High-Tech Med — Longwood Seminar

Articles


Hello and good evening. It is such a great pleasure
to welcome you here tonight for our inaugural
Longwood Seminar for 2015. I’m Gina Vild. I’m the Associate Dean for
Communications and External Relations at Harvard
Medical School. Over the past 15
years, these seminars have enabled thousands
of individuals to learn about the
latest research and medical information that
emanates from Harvard Medical School. They have been successful
because of your interest. It’s your attendance
and, more recently, your participation on our
many social media channels that have made these seminars
a success, so thank you. And I see so many familiar
faces here tonight. Just a quick show of
hands, if you’ve attended a Longwood Seminar in the past. Great. Thank you, for returning. And for those of you who
are here for the first time, I’m hoping you
enjoy the experience and that we see you back in the
years and the months to come. I also want to say hello
to all who are watching through live streaming. If last year can
serve as a sampling, tonight, we have viewers joining
us from all over the world, including Saudi Arabia,
Mexico, Canada, Colombia, Italy, and the UK. So welcome, all. We select the topics, as you may
know, for the Longwood Seminars through crowd sourcing,
which means you tell us what you want to know. So this past year, hundreds
and hundreds of voters have weighed in through
our Facebook friends and through email. So the topics tonight
were what you told us was most important to you. So tonight, of course,
High Tech Medicine. On March 31, Understanding
Food Allergies. On April 14, Music is Medicine. And our final seminar on April
28, Diseases Gone Global. I know you’re anxious to get to
the program, so just a couple of announcements. And we should have a slide
soon that summarizes some of what I’m going to tell you. So you will see
information shortly on how to obtain
certificates of completion and professional development
points for teachers. We also want to
invite some of you view the Longwood
Seminar website, to see our past
Longwood Seminar videos. And all of this year’s videos
will be put on the website soon after the events are held. And it’s also a
fabulous place for you to access additional
supplemental reading material. We hope you will participate
in our Twitter conversation by using the hashtags that
you’ll find on the screen. And thank you, for turning
off your electronic devices. Today’s seminar is called
High Tech Med, The Newest Wave of Medical Innovation. Since its founding, Harvard
Medical School physician scientists have
been revolutionizing the way medicine is practiced
and the way in which health care is delivered. From Benjamin
Waterhouse’s introduction of the smallpox vaccine in
1799, to the first public demonstration of anesthesia
in surgery in 1846, the introduction of the
electrocardiograph in 1914, and the use of
the iron lung that helped polio-paralyzed
patients to breathe in the 1920s– and these are
just a few of the examples– Harvard researchers have
employed novel methods and technologies to improve
the health of people throughout the world. And they are curing disease. Today, our researchers
continue this proud tradition. Whether using their
knowledge to make surgical and diagnostic
procedures less invasive, or by developing more effective
instruments and biomaterials, our scientists are not
only on the cutting edge, they are the leaders,
bringing new technologies to the bedside of men,
women, and children. And it is truly a privilege
to be able to introduce you to a few of them tonight. We think of them as explorers,
inventors, innovators, and caretakers,
people who are shaping the medical
terminologies of today, the technologies for tomorrow. So I’m delighted to
introduce our experts. Dr. Conor Evans is a Harvard
Medical School Assistant Professor of Dermatology in
Massachusetts General Hospital. Dr. Jeffrey Karp is a Harvard
Medical School Associate Professor of Medicine at
Brigham and Women’s Hospital. But first, you’ll hear
from Dr. Elazer Edelman. Dr. Edelman is a professor of
medicine at Harvard Medical School, a senior attending
physician in the coronary unit at Brigham and Women’s Hospital,
and the Thomas D. and Virginia W. Cabot Professor of Health
Sciences and Technology at MIT. Dr. Edelman directs the
Harvard-MIT Biomedical Engineering Center
dedicated to applying the rigors of the
physical sciences to illuminate the fundamental
biological processes and the mechanisms of disease. Please, let’s give all of them
a warm welcome, and thank you. [APPLAUSE] Thank you, Gina Vild, and
welcome to all of you. It really is my honor to begin
this and to talk with you. So this isn’t going
to be a lecture. We’re going to have a discussion
about why and how innovation makes medicine today
a medical science and makes it a fertile field. So these are my disclosures. They’re not financial disclosure
so much as disclosures of people that I
work with in industry to help us realize the potential
of all that we work on. We work, really, and we
live in an amazing time. In our lifetimes,
irrespective of what state you live in, irrespective
of whether you live in a state where virtually
no one smokes, to one where everyone smokes, to
whether your meal is fish, or a cheeseburger, the incidence
of cardiovascular death has dropped six-fold over the
last 40 years, not 6%, 600%, six-fold. And even for a
lesser diseases– I’m a cardiologist, so lesser
diseases, like cancer– you still have found
that, in men and women, the incidence of cancer death
has dropped by 1/5 to 1/7. We live in a marvelous time. And the questions are twofold. One is, how did this come about? And two, how do we make sure
that it continues to happen? Anyone know who this man is? Dick Cheney. He’s a hero to us in medicine,
because Vice President Cheney has had five
myocardial infarctions. He’s had bypass grafting. He’s had endovascular stents. He’s had angioplasty. He’s had an implantable
defibrillator. He’s had saphenous vein graphs. He’s had pacemakers. And he had a heart transplant. And so, irrespective of whether
you agree with him politically or not, he’s a poster boy
for innovation in cardiology. This is an electrocardiogram. Not his, it’s any one of
my patient’s, a patient with an acute
myocardial infarction. And when President Eisenhower
had his myocardial infarction, he was advised to go
to bed for six weeks and snuggle with Mamie. [LAUGHTER] I don’t know who got
the worst of that. But in any case, his chance
of dying from his heart attack was 50% before he made it to
the hospital and 50% thereafter. And today, though
it’s still the case that half the people
who have a heart attack will die before they reach the
hospital, only 5% will die. 95% will survive. In fact, here’s the incidence
of cardiovascular death. It’s dropped dramatically. So who discovered the coronary
arteries, the arteries that surround the heart? Anyone know? So Leonardo da Vinci. So Leonardo da Vinci,
almost 500 years ago, discovered the
coronary arteries. But it took 500 years
before– because really, modern cardiology starts
at the time of Eisenhower, and it peaks at
the time of Cheney. And the question is what
drove us, number one, and what took so long. This man defined the
circulation in 1600. This man coined the term
“angina pectoris” in 1770. This man, the man who
incidentally discovered sickle cell anemia, was
also the first person to diagnose a heart
attack before it occurred. So why did it take 500 years
to go from here to here? Anybody? What did we need
that we didn’t have? [INAUDIBLE] Yeah. We didn’t have technology. We didn’t have
electrocardiography. We didn’t have x-rays. And that’s why innovation
is still important. More in my lifetime–
how many people here know someone who’s
had bypass surgery? How many people here know
someone who’s had a stent? How many people here know that
all the commercially available stents were developed
and evaluated in the Harvard MIT system? So when Vice President Cheney
had his bypass surgery, he had a 91% chance of
not having any problem up to a year. And around that time
that was happening, people, especially
in Emory University, were inventing
balloon angioplasty, the ability to stick
a balloon in an artery and blow it up and open it up. And it worked great, except that
40% of patients, within a year, would have to come back
for something else. And around that time,
Campbell Rogers and I, working across the street,
Building C and Building D, started to ask basic questions
about what the processes were that drove this. Now, at that time, this
was the first section of an artery that was
ever double-stained. It was stained with
two things, one that showed that it had
a lot of smooth muscle cells, and the other, in
brown, a lot of proliferation. And the thought was that this
was a proliferating lesion. And I’m not going to go
through this in great detail, but what we showed was
that, whatever was going on was incredibly complex in
time, and space, and cells, and molecular targets. And it took us years to define
exactly what was going on, except we eventually figured
out that there was clotting, and there was inflammation,
and there was proliferation. And all of these
things were critically important to understanding
what happened when you put a balloon in an
artery or you bypassed it. And what we suggested
