My big question is, can you discovery one day be used to extend the human lifespan?

Well, there may be a couple of people in the audience who may not exactly know what induced pluripotent stem cells are, why they're important.

So please bear with me.

I'll just go through a few slides.

Just make sure we're all on the same page to begin with.

I'm going to go back to 1998, when, scientists first arrived, human embryonic stem cells from fertility clinic embryos that were destined to be destroyed.

Derivation process is essentially taking an embryo at the 4 to 5 day stage.

This is about the time in which the fertility clinic would transfer this into a woman's uterus for pregnancy.

But again, these are embryos that the couple has decided they're not going to use, and they've decided to throw them away.

At that stage, you can derive embryonic stem cells from the inner cell mass, grow them out.

What's remarkable about the stem cells is that they could become any kind of human cell in the body, going down these three major lineages, they do have limitations.

However, if you're getting embryonic stem cells from fertility clinic embryos, you have very little control over the genetic composition of these cells.

You just basically have to get what you get.

2005, there was quite a bit of discussion of maybe getting customized embryonic like stem cells by using what we now call cloning technology.

And the proposal was to take a skin biopsy from a patient of interest, somebody with a genetic disease of interest, get an egg donor to provide her eggs for hormonal induction, and without fertilizing the egg, suck out the nucleus of the fertilized egg.

Replace that nucleus with the nucleus from the somatic cell donor.

Literally charge it up with electricity or chemicals to fool it into thinking that it became a fertilized egg.

And then you get your customized embryonic stem cells from that.

Now, this was the 80s, as you can imagine, very controversial, because where are you going to get all those eggs?

How many eggs?

Virginia, for this kind of work, are you going to pay the women like they normally get paid from fertility clinics?

Isn't this the same technique they used to clone Dolly the sheep?

Can you make human cloned babies this way?

Last, the controversy, and the field sort of stalled out at this point.

At this point, the President George W Bush Council on Bioethics came up with some proposals to come up with ethically derived embryonic stem cells, pluripotent stem cells.

And one of them, they had many proposals, but one of the proposals, they said, will solve everyone's problems.

Ethically, it would be to reprogram adult cells to behave like embryonic stem cells.

Now, they said in 2005, this is the furthest away.

This is the most pie in the sky dream.

Well, one year later, it was shown that it could be done in the mouse, and a year after that it could be done and human.

There was a study that was done at the Harvard Stem Cell Institute, where researchers fuzed a skin cell with a human embryonic stem cell using private funds, and this entire enormous fuel cell that has twice the number of chromosomes in its entirety served to behave like an embryonic stem cell.

So there must be something about the embryonic stem cell that can teach the skin cell to do what it does.

If you imagine the human DNA as an enormous keyboard, if it's a hard cell is playing, the hearts of those genes are activated.

If it's a stem cell is playing the stem cell.

So those genes are activated.

Can you teach the skin cell to play the heart cell, the stem cell song, without fuzing them together.

So Yamanaka did an incredible thing.

He has viruses to insert into the DNA of skin cells, to sort of try to teach the DNA to, to behave like an embryonic stem cell.

And he narrowed it down to four factor s that are extremely active in the stem cell state.

These are now called the Yamanaka factors.

This then allowed cloning without cloning.

Essentially, it allowed the dream of cloning for research without actually using cloning technology.

Because you could take an ALS patient.

Any patient of interest, get their skin cells or really any cell from their body in some noninvasive way, reprogram them to make pluripotent stem cells that could then become any kind of cell in the human body.

And this is extremely significant for lots of reasons.

Basic biology.

You can try to understand what goes wrong in the disease patient versus the healthy control.

What point do things start to go awry and develop it so you can compare.

It also gives you an unlimited source of cells for drug screening.

But for safety, using healthy cells like liver cells and also disease targeted a screening for disease.

So these are just a couple of the many, many applications we'll be talking about tonight.

as people say the rest is history.

In 2012, Shinya Yamanaka, along with John Gordon, got the Nobel Prize for Physiology or Medicine for the reprograming of mature cells.

I'm very excited now to bring out our guests.

Would you please welcome Shinya Yamanaka?

You are here because you ran the Boston Marathon a few days ago.

How was that?

Yeah, well, he walked here from there to here without limping.

Well, dying down in Boston has been my dream.

So, the dream came true.

But it was very long.

I was sick last week.

All these excuses.

Yeah, it was more.

I lost track, but I was still able to finish it, so.

And I most importantly, I really enjoyed it.

