TED2018
Luhan Yang: How to create a world where no one dies waiting for a transplant
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For nearly half a century, scientists have been trying to create a process for transplanting animal organs into humans, a theoretical dream that could help the hundreds of thousands of people in need of a lifesaving transplant. But the risks, specifically of transmitting the PERV virus from pigs to humans, have always been too great, stalling research -- until now. In a mind-blowing talk, geneticist Luhan Yang explains a breakthrough: using CRISPR, a technique for editing genes, she and her colleagues have created pigs that don't carry the virus, opening up the possibility of safely growing human-transplantable organs in pigs. Learn more about this cutting-edge science and how it could help solve the organ shortage crisis.
Luhan Yang - Biologist, geneticist
Dr. Luhan Yang is the co-founder and chief scientific officer at eGenesis, working to make xenotransplantation a routine medical procedure for the delivery of safe and effective human transplantable cells, tissues and organs. Full bio
Dr. Luhan Yang is the co-founder and chief scientific officer at eGenesis, working to make xenotransplantation a routine medical procedure for the delivery of safe and effective human transplantable cells, tissues and organs. Full bio
Double-click the English transcript below to play the video.
00:12
Hi everyone.
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I would like to introduce you to Laika.
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To most of us, Laika is simply
a very cute pig.
a very cute pig.
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However, to hundreds of thousands
of patients in need of a lifesaving organ
of patients in need of a lifesaving organ
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Laika is a symbol of hope.
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You see, ever since the 1970s,
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when organ transplants
became a real option
became a real option
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for patients with kidney failure
and other organ diseases,
and other organ diseases,
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organ supply has been an issue.
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Over the last few decades,
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the issue only worsened as organ demand
has exponentially increased.
has exponentially increased.
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Currently in the US,
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there are close to 115,000 patients
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in need of a lifesaving organ transplant.
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By the end of my talk,
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one more patient
will be added to this list.
will be added to this list.
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Today, about 100 people
will get a new organ,
will get a new organ,
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a chance to start their life anew,
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and yet by the end of today,
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20 others will die waiting.
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The situation is heartbreaking
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for patients, for their families
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and for the doctors who want to do more.
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In some parts of the world,
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the situation also becomes
a disturbing social issue.
a disturbing social issue.
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In Asia, for example,
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media outlets reported
that desperate patients
that desperate patients
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are obtaining organs
from the cruel black market.
from the cruel black market.
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It is clear that a solution
is needed to this crisis.
is needed to this crisis.
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Human lives are at stake.
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As a biologist and a geneticist,
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it has become my mission
to help solve this problem.
to help solve this problem.
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Today, I am optimistic to say
that we are on our way there,
that we are on our way there,
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thanks to Laika.
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Using gene editing technology,
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it's now possible to exquisitely create
a human-transplantable organ
a human-transplantable organ
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that can be safely grown in pigs.
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Before we jump into the incredible
science that makes it happen,
science that makes it happen,
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let's have a better understanding
what xenotransplantation is.
what xenotransplantation is.
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It's a process of transplanting
animal organs into humans.
animal organs into humans.
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You may want to ask, why pig organs?
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Because some pigs carry organs
with similar size and physiology
with similar size and physiology
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to human organs.
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Over the last half a century,
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pioneers of transplantation
have tried hard to make it happen,
have tried hard to make it happen,
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but with limited to no success.
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Why is that?
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Two fundamental hurdles stood in the way.
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First is a problem of rejection.
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When our immune system
sees a new organ as foreign,
sees a new organ as foreign,
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it will reject it.
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Second, and this one is specific
to the organs from the pig,
to the organs from the pig,
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every pig carries a virus
that is benign to the pig,
that is benign to the pig,
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but can be transmitted into humans.
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It is called the porcine
endogenous retrovirus (PERV),
endogenous retrovirus (PERV),
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and this virus has the potential
to cause a viral epidemic similar to HIV.
to cause a viral epidemic similar to HIV.
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Without an effective way
to address these issues,
to address these issues,
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the field of xenotransplantation
has been on hold for more than one decade.
has been on hold for more than one decade.
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Little progress has been made, until now.
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Let me share with you
how I got here today with Laika.
how I got here today with Laika.
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My journey started
from Emei Mountain in China.
from Emei Mountain in China.
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That is the place well described
in a lot of legendary stories,
in a lot of legendary stories,
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like the "Crouching Tiger, Hidden Dragon."
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That is the place I call home.
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Growing up in the mountain,
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I started to have
a strong connection with nature.
a strong connection with nature.
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This is me when I was seven years old
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standing in front
of an ancient Buddhist temple
of an ancient Buddhist temple
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with a monkey on my shoulder.
