’s effective in a small number of patients,

00:40:39 and a phase three trial to show that it’s safe and effective

00:40:42 in a large number of patients.

00:40:44 And that could end up being hundreds

00:40:46 or thousands of patients.

00:40:49 And they have to be really carefully controlled studies.

00:40:52 And you’d have to manufacture the drug,

00:40:55 you’d have to really watch those patients.

00:40:58 You have to be very concerned that it is gonna be safe.

00:41:03 And then you look and see, does it treat the disease better

00:41:07 than whatever the gold standard was before that?

00:41:10 Assuming there was one.

00:41:12 That’s a really interesting line.

00:41:14 Show that it’s safe first, and then that it’s effective.

00:41:17 First do no harm.

00:41:19 First do no harm, that’s right.

00:41:21 So how, again, if you can linger in a little bit,

00:41:26 how does the patenting process work?

00:41:29 Yeah, well, you do a certain amount of research,

00:41:32 though that’s not necessarily has to be the case.

00:41:35 But for us, usually it is.

00:41:36 Usually we do a certain amount of research

00:41:40 and make some findings.

00:41:41 And we had a hypothesis, let’s say we prove it,

00:41:46 or we make some discovery, we invent some technique.

00:41:49 And then we write something up, what’s called a disclosure.

00:41:52 We give it to MIT’s technology transfer office.

00:41:55 They then give it to some patent attorneys,

00:41:57 and they use that plus talking to us

00:42:00 and work on writing a patent.

00:42:03 And then you go back and forth with the USPTO,

00:42:07 that’s the United States Patent and Trademark Office.

00:42:09 And they may not allow it the first, second or third time,

00:42:14 but they will tell you why they don’t.

00:42:17 And you may adjust it,

00:42:18 and maybe you’ll eventually get it, and maybe you won’t.

00:42:21 So you’ve been part of launching 40 companies

00:42:24 together worth, again, numbers could be outdated,

00:42:28 but an estimated $23 billion.

00:42:33 You’ve described your thoughts

00:42:34 on a formula for startup success.

00:42:36 So perhaps you can describe that formula

00:42:38 and in general describe what does it take

00:42:41 to build a successful startup?

00:42:44 Well, I’d break that down into a couple of categories.

00:42:46 And I’m a scientist and certainly

00:42:48 from the science standpoint, I’ll go over that.

00:42:50 But I actually think that really the most important thing

00:42:54 is probably the business people that I work with.

00:42:57 And when I look back at the companies that have done well,

00:43:01 it’s been because we’ve had great business people.

00:43:03 And when they haven’t done as well,

00:43:05 we haven’t had as good business people.

00:43:06 But from a science standpoint,

00:43:08 I think about that we’ve made some kind of discovery

00:43:12 that is almost what I’d call a platform

00:43:15 that you could use it for different things.

00:43:17 And certainly the drug delivery system example

00:43:20 that I gave earlier is a good example of that.

00:43:22 You could use it for drug A, B, C, D, E and so forth.

00:43:27 And that I’d like to think that we’ve taken it far enough

00:43:30 so that we’ve written at least one really good paper

00:43:33 in a top journal, hopefully a number

00:43:36 that we’ve reduced it to practice and animal models

00:43:39 that we’ve filed patents, maybe had issued patents

00:43:45 that have what I’ll call very good and broad claims.

00:43:48 That’s sort of the key on a patent.

00:43:50 And then in our case, a lot of times when we’ve done it,

00:43:55 a lot of times it’s somebody in the lab

00:43:57 like a postdoc or graduate student

00:43:59 that spent a big part of their life doing it

00:44:01 and that they wanna work at that company

00:44:03 because they have this passion

00:44:04 that they wanna see something they did

00:44:06 make a difference in people’s lives.

00:44:09 Maybe you can mention the business component.

00:44:12 It’s funny to hear Grace had to say

00:44:15 that there’s value to business folks.

00:44:17 Oh yeah, well.

00:44:18 That’s not always said.

00:44:20 So what value, what business instinct is valuable

00:44:25 to make a startup successful, a company successful?

00:44:29 I think the business aspects are,

00:44:32 you have to be a good judge of people

00:44:35 so that you hire the right people.

00:44:37 You have to be strategic so you figure out

00:44:40 if you do have that platform

00:44:41 that could be used for all these different things.

00:44:44 And knowing that medical research is so expensive,

00:44:47 what thing are you gonna do first, second,

00:44:49 third, fourth and fifth?