and what we worked on was that it was better not to
just blow up a balloon, not just to take something
and stretch the vessel, but to put something
in and leave it there. And we worked on a variety
of designs of stents. And yes, with our
colleagues in industry, because you can’t innovate
without making something that has a lasting impact. And we eventually helped
people design and develop these devices, which are
stents, metal mesh tubes that stay in an artery and, unlike
a balloon, which blows things up, and then recoils back down,
permanently deforms the vessel. So when Vice
President Cheney had had the benefit
of his angioplasty and had to come back with
a problem, he got a stent. And the 40% failure
rate rose to 75%. The nice thing about being
a professor– and Professor Evans, and Karp, and
Dean Vild will tell you this– is that you work
with brilliant people. And the most important
thing is to not say anything when they walk
in your room was a great idea. So I always, when I
talk with my students, keep my hand in
front of my mouth, become I’m afraid I’ll
say something stupid. So when David Wu and
[INAUDIBLE] came in and they said, you know,
if we put drugs on a stent, we could deliver them
right to where things go. And so this was one of the
first drug eluting stents. We made it, if you
will, in our garage. We dipped a stent into a
solution with orange drug. And it looks kind of wooey,
and it looks kind of horrible. And you wouldn’t
put that in anybody. But we actually showed
that, when you put it in, you actually imprint deep
into the vessel drug– this is 200 microns deep into a vessel. You stamp drug into a vessel. And that opened up an era
of incredible innovation where whole schools of people
were now making these devices. So that when this got made
in an industrial setting, our woolly mammoth
stent looks like this. This is a metal stent with
a coating 2 to 20 microns in thickness that can release
drug for up to three months. And when you put it in,
now, as opposed to a failure rate of 40% or 25%,
the drug eluting stent does even better than the
gold standard bypass surgery. Now, the truth is that
innovation usually starts in academic settings. Name the top 100 innovations
in the last century, and I will tell you that
virtually all of them arrived or were devised
at some university. The electrocardiogram in
the University of Leiden, and x-rays at the
University of Wurzburg. Insulin was synthesized,
if you will, at the University of
Toronto, and on and on, and pacemakers, and angioplasty,
and the human genome. Everything that you will
hear from the speakers to come about detection,
the diagnosis, the design of drugs
and devices, was started by some student
in someone’s laboratory, because people like
you made it possible for them to do their work. And you explained why it was
important for that to happen. It’s no accident
that the incidence of cardiovascular
disease, the deaths from cardiovascular disease,
and the deaths from cancer have virtually
plummeted, because we are in this amazing
phase of innovation. We are in an incredible
time where academicians are provided with the resources
to make their innovations impactful. So I have a
fundamental question, because this is
all we think about. Who should get the Nobel prize? And when I pose this question
in front of my colleagues, I guess, oh, who should
get the Nobel prize? And then I put a red
line through that, and I say that’s not important. And then they all
sort of sit deflated. And they say, yeah. Oh, yeah. Uh, yeah. Right. It’s not important. [LAUGHTER] So the real question
is, how do we make sure we can
recapitulate this experience? Because there is,
at the same time as being in a wonderful setting,
a real crisis in this country. How I know that? Well, I edit a journal. I edit one of the– there’s
this wonderful journal, Science Translational Medicine. I’m one of the advisers
of the journal. And one of the editors,
tell Kelly LaMarco, and then a colleague, Marty
Leon, and I, we looked serially
at all the papers on where innovation is going. And until 2000, there
wasn’t much of a concern. But in the last 15
years, there are now 10,000 papers on whether
we are, in this country, suffering from a
crisis in innovation. So certainly, we’re not
suffering from a crisis in writing about whether
there’s a crisis, but we are suffering
from an issue. So very quickly,
because we really want to hear from our
speakers, what are the issues? Well, this country
spends virtually nothing on innovation. The GDP of this country is
$14 to $16 trillion dollars, and the life sciences
budget is only $30 billion. Good companies spend about
10% of their net value on f research and development. As a country, we spend 0.02%. This country has an
amazing literacy rate where virtually all can
read and all can write. But the truth is, the number
of people getting doctorates has plummeted. And in this country, if you
start getting a university degree, then the likelihood
that you’ll actually get it is only 66%. Contrast that to what happens
in Japan where it’s 92%. Look at the number of PhDs
in engineering and science in China, and look at what’s
happened over the last 15 years in the United States. There are multiple
barriers, and you’re going to hear
about these things. What are the barriers
to innovation? Well first, there’s barriers
to envisioning, conceptual science, innovation to
renew, to alter, to make new, the introduction of
new elements or forms, and the ability to realize
those improvements for people’s lives, envisioning,
implementing, conceptual science, engineering. I’m not talking about
entrepreneurship. Look at the way I’m dressed. I don’t care about money. [LAUGHTER] If I did, I wouldn’t be here. So I’m getting rid of that. That’s not what
we’re talking about, and that’s not what you’re
going to hear about. I’m going to skip over
this, for the sake of time, other than to say that
there’s a tension. We’re not introducing as
many drugs as we did before. We’re not introducing as many
devices as we did before. The time it takes for a new
device to be approved in Europe and the time it takes for
it to be approved the United States has widened and widened. When the stent was
first introduced, it was introduced one
month earlier in Europe than it was in
the United States. With the drug eluting
stent, 30 months. United States was
43rd in the world in introducing the new heart
valves that we work on, between Argentina and Chile. Primum non nocere, anybody
know what that means? Used to be part of
the Hippocratic oath. Yes. It means, above all, do no harm. You can’t do that in
medicine, sometimes, especially if you’re
an oncologist. Primum succurrere,
means rush to treat. So there’s a tension. If you, above all, do
no harm, then you never allow technology to
come into the community. If you rush to treat,
then you potentially leak technology too early. What do we do here? What do academicians do? Well, because it’s
Latin, it sounds a lot better if I made it,
so I made my own Latin term. [LAUGHTER] Primum sciere, above
all, seek to understand. And that’s what you’re
going to hear about from professors Evans and Karp. Above all, seek to understand. I’m going to leave you
with some questions, and you’re going to
hear the answers to it. And then I’m going to make a
pithy statement at the end, and you’re going to applaud. [LAUGHTER] Are we funding the
right projects? Are we working on
the right things? Are we training people
properly to be innovative? Is our educational system
optimized for innovation? And how can innovation, science,
and medicine mix optimally? You’re going to hear about that
from these wonderful people. Here’s my pithy statement. Medicine without science
is just an art form. And without innovation,
it’s simply sterile. I want to show you today, by
introducing, first, Professor Evans, then Professor Karp, how
to make science and medicine, engineering and
innovation mix, so we have something that is
simultaneously scientific and simultaneously fertile. Thank you. [APPLAUSE] So now, it’s my
honor and pleasure to introduce
Professor Conor Evans, as you heard from Dean Vild. He is Assistant Professor
at the Wellman Center for Photomedicine
at Harvard Medical School at the Massachusetts
General Hospital. And his work has
revolutionized photomedicine, our ability to image and detect,
our ability to define events, and to treat them as
well, using light– like we can see and
light that we can’t. And so with that, I’d like
to ask Professor Evans to come up and take the podium. Well, thank you so much
for the introduction. And as a young faculty
member at Harvard, I hope to live up to the
height of my introduction. I’d like to talk to you all
about two things tonight that are very near
and dear to my heart, and that is the topic
of photomedicine, that is the interaction of light
and tissue, light and cells, and how we can use
photomedicine to solve problems. And instead of introducing the
whole field of photomedicine– because I could do this
for hours, trust me, I bore my students at Harvard
constantly with this– I’m going to try to
talk about three stories and introduce how
we bring innovation to medicine with photomedicine. So first, let me jump
into photomedicine itself. It’s the title of my
center, the Wellness Center for Photomedicine. And I’m sure every one
of you have interacted with photomedicine
