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Robert 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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candidate. Quick summary of the ads to sponsors cash app and
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dot com slash Lex to get a discount and to support this
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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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way or form.
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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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more spontaneous?
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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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things.
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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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go.
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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 happen. But
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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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useful for what?
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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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wanted it to go.
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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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assay?
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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
link |
00:17:39.640
stuff too, but ultimately to make a new drug takes billions
link |
00:17:43.760
of dollars. So what happened was there were different growth
link |
00:17:47.920
factors that people would isolate, sometimes using the
link |
00:17:50.760
techniques that we developed. And then they would figure out
link |
00:17:55.760
using some of those techniques, ways to stop those growth
link |
00:17:58.720
factors and ways to stop the blood vessels from growing. That
link |
00:18:02.400
like I say, it took 28 years, it took billions of dollars and
link |
00:18:05.040
work by many companies like Genetec. But in 2004, 28 years
link |
00:18:11.160
after we started, the first one of those Avastin got approved
link |
00:18:15.720
by the FDA. And that's become, you know, one of the top
link |
00:18:20.920
biotech selling drugs in history. And it's been approved
link |
00:18:23.920
for all kinds of cancers and actually for many eye diseases
link |
00:18:27.200
too, where you have abnormal blood vessel growth, macular.
link |
00:18:30.640
So in general, one of the key ways you can alleviate, what's
link |
00:18:38.480
the hope in terms of tumors associated with cancerous
link |
00:18:41.960
tumors? What can you help by being able to control the
link |
00:18:46.640
growth of vessels?
link |
00:18:47.840
So if you cut off the blood supply, you cut off the, it's
link |
00:18:52.680
kind of like a war almost, right? If the nutrition is going
link |
00:18:56.600
to the tumor and you can cut it off, I mean, you starve the
link |
00:19:01.480
tumor and it becomes very small, it may disappear or it's going
link |
00:19:05.240
to be much more amenable to other therapies because it is
link |
00:19:08.120
tiny, you know, like, you know, chemotherapy or immunotherapy
link |
00:19:12.200
is going to be, have a much easier time against a small
link |
00:19:15.000
tumor than a big one.
link |
00:19:16.000
Is that an obvious idea? I mean, it seems like a very clever
link |
00:19:20.880
strategy in this war against cancer.
link |
00:19:23.880
Well, you know, in retrospect, it's an obvious idea, but when
link |
00:19:27.480
Dr. Folkman, my boss first proposed it, it wasn't, a lot of
link |
00:19:31.880
people didn't thought he was pretty crazy.
link |
00:19:33.600
And so in what sense, if you can sort of linger on it, when
link |
00:19:39.360
you're thinking about these ideas at the time, were you
link |
00:19:42.280
feeling you're out in the dark?
link |
00:19:43.560
So how much mystery is there about the whole thing?
link |
00:19:46.760
How much just blind experimentation, if you can put
link |
00:19:50.520
yourself in that mindset from years ago?
link |
00:19:52.400
Yeah.
link |
00:19:52.840
Well, there was, I mean, for me, actually, it wasn't just
link |
00:19:56.480
the idea.
link |
00:19:56.960
It was that I didn't know a lot of biology or biochemistry.
link |
00:19:59.520
So I certainly felt I was in the dark, but I kept trying and
link |
00:20:03.440
I kept trying to learn and I kept plugging.
link |
00:20:06.040
But I mean, a lot of it was being in the dark.
link |
00:20:08.520
So the human body is complicated, right?
link |
00:20:11.320
We'll establish this.
link |
00:20:12.280
Quantum mechanics in physics is a theory that works incredibly
link |
00:20:16.680
well, but we don't really necessarily understand the underlying
link |
00:20:19.720
nature of it.
link |
00:20:20.360
So are drugs the same in that you're ultimately trying to
link |
00:20:25.280
show that the thing works to do something that you try to do,
link |
00:20:29.880
but you don't necessarily understand the fundamental
link |
00:20:33.520
mechanisms by which it's doing it?
link |
00:20:35.360
It really varies.
link |
00:20:36.760
I think sometimes people do know them because they've figured
link |
00:20:40.200
out pathways and ways to interfere with them.
link |
00:20:42.640
Other times it is shooting in the dark.
link |
00:20:45.160
It really has varied.
link |
00:20:46.640
Okay.
link |
00:20:47.160
And sometimes people make serendipitous discoveries and
link |
00:20:49.960
they don't even realize what they did.
link |
00:20:51.840
So what is the discovery process for a drug?
link |
00:20:55.960
You said a bunch of people trying to work with this.
link |
00:20:59.120
Is it a kind of a mix of serendipitous discovery and art,
link |
00:21:08.360
or is there a systematic science to trying different chemical
link |
00:21:12.840
reactions and how they affect whatever you're trying to do,
link |
00:21:16.960
like shrink blood vessels?
link |
00:21:18.840
Yeah, I don't think there's a single way to go about
link |
00:21:22.480
something in terms of characterizing the entire drug
link |
00:21:25.320
discovery process.
link |
00:21:26.440
If I look at the blood vessel one,
link |
00:21:28.600
yeah, there the first step was to have the kinds of theories
link |
00:21:34.400
that Dr. Folkman had.
link |
00:21:35.400
The second step was to have the techniques where you could
link |
00:21:38.120
study blood vessel growth for the first time and at least
link |
00:21:40.880
quantitate or semi quantitate it.
link |
00:21:44.200
Third step was to find substances that would stop blood
link |
00:21:48.120
vessels from growing.
link |
00:21:49.680
Fourth step was to maybe purify those substances.
link |
00:21:54.440
There are many other steps too.
link |
00:21:55.760
I mean, before you have an effective drug,
link |
00:21:57.680
you have to show that it's safe.
link |
00:21:58.800
You have to show that it's effective.
link |
00:22:00.600
And you start with animals.
link |
00:22:01.880
You ultimately go to patients.
link |
00:22:03.600
And there are multiple kinds of clinical trials you have to do.
link |
00:22:06.400
If you step back, is it amazing to you
link |
00:22:08.720
that we descendants of great apes
link |
00:22:11.680
are able to create drugs, chemicals that
link |
00:22:18.040
are able to improve some aspects of our bodies?
link |
00:22:22.160
Or is it quite natural that we're
link |
00:22:25.240
able to discover these kinds of things?
link |
00:22:27.760
Well, at a high level, it is amazing.
link |
00:22:29.800
I mean, evolution is amazing.
link |
00:22:31.600
The way I look at your question, the fact
link |
00:22:33.960
that we have evolved the way we've done,
link |
00:22:36.320
I mean, it's pretty remarkable.
link |
00:22:38.600
So let's talk about drug delivery.
link |
00:22:41.200
What are the difficult problems in drug delivery?
link |
00:22:43.640
What is drug delivery from starting
link |
00:22:48.240
from your early seminal work in the field to today?
link |
00:22:51.160
Well, drug delivery is getting a drug
link |
00:22:55.840
to go where you want it, at the level you want it,
link |
00:22:57.960
in a safe way.
link |
00:22:59.720
Some of the big challenges, I mean, there are a lot.
link |
00:23:02.040
I mean, I'd say one is, could you target the right cell?
link |
00:23:06.520
Like, we talked about cancers or some way
link |
00:23:08.240
to deliver a drug just to a cancer cell and no other cell.
