- TED Talks
Good afternoon. There's a medical revolution happening all around
us, and it's one that's going to help us conquer some of society's
most dreaded conditions, including cancer. The revolution is called
angiogenesis, and it's based on the process that our bodies use to
grow blood vessels.
So why should we care about blood vessels? Well, the human body
is literally packed with them: 60,000 miles worth in a typical adult.
End to end, that would form a line that would circle the earth twice.
The smallest blood vessels are called capillaries; we've got 19
billion of them in our bodies. And these are the vessels of life, and,
as I'll show you, they can also be the vessels of death. Now the
remarkable thing about blood vessels is that they have this ability to
adapt to whatever environment they're growing in. For example, in
the liver they form channels to detoxify the blood; in the lung they
line air sacs for gas exchange; in muscle they corkscrew so that
muscles can contract without cutting off circulation; and in nerves
they course along like power lines, keeping those nerves alive. We
get most of these blood vessels when we're actually still in the
womb, And what that means is that as adults, blood vessels don't
normally grow. Except in a few special circumstances: In women,
blood vessels grow every month to build the lining of the uterus;
during pregnancy, they form the placenta, which connects mom and
baby. And after injury, blood vessels actually have to grow under
the scab in order to heal a wound. And this is actually what it looks
like, hundreds of blood vessels all growing toward the center of the
So the body has the ability to regulate the amount of blood vessels
that are present at any given time. It does this through an elaborate
and elegant system of checks and balances, stimulators and
inhibitors of angiogenesis, such that, when we need a brief burst of
blood vessels, the body can do this by releasing stimulators,
proteins called angiogenic factors that act as natural fertilizer and
stimulate new blood vessels to sprout. And when those excess
vessels are no longer needed, the body prunes them back to
baseline using naturally occurring inhibitors of angiogenesis. Now
there are other situations where we start beneath the baseline and
we need to grow more blood vessels just to get back to normal
levels -- for example, after an injury -- and a body can do that too,
but only to that normal level, that set point.
But what we now know is that for a number of diseases, there are
defects in the system where the body can't prune back extra blood
vessels or can't grow enough new ones in the right place at the
right time. And in these situations, angiogenesis is out of balance.
And when angiogenesis is out of balance, a myriad of diseases
result. For example, insufficient angiogenesis -- not enough blood
vessels -- leads to wounds that don't heal, heart attacks, legs
without circulation, death from stroke, nerve damage. And on the
other end, excessive angiogenesis -- too many blood vessels --
drives disease, and we see this in cancer, blindness, arthritis,
obesity, Alzheimer's disease. In total, there are more than 70 major
diseases affecting more than a billion people worldwide, that all
look on the surface to be different from one another, but all actually
share abnormal angiogenesis as their common denominator. And
this realization is allowing us to reconceptualize the way that we
actually approach these diseases by controlling angiogenesis.
Now I'm going to focus on cancer because angiogenesis is a
hallmark of cancer, every type of cancer. So here we go. This is a
tumor: dark, gray, ominous mass growing inside a brain. And under
the microscope, you can see hundreds of these brown staining
blood vessels, capillaries that are feeding cancer cells, bringing
oxygen and nutrients. But cancers don't start out like this. And, in
fact, cancers don't start out with a blood supply. They start out as
small, microscopic nests of cells that can only grow to one half a
cubic millimeter in size; that's the tip of a ballpoint pen. Then they
can't get any larger because they don't have a blood supply, so they
don't have enough oxygen or nutrients.
In fact, we're probably forming these microscopic cancers all the
time in our body. Autopsy studies from people who died in car
accidents have shown that about 40 percent of women between the
ages of 40 and 50 actually have microscopic cancers in their
breasts, about 50 percent of men in their 50s and 60s have
microscopic prostate cancers, and virtually 100 percent of us, by
the time we reach our 70s, will have microscopic cancers growing in
our thyroid. Yet, without a blood supply, most of these cancers will
never become dangerous. Dr. Judah Folkman, who was my mentor
and who was the pioneer of the angiogenesis field, once called this
"cancer without disease."