So thank you so much, Boston.

Thank you.

Thank you.

I I've heard you say that doing science is like running a marathon.

What do you mean by that?

just like life, science is really, marathon.

It takes long.

Sometime it goes well, but most of the time, like the day before yesterday, it doesn't go well, but nevertheless, you keep running.

No pain, no gain.

You know that you succeed in marathon and also in science.

So I've been learning a lot from marathon to be a scientist.

You and I first met in 2006, I. I'll never forget this.

It was a very small meeting in Norway at a very remote village in Norway.

I don't know why we were meeting there.

It was an invitation only small meeting.

I was there as a bioethicist.

And.

And you had, been there.

You arrived just after your mouse paper was was published in cell, 2006.

I remember at that meeting there were a few people, a few scientists there, and I kept doubting what you did.

One person said, are you sure your cell, culture wasn't contaminated?

And I thought, well, what kind of contaminant could possibly be?

I want to know what that contaminant is.

Now we make them fly our phone.

So did you face a lot of doubt when that paper first came out from other people?

Yeah.

Very much.

Pretty much.

So I, I attended another meeting in New York, Cold Spring Harbor meeting, and after I gave a talk, they have, very nice pub, so many people, drinking.

And, when I attended, I was able to listen, some people were talking on the phone.

Yes.

Yeah.

A bitter Then they identified me and they said, oh, look at this guy.

But, I think it was, very reasonable because, even to us, it is surprising, actually, when I, the first author, Chizu Takahashi, came to me look for a miracle.

It looks like we succeeded in making.

Yes, like, cells from mouse skin cells.

And I saw on the microscope the cells look like cells.

But I thought, Casa Takahashi, don't be excited.

99.9%.

This must be something.

Mistake.

This must be probably contamination of the cells.

Because we have many, many mouse cells in the lab.

We are very careful not to make any, contamination.

But, yes, cells are very tricky.

Only one cell contamination is sufficient to make us in trouble.

So I told him this must be some kind of mistake.

And I asked him to repeat it.

Repeat it, repeat it.

He repeated the same experiment again and again that it always worked, but I was not convinced enough.

So I have, 2 or 3 more senior members in my lab.

I asked them to repeat a very similar experiment, but in a little bit, different way.

And it all worked.

So now I'm, I was, we were, convinced.

So that's how, it happened to us.

Well, now, that was also right at the time that, a Korean group had claimed that they had done the cloning approach and got a patient specific stem cell lines that way.

I after the publication of their work, I started working with them to sort of come up with ethics policies for their institute, and then it became exposed as being fraudulent.

Now, that was a terrible time for the Korean teams because everybody that was on that paper, were investigated and there were many excellent young, young investigators that were had their careers ruined.

I noticed in your mouse paper there were just two authors.

Were you influenced at all by what happened in Korea?

We were, yes.

It was after, that Korean scandal in Korea.

We were very nervous.

So publishing that first paper, usually publishing a good paper is, doi for.

And it was a sell.

It was a great journal.

Yeah, it's a sell.

But for that particular paper, we were kind of afraid of, the response we will receive from the world, not only from scientists, but also from general, like, media people.

So, I talked to, cancer and other potential authors.

Maybe we should limit the number of, authors, small as possible.

So, the first course of cancer, who did the most, important part of the work and also myself has the corresponding author, to be listed as, only two authors of that paper, because we were responsible, we were responsible to receive any criticism from, scientists or, from media people.

So that's how, yeah, we published that.

Yeah.

First paper now before the publication, before you got your positive results, was there any doubt?

I mean, you were sort of doubtful when you got the result.

Was there anybody think this is a crazy experiment?

Why are we doing it this way?

Yeah.

So, we knew it's true because, we have repeated many times in the lab, but, once we submit the paper, or once we publish the paper, we have to see if other, scientists in other laboratories can, reproduce our work.

And it's going to be tricky because the stem cell looks like, like like, any, small differences, like, like, the quantity of water, can change the result.

So we that's one of the reason why we were so nervous.

We had.

No, we had good water in Kyoto.

Yeah.

We can, we could.

Maybe we should see all the water from Kyoto to Boston or to whatever, is required, but, we're very lucky.

Lucky or unlucky.

We didn't within that year, within like six months, people in Boston published another paper, reproducing our experiment.

So it was the beginning of, fierce race.

But at the same time, it was, huge relief for us.

So it was a very strange moment.

Yes.

I wonder why did you start with the mouse skin cells?