00:44:51 I think you need to have a good,

00:44:53 what I’ll call FDA regulatory clinical trial strategy.

00:44:58 I think you have to be able to raise money incredibly.

00:45:01 So there are a lot of things.

00:45:02 You have to be good with people, good manager of people.

00:45:05 So the money and the people part I get,

00:45:08 but the stuff before in terms of deciding the A, B, C, D,

00:45:13 if you have a platform which drugs to first take a testing,

00:45:16 you see nevertheless scientists

00:45:18 as not being always too good at that process.

00:45:22 Well, I think they’re a part of the process,

00:45:24 but I’d say there’s probably, I’m gonna just make this up,

00:45:28 but maybe six or seven criteria that you wanna use

00:45:31 and it’s not just science.

00:45:33 I mean, the kinds of things that I would think about

00:45:35 is, is the market big or small?

00:45:37 Is the, are there good animal models for it

00:45:41 so that you could test it and it wouldn’t take 50 years?

00:45:45 Are the clinical trials that could be set up

00:45:48 ones that have clear end points

00:45:51 where you can make a judgment?

00:45:53 And another issue would be competition.

00:45:58 Are there other ways that some companies

00:46:00 out there are doing it?

00:46:01 Another issue would be reimbursement.

00:46:05 You know, can it get reimbursed?

00:46:07 So a lot of things that you have manufacturing issues

00:46:10 you’d wanna consider.

00:46:11 So I think there are really a lot of things

00:46:13 that go into whether you,

00:46:15 what you do first, second, third, or fourth.

00:46:19 So you lead one of the largest academic labs in the world

00:46:23 with over $10 million in annual grants

00:46:27 and over a hundred researchers,

00:46:28 probably over a thousand since the lab’s beginning.

00:46:31 Researchers can be individualistic and eccentric.

00:46:37 How do I put it nicely?

00:46:38 There you go, eccentric.

00:46:40 So what insights into research leadership can you give

00:46:43 having to run such a successful lab

00:46:45 with so much diverse talent?

00:46:49 Well, I don’t know that I’m any expert.

00:46:50 I think that what you do to me,

00:46:53 I mean, I just want,

00:46:54 I mean, this is gonna sound very simplistic,

00:46:56 but I just want people in the lab to be happy,

00:46:58 to be doing things that I hope

00:47:00 will make the world a better place,

00:47:02 to be working on science

00:47:04 that can make the world a better place.

00:47:06 And I guess my feeling is if we’re able to do that,

00:47:11 you know, it kind of runs itself.

00:47:13 So how do you make a researcher happy in general?

00:47:17 I think when people feel,

00:47:19 I mean, this is gonna sound like, again,

00:47:21 simplistic or maybe like motherhood and apple pie,

00:47:23 but I think if people feel they’re working on something

00:47:26 really important that can affect many other people’s lives

00:47:30 and they’re making some progress,

00:47:32 they’ll feel good about it

00:47:34 and they’ll feel good about themselves

00:47:35 and they’ll be happy.

00:47:37 But through brainstorming and so on,

00:47:39 what’s your role and how difficult is it as a group

00:47:43 in this collaboration to arrive at these big questions

00:47:49 that might have impact?

00:47:51 Well, the big questions come from many different ways.

00:47:54 Sometimes it’s trying to, things that I might think of

00:47:57 or somebody in the lab might think of,

00:47:59 which could be a new technique

00:48:00 or to understand something better.

00:48:02 But gee, we’ve had people like Bill Gates

00:48:05 and the Gates Foundation come to us

00:48:07 and Juvenile Diabetes Foundation come to us and say,

00:48:10 gee, could you help us on these things?

00:48:11 And I mean, that’s good too.

00:48:13 It doesn’t happen just one way.

00:48:16 And I mean, you’ve kind of mentioned it, happiness,

00:48:20 but is there something more,

00:48:24 how do you inspire a researcher

00:48:26 to do the best work of their life?

00:48:28 So you mentioned passion and passion is a kind of fire.

00:48:32 Do you see yourself having a role to keep that fire going,

00:48:35 to build it up, to inspire the researchers

00:48:39 through the pretty difficult process

00:48:42 of going from idea to big question, to big answer?

00:48:47 I think so.

00:48:48 I think I try to do that by talking to people

00:48:52 going over their ideas and their progress.

00:48:56 I try to do it as an individual.

