back to indexRobert Langer: Edison of Medicine | Lex Fridman Podcast #105
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The following is a conversation with Bob Langer, professor at
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MIT, and one of the most cited researchers in history,
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specializing in biotechnology fields of drug delivery systems
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and tissue engineering. He has bridged theory and practice by
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being a key member and driving force in launching many
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successful biotech companies out of MIT. This conversation was
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recorded before the outbreak of the coronavirus pandemic. His
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research and companies are at the forefront of developing
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treatment for COVID 19, including a promising vaccine
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podcast. And now here's my conversation with Bob Langer.
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You have a bit of a love for magic. Do you see a connection
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between magic and science?
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I do. I think magic can surprise you. And, uh, you know, and I
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think science can surprise you. And there's something magical
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about, about science. I mean, making discoveries and things
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like that. Yeah. So on the, and then on the magic side, is
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there some kind of engineering scientific process to the tricks
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themselves? Do you see, cause there's a duality to it. One is
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you're the, um, you're, you're sort of the person inside that
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knows how the whole thing works, how the universe of the magic
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trick works. And then from the outside observer, which is kind
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of the role of the scientists, you, the people that observe
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the magic trick don't know at least initially anything that's
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going on. Do you see that kind of duality?
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Well, I think the duality that I see is fascination. You know,
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I think of it, you know, when I watch magic myself, I'm always
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fascinated by it. Sometimes it's a puzzle to think how it's done,
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but just the sheer fact that something that you never thought
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could happen does happen. And I think about that in science too,
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you know, sometimes you, it's something that, that you might
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dream about and hoping to discover, maybe you do in some
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What is the most amazing magic trick you've ever seen?
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Well, there's one I like, which is called the invisible pack.
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And the way it works is you have this pack and you hold it up.
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Well, first you say to somebody, this is invisible and this deck
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and you say, well, shuffle it. They shuffle it, but you know,
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they're sort of make believe. And then you say, okay, I'd like
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you to pick a card, any card and show it to me. And you show it
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to me and I look at it. And let's say it's the three of
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hearts. I said, we'll put it back in the deck. But what I'd
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like you to do is turn it up upside down from every other
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card in the deck. So they do that imaginary. And I say,
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do you want to shuffle it again? And they shuffle it. And I said,
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well, so there's still one card upside down from every other
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card in the deck. I said, what is that? And they said, well,
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three hearts. So what just so happens in my back pocket, I
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have this deck, it's, you know, it's a real deck. I show it to
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you and I just open it up. And there's just one card upside
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down. And it's the three of hearts.
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And, and you can do this trick.
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I can, if I don't, I would have probably brought it.
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All right. Well, beautiful. Let's get into the, into the
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science. As of today, you have over 295,000 citations. An H
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index of 269. You're one of the most cited people in history and
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the most cited engineer in history. And yet nothing great,
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I think is ever achieved without failure. So the interesting
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part, what rejected papers, ideas, efforts in your life or
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most painful, or had the biggest impact on your life?
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Well, it's interesting. I mean, I've had plenty of rejection too,
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you know, but I suppose one way I think about this is that when
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I first started, and this certainly had an impact both
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ways, you know, I first started, we made two big discoveries and
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they were kind of interrelated. I mean, one was, I was trying to
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isolate with my postdoctoral advisor, Judah Folkman,
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substances that could stop blood vessels from growing and nobody
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had done that before. And so that was part A, let's say part B
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is we had to develop a way to study that. And what was
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critical to study that was to have a way to slowly release
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those substances for, you know, more than a day, you know, maybe
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months. And that had never been done before either. So we
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published the first one we sent to Nature, the journal, and they
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rejected it. And then we sent it, we revised it, we sent it to
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Science and they accepted it. And the other, the opposite
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happened, we sent it to Science and they rejected it. And then
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we sent it to Nature and they accepted it. But I have to tell
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you, when we got the rejections, it was really upsetting. I
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thought, you know, I'd done some really good work. And Dr.
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Folkman thought we'd done some really good work. And, and, but
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it was very depressing to, you know, get rejected like that.
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If you can linger on just the feeling or the thought process
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when you get the rejection, especially early on in your
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career, what, I mean, you don't know, now people know you as a
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brilliant scientist, but at the time, I'm sure you're full of
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self doubt. And did you believe that maybe this idea is actually
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quite terrible, that it could have been done much better? Or
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is there underlying confidence? What was the feelings?
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Well, you feel depressed and I felt the same way when I got
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grants rejected, which I did a lot in the beginning. I guess
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part of me, you know, you have multiple emotions. One is being
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sad and being upset and also being maybe a little bit angry
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because you didn't feel the reviewers didn't get it. But
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then as I thought about it more, I thought, well, maybe I just
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didn't explain it well enough. And you know, that, you know,
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that you go through stages. And so you say, well, okay, I'll
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explain it better next time. And certainly you get reviews and
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when you get the reviews, you see what they either didn't like
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or didn't understand. And then you try to incorporate that into
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your next versions.
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You've given advice to students to do something big, do
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something that really can change the world rather than something
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incremental. How did you yourself seek out such ideas? Is
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there a process? Is there a sort of a rigorous process? Or is it
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It's more spontaneous. I mean, part of its exposure to things,
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part of its seeing other people, like I mentioned, Dr. Folkman,
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he was my postdoctoral advisor, he was very good at that, you
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could sort of see that he had big ideas. And I certainly met a
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lot of people who didn't. And I think you could spot an idea
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that might have potential when you see it, you know, because it
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could have very broad implications, whereas a lot of
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people might just keep doing derivative stuff. And so I
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don't know. But it's not something that I've ever done.
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Systematically, I don't think.
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So in the space of ideas, how many are just when you see them?
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It's just magic. It's something that you see that could be
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impactful if you dig deeper.
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Yeah, it's sort of hard to say because there's multiple levels
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of ideas. One type of thing is like a new, you know, creation
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that you could engineer tissues for the first time or make
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dishes from scratch on the first time. But another thing is
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really just deeply understanding something. And that's important
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too. So and that may lead to other things. So sometimes you
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could think of a new technology, or I thought of a new
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technology. But other times, things came from just the
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process of trying to discover things. So it's never and you
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don't necessarily know, like people talk about aha moments,
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but I don't know if I've, I mean, I certainly feel like I've
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had some ideas that I really like. But it's taken me a long
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time to go from the thought process of starting it to all of
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a sudden, knowing that it might work.