Why didn't you just start with human?

Well, it's a very good question.

Because, for many reasons, mouse is much easier than human cells.

For example.

Or if you want to convert, normal human cells to cancer cells, it's much more difficult than, muscle cells.

So in order to, may make mouse cancer cells, all you need is, only 1 or 2, oncogenes.

But in human cells, we know that we need three or 4 or 5, combination.

So, from that was one reason why we thought we should start on mice.

Were you surprised that it was the same for Yamanaka factors.

I work for human.

We are very surprised because of that cancer.

Example we thought in mice it was four factors.

But we thought in human it would take probably 6 or 7 factors.

So all combination four is complicated enough.

That complicated combination of 6 or 7 is even more complicated.

So we thought, wow, I don't know how long it would take from mouse to move from us to human, but to our surprise, the same for factor worked on both mouse and human.

So it didn't take that long.

It took, less than a year to move from mouse to human.

A few very key teams site almost simultaneously published in different journals human explorer Jamie Thomson's lab in Wisconsin use Lin 28, so they actually use one factor that was different.

Did that surprise you?

It does.

It does.

Surprising, actually, out of four factors.

They also used four factors to, common octal and Sox2 are common.

But the remaining two factors are totally different.

So it was surprising.

Now, what were you doing when Stockholm called you?

It's a very good question.

It was a holiday in Japan, 12 years ago, 2012.

I was at home, my wife here, she asked me to fix, washing machine.

So I lay down, and, I was doing my best to fix, washing machine, because otherwise my wife would upset.

But all of a sudden, my cell phone.

Yes, I got the cell phone call.

And, it was in English, and, he said, well, Doctor Malaka, we have decided to award you this year's Nobel Prize.

And to my surprise.

And then he asked me, would you accept?

It.

I was very surprised.

And of course I answered yes.

Yes by no.

Did you finish, fixing your washing machine?

I said I failed, but that, our government, Japanese government was kind enough.

they, gave me, enough money to buy a new washing machine.

That's great.

I'm glad to hear.

Now, how old were your daughters when this happened?

Oh, they they got surprised, of course.

But to my surprise, they, they maintained, calmness.

So, yeah, it was, yes, I it was, it was very good response.

I thought it made, make them very unhappy, but, they took it very naturally.

So it does.

It does.

Okay.

Well, now it's funny because the award is the Nobel Prize for physiology or Medicine.

You know, you pick.

Now, your discovery is important for both.

What are some of the applications of IPR.

So technology today that you find very exciting.

So at that time, we are trying to use IPS cells and disease modeling and drug discovery, as you just explained.

And of course, another very important application is cell therapy to transplant, the heart cells from IPS cells to patients from, suffering from heart failure.

So those are the two major medical applications of IPS cells for for patients.

And we have been working very hard to realize those two medical applications.

Now, when you first made the discovery, were there any potential uses of IPSC technology that you thought were a little bit concerning to you?

Yes.

That's that's very true.

In the beginning, in the, first week after we succeeded, we published, first mouse paper.

We are very happy because we thought we have overcome a big ethical issue about tumor cells in that we don't have to use human, embryos.

So, I thought, well, we have overcome, huge ethical, issue.

But after a week, I realized, wait a minute, we can now make, like, germ cells from IPS.

Cells from your skin cells or from your blood cells.

Well, probably we have generated even bigger ethical, issue by making IPS cells.

So, it was, kind of shocking moment to me.

I went to the Japanese government ministry of, education and asked them to start, ethical company conversation about that kind of, ethical issue of IPS cells.

And they, quickly responded.

And at that time, I took well, at least in theory, we could make germ cells like sperm and eggs from my cells.

But, it was already 70, 70 years ago.

I thought it was just my theory.

It it would.

I thought it would take very long.

20 years.

30 years before we can actually make germ cells from IPS cells.

But, it took, much, much shorter than that.

So within like five years, one of our colleagues in Kyoto University, they succeeded in making sperm and, now even, eggs from mouse IPS cells from male mice.

Yeah.

Now, yes, they can make, eggs even from male, IPS cells.

And they made mouse pups there.

Yeah, exactly.

And that that doctor, doctor Hayashi is, is one of the, time 100 most important person this year.

So it it it's moving very quickly.

It's moving very quickly.

So yes, we have generated new kind of ethical old questions.

Yeah.

Yeah.

As a bioethics, as people tell me when your discovery was made.

Oh doctor here and I think your work is done now with stem cells because now they can make them from any cell.