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I still vividly remember
how my friends and I
how my friends and I
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would toss peanuts around
to distract the monkeys
to distract the monkeys
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so that we could cross
to hike through the valley.
to hike through the valley.
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I love nature.
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When it was time
to choose a field of study,
to choose a field of study,
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I chose to study biology
at Peking University in Beijing.
at Peking University in Beijing.
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However, the more I learned,
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the more questions I had.
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How could our genetic makeup
be so similar to animals
be so similar to animals
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and yet we look so different?
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How is our immune system capable
of fighting off so many pathogens
of fighting off so many pathogens
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but smart enough not to attack ourselves.
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Questions like this tormented me.
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I know it sounds nerdy,
but you know I'm a scientist.
but you know I'm a scientist.
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After college, I decided
I didn't want to just ask the questions,
I didn't want to just ask the questions,
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I wanted to answer them, so I did.
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In 2008, I was lucky enough to be accepted
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into the PhD program at Harvard University
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and worked with Dr. George Church.
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While working in Church's lab,
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I started to learn and experiment
with the genetic makeup of mammals.
with the genetic makeup of mammals.
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Among all the experiments,
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one particular one
took me closer to Laika.
took me closer to Laika.
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In 2013, my colleagues and I
made changes in a human cell
made changes in a human cell
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using a tool you may have heard about
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called CRISPR.
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We were one of the first two groups
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to report the successful use
of such a tool in changing our DNA.
of such a tool in changing our DNA.
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It was an exciting moment
in scientific discovery.
in scientific discovery.
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The gene-editing tool CRISPR
has two components.
has two components.
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It has a scissor called the enzyme CRISPR
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and what is called a guide RNA.
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Think about it as genetic scissors
with a microscope.
with a microscope.
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The microscope is a guide RNA,
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which brings the scissors
to the place we want to cut
to the place we want to cut
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and says, "Here it is,"
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and the enzyme CRISPR just cuts
and repairs the DNA in the way we want.
and repairs the DNA in the way we want.
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Shortly after we reported our study,
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physicians at Mass General Hospital
were intrigued by the medical applications
were intrigued by the medical applications
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of our research.
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They reached out to us,
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and together, we began to see
the potential to use CRISPR
the potential to use CRISPR
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to solve the organ shortage crisis.
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How do we do it?
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It is simple, yet very complex.
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We started by making changes
in a pig's cell to make it virus-free
in a pig's cell to make it virus-free
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and human-immune-compatible.
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The nucleus of that cell
is then implanted into a pig egg
is then implanted into a pig egg
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and allowed to divide into an embryo.
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The resulting embryo is then placed
into the uterus of a surrogate mother
into the uterus of a surrogate mother
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and allowed to divide into a pig.
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Basically, it's a process of cloning.
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The piglet then carries organs
whose genetic makeup
whose genetic makeup
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hopefully wouldn't be rejected
by the human immune system.
by the human immune system.
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In 2015, our team decided to tackle
the viral transmission problem first.
the viral transmission problem first.
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We wanted to take out
all 62 copies of the PERV virus
all 62 copies of the PERV virus
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from the pig genome,
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but at the time,
it was nearly mission impossible.
it was nearly mission impossible.
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Even with CRISPR,
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we could only do one or two
modifications within a cell.
modifications within a cell.
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The record for number of modifications
we can do in a particular cell was five.
we can do in a particular cell was five.
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We had to increase the throughput
by more than tenfold to achieve that.
by more than tenfold to achieve that.
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With very careful design
and hundreds of trials,
and hundreds of trials,
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we successfully took out all the virus,
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broke the record.
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More importantly, our studies showed
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that we could eliminate
the possibility of this dangerous virus
the possibility of this dangerous virus
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being transmitted into humans.
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Last year, with a modified cell
and cloning technology,
and cloning technology,
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our startup, eGenesis, produced Laika,
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the first pig of its kind
born without PERV.
born without PERV.
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(Applause)
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Laika represents the first critical step
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in establishing safe xenotransplantation.
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It is also a platform
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that we can do further
genetic modification on
genetic modification on
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to solve the immunology problem.
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Since then, we have created
more than 30 pigs without PERV,
more than 30 pigs without PERV,
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and they may be the most advanced
geno-modified animal living on earth.
geno-modified animal living on earth.
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We named Laika after the Soviet dog
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who was the first animal
to orbit the earth.
to orbit the earth.
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We hope Laika and her siblings
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can lead us into a new frontier
of science and medicine.
of science and medicine.
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Imagine a world where patients
who suffer from liver failure
who suffer from liver failure
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can be saved with a new liver
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without having to wait for a donation
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or another human to die.