00:49:00 Certainly when I talk about my own career,

00:49:01 I had my setbacks at different times

00:49:04 and people know that, that know me.

00:49:06 And you just try to keep pushing and so forth.

00:49:12 But yeah, I think I try to do that.

00:49:15 But yeah, I think I try to do that

00:49:17 as the one who leads the lab.

00:49:20 So you have this exceptionally successful lab

00:49:23 and one of the great institutions in the world, MIT.

00:49:29 And yet sort of, at least in my neck of the woods

00:49:32 in computer science and artificial intelligence,

00:49:36 a lot of the research is kind of,

00:49:40 a lot of the great researchers, not everyone,

00:49:43 but some are kind of going to industry.

00:49:46 A lot of the research is moving to industry.

00:49:49 What do you think about the future of science in general?

00:49:52 Is there drawbacks?

00:49:54 Is there strength to the academic environment

00:49:58 that you hope will persist?

00:49:59 How does it need to change?

00:50:02 What needs to stay the same?

00:50:04 What are your thoughts on this whole landscape

00:50:05 of science and its future?

00:50:08 Well, first I think going to industry is good,

00:50:10 but I think being in academia is good.

00:50:12 You know, I have lots of students who’ve done both

00:50:15 and they’ve had great careers doing both.

00:50:18 I think from an academic standpoint,

00:50:21 I mean, the biggest concern probably that people feel today,

00:50:24 you know, at a place like MIT

00:50:26 or other research heavy institutions is gonna be funding

00:50:30 and particular funding that’s not super directed,

00:50:34 you know, so that you can do basic research.

00:50:37 I think that’s probably the number one thing,

00:50:39 but you know, it would be great if we as a society

00:50:43 could come up with better ways to teach,

00:50:45 you know, so that people all over could learn better.

00:50:50 You know, so I think there are a number of things

00:50:51 that would be good to be able to do better.

00:50:55 So again, you’re very successful in terms of funding,

00:50:58 but do you still feel the pressure of that,

00:51:01 of having to seek funding?

00:51:04 Does it affect the science or is it,

00:51:07 or can you simply focus on doing the best work of your life

00:51:11 and the funding comes along with that?

00:51:14 I’d say the last 10 or 15 years,

00:51:16 we’ve done pretty well funding,

00:51:18 but I always worry about it.

00:51:19 You know, it’s like you’re still operating

00:51:23 on more soft money than hard.

00:51:25 And so I always worry about it,

00:51:27 but we’ve been fortunate that places have come to us

00:51:33 like the Gates Foundation and others,

00:51:34 Juvenile Diabetes Foundation, some companies,

00:51:37 and they’re willing to give us funding

00:51:39 and we’ve gotten government money as well.

00:51:42 We have a number of NIH grants and I’ve always had that

00:51:44 and that’s important to me too.

00:51:47 So I worry about it, but you know,

00:51:51 I just view that as a part of the process.

00:51:53 Now, if you put yourself in the shoes of a philanthropist,

00:51:57 like say I gave you $100 billion right now,

00:52:02 but you couldn’t spend it on your own research.

00:52:05 So how hard is it to decide which labs to invest in,

00:52:12 which ideas, which problems, which solutions?

00:52:16 You know, cause funding is so much,

00:52:19 such an important part of progression of science

00:52:22 in today’s society.

00:52:24 So if you put yourself in the shoes of a philanthropist,

00:52:26 how hard is that problem?

00:52:27 How would you go about solving it?

00:52:29 Sure, well, I think what I do, the first thing is different

00:52:32 philanthropists have different visions.

00:52:34 And I think the first thing is to form a concrete vision

00:52:37 of what you want.

00:52:38 Some people, I mean, I’ll just give you two examples

00:52:41 of people that I know.

00:52:44 David Koch was very interested in cancer research

00:52:47 and part of that was that he had prostate cancer.

00:52:51 And a number of people do that along those lines.

00:52:55 They’ve had somebody, they’ve either had cancer themselves

00:52:57 or somebody they loved had cancer

00:53:00 and they wanna put money into cancer research.

00:53:02 Bill Gates, on the other hand,

00:53:04 I think when he had got his fortune,

00:53:06 I mean, he thought about it and felt, well,

00:53:08 how could he have the greatest impact?

00:53:10 And he thought about, you know, helping people

00:53:12 in the developing world and medicines

00:53:15 and different things like that, like vaccines

00:53:18 that might be really helpful for people

00:53:20 in the developing world.

00:53:21 And so I think first you start out with that vision.