link |
00:23:11.880
Another challenge is to get drugs
link |
00:23:14.640
across different barriers.
link |
00:23:15.840
Like, could you ever give insulin orally?
link |
00:23:17.640
Could you, or give it passively transdermally?
link |
00:23:21.320
Can you get drugs across the blood brain barrier?
link |
00:23:24.000
I mean, there are lots of big challenges.
link |
00:23:26.240
Can you make smart drug delivery systems
link |
00:23:29.040
that might respond to physiologic signals in the body?
link |
00:23:32.400
Oh, interesting.
link |
00:23:33.240
So smart, they have some kind of sense,
link |
00:23:37.040
a chemical sensor, or is there something more
link |
00:23:39.280
than a chemical sensor that's able to respond
link |
00:23:41.280
to something in the body?
link |
00:23:43.120
Could be either one.
link |
00:23:44.040
I mean, one example might be if you were diabetic,
link |
00:23:48.600
if you got more glucose, could you get more insulin?
link |
00:23:53.320
But that's just an example.
link |
00:23:57.040
Is there some way to control the actual mechanism
link |
00:23:59.480
of delivery in response to what the body's doing?
link |
00:24:02.240
Yes, there is.
link |
00:24:03.200
I mean, one of the things that we've done
link |
00:24:05.000
is encapsulate what are called beta cells.
link |
00:24:07.520
Those are insulin producing cells in a way
link |
00:24:09.840
that they're safe and protected.
link |
00:24:11.800
And then what'll happen is glucose will go in
link |
00:24:15.280
and the cells will make insulin.
link |
00:24:20.360
And so that's an example.
link |
00:24:23.000
So from an AI robotics perspective,
link |
00:24:25.880
how close are these drug delivery systems
link |
00:24:29.280
to something like a robot?
link |
00:24:31.040
Or is it totally wrong to think about them
link |
00:24:33.640
as intelligent agents?
link |
00:24:35.480
And how much room is there to add that kind of intelligence
link |
00:24:39.600
into these delivery systems, perhaps in the future?
link |
00:24:42.080
Yeah, I think it depends on the particular delivery system.
link |
00:24:45.280
Of course, one of the things people are concerned about
link |
00:24:47.040
is cost, and if you add a lot of bells and whistles
link |
00:24:49.560
to something, it'll cost more.
link |
00:24:51.400
But I mean, we, for example, have made
link |
00:24:54.200
what I'll call intelligent microchips
link |
00:24:55.920
that can, where you can send a signal
link |
00:24:58.840
and you'll release drug in response to that signal.
link |
00:25:01.840
And I think systems like that microchip someday
link |
00:25:04.600
have the potential to do what you and I
link |
00:25:06.040
were just talking about,
link |
00:25:07.400
that there could be a signal like glucose
link |
00:25:09.480
and it could have some instruction to say
link |
00:25:11.600
when there's more glucose, deliver more insulin.
link |
00:25:14.360
So do you think it's possible that there,
link |
00:25:16.000
that could be robotic type systems roaming our body
link |
00:25:19.640
sort of long term and be able to deliver
link |
00:25:21.640
certain kinds of drugs in the future?
link |
00:25:23.600
You see, do you see that kind of future?
link |
00:25:26.320
Someday, I don't think we're very close to it yet,
link |
00:25:29.000
but someday, you know that that's nanotechnology
link |
00:25:31.880
and that would mean even miniaturizing
link |
00:25:33.720
some of the things that I just discussed.
link |
00:25:35.760
And we're certainly not at that point yet,
link |
00:25:37.800
but someday I expect we will be.
link |
00:25:40.120
So some of it is just the shrinking of the technology.
link |
00:25:44.240
That's a part of it, that's one of the things.
link |
00:25:47.280
In general, what role do you see AI sort of,
link |
00:25:52.200
there's a lot of work now with using data
link |
00:25:55.160
to make intelligent, create systems
link |
00:25:57.200
that make intelligent decisions.
link |
00:25:59.080
Do you see any of that data driven kind of computing systems
link |
00:26:04.080
having a role in any part of this,
link |
00:26:09.480
into the delivery of drugs, the design of drugs
link |
00:26:13.320
and any part of the chain?
link |
00:26:15.240
I do, I think that AI can be useful
link |
00:26:18.080
in a number of parts of the chain.
link |
00:26:20.040
I mean, one, I think if you get a large amount
link |
00:26:22.880
of information, you know, say you have some chemical data
link |
00:26:26.320
because you've done high throughput screens
link |
00:26:29.040
and let's, I'll just make this up,
link |
00:26:30.600
but let's say I have a, I'm trying to come up with a drug
link |
00:26:33.560
to treat disease X, whatever that disease is
link |
00:26:37.800
and I have a test for that and hopefully a fast test
link |
00:26:43.520
and let's say I test 10,000 chemical substances
link |
00:26:47.520
and a couple work, most of them don't work,
link |
00:26:49.960
some maybe work a little, but if I had a,
link |
00:26:52.640
with the right kind of artificial intelligence,
link |
00:26:54.920
maybe you could look at the chemical structures
link |
00:26:57.160
and look at what works and see
link |
00:26:58.480
if there's certain commonalities,
link |
00:26:59.760
look at what doesn't work and see what commonalities
link |
00:27:02.480
there are and then maybe use that somehow
link |
00:27:05.240
to predict the next generation of things
link |
00:27:07.040
that you would test.
link |
00:27:08.520
As a tangent, what are your thoughts
link |
00:27:10.760
on our society's relationship with pharmaceutical drugs?
link |
00:27:14.840
Do we, and perhaps I apologize
link |
00:27:17.400
if this is a philosophical broader question,
link |
00:27:19.880
but do we over rely on them?
link |
00:27:22.240
Do we improperly prescribe them?
link |
00:27:24.720
In what ways is the system working well
link |
00:27:26.560
and what way can it improve?
link |
00:27:28.040
Well, I think pharmaceutical drugs are really important.
link |
00:27:33.040
I mean, the life expectancy and life quality of people
link |
00:27:37.080
over many, many years has increased tremendously
link |
00:27:40.200
and I think that's a really good thing.
link |
00:27:42.120
I think one thing that would also be good
link |
00:27:44.080
is if we could extend that more and more
link |
00:27:45.920
to people in the developing world,
link |
00:27:47.720
which is something that our lab has been doing
link |
00:27:49.920
with the Gates Foundation or trying to do.
link |
00:27:53.800
So I think ways in which it could improve,
link |
00:27:55.800
I mean, if there was some way to reduce costs,
link |
00:27:59.320
that's certainly an issue people are concerned about.
link |
00:28:01.680
If there was some way to help people in poor countries,
link |
00:28:05.280
that would also be a good thing.
link |
00:28:06.880
And then of course, we still need to make better drugs
link |
00:28:10.680
for so many diseases.
link |
00:28:12.360
I mean, cancer, diabetes.
link |
00:28:14.200
I mean, there's heart disease and rare diseases.
link |
00:28:17.680
There are many, many situations where it'd be great
link |
00:28:20.360
if we could do better and help more people.
link |
00:28:22.880
Can we talk about another exciting space,
link |
00:28:27.760
which is tissue engineering?