in some way, today, but actually have not
even known about it. So what is it? It is when light
interacts with tissues. So we take a ray of light,
and we take a laser, we zap tissue with it. And what happens? Well, a lot of
things can happen. And that’s the neat part
about photomedicine. But in general, we can think
about four major things happening. One that can happen is
that light can scatter. And scattering is something that
you are all very familiar with. You hold your hand up,
and you look at your hand. What you’re seeing is light
scattering off of your hand. It’s the white creaminess. It’s not transparent. And the how light
scatters, the way it scatters and the
information it carries, we can actually use
to make diagnostics and to do very
neat science with. Light can also emit. So a molecule can absorb
light, and then it can re-emit that light. And we can utilize that to tell
something about our samples. And in fact,
scattering and emission are the foundations of
imaging, microscopy, and a lot of the diagnostic
methodologies that we use. Light can also do chemistry. And in fact, the reason that
you are seeing at all right now is because there’s a chemical
reaction going on in your eyes at all time. Light is striking your
retina, is converting cis to trans-retinal. And in doing so, you are seeing. It conducts vision. So photomedicine occurs. And in photomedicine, we can
do some very neat things. We can have
light-activated therapies. We can kill cancer with light. And we can also engineer
tissue, using some of our light. Now, what’s very interesting
is that we can also use light to do work. We can heat things. We can create pressure. We can make plasma. This is where we have
laser surgery, where we have smart devices that
surgeons can introduce, that can make
their lives easier, that could have higher
resolution imaging, that can do a number of neat tools. And lastly, light can also
have a negative consequence. And a large part
of photomedicine actually is in studying
the negative parts of this. If you walk out into
the sun– I know we haven’t seen
much of it so far in the last couple of
months– but UV light can give you a sunburn. It can generate a cancer. It can cause mutations. And that is a large part
about studying photomedicine. So as my partner in crime,
Jeff, will talk a little bit more about, a big
part about what we have to do in medicine, and
especially in photomedicine, is translating our
tools to the clinic. We have to start somewhere,
usually by my bench. And eventually, we have
to get to the bedside. And as was mentioned,
that means we have to interact with a whole
lot of people along the way. So rather than describe
the translational pipeline, I want to illustrate it by
sharing with you three stories, technologies that have
come from my center, from the Wellman Center
for Photomedicine, that are along this pipeline. So I’ll talk to you a
little about smart bandages, some tools that we’re
building in my laboratory, about virtual biopsies,
which are coming from Gary Tearney in
his lab, and colleagues that are somewhere in between. And I’ll start off with laser
hair removal, which is actually photomedicine that you may not
actually have thought about. So let’s talk about
laser hair removal. Now, contrary to
most people’s belief, laser hair removal
was not started because people wanted to get
rid of the little mustache, or trim their bikini lines. It actually started
with a request from the United States Army. So why was this? Well, there’s a problem. And anyone in the audience
who has a beard, like mine, or people who have to
shave parts of their body know that we can get this
thing called pseudofolliculitis barbae. What is that? That’s barber’s itch. That is these little pimples
that can appear on your face. And anyone who’s had
a very close shave knows this can be a problem. Now why is this an issue? Well, the US Army
requires their servicemen to shave close, have a
very nice, close shave. And especially for
servicemen of color, this can be a problem, because
they have very curly hair, very curly beard hair. It can curl right inside, and
it can cause ingrown hairs. And these can become infected. And this actually
prevented soldiers from putting on gas masks and
became an actual challenge during the original Iraq war,
because people couldn’t wear their gas masks in the field. And they were ill-fitting. So the Army came by
and said, can you do something about this? Well, the interesting
thing is, yes, we can. Hair growth actually
pretty interesting. Hair growth passes through
three phases, anagen, catagen, and telogen. Anagen’s the
phase that we all know. It’s the hair that grows. Now, your hair
normally does fall out. Hairs can stop growing
and then are replaced by new hairs that grow in. So the hairs that you find
on the floor and whatnot, that’s normal. You’re supposed to lose hair. It’s part of the cycle. And a lot of work, I
see, went into trying to slow down or stop the
hair growth process entirely, but that was really hard. Now, when you’re
working with lasers, there’s this tendency to try
to think that everything can be solved by blowing things up. And it’s pretty true
in a lot of cases that you can solve problems. So one of the things
that came to mind was, well, if we can’t
stop hair growth, can we eliminate the
hair follicle altogether? Can we selectively go in and
destroy just the follicle with very, very high precision? And the answer is, yes. And absolutely that can be done. And the way it’s
done is by using one of three interactions. And you’ll see this
slide a few times. We can introduce
light to tissue, and it could do a
couple of things. It can scatter. It can emit. And we’re going to
talk about absorption. Now, absorption is what
gives things color. It’s the reason that
my shirt is blue. It’s the reason the lady in the
front has an orange sweater. Molecules absorb. And the light that
does not absorb is what we see as its color. Now, we are all naturally,
even without all our clothes on, carrying around
chromophores, carrying around the molecules that can absorb. And the main molecule that
we carry around with us, unless you are a redhead, and I
don’t see many in the audience, is a melanin molecule
called, eumelanin. It’s what gives our hair
its brown color, what gives the dark hair colors. It’s what gives
us our skin tone. And the amount of
eumelanin that we have is actually controlling
the color that we have. Now what’s interesting
about eumelanin is it’s been designed
over millions of years by evolution to be
excellent at absorbing light to protect your skin. And it’s very
interesting how it works. So eumelanin looks
something like this. It’s a polymer. It has lots of individual
pieces that link together. And eumelanin is
this enormous polymer that absorbs light across
a huge range of wavelengths all away from the ultraviolet,
all the way out to the IR, beyond where your eyes can see. Now what’s interesting
is– and anyone who has very dark here who walks
out in the sun can tell you this– is that when
eumelanin absorbs light, it actually emits that energy. It stores that energy and
then emits it as heat. So yes, if you have dark
hair and you’re walking out in the sunlight, your hair
is heating up, actually, from the visible light
that’s being absorbed. Now what came to mind to Rox
Anderson, to John Parrish, and to colleagues at the
Wellman Center of Photomedicine is could we actually do
something with this heat. And the idea is that we
have all these follicles. These hairs come down
to this follicle. And in the follicle, on
the edge of the follicle, are what we call stem cells. Now, stem cells, you
may have heard about. These are cells that
make other cells. These are cells that
renew the follicles. Different cells in the
follicle will die all the time, but these stem cells will
differentiate, will grow, and regrow follicles
all the time. These are the ones you
have to get rid of, if you want to get
rid of the follicle. So how can we do that? Why not put a whole lot of
heat in a small period of time in one location, specifically? Specifically, right here. This is all the eumelanin
in the hair shaft. And so what was
designed was a laser that could actually deliver
light and create so much heat that it actually introduced
a catatonic shock wave, just like one blows
up a hot air balloon. You introduce heat,
and it expands. In the same way, you
could expand tissue. And laser hair removal
works this way. You expand the tissue so
quickly with a pulse of light that it actually kills all the
cells surrounding the hair, including the stem cells. And then, naturally, over
time, the follicles go away. Now remember, I mentioned
that hair grows in cycles. Only when there’s
a hair, only one here is growing can you actually
take out those follicles. So that’s why you
have to go back, if you have hair removal,
to catch hair that is not in its active growth cycle. So it takes a few cycles,
but that’s how it works. And it worked very well. So this is actually
the original laser. This is what it looks
like in our laboratories. This is a ruby laser. There’s actually a piece
of polished ruby in here that creates the pulse laser. Here is a woman who came
in for the initial study, had hair on her lip,
and it has been removed. And thanks to
translation, thanks to the involvement of
doctors, and physicians, and numerous engineers, you can
