Kind: captions
Language: en
the following is a conversation was 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
corona virus pandemic his research and
companies are at the forefront of
developing treatments for covert 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 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 you know so on then
on the magic side is there some kind of
engineering scientific process to the
tricks themselves do you see because
there's a duality to it one is your the
your you're sort of the person inside
there 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's 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 you might dream about and helping
to discover maybe you do or 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
but first you say to somebody is this is
invisible and this deck and you say well
shuffle it and I shuffle it but you know
there's 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 and I look at it and let's say it's
the three of hearts and said we'll put
it back in the deck but what I'd like
you to do is turn it upside down from
every other cards in the deck so they
they do that imaginary and I said you
want to shuffle it again 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 all three hearts so it just so
happens in my back pocket I have this
deck it's you know it's a real deck I
show - you know it's 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-55
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 two hundred ninety five
thousand citation an h-index of 269
you're one of the most sighted 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 to you know I 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 post-doctorate
advisor Judah Folkman substances that
could stop blood vessels from growing
and nobody 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 I 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
revise tenets of 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've 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 uh as 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 been done
much better or is the underlying
confidence what was the feelings well
you feel to feel depressed that 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 the you to 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 go through
stages and so you say well okay I'll
explain it better next time and
certainly you get reviews and what 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 mmm 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 more
spontaneous 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 post doctoral
adviser 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 and I think you could spot an
idea that might have potential when you
see it you know because it could have a
very broad implications where a lot of
people might just keep doing derivative
stuff and so 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 if if you dig
deeper yeah it's it's sort of hard to
say because there's 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
dishes from scratch from the first time
but another thing is really just deeply
understanding something and that's
important too so and 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 and 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 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 yeah 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 it 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
discover different principles for
aerosols for delivering you know genetic
therapy agents you know all kinds of
things so let's explore some of the key
ideas you've touched on in your life
some let's 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 it's but so that you know
for me especially coming from the field
of computer science and computer
engineering and robotics it's
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 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 go are there I mean if
you just look are there other things
that are there knobs that are reliably
controllable about the human body if you
could service 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
about 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 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 sec sure what is
the 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 it you know provides oxygen it
provides nutrients gets rid of waste so
you know two different parts of your
body if you soso 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 event which means
spread throughout the body and
ultimately kill somebody so that was
part of what we were trying to do we
shot 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
essay to study blood vessel growth again
there wasn't one that's where we needed
polymer systems because the blood
vessels grew slowly took months that so
after we had the polymer system and we
had the bioassay then I had 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 of blood
vessel inhibitors so there's a lot of
words there yeah that's the the first of
all polymer molecules big big molecules
so the water polymers
what's bio sa the the what is the
process is 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 ideas that there would be
particular blood vessels that you can
target say they're connected some
Auto tumour you could target and over a
long period of time to be able to place
the polymer there and it be delivering a
certain kind of chemical that's correct
I think what you said it's good so so
that it would deliver the 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 sa is the way that we would
study that so size of what is a by us
which part is the bio sa all of it in
other words the bio SAS is the way you
study blood vessel growth the blood
vessel growth and you can control this
somehow with is there an understanding
what kind of chemicals can control the
growth of a blood 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 said
even isolated fractions you know groups
of substances that would would do it but
what would happen over the next we did
that in 1976 we published that what
would happen over the next twenty eight
years as 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 I
thought like you say it took 28 years it
took billions of dollars and work by
many companies like Genentech but in
2004 28 years after we started the first
one of those Avastin got approved by the
fda and that that be 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 to where you have
abnormal blood vessel growth macula so
