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
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podcast. 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, uh, you know, and I
think science can surprise you. And there’s something magical
about, about science. I mean, making discoveries and things
like that. Yeah. So on the, and then on the magic side, is
there some kind of engineering scientific process to the tricks
themselves? Do you see, cause there’s a duality to it. One is
you’re the, um, you’re, 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, it’s something that, that you might
dream about and hoping 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’re 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, we’ll put it back in the deck. But what I’d
like you to do is turn it up upside down from every other
card in the deck. So they do that imaginary. And I say,
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, if 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 citations. 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 or
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
had done that before. And so that was part A, let’s say 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’d done some really good work. And Dr.
Folkman thought we’d done some really good work. And, 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 rejection, 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 didn’t 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, that, you know,
that 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 a sort of a rigorous process? Or is it
It’s more spontaneous. I mean, part of its exposure to things,
part of its 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. And so I
don’t know. 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
that you could engineer tissues for the first time or make
dishes from scratch on the first time. But another thing is
really just deeply understanding something. And that’s important
too. So 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 aha 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 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. I mean, there, we had to invent something that
would do that. But other times, it’s, it’s, it’s different.
Sometimes it’s really understanding what goes on in
terms of understanding the mechanisms. And so it’s, it’s,
it’s not a single thing. And there are many different parts
to it, you know, over the years, we’ve invented different or
discovered different principles for aerosols for delivering,
you know, genetic therapy agents, you know, all kinds of
So let’s explore some of the key ideas you’ve touched on in your
life. Let’s start with the basics. Okay. So 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.
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 its
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
Are there? I mean, if you just look at the other things that
are there knobs that are reliably controllable about the
human body, if you consider is there is it? 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 there are 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 an example, which goes back to
what I said before. So when I was doing my postdoctoral work
with Judah 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 and which means spread throughout the body and
ultimately kill somebody. So that was part of what we were
trying to do. We tried what 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 bio
assay 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. That so after we had the
polymer system and we had the bio assay, 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 science in 1976. Those were
really the isolation of some of the very first angiogenesis and
blood vessel inhibitors.
So there’s a lot of words there. Yeah, let’s go. First of all,
polymer molecules, big, big molecules. So the what are
polymers? What’s bio assay? What is the process of trying to
isolate this whole thing simplified to where you can
control and experiment with it?
Polymers are like plastics or like plastics or rubber. What
were some of the other questions?
Sorry, 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 idea is that there would be a
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 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 the what we call
the bio assay is the way that we would study that.
So, sorry, so what is a bio assay? Which part is the bio
All of it. In other words, the bio assay 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 that gets to your original question. So you
go through various steps. We did the first steps. We showed
that a 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 growth
factors and ways to stop the blood vessels from growing. That
like I say, it took 28 years, it took billions of dollars and
work by many companies like Genetec. 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, macular.
So in general, one of the key ways you can alleviate, 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? 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, you know, chemotherapy or immunotherapy
is going to be, 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 can sort of linger on it, when
you’re thinking about these ideas at the time, were you
feeling you’re out 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?
Well, there was, I mean, for me, actually, it wasn’t just
It was that I didn’t know a lot of biology or biochemistry.
So I certainly felt I was in the dark, but I kept trying and
I kept trying to learn and I kept plugging.
But I mean, a lot of it was being in the dark.
So the human body is complicated, right?
We’ll establish this.
Quantum mechanics in 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’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 dark.
It really has varied.
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 trying to work with this.
Is it a kind of a mix of serendipitous discovery and art,
or is there a systematic science to trying different chemical
reactions and how they affect whatever you’re trying to do,
like shrink blood vessels?
Yeah, I don’t think there’s a single way to go about
something in terms of characterizing the entire drug
If I look at the blood vessel one,
yeah, there the first step was to have 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 at least
quantitate or semi quantitate it.
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 drugs, chemicals that
are able to improve some aspects of our bodies?
Or is it quite natural that we’re
able to discover these kinds of things?
Well, at a high level, it is amazing.
I mean, evolution is amazing.
The way I look at your question, the fact
that we 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 from starting
from your early seminal work in the field to 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 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?
So 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, one example might be if you were diabetic,
if you got more glucose, could you get more insulin?
But that’s just an example.
Is there some way to control the actual mechanism
of delivery in response to what the body’s 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 the cells will make insulin.
And so 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.
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, where you can send a signal
and you’ll 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 of 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, you know, say you have some chemical data
because you’ve done high throughput screens
and let’s, I’ll just make this up,
but let’s say I have a, 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 a,
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 rely on them?
Do we improperly prescribe them?
In what ways is the system working well
and 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 or trying to do.
So I think ways in which it could improve,
I mean, if there was 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 we and others are trying to do,
which might lead to better drug testing
and maybe less testing on animals or people.
Organs on a chip, that sounds fascinating.
So what are the various ways to generate tissue?
And how do, so is it, you know,
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 Vacanti 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 the scaffold, sorry to interrupt,
is kind of like a canvas that’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.
You know, 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, you know, 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 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?
What would, yeah.
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.
Oh, that’s amazing.
So human skin can be grown.
That’s already approved in the entire, the FDA process.
So that means what,
so one, that means you can grow that tissue
and do various kinds of experiments
in terms of drugs and so on.