link |
00:28:29.520
What is tissue engineering or regenerative medicine?
link |
00:28:32.360
Yeah, so that tissue engineering or regenerative medicine
link |
00:28:35.440
have to do with building an organ or tissue from scratch.
link |
00:28:38.880
So someday maybe we can build a liver
link |
00:28:43.080
or make new cartilage and also would enable you
link |
00:28:47.360
to someday create organs on a chip,
link |
00:28:49.960
which we and others are trying to do,
link |
00:28:52.520
which might lead to better drug testing
link |
00:28:54.520
and maybe less testing on animals or people.
link |
00:28:57.920
Organs on a chip, that sounds fascinating.
link |
00:29:01.240
So what are the various ways to generate tissue?
link |
00:29:06.120
And how do, so is it, you know,
link |
00:29:08.320
the one is of course from stem cells.
link |
00:29:10.600
Is there other methods?
link |
00:29:11.960
What are the different possible flavors here?
link |
00:29:14.240
Yeah, well, I think, I mean, there's multiple components.
link |
00:29:17.440
One is having generally some type of scaffold.
link |
00:29:19.800
That's what Jay Vacanti and I started many, many years ago.
link |
00:29:23.800
And then on that scaffold,
link |
00:29:26.160
you might put different cell types,
link |
00:29:28.360
which could be a cartilage cell, a bone cell,
link |
00:29:30.600
could be a stem cell that might differentiate
link |
00:29:32.640
into different things, could be more than one cell.
link |
00:29:35.520
And the scaffold, sorry to interrupt,
link |
00:29:37.520
is kind of like a canvas that's a structure
link |
00:29:39.680
that you can, on which the cells can grow?
link |
00:29:43.000
I think that's a good explanation what you just did.
link |
00:29:44.960
I'll have to use that, the canvas, that's good.
link |
00:29:47.840
Yeah, so I think that that's fair.
link |
00:29:49.600
You know, and the chip could be such a canvas.
link |
00:29:52.600
Could be fibers that are made of plastics
link |
00:29:55.440
that you'd put in the body someday.
link |
00:29:57.080
And when you say chip, do you mean electronic chip?
link |
00:29:59.840
Like a...
link |
00:30:00.680
Not necessarily, it could be though.
link |
00:30:02.160
But it doesn't have to be, it could just be a structure
link |
00:30:04.820
that's not in vivo, so to speak,
link |
00:30:08.400
that's, you know, that's outside the body.
link |
00:30:10.920
So is there...
link |
00:30:11.760
Canvas is not a bad word.
link |
00:30:13.280
So is there a possibility to weave into this canvas
link |
00:30:20.200
a computational component?
link |
00:30:22.160
So if we talk about electronic chips,
link |
00:30:23.880
some ability to sense, control,
link |
00:30:28.000
some aspect of this growth process for the tissue.
link |
00:30:31.320
I would say the answer to that is yes.
link |
00:30:33.340
I think right now people are working mostly
link |
00:30:36.760
on validating these kinds of chips for saying,
link |
00:30:40.660
well, it does work as effectively,
link |
00:30:43.560
or hopefully as just putting something in the body.
link |
00:30:47.220
But I think someday what you suggested,
link |
00:30:49.380
you certainly would be possible.
link |
00:30:51.240
So what kind of tissues can we engineer today?
link |
00:30:53.600
What would, yeah.
link |
00:30:54.440
Yeah, well, so skin's already been made
link |
00:30:57.200
and approved by the FDA.
link |
00:30:58.780
There are advanced clinical trials,
link |
00:31:00.860
like what are called phase three trials,
link |
00:31:03.020
that are at complete or near completion
link |
00:31:05.440
for making new blood vessels.
link |
00:31:08.360
One of my former students, Laura Nicholson,
link |
00:31:10.480
led a lot of that.
link |
00:31:13.240
Oh, that's amazing.
link |
00:31:14.160
So human skin can be grown.
link |
00:31:16.240
That's already approved in the entire, the FDA process.
link |
00:31:20.480
So that means what,
link |
00:31:23.600
so one, that means you can grow that tissue
link |
00:31:27.920
and do various kinds of experiments
link |
00:31:30.040
in terms of drugs and so on.
link |
00:31:34.200
But what does that, does that mean
link |
00:31:35.760
that some kind of healing and treatment
link |
00:31:38.040
of different conditions for unhuman beings?
link |
00:31:41.240
Yes, I mean, they've been approved now for,
link |
00:31:43.560
I mean, different groups have made them,
link |
00:31:45.180
different companies and different professors,
link |
00:31:47.620
but they've been approved for burn victims
link |
00:31:50.600
and for patients with diabetic skin ulcers.
link |
00:31:53.240
That's amazing.
link |
00:31:54.960
Okay, so skin, what else?
link |
00:31:59.540
Well, at different stages,
link |
00:32:01.940
people are, like skin, blood vessels,
link |
00:32:05.240
there's clinical trials going now for helping patients
link |
00:32:08.580
hear better, for patients that might be paralyzed,
link |
00:32:12.320
for patients that have different eye problems.
link |
00:32:15.480
I mean, and different groups have worked on
link |
00:32:18.400
just about everything, new liver, new kidneys.
link |
00:32:20.840
I mean, there've been all kinds of work done in this area.
link |
00:32:24.480
Some of it's early, but there's certainly
link |
00:32:26.680
a lot of activity.
link |
00:32:27.680
What about neural tissue?
link |
00:32:30.300
Yeah.
link |
00:32:31.480
The nervous system and even the brain.
link |
00:32:34.160
Well, there've been people out of working on that too.
link |
00:32:36.200
We've done a little bit with that,
link |
00:32:37.440
but there are people who've done a lot on neural stem cells
link |
00:32:40.360
and I know Evan Snyder, who's been one of our collaborators
link |
00:32:43.280
on some of our spinal cord works done work like that
link |
00:32:46.200
and there've been other people as well.
link |
00:32:48.040
Is there challenges for the,
link |
00:32:51.120
when it is part of the human body,
link |
00:32:52.800
is there challenges to getting the body to accept
link |
00:32:55.780
this new tissue that's being generated?
link |
00:32:58.040
How do you solve that kind of challenge?
link |
00:33:00.120
There can be problems with accepting it.
link |
00:33:02.780
I think maybe in particular,
link |
00:33:04.600
you might mean rejection by the body.
link |
00:33:07.160
So there are multiple ways that people are trying
link |
00:33:09.340
to deal with that.
link |
00:33:10.180
One way is, which was what we've done with Dan Anderson,
link |
00:33:14.680
who was one of my former postdocs
link |
00:33:16.060
and I mentioned this a little bit before for a pancreas,
link |
00:33:19.520
is encapsulating the cells.
link |
00:33:20.840
So immune cells or antibodies can't get in and attack them.
link |
00:33:26.880
So that's a way to protect them.
link |
00:33:28.920
Other strategies could be making the cells non immunogenic,
link |
00:33:34.240
which might be done by different either techniques
link |
00:33:36.960
which might mask them or using some gene editing approaches.
link |
00:33:40.760
So there are different ways that people
link |
00:33:42.160
are trying to do that.
link |
00:33:43.600
And of course, if you use the patient's own cells
link |
00:33:45.560
or cells from a close relative, that might be another way.