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So if you take drug delivery, for example, is the notion is
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the initial notion, kind of a very general one, that we should
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be able to do something like this. And then you start to ask
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the questions of Well, how would you do it and then and then
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digging and digging and digging?
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I think that's right. I think it depends. I mean, there are
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many different examples. The example I gave about delivering
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large molecules, which we used to study these blood vessel
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inhibitors. I mean, there, we had to invent something that
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would do that. But other times, it's, it's, it's different.
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Sometimes it's really understanding what goes on in
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terms of understanding the mechanisms. And so it's, it's,
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it's not a single thing. And there are many different parts
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to it, you know, over the years, we've invented different or
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discovered different principles for aerosols for delivering,
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you know, genetic therapy agents, you know, all kinds of
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So let's explore some of the key ideas you've touched on in your
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life. Let's start with the basics. Okay. So first, let me
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ask, how complicated is the biology and chemistry of the
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human body from the perspective of trying to affect some parts
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of it in a positive way? So that you know, for me, especially
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coming from the field of computer science and computer
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engineering and robotics, it seems that the human body is
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exceptionally complicated, and how the heck you can figure out
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anything is amazing.
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I agree with you. I think it's super complicated. I mean,
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we're still just scratching the surface in many ways. But I feel
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like we have made progress in different ways. And some of its
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by really understanding things like we were just talking about
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other times, you know, you might, or somebody might we or
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others might invent technologies that might be helpful on
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exploring that. And I think over many years, we've understood
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things better and better, but we still have such a long ways to
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Are there? I mean, if you just look at the other things that
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are there knobs that are reliably controllable about the
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human body, if you consider is there is it? So if you start to
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think about controlling various aspects of when we talk about
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drug delivery a little bit, but controlling various aspects
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chemically of the human body, is there a solid understanding
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across the populations of humans that are solid, reliable knobs
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that can be controlled?
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I think that's hard to do. But on the other hand, whenever we
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make a new drug or medical device, to a certain extent,
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we're doing that, you know, in a small way, what you just said,
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but I don't know that there are great knobs. I mean, and we're
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learning about those knobs all the time. But if there's a
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biological pathway or something that you can affect, or
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understand, I mean, then that might be such a knob.
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So what is a pharmaceutical drug? How do you do? How do you
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discover a specific one? How do you test it? How do you
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understand it? How do you ship it?
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Yeah, well, I'll give an example, which goes back to
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what I said before. So when I was doing my postdoctoral work
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with Judah Folkman, we wanted to come up with drugs that would
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stop blood vessels from growing or alternatively make them grow.
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And actually, people didn't even believe that, that those things
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could we pause on that for a second? Sure. What is a blood
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vessel? What does it mean for a blood vessel to grow and shrink?
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And why is that important?
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Sure. So a blood vessel is could be an artery or vein or a
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capillary. And it, you know, provides oxygen, it provides
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nutrients gets rid of waste. So, you know, to different parts of
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your body if you so so the blood vessels end up being very, very
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important. And, you know, if you have cancer, blood vessels grow
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into the tumor. And that's part of what enables the tumor to get
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bigger. And that's also part of what enables the tumor to
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metastasize and which means spread throughout the body and
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ultimately kill somebody. So that was part of what we were
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trying to do. We tried what we wanted to see if we could find
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substances that could stop that from happening. So first, I
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mean, there are many steps. First, we had to develop a bio
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assay to study blood vessel growth. Again, there wasn't
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one. That's where we needed the polymer systems because the
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blood vessels grew slowly took months. That so after we had the
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polymer system and we had the bio assay, then I isolated many
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different molecules initially from cartilage. And almost all
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of them didn't work. But we were fortunate we found one it wasn't
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purified, but we found one that did work. And that paper that
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was this paper I mentioned science in 1976. Those were
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really the isolation of some of the very first angiogenesis and
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blood vessel inhibitors.
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So there's a lot of words there. Yeah, let's go. First of all,
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polymer molecules, big, big molecules. So the what are
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polymers? What's bio assay? What is the process of trying to
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isolate this whole thing simplified to where you can
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control and experiment with it?
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Polymers are like plastics or like plastics or rubber. What
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were some of the other questions?
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Sorry, so a polymer, some plastics and rubber, and that
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means something that has structure and that could be
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Well, in this case, it would be something that could be useful
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for delivering a molecule for a long time. So it could slowly
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diffuse out of that at a controlled rate to where you
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So then you would find the idea is that there would be a
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particular blood vessels that you can target, say they're
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connected somehow to a tumor that you could target and over
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a long period of time to be able to place the polymer there
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and it'd be delivering a certain kind of chemical.
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That's correct. I think what you said is good. So so that it
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would deliver the molecule or the chemical that would stop
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the blood vessels from going over a long enough time so that
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it really could happen. So that was sort of the what we call
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the bio assay is the way that we would study that.
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So, sorry, so what is a bio assay? Which part is the bio
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All of it. In other words, the bio assay is the way you study
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blood vessel growth.
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The blood vessel growth and you can control that somehow with
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is there an understanding what kind of chemicals could control
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the growth of a blood vessel?
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Sure. Well, now there is, but then when I started, there
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wasn't and that that gets to your original question. So you
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go through various steps. We did the first steps. We showed
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that a such molecules existed and then we developed
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techniques for studying them. And we even isolated fractions,
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you know, groups of substances that would do it. But what
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would happen over the next, we did that in 1976, we published
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that what would happen over the next 28 years is other people
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would follow in our footsteps. I mean, we tried to do some
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stuff too, but ultimately to make a new drug takes billions
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of dollars. So what happened was there were different growth
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factors that people would isolate, sometimes using the
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techniques that we developed. And then they would figure out
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using some of those techniques, ways to stop those growth
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factors and ways to stop the blood vessels from growing. That
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like I say, it took 28 years, it took billions of dollars and
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work by many companies like Genetec. But in 2004, 28 years
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after we started, the first one of those Avastin got approved
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by the FDA. And that's become, you know, one of the top
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biotech selling drugs in history. And it's been approved
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for all kinds of cancers and actually for many eye diseases
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too, where you have abnormal blood vessel growth, macular.