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Imagine a world where people with diabetes
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do not have to rely
on insulin after every meal
on insulin after every meal
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because we can provide them
with good pancreatic cells
with good pancreatic cells
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that can produce insulin on their own.
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And imagine a world
where patients with kidney failure
where patients with kidney failure
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do not have to face
the burden of dialysis.
the burden of dialysis.
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We are striving to create that world,
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a world without organ shortage.
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We finally have the tool
to tackle the problem
to tackle the problem
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we could never tackle before,
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and Laika is just
the beginning of our journey.
the beginning of our journey.
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We have to be very humble
in front of nature,
in front of nature,
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because there are more issues
to be addressed,
to be addressed,
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including immunology
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and things we couldn't even
anticipate at this point.
anticipate at this point.
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However, it is our responsibility
to translate the cutting-edge science
to translate the cutting-edge science
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into medicine to save the lives
of all the patients who are waiting.
of all the patients who are waiting.
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Thank you very much.
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(Applause)
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Chris Anderson: I mean, Luhan,
this is extraordinary work here.
this is extraordinary work here.
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Come forward.
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So what's the next steps here?
You've got rid of the virus.
You've got rid of the virus.
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The next steps involve
trying to get to the point
trying to get to the point
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where a human body
won't reject a transplant.
won't reject a transplant.
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What's involved in solving that?
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Luhan Yang: It's a very
complicated process.
complicated process.
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So we need to take out
the antigen of the pigs.
the antigen of the pigs.
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In addition, we can learn
a lot from cancer.
a lot from cancer.
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How can cancer invade
or circumvent our immune system
or circumvent our immune system
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so that we can utilize the trick of cancer
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and implement that on the pig organ
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to fool our immune system
to not attack the organ.
to not attack the organ.
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CA: When would you estimate,
when do you hope
when do you hope
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that the first successful
transplant would happen?
transplant would happen?
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LY: It would be irresponsible for me
to give you any number.
to give you any number.
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CA: We're at TED.
We're always irresponsible.
We're always irresponsible.
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LY: But we are working day and night
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trying to make this happen
for the patients.
for the patients.
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CA: So not even, you won't say
that you think it could happen
that you think it could happen
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within a decade or within
five years or something?
five years or something?
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LY: For sure we hope it happens
within one decade.
within one decade.
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(Laughter)
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CA: So there's a lot of people here
who would be very, very excited at that,
who would be very, very excited at that,
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the potential is extraordinary.
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There will be some other
people here who are going,
people here who are going,
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"That pig is too cute.
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Humans shouldn't be exploiting
something so cute for our benefit."
something so cute for our benefit."
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Do you have any response to that?
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LY: Yeah, sure.
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So imagine one pig
can save eight people's lives.
can save eight people's lives.
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In addition, similar to human donation,
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if we only harvest
one kidney from the pig,
one kidney from the pig,
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the pig can still be alive,
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so we are very mindful about the issues,
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but I think our goal is just to address
the unmet medical need
the unmet medical need
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for those patients and their families.
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CA: Plus, no one can say that to you
if they eat bacon, right?
if they eat bacon, right?
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LY: That's a good point.
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(Laughter)
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CA: Luhan, thank you so much.
LY: Thank you so much.
LY: Thank you so much.
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(Applause)
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ABOUT THE SPEAKER
Luhan Yang - Biologist, geneticistDr. Luhan Yang is the co-founder and chief scientific officer at eGenesis, working to make xenotransplantation a routine medical procedure for the delivery of safe and effective human transplantable cells, tissues and organs.
Why you should listen
With the mission to translate scientific innovation into a life-saving medical procedure, Dr. Luhan Yang is leading a team of world-renowned scientists to leverage CRISPR technology and its potential to deliver safe and effective human transplantable organs to the hundreds of thousands of patients worldwide who are in dire need.
In the US alone, more than 116,000 people annually are in need of a lifesaving organ transplant, and 20 people die every day waiting for a transplant. To address this issue, scientists have been trying to engineer animal organs for human transplantation for more than 100 years. However, concern for issues such as pig-to-human immunological compatibility and cross-species transmission of porcine endogenous retroviruses (PERV) have proven to be two insurmountable obstacles -- until now.
In a breakthrough paper published in Science, Yang and her team demonstrated for the first time the inactivation of PERV to prevent cross-species viral transmission, an important milestone for xenotransplantation. As co-founder and chief scientific officer, Yang has been at the center of eGenesis' success. In addition to recruiting and leading a high-caliber scientific team, she has played an integral role in daily management of the company, business strategy and planning, as well as negotiating with investors for early round funding.
Yang holds BS degrees in biology and psychology from Peking University and a PhD in human biology and translational medicine from Harvard Medical School.
Luhan Yang | Speaker | TED.com