link |
00:33:50.240
It increases the likelihood that it'll get accepted
link |
00:33:52.720
if you use the patient's own cells.
link |
00:33:54.440
Yes.
link |
00:33:55.320
And then finally, there's immunosuppressive drugs,
link |
00:33:57.700
which will suppress the immune response.
link |
00:34:00.320
That's right now what's done, say, for a liver transplant.
link |
00:34:03.940
The fact that this whole thing works is fascinating,
link |
00:34:06.240
at least from my outside perspective.
link |
00:34:09.880
Will we one day be able to regenerate any organ
link |
00:34:13.220
or part of the human body?
link |
00:34:15.640
Any of you?
link |
00:34:16.880
I mean, it's exciting to think about future possibilities
link |
00:34:19.400
of tissue engineering.
link |
00:34:22.720
Do you see some tissues more difficult than others?
link |
00:34:25.100
What are the possibilities here?
link |
00:34:27.000
Yeah, well, of course, I'm an optimist.
link |
00:34:29.160
And I also feel the timeframe,
link |
00:34:30.760
if we're talking about someday,
link |
00:34:32.320
someday could be hundreds of years.
link |
00:34:33.860
But I think that, yes, someday,
link |
00:34:36.080
I think we will be able to regenerate many things.
link |
00:34:39.280
And there are different strategies that one might use.
link |
00:34:41.840
One might use some cells themselves.
link |
00:34:44.840
One might use some molecules
link |
00:34:47.600
that might help regenerate the cells.
link |
00:34:49.700
And so I think there are different possibilities.
link |
00:34:51.920
What do you think that means for longevity?
link |
00:34:54.720
If we look maybe not someday, but 10, 20 years out,
link |
00:35:00.000
the possibilities of tissue engineering,
link |
00:35:01.840
the possibilities of the research that you're doing,
link |
00:35:04.440
does it have a significant impact
link |
00:35:06.800
on the longevity of human life?
link |
00:35:10.040
I don't know that we'll see
link |
00:35:11.120
a radical increase in longevity,
link |
00:35:12.800
but I think that in certain areas,
link |
00:35:15.900
we'll see people live better lives
link |
00:35:19.420
and maybe somewhat longer lives.
link |
00:35:21.700
What's the most beautiful scientific idea
link |
00:35:25.740
in bioengineering that you've come across
link |
00:35:28.220
in your years of research?
link |
00:35:30.740
I apologize for the romantic question.
link |
00:35:33.460
No, that's an interesting question.
link |
00:35:35.460
I certainly think what's happening right now
link |
00:35:37.900
with CRISPR is a beautiful idea.
link |
00:35:39.580
That certainly wasn't my idea.
link |
00:35:42.100
I mean, but I think it's very interesting here
link |
00:35:45.980
what people have capitalized on
link |
00:35:48.820
is that there's a mechanism by which bacteria
link |
00:35:52.980
are able to destroy viruses.
link |
00:35:54.780
And that understanding that leads to machinery
link |
00:35:58.620
to sort of cut and paste genes and fix a cell.
link |
00:36:06.860
So that kind of, do you see a promise
link |
00:36:09.380
for that kind of ability to copy and paste?
link |
00:36:13.700
I mean, like we said, the human body is complicated.
link |
00:36:16.860
Is that, that seems exceptionally difficult to do.
link |
00:36:23.260
I think it is exceptionally difficult to do,
link |
00:36:25.220
but that doesn't mean that it won't be done.
link |
00:36:27.940
There's a lot of companies and people trying to do it.
link |
00:36:30.460
And I think in some areas it will be done.
link |
00:36:32.500
Some of the ways that you might lower the bar
link |
00:36:36.300
are not, are just taking,
link |
00:36:39.180
like not necessarily doing it directly,
link |
00:36:40.900
but you could take a cell that might be useful,
link |
00:36:45.780
but you want to give it some cancer killing capabilities,
link |
00:36:48.740
something like what's called a CAR T cell.
link |
00:36:50.980
And that might be a different way
link |
00:36:52.380
of somehow making a CAR T cell and maybe making it better.
link |
00:36:56.260
So there might be sort of easier things
link |
00:36:58.460
and rather than just fixing the whole body.
link |
00:37:01.540
So the way a lot of things have moved with medicine
link |
00:37:04.100
over time is stepwise.
link |
00:37:06.140
So I can see things that might be easier to do
link |
00:37:10.260
than say, fix a brain.
link |
00:37:11.860
That would be very hard to do,
link |
00:37:13.940
but maybe someday that'll happen too.
link |
00:37:16.420
So in terms of stepwise, that's an interesting notion.
link |
00:37:19.260
Do you see that if you look at medicine or bioengineering,
link |
00:37:25.180
do you see that there is these big leaps
link |
00:37:29.140
that happen every decade or so, or some distant period,
link |
00:37:33.460
or is it a lot of incremental work?
link |
00:37:36.500
Not, I don't mean to reduce its impact
link |
00:37:39.020
by saying it's incremental,
link |
00:37:40.060
but is there sort of phase shifts in the science,
link |
00:37:46.300
big leaps?
link |
00:37:48.220
I think there's both.
link |
00:37:49.700
Every so often a new technique or a new technology comes out.
link |
00:37:54.300
I mean, genetic engineering was an example.
link |
00:37:56.660
I mentioned CRISPR.
link |
00:37:58.820
I think every so often things happen
link |
00:38:01.300
that make a big difference,
link |
00:38:03.340
but still there's to try to really make progress,
link |
00:38:07.580
make a new drug, make a new device.
link |
00:38:09.820
There's a lot of things.
link |
00:38:11.100
I don't know if I'd call them incremental,
link |
00:38:12.740
but there's a lot, a lot of work that needs to be done.
link |
00:38:15.780
Absolutely.
link |
00:38:16.940
So you have over, numbers could be off,
link |
00:38:20.900
but it's a big amount.
link |
00:38:22.020
You have over 1,100 current or pending patents
link |
00:38:25.340
that have been licensed, sublicensed
link |
00:38:27.260
to over 300 companies.
link |
00:38:29.660
What's your view, what in your view are the strengths
link |
00:38:33.980
and what are the drawbacks of the patenting process?
link |
00:38:36.660
Well, I think for the most part, there's strengths.
link |
00:38:39.260
I think that if you didn't have patents,
link |
00:38:42.220
especially in medicine,
link |
00:38:43.540
you'd never get the funding that it takes
link |
00:38:45.940
to make a new drug or a new device.
link |
00:38:47.660
I mean, which according to Tufts,
link |
00:38:49.420
to make a new drug costs over $2 billion right now.
link |
00:38:52.700
And nobody would even come close to giving you that money,
link |
00:38:55.780
any of that money, if it weren't for the patent system,
link |
00:39:00.780
because then anybody else could do it.
link |
00:39:03.100
That then leads to the negative though.
link |
00:39:08.300
Sometimes somebody does have a very successful drug
link |
00:39:11.860
and you certainly wanna try to make it available
link |
00:39:14.380
to everybody.
link |
00:39:15.860
And so the patent system allowed it to happen
link |
00:39:21.140
in the first place, but maybe it'll impede it
link |
00:39:23.820
after a little bit, or certainly to some people
link |
00:39:26.700
or to some companies, once it is out there.