now go to your dermatologist and have treatment with
these medical lasers. So this is something that
is already in the clinic. It was an idea that
started back in ’94 and made its way all
the way into the clinic over a period of years. And it’s cosmetic
dermatology, so it actually went pretty quickly. And the US Army has been very
happy with their investment. Now, one of the interesting
things about this project is it’s very easy to see whether
or not we’ve had success, right? If you look at a patient, is the
hair there, or is it not there? Now, in a lot of
situations in medicine, what we want to look
for is not as apparent. You can’t see it, necessarily. It’s happening on
the level of cells. It’s happening on a
level of groups of cells. And what we do
normally, in order to understand what’s
happening, is we do a biopsy. And a lot of people
here have either had a biopsy, or known
someone who has had a biopsy. And the problem with biopsies
is we go in and remove tissue. Now, we can’t remove
tissue everywhere, right? For example, it’s very difficult
to go in and biopsy the retina, the back of your eye. You wouldn’t want to do that. You need that tissue. Biopsying the brain,
you can’t do very often. Or maybe you have an area
that’s just so large, say your entire
esophagus, that you can’t biopsy the whole thing. Well, what people have
been trying to do, and what we’ve been trying
to do at the Wellman Center, is to create virtual
biopsies, that is ways of actually replacing
the biopsy needle with imaging devices, so that you
can rapidly capture data at the cellular level, but
do so very efficiently. And people can ask, why don’t
we use things like MRI, PET, CT, CAT scan, and ultrasound? And very short
answer is the fact that these tools have
too low resolution. They can’t see individual cells. They’re millimeter scale. We need to get to
micrometer scale resolution. And how can we do that? Well, absorption, we’ve
already used for something. Let’s think about how
one might use scattering. Now, I mentioned ultrasound. How does ultrasound work? We launch sound into tissue,
and it bounces off of structures and comes back. And because sounds
pretty slowly, we can time how long it takes
to go in and to come back. And that allows us
to build up images. But light moves really quickly. It moves three times 10 to the
8th meters per second quickly, way too fast to time. What we can do is
we can actually race light against itself. And the way we do this is
with this very neat tool kit, called Optical
Coherence Tomography. And this was invented
right down the road at MIT and perfected at MIT and
at Mass General Hospital. And the way we do this is we
race light against itself. You take light, and you
split it into two paths. You send one light
down a race course where it just goes to
one end and comes back. The other side is
the race course that goes down into
the tissue where it can hit different structures
and bounce back to us. And then what we do is
we see which one wins. And we do this in a cool little
device called a interferometer. So we send light
down to the sample, and it bounces off of
different structures. And we send light
down a reference. Now, the really neat
thing about light is, when you race it against
itself, and they tie, what ends up happening is
we create interference. We create these little
blips, these little fringes. And we can measure them with
extremely high accuracy. And what we can do with that
is that these blips occur only where the race tracks
meet, only where you have reflections in the tissue. And in fact, we can take these,
and we can scan over tissue. And we can actually recreate
the entirety of the tissue. This is actually my friend,
Heil Park’s, finger tip. This is the epidermis,
the surface. This is the dermis. And this little squiggly
line right there is actually the sweat
duct in his fingertip. And we’re seeing this on a
cellular level resolution, because light is interacting
with those levels and bouncing back,
and we’re timing that. So how can we use this
for virtual biopsy? How can we use this to look
at a large area of tissue? Well, one big problem that
my colleague, Gary Tearney, has been working
out is the problem of the esophagus, specifically
Barrett’s esophagus. Barrett’s esophagus is
a pre-cancer condition that a lot of you may have
or may have in the future. And it’s difficult to
diagnose, because you have to look at the entirety
of the esophagus, which is quite long, quite complex. And if you really want
to know what’s happening, you need to take a biopsy. But Gary is a pathologist,
and he’d like to do better. He’d like to do his
pathology in living people, and not taking a look at the
biopsy they’re taking out. So he took this tool,
and with his colleagues, actually created this. This is a little
balloon– you want to talk high-tech med–
this is a little balloon. And that little OCT scan, that
Optical Coherence Tomography scan is happening
as it goes round, and around, and
around in a circle. And so this was designed– this
goes down in the esophagus. And what they do, while
the patient’s asleep, is you simply tug it. So how does this work? You’re going in a big
circle, and you pull it. And so it scans a spiral. And it just spirals all
the way up your esophagus. And so it collects. And what it can collect is
something that looks like this. This is actually an image
of a patient’s esophagus, as it scans all the way down. You’re looking at every single
layer, of mucosal layer, you’re looking at the
muscles in the esophagus, all the way deep. And you can get all this
information in real time, as you do the pull. Now, that’s pretty neat. And this can reveal
very quickly where you have regions
of abnormal tissue, such as Barrett’s esophagus. But I don’t know about you,
when I look at this, I really don’t feel like having
that down my throat, right? I have to be intubated. I have to be back. I have to be asleep
when this is done. So Gary went ahead and
did something even cooler, and that’s to actually
put all of OCT in a pill. I don’t know if you
can see it well, but he actually
put all that tech in a little pill that’s
the size of a penny. And you can swallow this. And you do not have to
be awake when it’s done. So let me show you how
this– this is the very first [INAUDIBLE] test. This guy is quite brave. And what we’re going to
show right now, what you’re going to see right now is
actually the very first time this is done. That’s the little camera. That’s the OCT pill. He’s going to go for it. [LAUGHTER] Yeah, that’s what I would do. And he’s going to swallow
it with some water. Now, it’s on a
tether at the end. You pull it right back
up out of the stomach. It’s not a problem. And here it does. Now, it’s going to start
spinning around in a circle, in a circle. And as he swallows, as
the natural swallowing motion occurs, it collects
this data in real time, as it goes down. And it can map the
entirety of the esophagus. This is technology that’s
just about in the clinic. This is the kind of
thing you’re going to see in the next
couple of years and a kind of
technology that’s going to make your life much easier. Because at the end of the day,
instead of taking biopsies, your clinician can take a drive
right down your esophagus. So really neat. This is all from my colleagues,
Gary Tearney, Brett Bouma, and others at the
Wellman Center who are building these very cool
cameras, these very cool tools, that I think are going to
change medicine a big way. All right. We got started late, so I’m
going to pretend that’s green and move forward. So what my team is doing
is a little bit different. And I’d like to spend a little
time talking about this. This is structural imaging. This gives you the
ability of actually seeing where things are. But if you want to take a
look at the health of tissues, if you want to take a look
at how things are recovering, say, from a wound
or from surgery, there’s one really big parameter
that’s important to measure, and that problem is
how to image oxygen. Now oxygen, you know, is
really important, right? If you hold your
breath, if you stop breathing– if a patient doesn’t
receive adequate oxygenation, cells die, tissues die. And this is really critical. Oxygen supply is very important. But oxygen is odorless
it is colorless. And it is really, really
difficult to detect. Now granted, you can start
sticking needles in people and doing things, but
that doesn’t give you the same capability. That doesn’t allow
you to see oxygen in tissues and the health
of tissues over large areas. So what do we turn to? We turn to emission,
specifically something called
phosphorescence. And I’ll move through
this a little quickly. Now, phosphorescence
is something that you all know very well. If you ever had glow-in-the-dark
pajamas as a kid– I know I did, the feet glow at
night– if you’ve had watches, like your watch face can
glow, these are all phosphors. And phosphorescence has
a really neat property. So phosphors can look like this. This is a phosphor
that I use in my lab. This is the phosphor
right in the middle, and these are molecules
that make it bind to things. So what’s neat about a phosphor
is that you can give it light, and then it takes that light
in, and it stores the energy. And phosphors can be stable for
quite a long period of time. It’s why your watch face can
glow for an hour or more. Now, the interesting thing is