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So in general, one of the key ways you can alleviate, what's
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the hope in terms of tumors associated with cancerous
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tumors? What can you help by being able to control the
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growth of vessels?
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So if you cut off the blood supply, you cut off the, it's
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kind of like a war almost, right? If the nutrition is going
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to the tumor and you can cut it off, I mean, you starve the
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tumor and it becomes very small, it may disappear or it's going
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to be much more amenable to other therapies because it is
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tiny, you know, like, you know, chemotherapy or immunotherapy
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is going to be, have a much easier time against a small
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tumor than a big one.
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Is that an obvious idea? I mean, it seems like a very clever
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strategy in this war against cancer.
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Well, you know, in retrospect, it's an obvious idea, but when
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Dr. Folkman, my boss first proposed it, it wasn't, a lot of
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people didn't thought he was pretty crazy.
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And so in what sense, if you can sort of linger on it, when
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you're thinking about these ideas at the time, were you
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feeling you're out in the dark?
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So how much mystery is there about the whole thing?
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How much just blind experimentation, if you can put
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yourself in that mindset from years ago?
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Well, there was, I mean, for me, actually, it wasn't just
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It was that I didn't know a lot of biology or biochemistry.
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So I certainly felt I was in the dark, but I kept trying and
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I kept trying to learn and I kept plugging.
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But I mean, a lot of it was being in the dark.
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So the human body is complicated, right?
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We'll establish this.
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Quantum mechanics in physics is a theory that works incredibly
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well, but we don't really necessarily understand the underlying
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So are drugs the same in that you're ultimately trying to
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show that the thing works to do something that you try to do,
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but you don't necessarily understand the fundamental
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mechanisms by which it's doing it?
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I think sometimes people do know them because they've figured
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out pathways and ways to interfere with them.
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Other times it is shooting in the dark.
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It really has varied.
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And sometimes people make serendipitous discoveries and
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they don't even realize what they did.
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So what is the discovery process for a drug?
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You said a bunch of people trying to work with this.
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Is it a kind of a mix of serendipitous discovery and art,
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or is there a systematic science to trying different chemical
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reactions and how they affect whatever you're trying to do,
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like shrink blood vessels?
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Yeah, I don't think there's a single way to go about
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something in terms of characterizing the entire drug
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discovery process.
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If I look at the blood vessel one,
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yeah, there the first step was to have the kinds of theories
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that Dr. Folkman had.
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The second step was to have the techniques where you could
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study blood vessel growth for the first time and at least
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quantitate or semi quantitate it.
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Third step was to find substances that would stop blood
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vessels from growing.
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Fourth step was to maybe purify those substances.
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There are many other steps too.
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I mean, before you have an effective drug,
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you have to show that it's safe.
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You have to show that it's effective.
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And you start with animals.
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You ultimately go to patients.
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And there are multiple kinds of clinical trials you have to do.
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If you step back, is it amazing to you
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that we descendants of great apes
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are able to create drugs, chemicals that
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are able to improve some aspects of our bodies?
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Or is it quite natural that we're
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able to discover these kinds of things?
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Well, at a high level, it is amazing.
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I mean, evolution is amazing.
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The way I look at your question, the fact
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that we have evolved the way we've done,
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I mean, it's pretty remarkable.
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So let's talk about drug delivery.
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What are the difficult problems in drug delivery?
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What is drug delivery from starting
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from your early seminal work in the field to today?
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Well, drug delivery is getting a drug
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to go where you want it, at the level you want it,
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Some of the big challenges, I mean, there are a lot.
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I mean, I'd say one is, could you target the right cell?
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Like, we talked about cancers or some way
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to deliver a drug just to a cancer cell and no other cell.
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Another challenge is to get drugs
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across different barriers.
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Like, could you ever give insulin orally?
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Could you, or give it passively transdermally?
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Can you get drugs across the blood brain barrier?
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I mean, there are lots of big challenges.
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Can you make smart drug delivery systems
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that might respond to physiologic signals in the body?
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So smart, they have some kind of sense,
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a chemical sensor, or is there something more
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than a chemical sensor that's able to respond
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to something in the body?
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Could be either one.
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I mean, one example might be if you were diabetic,
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if you got more glucose, could you get more insulin?
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But that's just an example.
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Is there some way to control the actual mechanism
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of delivery in response to what the body's doing?
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I mean, one of the things that we've done
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is encapsulate what are called beta cells.
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Those are insulin producing cells in a way
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that they're safe and protected.
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And then what'll happen is glucose will go in
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and the cells will make insulin.
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And so that's an example.
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So from an AI robotics perspective,
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how close are these drug delivery systems
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to something like a robot?
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Or is it totally wrong to think about them
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as intelligent agents?
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And how much room is there to add that kind of intelligence
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into these delivery systems, perhaps in the future?
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Yeah, I think it depends on the particular delivery system.
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Of course, one of the things people are concerned about
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is cost, and if you add a lot of bells and whistles
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to something, it'll cost more.
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But I mean, we, for example, have made
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what I'll call intelligent microchips
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that can, where you can send a signal
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and you'll release drug in response to that signal.
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And I think systems like that microchip someday
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have the potential to do what you and I
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were just talking about,
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that there could be a signal like glucose
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and it could have some instruction to say
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when there's more glucose, deliver more insulin.
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So do you think it's possible that there,
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that could be robotic type systems roaming our body
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sort of long term and be able to deliver
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certain kinds of drugs in the future?
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You see, do you see that kind of future?
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Someday, I don't think we're very close to it yet,
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but someday, you know that that's nanotechnology
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and that would mean even miniaturizing
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some of the things that I just discussed.
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And we're certainly not at that point yet,
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but someday I expect we will be.
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So some of it is just the shrinking of the technology.
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That's a part of it, that's one of the things.
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In general, what role do you see AI sort of,
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there's a lot of work now with using data
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to make intelligent, create systems
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that make intelligent decisions.