But what does that, does that mean
that some kind of healing and treatment
of different conditions for unhuman 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.
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, and 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?
The nervous system and even the brain.
Well, there’ve 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’ve 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 with Dan Anderson,
who was one of my former postdocs
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.
It increases the likelihood that it’ll get accepted
if you use the patient’s own cells.
And then finally, there’s immunosuppressive drugs,
which will suppress the immune response.
That’s right now what’s done, say, for a liver transplant.
The fact that this whole thing works is fascinating,
at least from my outside perspective.
Will we one day be able to regenerate any organ
or part of the human body?
Any of you?
I mean, it’s exciting to think about future possibilities
of tissue engineering.
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 the 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 of 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 question.
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 that understanding that leads to machinery
to sort of 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?
I mean, like we said, the human body is complicated.
Is that, 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 not, are just taking,
like not necessarily doing it directly,
but you could take a cell that might be useful,
but you want to give it some cancer killing capabilities,
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 sort of easier things
and rather than just fixing the whole body.
So the way a lot of things have moved with 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 sort of phase shifts in the science,
I think there’s both.
Every so often a new technique or a 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 there’s 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.
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, sublicensed
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.
I mean, 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 wanna try to make it available
And so the patent system 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 the, 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, it’s hard to know.
I mean, but usually proving things that are,
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 it 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 a 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 gonna be safe.
And then you look and see, 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 how, again, if you can linger in a little bit,
how does the patenting process work?
Yeah, well, you do a certain amount of research,
though 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 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 had 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 on 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 postdoc or graduate student
that spent a big part of their life doing it
and that they wanna work at that company
because they have this passion
that they wanna see something they did
make a difference in people’s lives.
Maybe you can mention the business component.
It’s funny to hear Grace 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 gonna do first, second,
third, fourth and fifth?
I think you need to have a good,
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 A, B, C, D,
if you have a platform which drugs to first 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 gonna just make this up,
but maybe six or seven criteria that you wanna use
and it’s not just science.
I mean, the kinds of things that I would think about
is, is the market big or small?
Is the, 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 end points
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.
You know, can it get reimbursed?
So a lot of things that you have manufacturing issues
you’d wanna consider.
So I think there are really a lot of things
that go into whether you,
what you do first, second, third, or fourth.
So you lead one of the largest academic labs in the world
with over $10 million in annual grants
and over a hundred 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 mean, this is gonna 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?
I think when people feel,
I mean, this is gonna 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 it
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 is it as a group
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 the 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 at 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.
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 sort of, 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 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.
You know, I have lots of students who’ve done both
and they’ve had great careers doing both.
I think from an academic standpoint,
I mean, the biggest concern probably that people feel today,
you know, at a place like MIT
or other research heavy institutions is gonna be funding
and particular funding that’s not super directed,
you know, so that you can do basic research.
I think that’s probably the number one thing,
but you know, it would be great if we as a society
could come up with better ways to teach,
you know, so that people all over could learn better.
You know, 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 you know,
I just view that as a part of the process.
Now, if you put yourself in the shoes of a philanthropist,
like 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?
You know, cause 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 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 wanna put money into cancer research.
Bill Gates, on the other hand,
I think when he had got his fortune,
I mean, he thought about it and felt, well,
how could he have the greatest impact?
And he thought about, you know, 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.
Yeah, 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, you know, what you really want to do,
and 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 far more, a lab like ours,
which is, you know, I’m older, is, you know,
might be very good at addressing some of those kinds
of problems, but, you know, I’m not young.
I train a lot of people who are young,
but it’s not the same as helping somebody
who’s an assistant professor someplace.
So I think what’s, I think, been good about our thing,
our society, or things overall,
are 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 know,
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.
You know, I’d say both David Koch and Bill Gates
did exactly that.
They sought out people, both of them, you know,
or their foundations that they were involved in,
sought out people like myself.
But they also had requests for proposals.
Now, 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.
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 that, I think the department heads
have to have a vision, you know, and some of them do.
Every so often, you know, 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 Gio Traverso, who is one of my,
he was a fellow with me, but he’s actually
a molecular biologist and a gastroenterologist.
And, you know, 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.
And they picked him, and boy, I give them a lot of credit.
I mean, that’s vision, to pick somebody.
And I think, you know, they’ll be the richer four.
I think the Media Lab has certainly hired, you know,
people like Ed Boyden and others who have done,
you know, very different things.
And so I think that, you know, that’s part of the vision
of the leadership who do things like that.
Do you think one day, you’ve mentioned David Koch and cancer,
do you think one day we’ll cure cancer?
Yeah, I mean, of course, one day,
I don’t know how long that day will come.
Yeah, soon, 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.
No, 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 Aquarium
and the chocolate cookies, the Soho Globs
from Rosie’s Bakery in 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 are just look incredible.
The Soho Globs just 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 postdocs 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 and so I think 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.
Well, I dream of that day as well.
So 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 1,000 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.
I mean, they’ve been CEOs of companies,
presidents of universities and they’ve done,
I think eight are faculty at MIT,
maybe about 12 at Harvard.
I mean, so 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 it 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 to me.
It was an honor.
Thanks for listening to this conversation with Bob Langer
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And now let me leave you with some words from Bill Bryson
in his book, A Short History of Nearly Everything.
If 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.