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  • 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)

Hi everyone.

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B1 INT US TED pig organ crispr virus ca

【TED】Luhan Yang: How to create a world where no one dies waiting for a transplant (How to create a world where no one dies waiting for a transplant | Luhan Yang)

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    林宜悉   posted on 2018/10/05
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