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