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Do you see any of that data driven kind of computing systems
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having a role in any part of this,
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into the delivery of drugs, the design of drugs
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and any part of the chain?
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I do, I think that AI can be useful
link |
in a number of parts of the chain.
link |
I mean, one, I think if you get a large amount
link |
of information, you know, say you have some chemical data
link |
because you've done high throughput screens
link |
and let's, I'll just make this up,
link |
but let's say I have a, I'm trying to come up with a drug
link |
to treat disease X, whatever that disease is
link |
and I have a test for that and hopefully a fast test
link |
and let's say I test 10,000 chemical substances
link |
and a couple work, most of them don't work,
link |
some maybe work a little, but if I had a,
link |
with the right kind of artificial intelligence,
link |
maybe you could look at the chemical structures
link |
and look at what works and see
link |
if there's certain commonalities,
link |
look at what doesn't work and see what commonalities
link |
there are and then maybe use that somehow
link |
to predict the next generation of things
link |
that you would test.
link |
As a tangent, what are your thoughts
link |
on our society's relationship with pharmaceutical drugs?
link |
Do we, and perhaps I apologize
link |
if this is a philosophical broader question,
link |
but do we over rely on them?
link |
Do we improperly prescribe them?
link |
In what ways is the system working well
link |
and what way can it improve?
link |
Well, I think pharmaceutical drugs are really important.
link |
I mean, the life expectancy and life quality of people
link |
over many, many years has increased tremendously
link |
and I think that's a really good thing.
link |
I think one thing that would also be good
link |
is if we could extend that more and more
link |
to people in the developing world,
link |
which is something that our lab has been doing
link |
with the Gates Foundation or trying to do.
link |
So I think ways in which it could improve,
link |
I mean, if there was some way to reduce costs,
link |
that's certainly an issue people are concerned about.
link |
If there was some way to help people in poor countries,
link |
that would also be a good thing.
link |
And then of course, we still need to make better drugs
link |
for so many diseases.
link |
I mean, cancer, diabetes.
link |
I mean, there's heart disease and rare diseases.
link |
There are many, many situations where it'd be great
link |
if we could do better and help more people.
link |
Can we talk about another exciting space,
link |
which is tissue engineering?
link |
What is tissue engineering or regenerative medicine?
link |
Yeah, so that tissue engineering or regenerative medicine
link |
have to do with building an organ or tissue from scratch.
link |
So someday maybe we can build a liver
link |
or make new cartilage and also would enable you
link |
to someday create organs on a chip,
link |
which we and others are trying to do,
link |
which might lead to better drug testing
link |
and maybe less testing on animals or people.
link |
Organs on a chip, that sounds fascinating.
link |
So what are the various ways to generate tissue?
link |
And how do, so is it, you know,
link |
the one is of course from stem cells.
link |
Is there other methods?
link |
What are the different possible flavors here?
link |
Yeah, well, I think, I mean, there's multiple components.
link |
One is having generally some type of scaffold.
link |
That's what Jay Vacanti and I started many, many years ago.
link |
And then on that scaffold,
link |
you might put different cell types,
link |
which could be a cartilage cell, a bone cell,
link |
could be a stem cell that might differentiate
link |
into different things, could be more than one cell.
link |
And the scaffold, sorry to interrupt,
link |
is kind of like a canvas that's a structure
link |
that you can, on which the cells can grow?
link |
I think that's a good explanation what you just did.
link |
I'll have to use that, the canvas, that's good.
link |
Yeah, so I think that that's fair.
link |
You know, and the chip could be such a canvas.
link |
Could be fibers that are made of plastics
link |
that you'd put in the body someday.
link |
And when you say chip, do you mean electronic chip?
link |
Not necessarily, it could be though.
link |
But it doesn't have to be, it could just be a structure
link |
that's not in vivo, so to speak,
link |
that's, you know, that's outside the body.
link |
Canvas is not a bad word.
link |
So is there a possibility to weave into this canvas
link |
a computational component?
link |
So if we talk about electronic chips,
link |
some ability to sense, control,
link |
some aspect of this growth process for the tissue.
link |
I would say the answer to that is yes.
link |
I think right now people are working mostly
link |
on validating these kinds of chips for saying,
link |
well, it does work as effectively,
link |
or hopefully as just putting something in the body.
link |
But I think someday what you suggested,
link |
you certainly would be possible.
link |
So what kind of tissues can we engineer today?
link |
Yeah, well, so skin's already been made
link |
and approved by the FDA.
link |
There are advanced clinical trials,
link |
like what are called phase three trials,
link |
that are at complete or near completion
link |
for making new blood vessels.
link |
One of my former students, Laura Nicholson,
link |
led a lot of that.
link |
Oh, that's amazing.
link |
So human skin can be grown.
link |
That's already approved in the entire, the FDA process.
link |
So that means what,
link |
so one, that means you can grow that tissue
link |
and do various kinds of experiments
link |
in terms of drugs and so on.
link |
But what does that, does that mean
link |
that some kind of healing and treatment
link |
of different conditions for unhuman beings?
link |
Yes, I mean, they've been approved now for,
link |
I mean, different groups have made them,
link |
different companies and different professors,
link |
but they've been approved for burn victims
link |
and for patients with diabetic skin ulcers.
link |
Okay, so skin, what else?
link |
Well, at different stages,
link |
people are, like skin, blood vessels,
link |
there's clinical trials going now for helping patients
link |
hear better, for patients that might be paralyzed,
link |
for patients that have different eye problems.
link |
I mean, and different groups have worked on
link |
just about everything, new liver, new kidneys.
link |
I mean, there've been all kinds of work done in this area.
link |
Some of it's early, but there's certainly
link |
a lot of activity.
link |
What about neural tissue?
link |
The nervous system and even the brain.
link |
Well, there've been people out of working on that too.
link |
We've done a little bit with that,
link |
but there are people who've done a lot on neural stem cells
link |
and I know Evan Snyder, who's been one of our collaborators
link |
on some of our spinal cord works done work like that
link |
and there've been other people as well.
link |
Is there challenges for the,
link |
when it is part of the human body,
link |
is there challenges to getting the body to accept
link |
this new tissue that's being generated?