in general one of the key ways you can
alleviate
so what's the hope in terms of tumors
associated with cancerous tumors they
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 and you 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 gonna
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 yeah
cancer well you know in retrospect it's
an obvious idea but when dr. Folkman and
my boss first proposed it it wasn't a
lot of people didn't thought it was
pretty crazy and so they in what sense
if you could sort of linger on it when
you're thinking about this 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 yeah well
there was I mean for me actually it
wasn't just the idea was that I didn't
know a lot of biology or biochemistry so
I've certainly felt a host 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'll
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 our drugs the same and 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
wish to interfere them with them other
times is shooting in the dark is it
really has varied okay
and sometimes people make sure--and
Jupitus discoveries and they don't even
realize what they did so what is the
discovery process for a drug ze said a
bunch of people of trying to work with
this is it is it a kind of mix of
serendipitous discovery and art or is
there a systematic science to trying
different chemical reactions and how
they how they affect whatever you trying
to do like shrink blood vessels yeah I
don't think there's a single way you
know single way to go about something in
terms of characterizing the entire drug
discovery process if I look at the blood
vessel one yeah they're the first step
was to do to have that those 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-quantitative
a third step was to find substances that
would stop blood vessels from growing
for 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 those 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 there you know are the
create drugs chemicals that are able to
improve some aspects of our bodies Hey
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 yeah 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 that today well drug delivery is
getting a drug to to be good 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 the cancer
cell and no other cell another challenge
is to get drugs across different
barriers like could you ever give
insulin orally could you give a train
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 it's just think so smart
smart they have some kind of sense a
chemical sensor or is this something
more than a chemical sense that it's
able to respond to something in the body
could be either one I mean you know I I
mean one example might be if you that
were diabetic if you had more it 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 a
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 will
happen is glucose will go in and you
know to sell so we'll 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 they're
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 don't
you know where you can send a signal and
you know release drug in response to
that say no and I think systems like
that microchip someday have the
potential to do it 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 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 there's a
lot of work now with using data to make
intelligent and 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 and drugs the the
design of drugs and any part of the
chain I do I think that AI can be useful
and 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
out I'll just make this up but let's say
I have I'm trying to come up with a drug
to treat disease X and whatever that
disease is and I have a test for that
and hopefully a fast test and let's say
I test ten thousand chemical substances
you know and a couple work most of them
don't work so I maybe work a little but
if I had a few 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 project
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 properly
prescribed them and what ways the system
working well what way can improve
well I think you know 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 as 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 I saw I think ways in which it could
improve I mean our if there was some way
to reduce costs you know that that's
certainly an issue people are concerned
about if there was some way to help
people and 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 we you know it's hard to see some
rare diseases there are many many
situations where it would be great if we
could do better and help more people can
we talk about another exciting another
exciting space which is tissue
engineering
what is tissue engineering or
regenerative medicine you know so that
tissue engineering regenerative medicine
have to do with building an organ or
tissue from scratch so you know someday
maybe we can build the liver you know or
make new cartilage and also would enable
you to you know 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 for people organs and I chip it
sounds fascinating so what what are the
various ways to generate tissue and how
do so is it you know that one is of
course from stem cells is there are
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
though it might differentiate into
different things could be more than one
cell and the scaffold
sorry to interrupt is kind of like a
canvas that it's a structure that you
can on which the
the Susskind girl I think that's a good
explanation when you just enough to use
that the caskets that's good
yeah so I think that that's fair you
know when the chip could be such a
canvas some could be fibers that are
made of plastics and that you'd put in
the body someday and we need a chip do
you mean electronic chip like
necessarily it could be though but it
doesn't have to be it could just be a
structure that's not not in vivo so to
speak that's you know that's outside the
body so is there a nervousness it's not
a bad word says there possibility to
weave into the scanner as a
computational component so if we talk
about electron ships some 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 con chips for saying
well it does work as effectively or
hopefully as just putting something in
the body but I think someday will you
suggest it you certainly would be
possible so what kind of tissues can we
engineer today what would yeah yeah well
well so skin has already been made and
approved by the FDA their 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 Lorin