So the body's ability to balance angiogenesis, when it's working
properly, prevents blood vessels from feeding cancers. And this
turns out to be one of our most important defense mechanisms
against cancer. In fact, if you actually block angiogenesis and
prevent blood vessels from ever reaching cancer cells, tumors
simply can't grow up. But once angiogenesis occurs, cancers can
grow exponentially. And this is actually how a cancer goes from
being harmless to deadly. Cancer cells mutate and they gain the
ability to release lots of those angiogenic factors, natural fertilizer,
that tip the balance in favor of blood vessels invading the cancer.
And once those vessels invade the cancer, it can expand, it can
invade local tissues. And the same vessels that are feeding tumors
allow cancer cells to exit into the circulation as metastases. And,
unfortunately, this late stage of cancer is the one at which it's most
likely to be diagnosed, when angiogenesis is already turned on and
cancer cells are growing like wild.
So, if angiogenesis is a tipping point between a harmless cancer and
a harmful one, then one major part of the angiogenesis revolution
is a new approach to treating cancer by cutting off the blood
supply. We call this antiangiogenic therapy, and it's completely
different from chemotherapy because it selectively aims at the
blood vessels that are feeding the cancers. And we can do this
because tumor blood vessels are unlike normal, healthy vessels we
see in other places of the body: They're abnormal; they're very
poorly constructed; and, because of that, they're highly vulnerable
to treatments that target them. In effect, when we give cancer
patients antiangiogenic therapy -- here, an experimental drug for a
glioma, which is a type of brain tumor -- you can see that there are
dramatic changes that occur when the tumor is being starved.
Here's a woman with a breast cancer being treated with the
antiangiogenic drug called Avastin, which is FDA approved. And you
can see that the halo of blood flow disappears after treatment.
Well, I've just shown you two very different types of cancer that both
responded to antiangiogenic therapy. So, a few years ago, I asked
myself, "Can we take this one step further and treat other cancers,
even in other species?" So here is a nine year-old boxer named Milo
who had a very aggressive tumor called a malignant neurofibroma
growing on his shoulder. It invaded into his lungs. His veterinarian
only gave him three months to live. So we created a cocktail of
antiangiogenic drugs that could be mixed into his dog food as well
as an antiangiogenic cream that could be applied on the surface of
the tumor. And within a few weeks of treatment, we were able to
slow down that cancer's growth such that we were ultimately able to
extend milo's survival to six times what the veterinarian had initially
predicted, all with a very good quality of life.
And we subsequently treated more than 600 dogs. We have about a
60 percent response rate and improved survival for these pets that
were about to be euthanized. So let me show you a couple of even
more interesting examples. This is 20-year-old dolphin living in
Florida, and she had these lesions in her mouth that, over the
course of three years, developed into invasive squamous cell
cancers. So we created an antiangiogenic paste. We had it painted
on top of the cancer three times a week. And over the course of
seven months, the cancers completely disappeared, and the
biopsies came back as normal.
Here's a cancer growing on the lip of a Wuarter horse named
Guinness. It's a very, very deadly type of cancer called an
angiosarcoma. It had already spread to his lymph nodes, so we used
an antiangiogenic skin cream for the lip and an oral cocktail, so we
could treat from the inside as well as the outside. And over the
course of six months, he experienced a complete remission. And
here he is six years later, Guinness, with his very happy owner.