link |
How do you solve that kind of challenge?
link |
There can be problems with accepting it.
link |
I think maybe in particular,
link |
you might mean rejection by the body.
link |
So there are multiple ways that people are trying
link |
to deal with that.
link |
One way is, which was what we've done with Dan Anderson,
link |
who was one of my former postdocs
link |
and I mentioned this a little bit before for a pancreas,
link |
is encapsulating the cells.
link |
So immune cells or antibodies can't get in and attack them.
link |
So that's a way to protect them.
link |
Other strategies could be making the cells non immunogenic,
link |
which might be done by different either techniques
link |
which might mask them or using some gene editing approaches.
link |
So there are different ways that people
link |
are trying to do that.
link |
And of course, if you use the patient's own cells
link |
or cells from a close relative, that might be another way.
link |
It increases the likelihood that it'll get accepted
link |
if you use the patient's own cells.
link |
And then finally, there's immunosuppressive drugs,
link |
which will suppress the immune response.
link |
That's right now what's done, say, for a liver transplant.
link |
The fact that this whole thing works is fascinating,
link |
at least from my outside perspective.
link |
Will we one day be able to regenerate any organ
link |
or part of the human body?
link |
I mean, it's exciting to think about future possibilities
link |
of tissue engineering.
link |
Do you see some tissues more difficult than others?
link |
What are the possibilities here?
link |
Yeah, well, of course, I'm an optimist.
link |
And I also feel the timeframe,
link |
if we're talking about someday,
link |
someday could be hundreds of years.
link |
But I think that, yes, someday,
link |
I think we will be able to regenerate many things.
link |
And there are different strategies that one might use.
link |
One might use some cells themselves.
link |
One might use some molecules
link |
that might help regenerate the cells.
link |
And so I think there are different possibilities.
link |
What do you think that means for longevity?
link |
If we look maybe not someday, but 10, 20 years out,
link |
the possibilities of tissue engineering,
link |
the possibilities of the research that you're doing,
link |
does it have a significant impact
link |
on the longevity of human life?
link |
I don't know that we'll see
link |
a radical increase in longevity,
link |
but I think that in certain areas,
link |
we'll see people live better lives
link |
and maybe somewhat longer lives.
link |
What's the most beautiful scientific idea
link |
in bioengineering that you've come across
link |
in your years of research?
link |
I apologize for the romantic question.
link |
No, that's an interesting question.
link |
I certainly think what's happening right now
link |
with CRISPR is a beautiful idea.
link |
That certainly wasn't my idea.
link |
I mean, but I think it's very interesting here
link |
what people have capitalized on
link |
is that there's a mechanism by which bacteria
link |
are able to destroy viruses.
link |
And that understanding that leads to machinery
link |
to sort of cut and paste genes and fix a cell.
link |
So that kind of, do you see a promise
link |
for that kind of ability to copy and paste?
link |
I mean, like we said, the human body is complicated.
link |
Is that, that seems exceptionally difficult to do.
link |
I think it is exceptionally difficult to do,
link |
but that doesn't mean that it won't be done.
link |
There's a lot of companies and people trying to do it.
link |
And I think in some areas it will be done.
link |
Some of the ways that you might lower the bar
link |
are not, are just taking,
link |
like not necessarily doing it directly,
link |
but you could take a cell that might be useful,
link |
but you want to give it some cancer killing capabilities,
link |
something like what's called a CAR T cell.
link |
And that might be a different way
link |
of somehow making a CAR T cell and maybe making it better.
link |
So there might be sort of easier things
link |
and rather than just fixing the whole body.
link |
So the way a lot of things have moved with medicine
link |
over time is stepwise.
link |
So I can see things that might be easier to do
link |
than say, fix a brain.
link |
That would be very hard to do,
link |
but maybe someday that'll happen too.
link |
So in terms of stepwise, that's an interesting notion.
link |
Do you see that if you look at medicine or bioengineering,
link |
do you see that there is these big leaps
link |
that happen every decade or so, or some distant period,
link |
or is it a lot of incremental work?
link |
Not, I don't mean to reduce its impact
link |
by saying it's incremental,
link |
but is there sort of phase shifts in the science,
link |
I think there's both.
link |
Every so often a new technique or a new technology comes out.
link |
I mean, genetic engineering was an example.
link |
I mentioned CRISPR.
link |
I think every so often things happen
link |
that make a big difference,
link |
but still there's to try to really make progress,
link |
make a new drug, make a new device.
link |
There's a lot of things.
link |
I don't know if I'd call them incremental,
link |
but there's a lot, a lot of work that needs to be done.
link |
So you have over, numbers could be off,
link |
but it's a big amount.
link |
You have over 1,100 current or pending patents
link |
that have been licensed, sublicensed
link |
to over 300 companies.
link |
What's your view, what in your view are the strengths
link |
and what are the drawbacks of the patenting process?
link |
Well, I think for the most part, there's strengths.
link |
I think that if you didn't have patents,
link |
especially in medicine,
link |
you'd never get the funding that it takes
link |
to make a new drug or a new device.
link |
I mean, which according to Tufts,
link |
to make a new drug costs over $2 billion right now.
link |
And nobody would even come close to giving you that money,
link |
any of that money, if it weren't for the patent system,
link |
because then anybody else could do it.
link |
That then leads to the negative though.
link |
Sometimes somebody does have a very successful drug
link |
and you certainly wanna try to make it available
link |
And so the patent system allowed it to happen
link |
in the first place, but maybe it'll impede it
link |
after a little bit, or certainly to some people
link |
or to some companies, once it is out there.
link |
What's the, on the point of the cost,
link |
what would you say is the most expensive part
link |
of the $2 billion of making a drug?
link |
Human clinical trials.
link |
That is by far the most expensive.
link |
In terms of money or pain or both?
link |
Well, money, but pain goes, it's hard to know.
link |
I mean, but usually proving things that are,
link |
proving that something new is safe and effective in people
link |
is almost always the biggest expense.
link |
Could you linger on that for just a little longer
link |
and describe what it takes to prove,
link |
for people that don't know, in general,
link |
what it takes to prove that something is effective on humans?