00:53:25 Once you start out with that vision, whatever vision it is,

00:53:29 then I think you try to ask the question,

00:53:33 who in the world does the best work if that was your goal?

00:53:38 I mean, but you really, I think have to have

00:53:40 a defined vision.

00:53:41 Vision first.

00:53:41 Yeah, and I think that’s what people do.

00:53:45 I mean, I have never seen anybody do it otherwise.

00:53:48 I mean, and that, by the way,

00:53:49 may not be the best thing overall.

00:53:53 I mean, I think it’s good that all those things happen,

00:53:55 but, you know, what you really want to do,

00:53:57 and I’ll make a contrast in a second,

00:54:00 in addition to funding important areas,

00:54:02 like what both of those people did, is to help young people.

00:54:07 And they may be at odds with each other

00:54:10 because a far more, a lab like ours,

00:54:13 which is, you know, I’m older, is, you know,

00:54:15 might be very good at addressing some of those kinds

00:54:18 of problems, but, you know, I’m not young.

00:54:20 I train a lot of people who are young,

00:54:22 but it’s not the same as helping somebody

00:54:24 who’s an assistant professor someplace.

00:54:26 So I think what’s, I think, been good about our thing,

00:54:30 our society, or things overall,

00:54:33 are that there are people who come at it

00:54:35 from different ways, and the combination,

00:54:37 the confluence of the government funding,

00:54:40 the certain foundations that fund things,

00:54:43 and other foundations that, you know,

00:54:46 want to see disease treated,

00:54:48 well, then they can go seek out people,

00:54:51 or they can put a request for proposals

00:54:53 and see who does the best.

00:54:54 You know, I’d say both David Koch and Bill Gates

00:54:58 did exactly that.

00:54:58 They sought out people, both of them, you know,

00:55:02 or their foundations that they were involved in,

00:55:04 sought out people like myself.

00:55:07 But they also had requests for proposals.

00:55:11 Now, you mentioned young people,

00:55:12 and that reminds me of something you said

00:55:14 in an interview of Written Somewhere,

00:55:17 that said some of your initial struggles

00:55:21 in terms of finding a faculty position, or so on,

00:55:28 that you didn’t quite, for people,

00:55:30 fit into a particular bucket, a particular.

00:55:33 Right.

00:55:35 Can you speak to that?

00:55:38 How, do you see limitations to the academic system

00:55:41 that it does have such buckets?

00:55:44 Is there, how can we allow for people

00:55:49 who are brilliant, but outside the disciplines

00:55:56 of the previous decade?

00:55:59 Yeah, well, I think that’s a great question.

00:56:01 I think that, I think the department heads

00:56:03 have to have a vision, you know, and some of them do.

00:56:07 Every so often, you know, there are institutes

00:56:11 or labs that do that.

00:56:13 I mean, at MIT, I think that’s done sometimes.

00:56:17 I know mechanical engineering department just had a search,

00:56:21 and they hired Gio Traverso, who is one of my,

00:56:25 he was a fellow with me, but he’s actually

00:56:28 a molecular biologist and a gastroenterologist.

00:56:32 And, you know, he’s one of the best in the world,

00:56:34 but he’s also done some great mechanical engineering

00:56:37 and designing some new pills and things like that.

00:56:39 And they picked him, and boy, I give them a lot of credit.

00:56:43 I mean, that’s vision, to pick somebody.

00:56:46 And I think, you know, they’ll be the richer four.

00:56:49 I think the Media Lab has certainly hired, you know,

00:56:52 people like Ed Boyden and others who have done,

00:56:55 you know, very different things.

00:56:56 And so I think that, you know, that’s part of the vision

00:57:00 of the leadership who do things like that.

00:57:03 Do you think one day, you’ve mentioned David Koch and cancer,

00:57:07 do you think one day we’ll cure cancer?

00:57:10 Yeah, I mean, of course, one day,

00:57:12 I don’t know how long that day will come.

00:57:14 Soon.

00:57:15 Yeah, soon, soon, no, but I think.

00:57:17 So you think it is a grand challenge,

00:57:19 it is a grand challenge,

00:57:20 it’s not just solvable within a few years.

00:57:22 No, I don’t think very many things

00:57:24 are solvable in a few years.

00:57:25 There’s some good ideas that people are working on,

00:57:28 but I mean, all cancers, that’s pretty tough.

00:57:32 If we do get the cure, what will the cure look like?