that, eventually, eventually, it’ll release that energy. And it can release
it by emitting light. And that is the phosphorescence
that your eyes see. Now another way it can lose
its energy is to oxygen. So oxygen can come by,
and just like two people bumping into each other
in a crowded hallway, oxygen can collide
with the phosphor, and it can take
away that energy. And when it does so, the
phosphor can no longer glow. It can no longer emit any more. So this is actually
a way of detecting oxygen. It’s a bit indirect,
but you’re detecting oxygen by what it bumps into, by
the phosphors it bumps into. Now, if oxygen is not there,
if there’s no oxygen present, whatsoever, the phosphor
will eventually emit. And this phosphor,
in particular, emits very bright red
light that you can see. So what did we do? We decided to take phosphors
and actually create a way of looking at oxygenation
over large areas in a bandage. And we call this
a smart bandage. We actually have a bandage
that is a liquid bandage. You can apply it by painting
it or spraying it over. And what it does when you shine
blue light on it is it emits. Now, if the tissue is healthy,
if there’s plenty of oxygen, the oxygen is stealing
away all of the energy from the phosphor, so the
bandage just emits green light. Green, good. The tissue is OK. If there’s not a lot of
oxygen, that phosphor can start glowing. And it glows bright, bright red. And you can see
that with your eye. And you can see areas
of the tissue that actually have low oxygen. And
this can be seen by anyone. Anyone can use this. And we’ve designed
it specifically so it’s something that’s
pretty simple to use. So for example, if we
have a burn, for example, and we were to put– this is
actually what the burn looks like, if we cut it
up and do a biopsy– and we were to put the
bandage over top of it and take a picture
with a camera, this is actually
what it looks like. You can see the full
extent of the burn. And by simply taking
the red ratio here, by looking at that
color, you can actually measure quantitatively
what the oxygen levels are. And this is something that
can be done very easily. This, in fact, was taken
with just a Nikon camera. So the trick, the complexity,
the high-tech-ness of this is actually all in the chemistry
and making the chemistry work. And in fact, the whole
goal, at the end of the day, is to make sure that we can
do the entire thing with one of these. And we just have
created new molecules in the lab that actually
allow us to do the whole thing with just a simple cell phone. So just to show you it
works– and stop the red light from blinking–
I’ll show you this is actually done
in a graphed model. This is actually on
pigs, because we’re not yet in patients. We’re just about to start in
patients this coming year. And if we do two
different kinds of graphs, there’s what’s called
a full thickness skin graft where we
take healthy tissue and we attach it onto a wound. And there’s partial
thickness skin grafts, which are just the top
layer of skin, mostly dead. And we attach it to a wound. When we take a look at what
the oxygenation looks like, we see that the full
thickness graph, which is what it should be, is
very healthy on both sides with green is go. Now, the partial thickness
graph, which is damaged tissue, is giving us a
bright red signal. It’s telling us
it’s not healthy, and the tissue
has not taken yet. But if you come back a month
later to the same site– it’s a little washed out
up here, I apologize– but it’s totally green. What we see in our
camera indicates that the wound has healed well. And that’s tissue that is
now viable and is useful. Now, this is probably
a few years out. I’m hoping that
this is something that you may see with
a clinician in three to four years, and
something maybe that you can pick up in a
CVS five to seven years out. So with that, I’ll stop, because
I’m getting a lot of blinks. And I want to acknowledge
the people who’ve provided some of the
slides I was able to show, especially Gary, who’s taking
all that very interesting body camera work in my laboratory. And thank you, very much. [APPLAUSE] Thanks. That was great. So thank you, very
much, Professor Evans. I would encourage you,
again, if you have questions, please fill out the
cards and pass them to the proctors who
are walking about. We now turn to
Professor Jeff Karp. He’s the Associate
Professor, as you heard, at the Brigham and Women’s
Hospital and Harvard Medical School. And he’s principal faculty
at the Harvard Stem Cell Institute. He’s also affiliated with
MIT through the Harvard MIT Division of Health
Sciences and Technology. And he really is a
pioneer in innovation. His work has had
profound effects on basic understanding
of stem cells, on emerging new
materials that can adhere not only
in dry conditions, but in wet conditions. He’s started companies. He’s taught. He is the real threat
across the board. And it will be a pleasure
now to hear his views on emerging innovation. Thank you. Right. Thank you, so much, for
the nice introduction. And good evening. In my laboratory, I try
to establish a paradigm. And that paradigm is where
we don’t just conduct science for the sake of science, for
the sake of publishing papers, but rather for
the sake of trying to have improvements in the
quality of life of patients. How can we develop technologies
in the lab that can’t just make it to the clinic, but
can be rapidly accelerated to the clinic? And I’ve got to tell you that
science, especially when you’re dealing with biology, is
extraordinarily challenging. Nine times out of 10, when
we conduct an experiment, it fails. Now, when you try then
to take that science and translate it into products
that can help patients, the challenges increase
by orders of magnitude. So one of the things
that I have learned is that solving medical
problems is crazy challenging. And I think that one of the
reasons why it’s so difficult is because of the
education system that we’ve all
been subjected to. I think that what happens is,
when we encounter failure, when we encounter challenges
in our lives or in the lab, we actually approach
those challenges the same way every time, and
we expect different outcomes. How many people have seen
the Ted Talk by Ken Robinson. I think it’s one of the
most watched Ted Talks of all time, something like
30 million views on YouTube. Everyone, I think,
should watch it. It’s really amazing. And what he talks
about in that lecture is how the education system–
how we’re all born creative. You know? Just watch kids play. But the education system
has actually educated us out of being creative. And I think that
that actually impacts how we approach problems,
how we approach challenges, how we approach failure. And I think it ends
up really keeping us on a narrow trajectory. Now, let me show you an example
of what I think really kind of emphasizes this point. This is a problem. Here we see a car that’s
fallen into the water. And we have the
problem solvers that are lined up here to try
to figure out what to do. So they get a crane. And things look like
they’re going well, but then this happens. [AUDIENCE OHS AND LAUGHTER] So what do you think the problem
solvers are going to do next? [VARIOUS AUDIENCE RESPONSES] [LAUGHTER] They get a bigger crane. They come at the problem
from exactly the same angle. And then what happens next? [AUDIENCE GASPS] So I think the challenge
that we and they face is how do you break free
from this repetitive thought process? And I would argue that
our brains, in general, like to operate in a
very low energy state. It likes repetition. And I bet that, if most of you
go home and go into the shower and move where you have your
shampoo bottle or your soap to a different location,
wake up in the morning, you will probably
reach for the location that it was previously,
and not the new location. So I think there’s many
ways to actually break free from this repetitive
thought process. And one of the ways
that we’ve been trying to do this in my
laboratory is to look at nature for inspiration. And it’s this idea that
every plant, every animal, every living creature
that exists today is here because it has solved an
incredible number of problems. And those that haven’t have
quickly become extinct. So in essence, we are
surrounded by solutions, ideas for solving problems. And I wanted to share with you
some examples of how we applied this principle of bioinspiration
to overcome what were seemingly insurmountable
challenges that we were faced in the laboratory. Here’s one. One late summer evening in
2009, Dr. Pedro del Nido, who’s shown here, who’s chief
of cardiac surgery at Boston Children’s Hospital,
sent me this email. And there’s an excerpt here. And what he said is that
he’s treating patients, kids, who have septal defects. These are holes in between
the chambers of the heart. And he said, you
know, there’s devices that have been developed that
work fairly well for adults. But they’re permanent. They’re non-degradable. And a lot of groups are trying
to figure out how you can just downsize these. And that’s problematic, because
those hearts are growing. And so these kids are going
to need to have revision, after revision, after revision
procedure as their heart grows. And he says, you know,
we’ve tried to suture this, but many times, it just tears. And we have nothing available