link |
Well, you'd have to take a particular disease,
link |
but the process is you start out with,
link |
usually you start out with cells,
link |
then you'd go to animal models.
link |
Usually you have to do a couple animal models.
link |
And of course the animal models aren't perfect for humans.
link |
And then you have to do three sets of clinical trials
link |
at a minimum, a phase one trial to show that it's safe
link |
in small number of patients, a phase two trial
link |
to show that it's effective in a small number of patients,
link |
and a phase three trial to show that it's safe and effective
link |
in a large number of patients.
link |
And that could end up being hundreds
link |
or thousands of patients.
link |
And they have to be really carefully controlled studies.
link |
And you'd have to manufacture the drug,
link |
you'd have to really watch those patients.
link |
You have to be very concerned that it is gonna be safe.
link |
And then you look and see, does it treat the disease better
link |
than whatever the gold standard was before that?
link |
Assuming there was one.
link |
That's a really interesting line.
link |
Show that it's safe first, and then that it's effective.
link |
First do no harm, that's right.
link |
So how, again, if you can linger in a little bit,
link |
how does the patenting process work?
link |
Yeah, well, you do a certain amount of research,
link |
though that's not necessarily has to be the case.
link |
But for us, usually it is.
link |
Usually we do a certain amount of research
link |
and make some findings.
link |
And we had a hypothesis, let's say we prove it,
link |
or we make some discovery, we invent some technique.
link |
And then we write something up, what's called a disclosure.
link |
We give it to MIT's technology transfer office.
link |
They then give it to some patent attorneys,
link |
and they use that plus talking to us
link |
and work on writing a patent.
link |
And then you go back and forth with the USPTO,
link |
that's the United States Patent and Trademark Office.
link |
And they may not allow it the first, second or third time,
link |
but they will tell you why they don't.
link |
And you may adjust it,
link |
and maybe you'll eventually get it, and maybe you won't.
link |
So you've been part of launching 40 companies
link |
together worth, again, numbers could be outdated,
link |
but an estimated $23 billion.
link |
You've described your thoughts
link |
on a formula for startup success.
link |
So perhaps you can describe that formula
link |
and in general describe what does it take
link |
to build a successful startup?
link |
Well, I'd break that down into a couple of categories.
link |
And I'm a scientist and certainly
link |
from the science standpoint, I'll go over that.
link |
But I actually think that really the most important thing
link |
is probably the business people that I work with.
link |
And when I look back at the companies that have done well,
link |
it's been because we've had great business people.
link |
And when they haven't done as well,
link |
we haven't had as good business people.
link |
But from a science standpoint,
link |
I think about that we've made some kind of discovery
link |
that is almost what I'd call a platform
link |
that you could use it for different things.
link |
And certainly the drug delivery system example
link |
that I gave earlier is a good example of that.
link |
You could use it for drug A, B, C, D, E and so forth.
link |
And that I'd like to think that we've taken it far enough
link |
so that we've written at least one really good paper
link |
in a top journal, hopefully a number
link |
that we've reduced it to practice and animal models
link |
that we've filed patents, maybe had issued patents
link |
that have what I'll call very good and broad claims.
link |
That's sort of the key on a patent.
link |
And then in our case, a lot of times when we've done it,
link |
a lot of times it's somebody in the lab
link |
like a postdoc or graduate student
link |
that spent a big part of their life doing it
link |
and that they wanna work at that company
link |
because they have this passion
link |
that they wanna see something they did
link |
make a difference in people's lives.
link |
Maybe you can mention the business component.
link |
It's funny to hear Grace had to say
link |
that there's value to business folks.
link |
That's not always said.
link |
So what value, what business instinct is valuable
link |
to make a startup successful, a company successful?
link |
I think the business aspects are,
link |
you have to be a good judge of people
link |
so that you hire the right people.
link |
You have to be strategic so you figure out
link |
if you do have that platform
link |
that could be used for all these different things.
link |
And knowing that medical research is so expensive,
link |
what thing are you gonna do first, second,
link |
third, fourth and fifth?
link |
I think you need to have a good,
link |
what I'll call FDA regulatory clinical trial strategy.
link |
I think you have to be able to raise money incredibly.
link |
So there are a lot of things.
link |
You have to be good with people, good manager of people.
link |
So the money and the people part I get,
link |
but the stuff before in terms of deciding the A, B, C, D,
link |
if you have a platform which drugs to first take a testing,
link |
you see nevertheless scientists
link |
as not being always too good at that process.
link |
Well, I think they're a part of the process,
link |
but I'd say there's probably, I'm gonna just make this up,
link |
but maybe six or seven criteria that you wanna use
link |
and it's not just science.
link |
I mean, the kinds of things that I would think about
link |
is, is the market big or small?
link |
Is the, are there good animal models for it
link |
so that you could test it and it wouldn't take 50 years?
link |
Are the clinical trials that could be set up
link |
ones that have clear end points
link |
where you can make a judgment?
link |
And another issue would be competition.
link |
Are there other ways that some companies
link |
out there are doing it?
link |
Another issue would be reimbursement.
link |
You know, can it get reimbursed?
link |
So a lot of things that you have manufacturing issues
link |
you'd wanna consider.
link |
So I think there are really a lot of things
link |
that go into whether you,
link |
what you do first, second, third, or fourth.
link |
So you lead one of the largest academic labs in the world
link |
with over $10 million in annual grants
link |
and over a hundred researchers,
link |
probably over a thousand since the lab's beginning.
link |
Researchers can be individualistic and eccentric.
link |
How do I put it nicely?
link |
There you go, eccentric.
link |
So what insights into research leadership can you give
link |
having to run such a successful lab
link |
with so much diverse talent?
link |
Well, I don't know that I'm any expert.
link |
I think that what you do to me,
link |
I mean, I just want,
link |
I mean, this is gonna sound very simplistic,
link |
but I just want people in the lab to be happy,
link |
to be doing things that I hope
link |
will make the world a better place,
link |
to be working on science
link |
that can make the world a better place.
link |
And I guess my feeling is if we're able to do that,
link |
you know, it kind of runs itself.
link |
So how do you make a researcher happy in general?