link |
00:39:31.220
What's the, on the point of the cost,
link |
00:39:34.660
what would you say is the most expensive part
link |
00:39:37.620
of the $2 billion of making a drug?
link |
00:39:40.980
Human clinical trials.
link |
00:39:42.900
That is by far the most expensive.
link |
00:39:44.620
In terms of money or pain or both?
link |
00:39:47.540
Well, money, but pain goes, it's hard to know.
link |
00:39:50.660
I mean, but usually proving things that are,
link |
00:39:54.140
proving that something new is safe and effective in people
link |
00:39:57.740
is almost always the biggest expense.
link |
00:40:00.420
Could you linger on that for just a little longer
link |
00:40:02.740
and describe what it takes to prove,
link |
00:40:06.300
for people that don't know, in general,
link |
00:40:09.580
what it takes to prove that something is effective on humans?
link |
00:40:12.940
Well, you'd have to take a particular disease,
link |
00:40:17.660
but the process is you start out with,
link |
00:40:20.460
usually you start out with cells,
link |
00:40:21.980
then you'd go to animal models.
link |
00:40:23.420
Usually you have to do a couple animal models.
link |
00:40:25.780
And of course the animal models aren't perfect for humans.
link |
00:40:28.660
And then you have to do three sets of clinical trials
link |
00:40:31.060
at a minimum, a phase one trial to show that it's safe
link |
00:40:34.140
in small number of patients, a phase two trial
link |
00:40:36.580
to show that it's effective in a small number of patients,
link |
00:40:39.220
and a phase three trial to show that it's safe and effective
link |
00:40:42.500
in a large number of patients.
link |
00:40:44.540
And that could end up being hundreds
link |
00:40:46.900
or thousands of patients.
link |
00:40:49.260
And they have to be really carefully controlled studies.
link |
00:40:52.620
And you'd have to manufacture the drug,
link |
00:40:55.060
you'd have to really watch those patients.
link |
00:40:58.860
You have to be very concerned that it is gonna be safe.
link |
00:41:03.140
And then you look and see, does it treat the disease better
link |
00:41:07.500
than whatever the gold standard was before that?
link |
00:41:10.860
Assuming there was one.
link |
00:41:12.780
That's a really interesting line.
link |
00:41:14.420
Show that it's safe first, and then that it's effective.
link |
00:41:17.980
First do no harm.
link |
00:41:19.220
First do no harm, that's right.
link |
00:41:21.380
So how, again, if you can linger in a little bit,
link |
00:41:26.140
how does the patenting process work?
link |
00:41:29.140
Yeah, well, you do a certain amount of research,
link |
00:41:32.660
though that's not necessarily has to be the case.
link |
00:41:35.300
But for us, usually it is.
link |
00:41:36.820
Usually we do a certain amount of research
link |
00:41:40.420
and make some findings.
link |
00:41:41.860
And we had a hypothesis, let's say we prove it,
link |
00:41:46.380
or we make some discovery, we invent some technique.
link |
00:41:49.580
And then we write something up, what's called a disclosure.
link |
00:41:52.940
We give it to MIT's technology transfer office.
link |
00:41:55.620
They then give it to some patent attorneys,
link |
00:41:57.820
and they use that plus talking to us
link |
00:42:00.900
and work on writing a patent.
link |
00:42:03.740
And then you go back and forth with the USPTO,
link |
00:42:07.700
that's the United States Patent and Trademark Office.
link |
00:42:09.900
And they may not allow it the first, second or third time,
link |
00:42:14.340
but they will tell you why they don't.
link |
00:42:17.140
And you may adjust it,
link |
00:42:18.180
and maybe you'll eventually get it, and maybe you won't.
link |
00:42:21.540
So you've been part of launching 40 companies
link |
00:42:24.980
together worth, again, numbers could be outdated,
link |
00:42:28.500
but an estimated $23 billion.
link |
00:42:33.260
You've described your thoughts
link |
00:42:34.700
on a formula for startup success.
link |
00:42:36.980
So perhaps you can describe that formula
link |
00:42:38.940
and in general describe what does it take
link |
00:42:41.540
to build a successful startup?
link |
00:42:44.180
Well, I'd break that down into a couple of categories.
link |
00:42:46.540
And I'm a scientist and certainly
link |
00:42:48.660
from the science standpoint, I'll go over that.
link |
00:42:50.700
But I actually think that really the most important thing
link |
00:42:54.180
is probably the business people that I work with.
link |
00:42:57.660
And when I look back at the companies that have done well,
link |
00:43:01.580
it's been because we've had great business people.
link |
00:43:03.860
And when they haven't done as well,
link |
00:43:05.220
we haven't had as good business people.
link |
00:43:06.940
But from a science standpoint,
link |
00:43:08.820
I think about that we've made some kind of discovery
link |
00:43:12.540
that is almost what I'd call a platform
link |
00:43:15.340
that you could use it for different things.
link |
00:43:17.860
And certainly the drug delivery system example
link |
00:43:20.540
that I gave earlier is a good example of that.
link |
00:43:22.660
You could use it for drug A, B, C, D, E and so forth.
link |
00:43:27.100
And that I'd like to think that we've taken it far enough
link |
00:43:30.420
so that we've written at least one really good paper
link |
00:43:33.300
in a top journal, hopefully a number
link |
00:43:36.340
that we've reduced it to practice and animal models
link |
00:43:39.340
that we've filed patents, maybe had issued patents
link |
00:43:45.380
that have what I'll call very good and broad claims.
link |
00:43:48.340
That's sort of the key on a patent.
link |
00:43:50.860
And then in our case, a lot of times when we've done it,
link |
00:43:55.020
a lot of times it's somebody in the lab
link |
00:43:57.780
like a postdoc or graduate student
link |
00:43:59.380
that spent a big part of their life doing it
link |
00:44:01.740
and that they wanna work at that company
link |
00:44:03.740
because they have this passion
link |
00:44:04.780
that they wanna see something they did
link |
00:44:06.580
make a difference in people's lives.
link |
00:44:09.380
Maybe you can mention the business component.
link |
00:44:12.980
It's funny to hear Grace had to say
link |
00:44:15.300
that there's value to business folks.
link |
00:44:17.940
Oh yeah, well.
link |
00:44:18.780
That's not always said.
link |
00:44:20.420
So what value, what business instinct is valuable
link |
00:44:25.220
to make a startup successful, a company successful?
link |
00:44:29.180
I think the business aspects are,
link |
00:44:32.180
you have to be a good judge of people
link |
00:44:35.740
so that you hire the right people.
link |
00:44:37.700
You have to be strategic so you figure out
link |
00:44:40.460
if you do have that platform
link |
00:44:41.820
that could be used for all these different things.
link |
00:44:44.700
And knowing that medical research is so expensive,
link |
00:44:47.620
what thing are you gonna do first, second,
link |
00:44:49.180
third, fourth and fifth?
link |
00:44:51.980
I think you need to have a good,
link |
00:44:53.660
what I'll call FDA regulatory clinical trial strategy.
link |
00:44:58.100
I think you have to be able to raise money incredibly.
link |
00:45:01.580
So there are a lot of things.
link |
00:45:02.740
You have to be good with people, good manager of people.