to seal these holes. We can do better than this. He said, can we work
together to develop a new type of adhesive that
would solve this challenge? And we had been developing
adhesives for some time, so he was aware of our work. And so what we did is we set
out to develop an adhesive that could work in the most
challenging environment in the body, inside
a beating heart. And with many of
the projects, what we try to do is not just take
something we already have and force it on the
solution, but we actually step back and say, what’s
the design criteria for the ideal solution? If we could come
up with it, what would some of those criteria be? And I’ve got to tell you
that this is really, really challenging to do, because
it’s easy to come up with a list of 20 or 30 things. The challenge is, how do you
break it down into five or six things, and then narrow
it further to one or two that’s going to completely
drive the solution that you want to be differentiated
from what anyone has ever tried before. And so we came up
with this short list. We thought, if we’re going
to put this into the heart, we don’t want it to be fouled
in the presence of blood. We don’t want blood to
react with this material and make it so it wouldn’t
attach to the tissue, which is the current case for a
number of glues or sealants that are in the clinic. We also want it to
be fully degradable. And as this degraded– we
initially thought of a patch. Could we just stick some
sort of a patch in there? And if that patch was
degradable and cells can migrate on top
of it and into it, it could be replaced with
the patient’s own tissue. And therefore, they wouldn’t
require any revision procedures. It would also need
to be elastic, because the heart’s contracting. You know, it’s expanding
and contracting over multiple cycles. It would also need
to resist washout. There’s a lot of
stresses, a lot of forces. There’s flowing
blood in the heart, and it can just wash away. And then we spoke to a
number of clinicians. And they said, you
know, we’d really like this to be on-demand adhesion. They said, we have a couple
of glues available to us in the clinic. And you know, they’re
not that great. They either cure within
one minute, or 10 minutes. And we want to be able to
cure it when we’re ready. We don’t want to be at the
mercy of the technology, we want to be in control. So it turned out
we ended up having some materials
that could address some of these challenges. But we had no idea how
to address these two. How could this work inside the
heart in the presence of blood, and not react with the blood? And how would it
remain in place, and not just be washed away? And so what we did is we turned
to nature for inspiration. And we looked at
creatures on the land and in the sea that exist within
wet, dynamic environments. And we looked at sand
castle worms in the sea, and slugs and
snails on the land. And what was really interesting
is that these creatures all had something in common, which
was viscous secretions that stay put, like honey on a plate. And when you look at
these viscous secretions, they also contain
hydrophobic agents. And hydrophobic agents
can repel water. So we thought, well, what
if we developed a material that was viscous and
hydrophobic, entirely hydrophobic, so when we
put it inside the heart and pushed up
against the surface, it would just repel the
blood away from the surface? And because it was viscous,
it would stay in place long enough for us to cure it. And for curing, we chose to
use light, light activation. There’s lots of ways, as you
saw from the previous lecture, of how to put light
into the body to cure these types of materials. Now, we spent a long time
working on this technology, multiple iterations. And I’m going to show
you some of the examples to demonstrate that
this can actually work. We were able to come up with
a material that addressed all of those criteria. And so, in the
interest of trying to bring this to patients
to improve quality of life, to enable new
surgical procedures, we started a company
called, Gecko Biomedical. We started this company
at the end of 2013. And during the past
14 or 15 months, the company has
taken the technology we developed in the
lab, they’ve scaled it up to tens of kilograms
that they can produce, they’ve stabilized it,
and they’re en route to be first in man by
the end of the year, perhaps even in
August or September. Now, we’re not going to go
after the septal defects as the first application. We’re keeping that in
the academic environment. And we’re still
advancing those studies. We haven’t yet shown we can
seal the hole inside a beating heart, but we’re
moving towards that. But this type of material
has so many applications in the clinic. We’re still using sutures
and staples, which have all kinds of limitations. And this has potential to
replace them or augment them almost everywhere in the body. Something else I wanted to
share with you that I alluded to at the beginning
is that I really think that innovation
requires being ready to fail
repeatedly, something that’s very difficult, I
think, to deal with sometimes. And what also I’ve
noticed– I’ve been reading a lot of
articles on failure– is that the most successful
people end up having the most spectacular failures. Let me give you an example. Steven Spielberg
had a movie once, his first movie, which
was The Sugarland Express. Complete disaster. It had a limited release, one of
the worst things that can ever happen to you in Hollywood. And so he had
trouble finding work. And he eventually, through
a lot of persistence, was able to convince someone
to fund a new movie that he wanted to create called, JAWS. And he said, you know, I
can do this movie, 55 days, no problem, $4.5 million budget. But there was a problem. He relied on a
mechanical shark, and it kept failing, and
failing, and failing. And the movie ended up
costing $10 million, more than double
the initial budget. And it took 159 days
to film the movie. Now imagine actors that
have dedicated– they’ve preset the time of 55 days. And now you have to keep
them three times longer. Imagine how challenging
that would be. And to then convince
the people who funded this movie to keep
adding more, and more, and more money– this
is the kiss of death in Hollywood, if you go
over budget this much both on time and money. But because he
was so persistent, because he wouldn’t
let go of this, something remarkable happened. And what he realized was that,
actually not showing the shark was more powerful than
showing the shark. It was actually scarier to
see these types of buoys being pulled in the water. And your imagination’s
running wild, because you’re
visualizing this shark at the end of this hook that
just has so much muscle power, it’s like pulling these
buoys and the boat along. And a lot of people attribute
the success of the movie to not showing the shark,
to really harnessing people’s imagination. And it’s this idea
of the persistence that he had to turn
failure into success. Now, I’ve really
tried to implement this in my laboratory. And let me tell you about
a failure that I had. When I started my laboratory,
I developed this technology. It was a stem cell therapy. And I had really nice,
what I considered, data supporting the idea
that we had generated. And I took it to
Noubar and Dave, who are partners at Flagship
Ventures, a venture capital firm, to see if they’d be
willing to invest money in this, to take
it further, so we could advance it to the clinic. And they looked at it and
they said, you know what? This is really interesting,
but this will never, ever, ever make it to the clinic. Your work is too complicated. There’s five steps
in your procedure. You know, it’s hard enough
to translate something that has a single step, you
have like a five-step synthesis. Like what are you thinking? There’s no way this
will ever– it’s going to make a great paper,
it will never help patients. And I went back to my lab,
shocked, first of all. But I reflected a lot on this. And I thought, you know what? I’m going to start projects in
my laboratory that take this to heart. How can we develop
technologies with this idea that we need to be able to
manufacture, we need to have batch-to-batch consistency. If we’re going to help
patients, we can’t just think of the innovation
in the laboratory, we have to think about
what happens later on, the manufacturing. If it can’t be manufactured,
it can’t help patients. And so I started thinking about
what problem could we work on. And I looked here at my hand–
and you see this kind of red here. And I was like, this
is really bothering me. This is a very itchy,
inflamed region of my hand. What’s going on? It’s next to my ring. What’s happening here? And I started reading up. And I realized that
this potentially is a nickel allergy. And I thought, how could
this be a nickel allergy? This is 24 karat gold. [LAUGHTER] That’s not possible. So I took it to the lab,
and I performed a reaction on my ring. And here you see this red here. This is reacting to show that
there’s nickel in my ring. And I realized I have
a nickel allergy. And so I thought, OK,
is this a big problem? Turns out 9% of the population
has a nickel allergy. And nickel is something that
you’re exposed to everywhere. It’s almost impossible to avoid. It’s in eyeglass
frames, keys, coins. It’s all over the place. And I looked into examples,
and there’s actually nothing to prevent this