link |
I think when people feel,
link |
I mean, this is gonna sound like, again,
link |
simplistic or maybe like motherhood and apple pie,
link |
but I think if people feel they're working on something
link |
really important that can affect many other people's lives
link |
and they're making some progress,
link |
they'll feel good about it
link |
and they'll feel good about themselves
link |
and they'll be happy.
link |
But through brainstorming and so on,
link |
what's your role and how difficult is it as a group
link |
in this collaboration to arrive at these big questions
link |
that might have impact?
link |
Well, the big questions come from many different ways.
link |
Sometimes it's trying to, things that I might think of
link |
or somebody in the lab might think of,
link |
which could be a new technique
link |
or to understand something better.
link |
But gee, we've had people like Bill Gates
link |
and the Gates Foundation come to us
link |
and Juvenile Diabetes Foundation come to us and say,
link |
gee, could you help us on these things?
link |
And I mean, that's good too.
link |
It doesn't happen just one way.
link |
And I mean, you've kind of mentioned it, happiness,
link |
but is there something more,
link |
how do you inspire a researcher
link |
to do the best work of their life?
link |
So you mentioned passion and passion is a kind of fire.
link |
Do you see yourself having a role to keep that fire going,
link |
to build it up, to inspire the researchers
link |
through the pretty difficult process
link |
of going from idea to big question, to big answer?
link |
I think I try to do that by talking to people
link |
going over their ideas and their progress.
link |
I try to do it as an individual.
link |
Certainly when I talk about my own career,
link |
I had my setbacks at different times
link |
and people know that, that know me.
link |
And you just try to keep pushing and so forth.
link |
But yeah, I think I try to do that.
link |
But yeah, I think I try to do that
link |
as the one who leads the lab.
link |
So you have this exceptionally successful lab
link |
and one of the great institutions in the world, MIT.
link |
And yet sort of, at least in my neck of the woods
link |
in computer science and artificial intelligence,
link |
a lot of the research is kind of,
link |
a lot of the great researchers, not everyone,
link |
but some are kind of going to industry.
link |
A lot of the research is moving to industry.
link |
What do you think about the future of science in general?
link |
Is there drawbacks?
link |
Is there strength to the academic environment
link |
that you hope will persist?
link |
How does it need to change?
link |
What needs to stay the same?
link |
What are your thoughts on this whole landscape
link |
of science and its future?
link |
Well, first I think going to industry is good,
link |
but I think being in academia is good.
link |
You know, I have lots of students who've done both
link |
and they've had great careers doing both.
link |
I think from an academic standpoint,
link |
I mean, the biggest concern probably that people feel today,
link |
you know, at a place like MIT
link |
or other research heavy institutions is gonna be funding
link |
and particular funding that's not super directed,
link |
you know, so that you can do basic research.
link |
I think that's probably the number one thing,
link |
but you know, it would be great if we as a society
link |
could come up with better ways to teach,
link |
you know, so that people all over could learn better.
link |
You know, so I think there are a number of things
link |
that would be good to be able to do better.
link |
So again, you're very successful in terms of funding,
link |
but do you still feel the pressure of that,
link |
of having to seek funding?
link |
Does it affect the science or is it,
link |
or can you simply focus on doing the best work of your life
link |
and the funding comes along with that?
link |
I'd say the last 10 or 15 years,
link |
we've done pretty well funding,
link |
but I always worry about it.
link |
You know, it's like you're still operating
link |
on more soft money than hard.
link |
And so I always worry about it,
link |
but we've been fortunate that places have come to us
link |
like the Gates Foundation and others,
link |
Juvenile Diabetes Foundation, some companies,
link |
and they're willing to give us funding
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and we've gotten government money as well.
link |
We have a number of NIH grants and I've always had that
link |
and that's important to me too.
link |
So I worry about it, but you know,
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I just view that as a part of the process.
link |
Now, if you put yourself in the shoes of a philanthropist,
link |
like say I gave you $100 billion right now,
link |
but you couldn't spend it on your own research.
link |
So how hard is it to decide which labs to invest in,
link |
which ideas, which problems, which solutions?
link |
You know, cause funding is so much,
link |
such an important part of progression of science
link |
in today's society.
link |
So if you put yourself in the shoes of a philanthropist,
link |
how hard is that problem?
link |
How would you go about solving it?
link |
Sure, well, I think what I do, the first thing is different
link |
philanthropists have different visions.
link |
And I think the first thing is to form a concrete vision
link |
Some people, I mean, I'll just give you two examples
link |
of people that I know.
link |
David Koch was very interested in cancer research
link |
and part of that was that he had prostate cancer.
link |
And a number of people do that along those lines.
link |
They've had somebody, they've either had cancer themselves
link |
or somebody they loved had cancer
link |
and they wanna put money into cancer research.
link |
Bill Gates, on the other hand,
link |
I think when he had got his fortune,
link |
I mean, he thought about it and felt, well,
link |
how could he have the greatest impact?
link |
And he thought about, you know, helping people
link |
in the developing world and medicines
link |
and different things like that, like vaccines
link |
that might be really helpful for people
link |
in the developing world.
link |
And so I think first you start out with that vision.
link |
Once you start out with that vision, whatever vision it is,
link |
then I think you try to ask the question,
link |
who in the world does the best work if that was your goal?
link |
I mean, but you really, I think have to have
link |
Yeah, and I think that's what people do.
link |
I mean, I have never seen anybody do it otherwise.
link |
I mean, and that, by the way,
link |
may not be the best thing overall.
link |
I mean, I think it's good that all those things happen,
link |
but, you know, what you really want to do,
link |
and I'll make a contrast in a second,
link |
in addition to funding important areas,
link |
like what both of those people did, is to help young people.
link |
And they may be at odds with each other
link |
because a far more, a lab like ours,
link |
which is, you know, I'm older, is, you know,
link |
might be very good at addressing some of those kinds
link |
of problems, but, you know, I'm not young.
link |
I train a lot of people who are young,
link |
but it's not the same as helping somebody
link |
who's an assistant professor someplace.