00:57:35 Do you think which mechanisms,

00:57:37 which disciplines will help us arrive at that cure

00:57:40 from all the amazing work you’ve done

00:57:42 that has touched on cancer?

00:57:44 No, I think it’ll be a combination

00:57:45 of biology and engineering.

00:57:46 I think it’ll be biology to understand

00:57:50 the right genetic mechanisms to solve this problem

00:57:54 and maybe the right immunological mechanisms

00:57:56 and engineering in the sense of producing the molecules,

00:58:00 developing the right delivery systems,

00:58:02 targeting it or whatever else needs to be done.

00:58:05 Well, that’s a beautiful vision for engineering.

00:58:08 So on a lighter topic, I’ve read that you love chocolate

00:58:11 and mentioned two places, Ben and Bill’s Chocolate Aquarium

00:58:16 and the chocolate cookies, the Soho Globs

00:58:20 from Rosie’s Bakery in Chestnut Hill.

00:58:22 I went to their website and I was trying

00:58:25 to finish a paper last night.

00:58:26 There’s a deadline today and yet I was wasting

00:58:30 way too much time at 3 a.m. instead of writing the paper,

00:58:34 staring at the Rosie Baker’s cookies,

00:58:36 which are just look incredible.

00:58:38 The Soho Globs just look incredible.

00:58:40 But for me, oatmeal white raisin cookies won my heart

00:58:44 just from the pictures.

00:58:46 Do you think one day we’ll be able to engineer

00:58:49 the perfect cookie with the help of chemistry

00:58:52 and maybe a bit of data driven artificial intelligence

00:58:55 or is cookies something that’s more art than engineering?

00:59:02 I think there’s some of both.

00:59:03 I think engineering will probably help someday.

00:59:06 What about chocolate?

00:59:08 Same thing, same thing.

00:59:09 You’d have to go to see some of David Edwards stuff.

00:59:12 He was one of my postdocs and he’s a professor at Harvard

00:59:15 but he also started Cafe Art Sciences

00:59:18 and it’s just a really cool restaurant around here.

00:59:22 But he also has companies that do ways

00:59:26 of looking at fragrances and trying to use engineering

00:59:30 in new ways and so I think that’s just an example.

00:59:34 But I expect someday that AI and engineering

00:59:38 will play a role in almost everything.

00:59:40 Including creating the perfect cookie.

00:59:42 Yes.

00:59:43 Well, I dream of that day as well.

00:59:45 So when you look back at your life,

00:59:47 having accomplished an incredible amount of positive impact

00:59:50 on the world through science and engineering,

00:59:53 what are you most proud of?

00:59:56 My students, I really feel when I look at that,

00:59:59 we’ve probably had close to 1,000 students

01:00:02 go through the lab and they’ve done incredibly well.

01:00:06 I think 18 are in the National Academy of Engineering,

01:00:09 16 in the National Academy of Medicine.

01:00:12 I mean, they’ve been CEOs of companies,

01:00:15 presidents of universities and they’ve done,

01:00:19 I think eight are faculty at MIT,

01:00:21 maybe about 12 at Harvard.

01:00:22 I mean, so it really makes you feel good

01:00:25 to think that the people, they’re not my children

01:00:28 but they’re close to my children in a way

01:00:31 and it makes you feel really good

01:00:32 to see them have such great lives

01:00:34 and them do so much good and be happy.

01:00:37 Well, I think that’s a perfect way to end it, Bob.

01:00:40 Thank you so much for talking to me.

01:00:41 My pleasure.

01:00:41 It was an honor.

01:00:42 Good questions.

01:00:43 Thank you.

01:00:44 Thanks for listening to this conversation with Bob Langer

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01:01:19 at Lex Friedman, spelled without the E, just F R I D M A N.

01:01:25 And now let me leave you with some words from Bill Bryson

01:01:28 in his book, A Short History of Nearly Everything.

01:01:31 If this book has a lesson,

01:01:33 it is that we’re awfully lucky to be here.

01:01:36 And by we, I mean every living thing.

01:01:39 To attain any kind of life in this universe of ours

01:01:42 appears to be quite an achievement.

01:01:44 As humans, we’re doubly lucky, of course.

01:01:47 We enjoy not only the privilege of existence,

01:01:50 but also the singular ability to appreciate it

01:01:53 and even in a multitude of ways to make it better.

01:01:57 It is talent we have only barely begun to grasp.

01:02:01 Thank you for listening and hope to see you next time.