reaction from happening. Once you reach a
certain exposure level, you’re sensitive
to nickel for life. Every time you
contact nickel, you’re going to have a reaction. And so I started thinking, maybe
we could solve this problem. Maybe we could prevent these
reactions from happening. Could we develop a prophylactic? And so what I did
is I went to a list. There’s a list of agents
on the FDA website that’s called Generally
Recognized As Safe– GRAS. These are agents that exist in
toothpaste and other consumer goods. And my thought was, these
exist in ton quantities. They’re extremely cheap. And maybe we could
find agents on there that would bind the nickel
on the surface of the skin and prevent the
nickel from going in. And maybe we could
use particles. Sunscreen has
nanoparticles in it that block the sun on the skin. What if we could
create nanoparticles that you coat on your skin,
and it binds to the nickel so the nickel can’t go through. And so we created a cream
that has particles from agents that are safe, according to FDA,
that could block the nickel. And here’s some of our results. So here, we’re looking at a
full thickness through skin. So if you have– here’s the
top of the skin and the bottom, if you just take your skin. And we put these particles,
calcium carbonate. This is in toothpaste,
calcium phosphate. And we put these particles
on the top of the skin, and we added– you see
the calcium signal here from these calcium-containing
particles– and we added lots of nickel. And the nickel bound
to the top of the skin. It didn’t go in. But if you don’t
have these particles, the nickel goes right through. And if you wash the skin,
the nickle and the particles go away. But it’s stays, if you
don’t have the particles. You can’t remove it. And so we published
this paper in 2011. And it was picked up by CNN,
and LA Times, and other outlets. And people started writing in. When can I have this cream? When’s it going to be available? And so we started this
company called, Skintifique. And within about two years
of starting this company, we were able to transfer the
technology into the company, scale the product,
and start selling it. And about 80% of the people
who have tried this, it works. One or two application
works for an entire day. And so I’m just really excited
about these technologies and the potential
that things that are developed in my laboratory
can make it to the clinic or en route to the clinic. And I think that one of the
critical components to this is also having an
exceptional entrepreneur, because we’re only doing
one of 10 steps that need to happen in
order to help patients, the development of the
initial technology. And what I’ve realized
in this process is that there’s a long way
to go after we published the paper, after we demonstrate
the proof of concept of these technologies. And this is something
that I’m committed to do in my laboratory. And I wanted to thank
you for your attention. And the people in my laboratory
and my funding sources. [LAUGHTER] [APPLAUSE] That was wonderful,
two wonderful talks. We’ll invite Professors Karp
and Evans to join at the table, and I’ll read some
of the questions. There have been fantastic
and wonderful questions. I can’t get to all of
them, so forgive me. I just put it there. So there have been
specific questions, and there are general questions. And I think we’ll start
with the general questions. And if we have time, we’ll
go to the specific ones. So the general question
for both of you is that many of the people are
wondering about the following, and that is, if all
three of us are correct, that we need innovation to
advance medical science, there’s two things to ask you. First, how do we
promote innovation? How do we incentivize
managing costs, especially as this country’s
expenditure on health care is approaching 20% of its GDP? How do we incentivize
industry, if we insist on costs being managed? And what’s the role
of basic research? So there are four things
for you to consider. Why don’t each of you
take a minute and a half to answer two of those. And I’ll say them again. What’s the role
for basic research? How do we manage cost
and support innovation? How do we incentivize industry
to become our partner, if we’re managing costs? And if you had to choose– I’ll
recast the fourth one– which of those many things would
you prioritize as number one? I’ll just start with a
few general comments. I gave a talk in the
University of Toronto a couple of weeks ago. It’s where I did my PhD. And there’s a
professor there who has developed a
technology that is en route to making
a major difference in the lives of patients. And he gave a talk
in this research day. And he said, you know what? It took me three decades
of basic research before I was ready to
have that technology leave the laboratory, till it was
ready to be manufactured and turned into a product. And I think it’s important to
emphasize that we really need the basic research in place. And we need to have a good
understanding of the biology and of the materials,
before the technologists can come in and really formulate
and create technologies that can leave the laboratory. So I think the basic
research is essential. So Jeff, I’ll interrupt
you, that’s the easy answer. The more difficult one is,
how do you simultaneously fund basic research innovation
and control medical costs? I think one of the
challenges is that, when you look at researchers
across the board, there’s very few
that have actually translated technologies
and helped patients. And when you look at the
makeup of the review committees for grants– I used to
submit a grant to the NIH, for example– it’s not clear to
me that the people on the panel actually have expertise in
translating technologies. And I think, so one possibility
would be to try to look at it and to search for those
people who have been involved in translation and have them
review more of these grants, to maximize potential, to pick
grants and fund projects that have potential to make a
difference in patients’ lives. So Conor, if industry is
essential to innovation– they take a huge laser, and
they make a medical laser, they take a big rod,
and they make a pill, how do we incentivize
industry, if we’re trying to manage costs? Well, part of that problem
lies above my pay grade, but I think, definitely,
the early stages. Having industry being involved
at the fundamental levels is very, very important. One of the things, I think, Mass
General Hospital and Brigham and Women’s Hospital
are doing quite well these days is actually to bring
industry partners into our labs to work with us at
very early stages. And that stops a
whole lot, right? I’ve had an experience
very similar to Jeff where I was developing
this bandage. And I had all these great ideas
and things I wanted to do. And an entrepreneur group had
come in and was talking to me. And they said, whoa,
stop, stop, stop. You’re going way overboard. That would take you 10 years
of research, 15 postdocs worth of time to do. And in the meanwhile,
we can take this piece and start rolling
with it right now. We can begin bringing
this out to patients. And we can bring in
the funding to do it. And I think, at least
on the research side, having those conversations
early and understanding what the outputs can be can
make the process more efficient. In terms of lowering
costs on the outset, I think there needs to
be– Jeff touched on it– I think there needs to be a very
strong push on the government side, on the funding
side, to actually incentivize, to de-risk a lot
of these early involvements, to bring in the companies,
to bring in entrepreneurs, to bring in investors that are
willing take a lot more risk to early technologies. It lowers their costs. It increases the
amount of things that make it out the door. And that speeds
up that pipeline, so it’s not 50 months till
we have something approved. I’d also add that I think,
in general, academics are unqualified to really do
things that are innovative, meaning to bring ideas, and
develop products, and actually help patients. We are trained in asking
questions, and formulating hypothesis, and putting together
experiments, and publishing papers, and presenting our work. But really, most
of us have no idea what happens when something
leaves the lab, what the next steps are. And there’s a lot of steps. And if we know more about
what happens, I think, we can impose criteria
early on, and pick ideas that have a better
chance of making it. And things like patents–
if you don’t file a patent and have intellectual property
and protection of your ideas, then no company’s going
to want to invest. And there’s really an art form
to writing patents and how you develop families of patents. Also, in terms of thinking
of clinical trial design, and manufacturing, and
how do you pick– often, we’ll develop a
technology, and we have no idea what’s the
best first application. It may be a platform. It could be used in
multiple areas in the body, but how do we figure out what’s
the best first application. And many of the times,
it’s not obvious. And it requires groups
of people coming together who have brought
technologies to the clinic and multiple clinicians. And it’s a big conversation. But I think, if we somehow
were able to have academics, especially those who
have access to tools and to develop technologies,