Nicholson led a lot of that he thought
that's amazing this human skin can be
grown that's already approved through
the entire the FDA process so that means
what so the one that means you can grow
that tissue and do various kinds of
experiments in terms of in terms of
drugs and so on but what is that does
that mean that some kind of healing and
treatment of different conditions for on
human beings yes I mean they've been
approved now for how many 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 here better for
patients that might be paralyzed for
patients that have different hai
problems I'm you know at different
groups have worked on just about
everything new liver and who kidneys I
mean there have been all kinds of work
done in this area some of its early but
but there's certainly a lot of activity
what about neural tissue yeah nurten the
nervous system and even the brain while
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
Schneider who's been one of our
collaborators on some of our spinal cord
works done work like that and ever been
other people as well as their challenges
for the when it is part of the human
bodies there's challenges to getting the
the body to accept this new tissue
that's being generated how do you solve
that kind of challenge there can be
problems with it 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 one of
my former postdocs and I mentioned this
a little bit before for a painted
pancreas is encapsulating the cell so
immune 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 not immuno genic which might be
done by different either techniques
which might mask them or using some gene
editing approaches so they're 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
doubt might be another way and it
increases the likelihood that they'll
get accepted if you use the patient's
own cells yes and then finally there's
some you know suppressive drugs which
you know will suppress the immune
response that's right now what's done
say for a liver transplant the fact that
this whole thing works just fascinating
at least from my
outside perspective well we one day be
able to regenerate any organ or part of
the the human body in your view and 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 Wow of course I'm an optimist
and I also feel a timeframe if we're
talking about some day some day could be
hundreds of years but I think that yes
some day I think we will be able to
regenerate many things and our different
strategies that one might use the one
might use some cells themselves one
might use you know 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 are the
possibilities that tissue engineering
the possibilities of the research that
you're doing does it have a significant
impact on the longevity 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 so somewhat
longer lives with the most beautiful
scientific idea in biology nearing 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 is happening right
now with CRISPR is a beautiful idea that
certainly wasn't wasn't my idea I mean
but you know I think it's very
interesting here what what people have
capitalized on is that there's a
mechanism by which bacteria are able to
destroy viruses and that understanding
that let leads the machinery to to put
you know to sort of cut and paste genes
and and you know fix the cell so that
kind of you see a promise for that kind
of ability to copy and paste I mean
everything like we said the human body
is complicated
is that Mele difficult to do I think it
is exceptionally difficult to do but
that doesn't mean they 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 make you might lower the bar are
not you know are just taking look like
not necessarily doing it directly but
you know you could take a cell that
might be useful but you want to give it
some cancer-killing capabilities
something collect what's called the cart
C cell and that might be a different way
of somehow making a cart C 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 to in 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 the
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 yeah is there sort of
phase shifts in in the science big big
leaps
I think there's both you know every so
often a new technique or new technology
comes out
I mean genetic engineering was an
example I mentioned CRISPR you know I
think every so often things happen that
you know 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
absolutely so you have over numbers
could be off but it's a big amount you
have over 1100 current or pending
patents that have been licensed sub
license to over 300 companies what's
your view
would in your view are the strengths and
what are the drawbacks of the patenting
process well I think for the most part
their 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 two billion
dollars right now and nobody would even
come close to giving you that money any
of that money if if it weren't for the
patent system because and then anybody
else could do it that that that then
leads to the negative though you know
sometimes somebody does up a very
successful drug and you certainly want
to try to make it available to everybody
and and so the patent system allows it
allowed it happen in the first place but
maybe it'll impede it after a little bit
or certainly to some people or some
companies you know once it's 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 two billion
dollars of making the drug given
clinical trials that is by far the most
in terms of money or pain or both well
money but a pain goes hard to know I
mean but but usually doing proving
things that are that are proving that
something new is safe and effective
in people this 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 at this
particular disease but what the process
is you start out with so usually you
start out with cells then you'd go to
animal models usually you have to do a
couple of 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
and small number of patients face to
trial to show that it's effective in a
small number of patients and a phase
three trial to show that a safe and
effective in a large number of pay
and you know that could end up being
hundreds or thousands of patients and
they have to be really carefully
controlled studies and you know you'd
have to manufacture the drug you'd have
to you know really watch those patients
you have to be very concerned if you
know that that it is gonna be safe and
and and and you look at see does it
doesn't treat the disease better than
what the whatever the gold standard was
