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