And I thought, just wait.

Yeah.

What I thought was significant was for embryonic stem cells.

The genetic source of the cell line is destroyed during derivation.

There's no existing cell line donor, but with IPS cells, she could have, you know, a lifetime where the.

In some cases, the pediatric patient has an ideal cell line and will grow up with this cell line in existence being shared all over the world.

And, so that could be concerning, because now stem cell research has brought on the baggage of genetic research and privacy, so many, many other things to think about.

What I find fascinating.

I'm curious to know your thoughts.

The animal work done with IPS cells and even conservation.

We're talking a little bit about the sperm and eggs made from that.

But there are people who are hoping to use IPS cells from endangered species to rescue them.

Is that something that you find, interesting?

Yeah.

It's another, very interesting and important, potential of IPS cells to preserve those, species in danger.

And I understand, some scientists, they're even make, like, mammoth by using, elephant IPS cells.

So, the potential is, you know, in addition to those two major medical applications, which you and I just, discussed, there are more, potentials of this technology.

So I, I have been just amazed.

Yeah.

Another area that's really exploded in stem cell research and also for the ethics of, is making little three dimensional models of either organs called organoids or even whole embryo models that seem to replay the first few weeks of, of embryo development using IPS cells, using embryonic stem cells, a kind of this or sit some way kind of go back to the embryo.

Even though initially it avoided embryo work.

There are some who are really fascinated by, but also a little bit concerned that IPS cells, skin cells can be transformed into pluripotent stem cells that then can be assembled together to replay the that the developmental tape of you when you were yeah, that's that's very true.

In the last few years, many, many scientists in the world, they, trying to recapitulate human embryos by using IPS cells or, yes, cells.

And it's moving very, very rapidly.

Yeah.

So this, series is called The Big Question.

And I have a big question for you.

My big question is, can you discovery one day be used to extend the human lifespan?

Well, so, we are doing our best to expand, health span.

I'm not sure about life lifespan itself.

If it's healthy, if we can live to 100 to 120, that would be great.

But I cannot imagine to live like, up to 200.

So it may be okay with that particular individual, but how about the society as a whole?

So, I just want to focus on, health.

Medical.

Yes, yes.

Yeah.

Now, we were in Stockholm for, meeting for the International Society for Stem Cell Research in 2015.

We're going running together that morning.

But later that day you don't know this.

Later that day I went to the Nobel Prize Museum.

Okay, so I walked in and, bus of Japanese tourists came into the museum and they went straight to the Yamanaka display.

So I followed them, and they're all looking at it, and I said, oh, doctor Yamanaka is here in Stockholm via Yamanaka here.

And I said, no, no, no, no, he's he's nearby for a meeting.

They do.

And he says, no.

Yamanaka here.

And I showed them a selfie that we had taken.

And I showed them and they all said about to me and I thought, no, no, no, no, no, no, look, that's for sure, but you are a cultural icon, a cultural treasure in Japan and around the world.

Have you been able to use that as an opportunity to, to serve?

You know, I don't know, bring up other people like, you know, like, like champion causes because that's a very unique platform, I think, for a scientist to have that cultural, weight and love.

Yeah.

Well, Nobel Prize, means probably a lot more in Japan, than in us, because here, there are many in Boston alone.

I don't know how many Nobel laureates.

But in Japan, we only have, less than 30 in total in history.

So, Yes.

Whenever I'm in Japan, many people can recognize my face.

So I need to behave very well.

But, I, I, I come to Japan.

No, no, no, I come to San Francisco every month.

I stay one week in San Francisco and three weeks in Osaka, Japan.

Whenever I'm in San Francisco, I can relax and I can do whatever I want.

I don't do anything but to be honest, but your wife is right.

Yeah, my wife is there, this, that in Japan?

Yes.

That's very true.

But I try to use it to raise, awareness, to tell people the importance of science and also to attract, young students to science.

So I, I do use that kind of status, you know, that to, promote, race, to say, social prestige of scientists, as general because, many, young people in Japan, if we ask, like ten year old boy or girl, they may say, I want to be a baseball player, I want to be a doctor, but only a few of them would answer, I want to be a scientist.

So I want to change that kind of atmosphere, by being in my country.

Well, speaking of you started off, you are a doctor.

So what first inspired you to become a doctor?

So it was, I had many reasons, but probably the biggest reason was my father.

He was, very healthy person.

But when I was a, junior high school student, he became sick.

And there was no cure for his disease.

So he became weaker and weaker, literally every day, every month.

