How to create a world where no one dies waiting for a transplant | Luhan Yang

112,777 views ・ 2018-10-05

TED


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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.
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However, to hundreds of thousands 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
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for patients with kidney failure 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.
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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.
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Today, about 100 people 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.
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In Asia, for example,
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media outlets reported that desperate patients
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are obtaining organs from the cruel black market.
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It is clear that a solution 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.
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Today, I am optimistic to say 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
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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,
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let's have a better understanding what xenotransplantation is.
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It's a process of transplanting 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
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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,
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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,
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it will reject it.
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Second, and this one is specific to the organs from the pig,
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every pig carries a virus 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),
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and this virus has the potential to cause a viral epidemic similar to HIV.
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Without an effective way to address these issues,
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the field of xenotransplantation 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.
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My journey started from Emei Mountain in China.
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That is the place well described 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.
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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
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with a monkey on my shoulder.
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I still vividly remember how my friends and I
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would toss peanuts around to distract the monkeys
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so that we could cross 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,
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I chose to study biology 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
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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
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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.
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After college, I decided 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.
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Among all the experiments,
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one particular one took me closer to Laika.
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In 2013, my colleagues and I 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.
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It was an exciting moment in scientific discovery.
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The gene-editing tool CRISPR 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.
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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
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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.
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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
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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
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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
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and human-immune-compatible.
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The nucleus of that cell 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
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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
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hopefully wouldn't be rejected by the human immune system.
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In 2015, our team decided to tackle the viral transmission problem first.
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We wanted to take out 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.
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Even with CRISPR,
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we could only do one or two modifications within a cell.
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The record for number of modifications 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.
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With very careful design 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
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being transmitted into humans.
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Last year, with a modified cell 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.
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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
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to solve the immunology problem.
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Since then, we have created more than 30 pigs without PERV,
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and they may be the most advanced 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.
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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.
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Imagine a world where patients 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
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because we can provide them 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
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do not have to face 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
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we could never tackle before,
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and Laika is just the beginning of our journey.
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We have to be very humble in front of nature,
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because there are more issues to be addressed,
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including immunology
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and things we couldn't even anticipate at this point.
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However, it is our responsibility to translate the cutting-edge science
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into medicine to save the lives 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.
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Come forward.
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So what's the next steps here? You've got rid of the virus.
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The next steps involve trying to get to the point
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where a human body 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.
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So we need to take out the antigen of the pigs.
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In addition, we can learn a lot from cancer.
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How can cancer invade 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.
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CA: When would you estimate, when do you hope
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that the first successful transplant would happen?
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LY: It would be irresponsible for me to give you any number.
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CA: We're at TED. 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.
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CA: So not even, you won't say that you think it could happen
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within a decade or within five years or something?
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LY: For sure we hope it happens 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,
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the potential is extraordinary.
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There will be some other 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."
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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.
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In addition, similar to human donation,
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if we only harvest 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
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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?
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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.
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(Applause)
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