link |
00:45:05.260
So the money and the people part I get,
link |
00:45:08.460
but the stuff before in terms of deciding the A, B, C, D,
link |
00:45:13.020
if you have a platform which drugs to first take a testing,
link |
00:45:16.660
you see nevertheless scientists
link |
00:45:18.900
as not being always too good at that process.
link |
00:45:22.580
Well, I think they're a part of the process,
link |
00:45:24.260
but I'd say there's probably, I'm gonna just make this up,
link |
00:45:28.180
but maybe six or seven criteria that you wanna use
link |
00:45:31.780
and it's not just science.
link |
00:45:33.300
I mean, the kinds of things that I would think about
link |
00:45:35.180
is, is the market big or small?
link |
00:45:37.900
Is the, are there good animal models for it
link |
00:45:41.260
so that you could test it and it wouldn't take 50 years?
link |
00:45:45.560
Are the clinical trials that could be set up
link |
00:45:48.420
ones that have clear end points
link |
00:45:51.960
where you can make a judgment?
link |
00:45:53.700
And another issue would be competition.
link |
00:45:58.860
Are there other ways that some companies
link |
00:46:00.420
out there are doing it?
link |
00:46:01.540
Another issue would be reimbursement.
link |
00:46:05.820
You know, can it get reimbursed?
link |
00:46:07.540
So a lot of things that you have manufacturing issues
link |
00:46:10.180
you'd wanna consider.
link |
00:46:11.860
So I think there are really a lot of things
link |
00:46:13.700
that go into whether you,
link |
00:46:15.540
what you do first, second, third, or fourth.
link |
00:46:19.300
So you lead one of the largest academic labs in the world
link |
00:46:23.100
with over $10 million in annual grants
link |
00:46:27.020
and over a hundred researchers,
link |
00:46:28.520
probably over a thousand since the lab's beginning.
link |
00:46:31.740
Researchers can be individualistic and eccentric.
link |
00:46:37.100
How do I put it nicely?
link |
00:46:38.580
There you go, eccentric.
link |
00:46:40.000
So what insights into research leadership can you give
link |
00:46:43.140
having to run such a successful lab
link |
00:46:45.340
with so much diverse talent?
link |
00:46:49.440
Well, I don't know that I'm any expert.
link |
00:46:50.780
I think that what you do to me,
link |
00:46:53.500
I mean, I just want,
link |
00:46:54.900
I mean, this is gonna sound very simplistic,
link |
00:46:56.380
but I just want people in the lab to be happy,
link |
00:46:58.940
to be doing things that I hope
link |
00:47:00.260
will make the world a better place,
link |
00:47:02.700
to be working on science
link |
00:47:04.460
that can make the world a better place.
link |
00:47:06.140
And I guess my feeling is if we're able to do that,
link |
00:47:11.300
you know, it kind of runs itself.
link |
00:47:13.940
So how do you make a researcher happy in general?
link |
00:47:17.360
I think when people feel,
link |
00:47:19.260
I mean, this is gonna sound like, again,
link |
00:47:21.460
simplistic or maybe like motherhood and apple pie,
link |
00:47:23.600
but I think if people feel they're working on something
link |
00:47:26.540
really important that can affect many other people's lives
link |
00:47:30.180
and they're making some progress,
link |
00:47:32.600
they'll feel good about it
link |
00:47:34.100
and they'll feel good about themselves
link |
00:47:35.420
and they'll be happy.
link |
00:47:37.240
But through brainstorming and so on,
link |
00:47:39.820
what's your role and how difficult is it as a group
link |
00:47:43.940
in this collaboration to arrive at these big questions
link |
00:47:49.420
that might have impact?
link |
00:47:51.100
Well, the big questions come from many different ways.
link |
00:47:54.620
Sometimes it's trying to, things that I might think of
link |
00:47:57.420
or somebody in the lab might think of,
link |
00:47:59.500
which could be a new technique
link |
00:48:00.900
or to understand something better.
link |
00:48:02.900
But gee, we've had people like Bill Gates
link |
00:48:05.560
and the Gates Foundation come to us
link |
00:48:07.180
and Juvenile Diabetes Foundation come to us and say,
link |
00:48:10.140
gee, could you help us on these things?
link |
00:48:11.740
And I mean, that's good too.
link |
00:48:13.540
It doesn't happen just one way.
link |
00:48:16.900
And I mean, you've kind of mentioned it, happiness,
link |
00:48:20.800
but is there something more,
link |
00:48:24.720
how do you inspire a researcher
link |
00:48:26.440
to do the best work of their life?
link |
00:48:28.300
So you mentioned passion and passion is a kind of fire.
link |
00:48:32.660
Do you see yourself having a role to keep that fire going,
link |
00:48:35.980
to build it up, to inspire the researchers
link |
00:48:39.900
through the pretty difficult process
link |
00:48:42.840
of going from idea to big question, to big answer?
link |
00:48:47.840
I think so.
link |
00:48:48.680
I think I try to do that by talking to people
link |
00:48:52.680
going over their ideas and their progress.
link |
00:48:56.840
I try to do it as an individual.
link |
00:49:00.000
Certainly when I talk about my own career,
link |
00:49:01.880
I had my setbacks at different times
link |
00:49:04.640
and people know that, that know me.
link |
00:49:06.920
And you just try to keep pushing and so forth.
link |
00:49:12.080
But yeah, I think I try to do that.
link |
00:49:15.760
But yeah, I think I try to do that
link |
00:49:17.920
as the one who leads the lab.
link |
00:49:20.960
So you have this exceptionally successful lab
link |
00:49:23.320
and one of the great institutions in the world, MIT.
link |
00:49:29.280
And yet sort of, at least in my neck of the woods
link |
00:49:32.680
in computer science and artificial intelligence,
link |
00:49:36.560
a lot of the research is kind of,
link |
00:49:40.520
a lot of the great researchers, not everyone,
link |
00:49:43.060
but some are kind of going to industry.
link |
00:49:46.920
A lot of the research is moving to industry.
link |
00:49:49.680
What do you think about the future of science in general?
link |
00:49:52.600
Is there drawbacks?
link |
00:49:54.440
Is there strength to the academic environment
link |
00:49:58.200
that you hope will persist?
link |
00:49:59.920
How does it need to change?
link |
00:50:02.120
What needs to stay the same?
link |
00:50:04.200
What are your thoughts on this whole landscape
link |
00:50:05.920
of science and its future?
link |
00:50:08.000
Well, first I think going to industry is good,
link |
00:50:10.400
but I think being in academia is good.
link |
00:50:12.840
You know, I have lots of students who've done both
link |
00:50:15.240
and they've had great careers doing both.
link |
00:50:18.480
I think from an academic standpoint,
link |
00:50:21.280
I mean, the biggest concern probably that people feel today,
link |
00:50:24.920
you know, at a place like MIT
link |
00:50:26.560
or other research heavy institutions is gonna be funding
link |
00:50:30.240
and particular funding that's not super directed,
link |
00:50:34.060
you know, so that you can do basic research.
link |
00:50:37.080
I think that's probably the number one thing,
link |
00:50:39.360
but you know, it would be great if we as a society
link |
00:50:43.400
could come up with better ways to teach,
link |
00:50:45.640
you know, so that people all over could learn better.
link |
00:50:50.160
You know, so I think there are a number of things
link |
00:50:51.820
that would be good to be able to do better.