before that if there was 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 it a little bit
how does the patenting process work yeah
well you you do a certain amount of
research though that's not necessarily
has to be the case but you for us
usually it is usually we do a certain
amount of research and make some
findings and you know we had a
hypothesis let's say we prove it or we
make some discovery we need to invent
some technique and then we write
something up what's called a disclosure
we give it to MIT technology transfer
office they then give it to some patent
attorneys and they use that and plus
talking to us and you know 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 you know 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
twenty three billion dollars you've
described your thoughts on a formula for
startup success so perhaps you can
describe that formula in general
describe what does it take to build a
successful startup well I I break that
down into a couple categories and I'm
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 then that
work with and you know they 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 have it 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 z' is a good example of that you
could use it for drug ABCDE 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
and a top journal hopefully a number
that we've reduced it to practice in
animal models that we've filed patents
maybe I had issued patents that of 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 postdoc or
graduate student 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 could mention
the business component it's funny to
hear great side to say that there's
value to business folks
oh yeah well that always said so what
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 of that platform
that could be used for all these
different things what one are you 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 Lex what
I'll call FDA regulatory clinical trial
trial strategy I think you have to be
able to raise money
incredibly so there are a lot of things
you have to be a good good with people
good manager people so the the money in
the people part I get but this the stuff
before in
deciding the ABCD if you have a platform
which trucks the first and taking
testing you see nevertheless scientist
is not being too always too good at that
process well I think there 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 want to 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 art there
are there good animal models for it so
that you could test it and it wouldn't
take you know fifty years are the
clinical trials that could be set up
ones that you know have clear end points
where you can make a judgement and and
another issue would be competition are
there other ways that some companies out
there or doing it another issue would be
reimbursement you know can I get
reimbursed so a lot of things that you
have manufacturing issues you'd want to
consider is it not so I think there are
really a lot of things that go into
whether you do what you do for a second
third or fourth so you lead one of the
largest academic labs in the world with
over ten million dollars in annual
grants and over 100 researchers probably
over a thousand since the labs beginning
researchers can be individualistic and
eccentric I don't put it nicely
there you go eccentric so what insights
into research leadership can you give
having to run such a successful lab was
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 that
missus 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 Peter
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 it 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 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 to build it up to inspire the
researchers through the you know pretty
difficult process of going from idea to
too 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 you know certainly when I
talk about my own career I had my
setbacks s you know different times and
people know that that know me and you
know you just try to keep pushing and
and so forth but but yeah I think I try
to do that as the one who leads the lab
so you have this exceptionally
successful lab and and one of the great
institutions in the world MIT what 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 them
researchers moving to industry deep what
do you think about the future of science
in general is there drawbacks is a
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 in this
whole landscape of science in its future
well first I think going to industry is
good but I think being an academia is
good you know I have lots of students
who have done both and they've had great
careers doing both I 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 going to
be funding and particularly 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 had come up with better ways to
teach you know so that people all over
could learn better you know so I think
there were 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 and so I
always worry about it but we've been
fortunate that places have come to us
like the Gates Foundation and others
jovan 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 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 it like
say I gave you a hundred billion dollars
right now but you couldn't spend on your
own research mm-hmm
so how how hard is it to decide which
labs to invest in which ideas which
problems which solutions you know cuz
funding is so much such an important
part of progression of science in
today's society if you put yourself in
the position of philanthropist how hard
is that problem how would you go about
solving it sure well I think what I do
for 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 give 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 are 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
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 and and and
medicines and different things like that
that like vaccines that might be really
helpful for people in the developing
world and and so 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
that comes and and and I think that's
what people do I mean I have never seen
anybody do it otherwise I mean and and
that by the way it may not be the best
thing overall I mean I think 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
is to help young people and that they
may be at odds with each other because a
farm or 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
trained 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