if we had better understanding what happens after
things leave the lab, I think we could make
better decisions of projects to start and pursue that have
a chance of helping patients. So do we run the risk,
though, of insisting that all science be innovative? And do we create
silos of excellence, of the haves and the
have nots, pushing down the independent basic
scientist, at the expense of the sophisticated
entrepreneurial scientist? I think you need both. You need to have both. And I think the challenge
we have right now, as Jeff said, we– you know, if
I take a look at my students, most of the students
that we prepare, the people who are
going to follow us, are still focusing on mostly
hypothesis-driven research. And that is really important. And it has to stay. It’s the bedrock. It’s the foundation of
what we do as scientists. But there has to be a training. There has to be a pipeline
model of bringing science from the very fundamental
eurekas all the way out to the patient. And I don’t think
that necessarily separates have and have not. I think it’s realizing
that there are strengths and there are weaknesses
to different approaches, and that we need to bring in
partners along the stages, at critical junctions
along that stage, who can help bring technologies
out to patients in an efficient way. So let’s take what
you’ve both said and address some of
the specific questions. What, in your mind, are the
two most essential and critical factors that are standing
in the way of a cure for cancer, solution for HIV,
bringing xenotransplantation to the clinic, any
of the big things? What are two factors,
two general factors? And my follow-up
question as you answer that will be, what
would you advise, if you were a
presidential advisor, for us to do immediately? Wow. I mean, I would turn
the question back to– I think I might as well. [LAUGHTER] –Dr. Edelman. I think he’s in
the best position to address such a question. OK. [LAUGHTER] So then I would answer the
question in the following way. We need to do everything,
and that’s impossible. So the most important thing
we need to do is to educate. We need to involve all of you. And the fact that
you’re here today is actually the very first step. We can’t do this alone. We need you, as an
educated public, to be willing to
fund our research. Because at the end
of the day, you’re not letting us have
a good time, though, we have the greatest
jobs in the world, but you’re actually
ensuring your future and the legacy of your children
and your children’s children. So the most important
thing that we need to do is project science
not as something that goes on in an ivory tower,
but rather something that goes on in the clinic,
in the laboratory, so that it can rapidly make
its way to the community. And the community has to
absorb science and innovation with the understanding that it
will fail, over and over again. And just give us a
little breathing room to make it better for you. Second thing we need to do is,
from a policy point of view, divorce essential elements of
what makes our lives better one from each other. We have a terrible
tension that exists today, is that the funding
for school lunches, and child vaccination,
and K through 12 education comes from the same budget
that funds these investigators, so that you have
to make a choice. You have to make a
choice between propelling photomedicine, or stem cell
biology, or innovations in the latest molecular
imaging, and providing lunches for inner city children. We can’t do that anymore. It just can’t happen. And that needs to
involve all of you. We have to set aside funds for
everyone in this United States, so that we all get the benefit. And it’s not that we go
to the back of the line, once we’ve gotten
the first choice. So those are the first
two things I would do. Now, I’ll turn it back to you. [LAUGHTER] I’m speechless. [LAUGHTER] Yes. Perfect answers. I can’t imagine. I’ve never known you
to be speechless. OK. [LAUGHTER] So I’m going to ask
both of you to finish, because we have five
minutes, in describing how you deal with failure. You both alluded to it. And what is it was
your most– you told us your
spectacular failure, but it really wasn’t a
failure, it was a success. And you told us Steven
Spielberg’s failure, but what is the recipe
for dealing with failure? So I’d say, when I started
my faculty position, I started applying for grants. I got my first grant,
which was a small grant. But then the next
nine, I didn’t get. And it turned out that, in
the first 2, 2 and 1/2 years, I submitted 100 grants,
most of them failures, but I was determined. And what I had
tried to do– there was a problem with my
approach at the time, which was I didn’t want to do
just incremental work based on things I’d done in the past. I wanted to pitch
completely new ideas. I wanted to get into new areas. And the reviewers kept
coming back and saying, but you have no
preliminary data for this. This is too high-risk. And so what happened was,
is through the persistence, I was able to turn that
failure into a success. And the way I was able
to do that was because, in many of those
failures, though failed grants, I got feedback on
the grants from the reviewers, saying exactly, putting
them together, putting all these failures
together, the recipe for how to write a really good grant. And so I’d say that,
now, when I write grants, I can almost envision the 10
people sitting around the table and know exactly what
they’re thinking, which I think now
maximizes– now, we don’t get every
grant that we apply for, but we get enough that
we can still pursue multiple avenues of research. And so I think that
one aspect, just like we saw with
Steven Spielberg, is having a lot of persistence. The other, I would
say, is having access to the right tools, the right
technologies, the right people. And one of the ways that we
try to do this in my laboratory is having a
multi-disciplinary team. So we have chemical engineers,
mechanical engineers, immunologists, basic biologists. We’ve had a
gastrointestinal surgeon. We’ve had a cardiac fellow come
through the lab, multiple MDs. And so there’s very
minimal overlap in expertise in the lab. Everybody brings
something unique. And when we get together to
brainstorm and solve problems, everyone feels validated. Everyone has something to offer. There’s minimal competition
of the people in the lab. And I think that
that has allowed us to come up with
lots and lots of ideas from all kinds of
different disciplines. And then we can pick the
best ideas to advance. And I think that
that’s really helped. I would agree with
all those points. And like Jeff, I’ve
probably written over 100 unsuccessful grants myself. I think what a
lot of people see, what we show others,
especially as scientists, is we’re like the
iceberg floating in the water, right? All you see is the tip. The success that he see is
what you see on the surface. The rest of the
iceberg, the part that’s beneath the
surface, is where all the hard work,
the blood, sweat, the tears, the overnights, the
late nights, and the failure is. And it’s funny
because, I think, one of the things you learn–
part of the process of getting a PhD, I think, is a
very humbling experience, because you learn that you are
going to fail all the time. And I think it’s
why you find PhDs are– why we’re the scientists. I tell every student who
comes to my laboratory that they need to
remember this one thing. That if an experiment
works on the first time, something’s gone horribly wrong. [LAUGHTER] Because it’s never going to
work the first / and it’s not going to work the second,
the third, or the fourth, or the fifth, and
probably not the 25th. But magically, on the 26th,
part of it’s going to work. And when that happens,
that’s the moment that you need to
sit up and go aha. Why did it only partially fail? Why did only a little bit of
it– where is that insight? And that’s where the
insight comes from. And I think it’s something
that we, as scientists, we beat ourselves over the
head with failure constantly and think it’s something
that people who aren’t– and you’re
going to see this. You go to the best innovators
in the world, the CEOs of your Fortune 500 companies,
they project success, but they are failing constantly. And it’s learning
from those failures. And it’s basically
setting yourself up to fail and fail
often that is probably the most important part
of doing any of this work. Now, in some cases,
you can’t fail. If I’m a doctor
treating a patient, you’d better hope I
don’t fail, right? But on the research
side, this is what gives us this flexibility. And I think it’s this mentality,
it’s this education mentality, that you’re going to try
to do something hard. You should expect
to fail, and you expect to learn from every
single one of those hundred thousand failures. Because the moment
you get it right is the moment that
you’ve integrated every bit of knowledge
you’ve learned along the way. And make failure
part of the process. Yes. It’s part of what you do. So unfortunately,
our time is up. But I want to thank,
first, Dean Vild, for making this possible, Angela
Alberti, for organizing this, for all of you for
coming and for allowing us to be a part of
your lives and allowing us to do what we love
and what is the most wonderful job in the world. So thank you, very
much, for coming. [APPLAUSE]

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