link |
00:50:55.320
So again, you're very successful in terms of funding,
link |
00:50:58.900
but do you still feel the pressure of that,
link |
00:51:01.980
of having to seek funding?
link |
00:51:04.640
Does it affect the science or is it,
link |
00:51:07.420
or can you simply focus on doing the best work of your life
link |
00:51:11.260
and the funding comes along with that?
link |
00:51:14.040
I'd say the last 10 or 15 years,
link |
00:51:16.240
we've done pretty well funding,
link |
00:51:18.460
but I always worry about it.
link |
00:51:19.760
You know, it's like you're still operating
link |
00:51:23.640
on more soft money than hard.
link |
00:51:25.860
And so I always worry about it,
link |
00:51:27.760
but we've been fortunate that places have come to us
link |
00:51:33.000
like the Gates Foundation and others,
link |
00:51:34.880
Juvenile Diabetes Foundation, some companies,
link |
00:51:37.600
and they're willing to give us funding
link |
00:51:39.760
and we've gotten government money as well.
link |
00:51:42.200
We have a number of NIH grants and I've always had that
link |
00:51:44.760
and that's important to me too.
link |
00:51:47.180
So I worry about it, but you know,
link |
00:51:51.480
I just view that as a part of the process.
link |
00:51:53.760
Now, if you put yourself in the shoes of a philanthropist,
link |
00:51:57.440
like say I gave you $100 billion right now,
link |
00:52:02.200
but you couldn't spend it on your own research.
link |
00:52:05.560
So how hard is it to decide which labs to invest in,
link |
00:52:12.800
which ideas, which problems, which solutions?
link |
00:52:16.460
You know, cause funding is so much,
link |
00:52:19.120
such an important part of progression of science
link |
00:52:22.960
in today's society.
link |
00:52:24.560
So if you put yourself in the shoes of a philanthropist,
link |
00:52:26.720
how hard is that problem?
link |
00:52:27.560
How would you go about solving it?
link |
00:52:29.320
Sure, well, I think what I do, the first thing is different
link |
00:52:32.400
philanthropists have different visions.
link |
00:52:34.760
And I think the first thing is to form a concrete vision
link |
00:52:37.620
of what you want.
link |
00:52:38.460
Some people, I mean, I'll just give you two examples
link |
00:52:41.100
of people that I know.
link |
00:52:44.320
David Koch was very interested in cancer research
link |
00:52:47.480
and part of that was that he had prostate cancer.
link |
00:52:51.640
And a number of people do that along those lines.
link |
00:52:55.440
They've had somebody, they've either had cancer themselves
link |
00:52:57.960
or somebody they loved had cancer
link |
00:53:00.000
and they wanna put money into cancer research.
link |
00:53:02.700
Bill Gates, on the other hand,
link |
00:53:04.160
I think when he had got his fortune,
link |
00:53:06.480
I mean, he thought about it and felt, well,
link |
00:53:08.560
how could he have the greatest impact?
link |
00:53:10.180
And he thought about, you know, helping people
link |
00:53:12.520
in the developing world and medicines
link |
00:53:15.660
and different things like that, like vaccines
link |
00:53:18.040
that might be really helpful for people
link |
00:53:20.160
in the developing world.
link |
00:53:21.120
And so I think first you start out with that vision.
link |
00:53:25.720
Once you start out with that vision, whatever vision it is,
link |
00:53:29.440
then I think you try to ask the question,
link |
00:53:33.760
who in the world does the best work if that was your goal?
link |
00:53:38.360
I mean, but you really, I think have to have
link |
00:53:40.240
a defined vision.
link |
00:53:41.060
Vision first.
link |
00:53:41.900
Yeah, and I think that's what people do.
link |
00:53:45.080
I mean, I have never seen anybody do it otherwise.
link |
00:53:48.360
I mean, and that, by the way,
link |
00:53:49.760
may not be the best thing overall.
link |
00:53:53.280
I mean, I think it's good that all those things happen,
link |
00:53:55.600
but, you know, what you really want to do,
link |
00:53:57.800
and I'll make a contrast in a second,
link |
00:54:00.440
in addition to funding important areas,
link |
00:54:02.680
like what both of those people did, is to help young people.
link |
00:54:07.760
And they may be at odds with each other
link |
00:54:10.120
because a far more, a lab like ours,
link |
00:54:13.080
which is, you know, I'm older, is, you know,
link |
00:54:15.680
might be very good at addressing some of those kinds
link |
00:54:18.680
of problems, but, you know, I'm not young.
link |
00:54:20.680
I train a lot of people who are young,
link |
00:54:22.720
but it's not the same as helping somebody
link |
00:54:24.480
who's an assistant professor someplace.
link |
00:54:26.480
So I think what's, I think, been good about our thing,
link |
00:54:30.960
our society, or things overall,
link |
00:54:33.280
are that there are people who come at it
link |
00:54:35.040
from different ways, and the combination,
link |
00:54:37.840
the confluence of the government funding,
link |
00:54:40.380
the certain foundations that fund things,
link |
00:54:43.880
and other foundations that, you know,
link |
00:54:46.640
want to see disease treated,
link |
00:54:48.280
well, then they can go seek out people,
link |
00:54:51.480
or they can put a request for proposals
link |
00:54:53.240
and see who does the best.
link |
00:54:54.680
You know, I'd say both David Koch and Bill Gates
link |
00:54:58.000
did exactly that.
link |
00:54:58.960
They sought out people, both of them, you know,
link |
00:55:02.200
or their foundations that they were involved in,
link |
00:55:04.200
sought out people like myself.
link |
00:55:07.480
But they also had requests for proposals.
link |
00:55:11.400
Now, you mentioned young people,
link |
00:55:12.720
and that reminds me of something you said
link |
00:55:14.160
in an interview of Written Somewhere,
link |
00:55:17.720
that said some of your initial struggles
link |
00:55:21.840
in terms of finding a faculty position, or so on,
link |
00:55:28.200
that you didn't quite, for people,
link |
00:55:30.120
fit into a particular bucket, a particular.
link |
00:55:33.000
Right.
link |
00:55:35.000
Can you speak to that?
link |
00:55:38.240
How, do you see limitations to the academic system
link |
00:55:41.760
that it does have such buckets?
link |
00:55:44.120
Is there, how can we allow for people
link |
00:55:49.120
who are brilliant, but outside the disciplines
link |
00:55:56.400
of the previous decade?
link |
00:55:59.600
Yeah, well, I think that's a great question.
link |
00:56:01.320
I think that, I think the department heads
link |
00:56:03.620
have to have a vision, you know, and some of them do.
link |
00:56:07.040
Every so often, you know, there are institutes
link |
00:56:11.040
or labs that do that.
link |
00:56:13.400
I mean, at MIT, I think that's done sometimes.
link |
00:56:17.480
I know mechanical engineering department just had a search,
link |
00:56:21.240
and they hired Gio Traverso, who is one of my,
link |
00:56:25.440
he was a fellow with me, but he's actually
link |
00:56:28.200
a molecular biologist and a gastroenterologist.
link |
00:56:32.000
And, you know, he's one of the best in the world,
link |
00:56:34.200
but he's also done some great mechanical engineering
link |
00:56:37.240
and designing some new pills and things like that.