Now, obviously, antiangiogenic therapy could be used for a wide
range of cancers. And, in fact, the first pioneering treatments for
people, as well as dogs, are already becoming available. There's 12
different drugs, 11 different cancer types. But the real question is:
How well do these work in practice? So here's actually the patient
survival data from eight different types of cancer. The bars
represent survival time taken from the era in which there was only
chemotherapy, or surgery, or radiation available. But starting in
2004, when antiangiogenic therapies first became available, well
you can see that there has been a 70 to 100 percent improvement
in survival for people with kidney cancer, multiple myeloma,
colorectal cancer, and gastrointestinal stromal tumors. That's
impressive. But for other tumors and cancer types, the
improvements have only been modest.
So I started asking myself, "Why haven't we been able to do better?"
And the answer, to me, is obvious; we're treating cancer too late in
the game, when it's already established and, oftentimes, it's already
spread or metastasized. And as a doctor, I know that once a disease
progresses to an advanced stage, achieving a cure can be difficult,
if not impossible. So I went back to the biology of angiogenesis and
started thinking: Could the answer to cancer be preventing
angiogenesis, beating cancer at its own game so the cancers could
never become dangerous? This could help healthy people as well as
people who've already beaten cancer once or twice and want to find
a way to keep it from coming back. So to look for a way to prevent
angiogenesis in cancer, I went back to look at cancer's causes. And
what really intrigued me was when I saw that diet accounts for 30 to
35 percent of environmentally caused cancers.
Now, the obvious thing is to think about what we could remove
from our diet, what to strip out, take away. But I actually took a
completely opposite approach and began asking: What could we be
adding to our diet that's naturally antiangiogenic, that could boost
the body's defense system and beat back those blood vessels that
are feeding cancers? In other words, can we eat to starve cancer?
(Laughter) Well, the answer's yes, and I'm going to show you how.
Our search for this has taken us to the market, the farm and to the
spice cabinet, because what we've discovered is that mother nature
has laced a large number of foods and beverages and herbs with
naturally occurring inhibitors of angiogenesis.
So here's a test system we developed. At the center is a ring from
which hundreds of blood vessels are growing out in a starburst
fashion. And we can use this system to test dietary factors at
concentrations that are obtainable by eating. So let me show you
what happens when we put in an extract from red grapes. The
active ingredient's resveratrol, it's also found in red wine. This
inhibits abnormal angiogenesis by 60 percent. Here's what happens
when we added an extract from strawberries; it potently inhibits
angiogenesis. And extract from soybeans. And here is a growing list
of our antiangiogenic foods and beverages that we're interested in
studying. For each food type, we believe that there are different
potencies within different strains and varietals. And we want to
measure this because, well, while you're eating a strawberry or
drinking tea, why not select the one that's most potent for
So here are four different teas that we've tested. They're all common
ones: Chinese jasmine, Japanese sencha, Earl Grey and a special
blend that we prepared. And you can see clearly that the teas vary
in their potency from less potent to more potent. But what's very
cool is when we actually combined the two less potent teas
together, the combination, the blend, is more potent than either
one alone. This means there's food synergy.
Here's some more data from our testing. Now, in the lab, we can
simulate tumor angiogenesis represented here in a black bar. And
using this system, we can test the potency of cancer drugs. So the
shorter the bar, less angiogenesis, that's good. And here are some
common drugs that have been associated with reducing the risk of
cancer in people. Statins, nonsteroidal anti-inflammatory drugs and
a few others, they inhibit angiogenesis too. And here are the dietary
factors going head to head against these drugs. You can see, they
clearly hold their own and, in some cases, they're more potent than
the actual drugs. Soy, parsley, garlic, grapes, berries; I could go
home and cook a tasty meal using these ingredients. So imagine if
we could create the world's first rating system in which we could
score foods according to their antiangiogenic, cancer-preventative
properties. And that's what we're doing right now.