link |
So I think what's, I think, been good about our thing,
link |
our society, or things overall,
link |
are that there are people who come at it
link |
from different ways, and the combination,
link |
the confluence of the government funding,
link |
the certain foundations that fund things,
link |
and other foundations that, you know,
link |
want to see disease treated,
link |
well, then they can go seek out people,
link |
or they can put a request for proposals
link |
and see who does the best.
link |
You know, I'd say both David Koch and Bill Gates
link |
They sought out people, both of them, you know,
link |
or their foundations that they were involved in,
link |
sought out people like myself.
link |
But they also had requests for proposals.
link |
Now, you mentioned young people,
link |
and that reminds me of something you said
link |
in an interview of Written Somewhere,
link |
that said some of your initial struggles
link |
in terms of finding a faculty position, or so on,
link |
that you didn't quite, for people,
link |
fit into a particular bucket, a particular.
link |
Can you speak to that?
link |
How, do you see limitations to the academic system
link |
that it does have such buckets?
link |
Is there, how can we allow for people
link |
who are brilliant, but outside the disciplines
link |
of the previous decade?
link |
Yeah, well, I think that's a great question.
link |
I think that, I think the department heads
link |
have to have a vision, you know, and some of them do.
link |
Every so often, you know, there are institutes
link |
or labs that do that.
link |
I mean, at MIT, I think that's done sometimes.
link |
I know mechanical engineering department just had a search,
link |
and they hired Gio Traverso, who is one of my,
link |
he was a fellow with me, but he's actually
link |
a molecular biologist and a gastroenterologist.
link |
And, you know, he's one of the best in the world,
link |
but he's also done some great mechanical engineering
link |
and designing some new pills and things like that.
link |
And they picked him, and boy, I give them a lot of credit.
link |
I mean, that's vision, to pick somebody.
link |
And I think, you know, they'll be the richer four.
link |
I think the Media Lab has certainly hired, you know,
link |
people like Ed Boyden and others who have done,
link |
you know, very different things.
link |
And so I think that, you know, that's part of the vision
link |
of the leadership who do things like that.
link |
Do you think one day, you've mentioned David Koch and cancer,
link |
do you think one day we'll cure cancer?
link |
Yeah, I mean, of course, one day,
link |
I don't know how long that day will come.
link |
Yeah, soon, soon, no, but I think.
link |
So you think it is a grand challenge,
link |
it is a grand challenge,
link |
it's not just solvable within a few years.
link |
No, I don't think very many things
link |
are solvable in a few years.
link |
There's some good ideas that people are working on,
link |
but I mean, all cancers, that's pretty tough.
link |
If we do get the cure, what will the cure look like?
link |
Do you think which mechanisms,
link |
which disciplines will help us arrive at that cure
link |
from all the amazing work you've done
link |
that has touched on cancer?
link |
No, I think it'll be a combination
link |
of biology and engineering.
link |
I think it'll be biology to understand
link |
the right genetic mechanisms to solve this problem
link |
and maybe the right immunological mechanisms
link |
and engineering in the sense of producing the molecules,
link |
developing the right delivery systems,
link |
targeting it or whatever else needs to be done.
link |
Well, that's a beautiful vision for engineering.
link |
So on a lighter topic, I've read that you love chocolate
link |
and mentioned two places, Ben and Bill's Chocolate Aquarium
link |
and the chocolate cookies, the Soho Globs
link |
from Rosie's Bakery in Chestnut Hill.
link |
I went to their website and I was trying
link |
to finish a paper last night.
link |
There's a deadline today and yet I was wasting
link |
way too much time at 3 a.m. instead of writing the paper,
link |
staring at the Rosie Baker's cookies,
link |
which are just look incredible.
link |
The Soho Globs just look incredible.
link |
But for me, oatmeal white raisin cookies won my heart
link |
just from the pictures.
link |
Do you think one day we'll be able to engineer
link |
the perfect cookie with the help of chemistry
link |
and maybe a bit of data driven artificial intelligence
link |
or is cookies something that's more art than engineering?
link |
I think there's some of both.
link |
I think engineering will probably help someday.
link |
What about chocolate?
link |
Same thing, same thing.
link |
You'd have to go to see some of David Edwards stuff.
link |
He was one of my postdocs and he's a professor at Harvard
link |
but he also started Cafe Art Sciences
link |
and it's just a really cool restaurant around here.
link |
But he also has companies that do ways
link |
of looking at fragrances and trying to use engineering
link |
in new ways and so I think that's just an example.
link |
But I expect someday that AI and engineering
link |
will play a role in almost everything.
link |
Including creating the perfect cookie.
link |
Well, I dream of that day as well.
link |
So when you look back at your life,
link |
having accomplished an incredible amount of positive impact
link |
on the world through science and engineering,
link |
what are you most proud of?
link |
My students, I really feel when I look at that,
link |
we've probably had close to 1,000 students
link |
go through the lab and they've done incredibly well.
link |
I think 18 are in the National Academy of Engineering,
link |
16 in the National Academy of Medicine.
link |
I mean, they've been CEOs of companies,
link |
presidents of universities and they've done,
link |
I think eight are faculty at MIT,
link |
maybe about 12 at Harvard.
link |
I mean, so it really makes you feel good
link |
to think that the people, they're not my children
link |
but they're close to my children in a way
link |
and it makes you feel really good
link |
to see them have such great lives
link |
and them do so much good and be happy.
link |
Well, I think that's a perfect way to end it, Bob.
link |
Thank you so much for talking to me.
link |
Thanks for listening to this conversation with Bob Langer
link |
and thank you to our sponsors, Cash App and Masterclass.
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Please consider supporting the podcast
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It's the best way to support this podcast
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at Lex Friedman, spelled without the E, just F R I D M A N.
link |
And now let me leave you with some words from Bill Bryson
link |
in his book, A Short History of Nearly Everything.
link |
If this book has a lesson,
link |
it is that we're awfully lucky to be here.
link |
And by we, I mean every living thing.
link |
To attain any kind of life in this universe of ours
link |
appears to be quite an achievement.
link |
As humans, we're doubly lucky, of course.
link |
We enjoy not only the privilege of existence,
link |
but also the singular ability to appreciate it
link |
and even in a multitude of ways to make it better.
link |
It is talent we have only barely begun to grasp.
link |
Thank you for listening and hope to see you next time.