link |
00:56:39.800
And they picked him, and boy, I give them a lot of credit.
link |
00:56:43.880
I mean, that's vision, to pick somebody.
link |
00:56:46.880
And I think, you know, they'll be the richer four.
link |
00:56:49.880
I think the Media Lab has certainly hired, you know,
link |
00:56:52.120
people like Ed Boyden and others who have done,
link |
00:56:55.400
you know, very different things.
link |
00:56:56.820
And so I think that, you know, that's part of the vision
link |
00:57:00.480
of the leadership who do things like that.
link |
00:57:03.560
Do you think one day, you've mentioned David Koch and cancer,
link |
00:57:07.320
do you think one day we'll cure cancer?
link |
00:57:10.520
Yeah, I mean, of course, one day,
link |
00:57:12.240
I don't know how long that day will come.
link |
00:57:14.280
Soon.
link |
00:57:15.120
Yeah, soon, soon, no, but I think.
link |
00:57:17.520
So you think it is a grand challenge,
link |
00:57:19.200
it is a grand challenge,
link |
00:57:20.120
it's not just solvable within a few years.
link |
00:57:22.680
No, I don't think very many things
link |
00:57:24.460
are solvable in a few years.
link |
00:57:25.940
There's some good ideas that people are working on,
link |
00:57:28.580
but I mean, all cancers, that's pretty tough.
link |
00:57:32.160
If we do get the cure, what will the cure look like?
link |
00:57:35.000
Do you think which mechanisms,
link |
00:57:37.260
which disciplines will help us arrive at that cure
link |
00:57:40.200
from all the amazing work you've done
link |
00:57:42.680
that has touched on cancer?
link |
00:57:44.000
No, I think it'll be a combination
link |
00:57:45.520
of biology and engineering.
link |
00:57:46.800
I think it'll be biology to understand
link |
00:57:50.440
the right genetic mechanisms to solve this problem
link |
00:57:54.040
and maybe the right immunological mechanisms
link |
00:57:56.400
and engineering in the sense of producing the molecules,
link |
00:58:00.400
developing the right delivery systems,
link |
00:58:02.200
targeting it or whatever else needs to be done.
link |
00:58:05.680
Well, that's a beautiful vision for engineering.
link |
00:58:08.920
So on a lighter topic, I've read that you love chocolate
link |
00:58:11.880
and mentioned two places, Ben and Bill's Chocolate Aquarium
link |
00:58:16.920
and the chocolate cookies, the Soho Globs
link |
00:58:20.280
from Rosie's Bakery in Chestnut Hill.
link |
00:58:22.620
I went to their website and I was trying
link |
00:58:25.400
to finish a paper last night.
link |
00:58:26.960
There's a deadline today and yet I was wasting
link |
00:58:30.700
way too much time at 3 a.m. instead of writing the paper,
link |
00:58:34.200
staring at the Rosie Baker's cookies,
link |
00:58:36.400
which are just look incredible.
link |
00:58:38.320
The Soho Globs just look incredible.
link |
00:58:40.680
But for me, oatmeal white raisin cookies won my heart
link |
00:58:44.680
just from the pictures.
link |
00:58:46.460
Do you think one day we'll be able to engineer
link |
00:58:49.040
the perfect cookie with the help of chemistry
link |
00:58:52.900
and maybe a bit of data driven artificial intelligence
link |
00:58:55.440
or is cookies something that's more art than engineering?
link |
00:59:02.480
I think there's some of both.
link |
00:59:03.600
I think engineering will probably help someday.
link |
00:59:06.960
What about chocolate?
link |
00:59:08.640
Same thing, same thing.
link |
00:59:09.900
You'd have to go to see some of David Edwards stuff.
link |
00:59:12.840
He was one of my postdocs and he's a professor at Harvard
link |
00:59:15.840
but he also started Cafe Art Sciences
link |
00:59:18.520
and it's just a really cool restaurant around here.
link |
00:59:22.440
But he also has companies that do ways
link |
00:59:26.960
of looking at fragrances and trying to use engineering
link |
00:59:30.360
in new ways and so I think that's just an example.
link |
00:59:34.280
But I expect someday that AI and engineering
link |
00:59:38.200
will play a role in almost everything.
link |
00:59:40.920
Including creating the perfect cookie.
link |
00:59:42.640
Yes.
link |
00:59:43.480
Well, I dream of that day as well.
link |
00:59:45.240
So when you look back at your life,
link |
00:59:47.760
having accomplished an incredible amount of positive impact
link |
00:59:50.640
on the world through science and engineering,
link |
00:59:53.600
what are you most proud of?
link |
00:59:56.320
My students, I really feel when I look at that,
link |
00:59:59.400
we've probably had close to 1,000 students
link |
01:00:02.320
go through the lab and they've done incredibly well.
link |
01:00:06.760
I think 18 are in the National Academy of Engineering,
link |
01:00:09.720
16 in the National Academy of Medicine.
link |
01:00:12.280
I mean, they've been CEOs of companies,
link |
01:00:15.280
presidents of universities and they've done,
link |
01:00:19.460
I think eight are faculty at MIT,
link |
01:00:21.200
maybe about 12 at Harvard.
link |
01:00:22.940
I mean, so it really makes you feel good
link |
01:00:25.680
to think that the people, they're not my children
link |
01:00:28.780
but they're close to my children in a way
link |
01:00:31.200
and it makes you feel really good
link |
01:00:32.720
to see them have such great lives
link |
01:00:34.660
and them do so much good and be happy.
link |
01:00:37.760
Well, I think that's a perfect way to end it, Bob.
link |
01:00:40.080
Thank you so much for talking to me.
link |
01:00:41.160
My pleasure.
link |
01:00:41.980
It was an honor.
link |
01:00:42.820
Good questions.
link |
01:00:43.660
Thank you.
link |
01:00:44.480
Thanks for listening to this conversation with Bob Langer
link |
01:00:48.000
and thank you to our sponsors, Cash App and Masterclass.
link |
01:00:52.120
Please consider supporting the podcast
link |
01:00:53.980
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link |
01:00:58.640
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01:01:02.720
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link |
01:01:05.360
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01:01:07.240
and the journey I'm on in my research and startup.
link |
01:01:11.240
If you enjoy this thing, subscribe on YouTube,
link |
01:01:13.840
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01:01:16.140
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link |
01:01:19.080
at Lex Friedman, spelled without the E, just F R I D M A N.
link |
01:01:25.360
And now let me leave you with some words from Bill Bryson
link |
01:01:28.080
in his book, A Short History of Nearly Everything.
link |
01:01:31.120
If this book has a lesson,
link |
01:01:33.880
it is that we're awfully lucky to be here.
link |
01:01:36.480
And by we, I mean every living thing.
link |
01:01:39.640
To attain any kind of life in this universe of ours
link |
01:01:42.500
appears to be quite an achievement.
link |
01:01:44.800
As humans, we're doubly lucky, of course.
link |
01:01:47.460
We enjoy not only the privilege of existence,
link |
01:01:50.080
but also the singular ability to appreciate it
link |
01:01:53.460
and even in a multitude of ways to make it better.
link |
01:01:57.600
It is talent we have only barely begun to grasp.
link |
01:02:01.800
Thank you for listening and hope to see you next time.