Now, I've shown you a bunch of lab data, and so the real question
is: What is the evidence in people that eating certain foods can
reduce angiogenesis in cancer? Well, the best example I know is a
study of 79,000 men followed over 20 years, in which it was found
that men who consumed cooked tomatoes two to three times a
week had up to a 50 percent reduction in their risk of developing
prostate cancer. Now, we know that tomatoes are a good source of
lycopene, and lycopene is antiangiogenic. But what's even more
interesting from this study is that in those men who did develop
prostate cancer, those who ate more servings of tomato sauce
actually had fewer blood vessels feeding their cancer. So this human
study is a prime example of how antiangiogenic substances present
in food and consumed at practical levels can impact on cancer. And
we're now studying the role of a healthy diet with Dean Ornish at
UCSF and Tufts University on the role of this healthy diet on
markers of angiogenesis that we can find in the bloodstream.
Now, obviously, what I've shared with you has some far-ranging
implications, even beyond cancer research. Because if we're right, it
could impact on consumer education, food services, public health
and even the insurance industry. And, in fact, some insurance
companies are already beginning to think along these lines. Check
out this ad from Blue Cross Blue Shield of Minnesota. And for many
people around the world, dietary cancer prevention may be the only
practical solution because not everybody can afford expensive end-
stage cancer treatments, but everybody could benefit from a healthy
diet based on local, sustainable, antiangiogenic crops.
Now, finally, I've talked to you about food, and I've talked to you
about cancer, so there's just one more disease that I have to tell you
about and that's obesity. Because it turns out that adipose tissue,
fat, is highly angiogenesis dependent. And, like a tumor, fat grows
when blood vessels grow. So the question is: Can we shrink fat by
cutting off its blood supply? So the top curve shows the body
weight of a genetically obese mouse that eats nonstop until it turns
fat, like this furry tennis ball. And the bottom curve is the weight of
a normal mouse.
If you take the obese mouse and give it an angiogenesis inhibitor, it
loses weight. Stop the treatment, gains the weight back. Restart the
treatment, loses the weight again. Stop the treatment, it gains the
weight back. And, in fact, you can cycle the weight up and down
simply by inhibiting angiogenesis. So this approach that we're
taking for cancer prevention may also have an application for
obesity. The really, truly interesting thing about this is that we can't
take these obese mice and make them lose more weight than what
the normal mouse's weight is supposed to be. In other words, we
can't create supermodel mice. (Laughter) And this speaks to the role
of angiogenesis in regulating healthy set points.
Albert Szent-Gyorgi once said that, "Discovery consists of seeing
what everyone has seen, and thinking what no one has thought." I
hope I've convinced you that, for diseases like cancer, obesity and
other conditions, that there may be a great power in attacking their
common denominator: angiogenesis. And that's what I think the
world needs now. Thank you.
June Cohen: I have a quick question for you. So these drugs aren't
exactly ... they're not exactly in mainstream cancer treatments right
now. For anyone out here who has cancer, what would you
recommend? Do you recommend pursuing these treatments now,
for most cancer patients?
William Li: So there are antiangiogenic treatments that are FDA
approved, and if you're a cancer patient or working for one or
advocating for one, you should ask about them. And there are many
clinical trials. The Angiogenesis Foundation is following almost 300
companies, and there are about 100 more drugs in that pipeline. So
consider the approved ones, look for clinical trials, but then
between what the doctor can do for you, we need to start asking
what can we do for ourselves. And this is one of the themes that I'm
talking about is we can empower ourselves to do the things that
doctors can't do for us, which is to use knowledge and take action.
And if Mother Nature has given us some clues, we think that there
might be a new future in the value of how we eat. And what we eat
is really our chemotherapy three times a day.
JC: Right. And along those lines, for people who might have risk
factors for cancer, would you recommend pursuing any treatments
sort of prophylactically or simply pursuing the right diet with lots of
WL: Well, you know, there's abundant epidemiological evidence. And
I think in the information age, it doesn't take long to go to a
credible source like PubMed, the National Library of Medicine, to
look for epidemiological studies for cancer risk reduction based on
diet and based on common medications. And that's certainly
something that anybody can look into.
JC: Okay. Well, thank you so much.
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