So that made me, very interested in medicine and also, my father wanted me to become a doctor.

Maybe he thought I would be able to help him.

So I listened to him and I went to medical school, and I became a doctor.

At that time, there was no cure yet when my father and unfortunately, he passed away soon after I became a doctor.

So it was it is very shocking, because I couldn't do anything for my own father and also for many other, patients.

As a young doctor, I, I felt, how to say powerless.

So that that was why I thought I should become a scientist.

Because it is science that could help those patients suffering from, intractable diseases.

Not now, but that in the future.

So, because of my father, I became a doctor.

And because of my father, I became a scientist.

I owe him a lot.

Right?

You know, when we were in Norway, I was struck.

We were struck by all these troll dolls everywhere.

And I asked our host, whose name was, Thor, by the way.

What what's the deal with all the trolls?

And he has a medical history, and he said what he thinks happened was Norway.

Norway was a seafaring nation.

They would build the big ships using the timber of the mountains and then go out to sea on the fjords.

And he thought that many of the sailors came back with syphilis.

And so what you're seeing in the door of mythology are basically sailors who went crazy living in the woods and under under bridges and had, you know, strange bumps on their faces.

But you still seeing the troll dolls?

He thinks that's probably where it came from.

So a lot of times when people don't understand something, they build a mythology around it.

Do you think there's mythology that's kind of building around itself and what they can do?

Do you think there's a little bit of the danger of people kind of filling in their lack of knowledge of the technology, with some other story?

Yeah.

That's, one way we want to use IPS cells.

So yes, that's.

Actually, I have been being amazed, how many applications are there about stem cells and about IPS cells?

So I really hope, many scientists would use IPS cells in many, many ways that I cannot even think.

Yeah.

Sinkhole.

Yeah.

I think one of the things that has come up, some people, some patients are very desperate for a cure, and they may hope that, you know, a clinic can give them their own IPS cells back because.

Because they're genetically matched to you.

Most people believe it won't be rejected by everybody.

So there may be some, unrealistic expectations about the technology where their unrealistic expectations about cures and and when when you became very well known in Japan.

And did you feel some of that pressure?

Yes.

It's, it's very important point.

It's many.

So there are many types of stem cells, IBS cells, some somatic stem cells that like bone marrow stem cells, but some kind of unproven so-called simple cells.

And for many patients, they do not distinguish those stem cells.

So it is, very important to explain very well, what's the difference between IPS cells and some kind of so-called stem cells?

And, we need to tell them, well, we are working very hard day by day, but it takes some time.

Yes.

Right.

Mason, we cannot finish it in one minute.

It takes, years.

It takes five years.

Ten years or even 20 years.

So that's what, I have been trying to do.

Trying to explain as much as possible in, very, understandable way.

But I found it actually very challenging.

Yes.

So you must be much better in doing that.

So I, I, I try, but this job also helps.

But, so your celebrated for your great success.

You must have had some failures, like, give me an example of a scientific failure that, that you experienced.

Well, I making failures every day.

Because science is full from failure.

That, in my very first experiment as, young, postdoc, I mean, graduate student, it has almost, I don't know, 35 years ago, I did a very simple experiment.

But the result, the outcome was something totally, unexpected.

It is very different.

From what?

And from what I and, my mentor expected.

So, it has kind of a big failure, but I was very excited.

Instead of being disappointed by that unexpected, result, by that kind of failure, I got very, very excited by the, unexpected outcome.

I was more surprised by my own response.

Than by the unexpected result itself.

So that that is that was the time I realized I should become a scientist instead of becoming a doctor, so that the first failure or unexpected result.

Played a very important role in my life.

And also, to making IPS cells.

So I was I in a sense, I was very lucky.

The first experiment did not go well.

Yeah.

Yeah.

I have one more question.

Before I turn to questions from the audience, do you think there's an important role for ethics in IPS cell research?

Yes, yes, many, many aspects.

Once again, we can generate germ cells.

We can generate, brain organoids, we can generate, human embryo models, and we can generate, like, human organs in pigs by using IPS cells.

So the question is how much we can do, how much we should do be maybe able to help many patients.

But, it's just like any other size.

It's very, double edged sword.

If we somebody tend to use it in, wrong way, we can make the world was place.

So, ethics is very, very important.

As a matter of fact, in our institute in Kyoto, we have a group of bioethicist, headed by, Mr.

Fujita, who must be a good friend.

So I think it's very important to work together.

To work.

The scientists and bioethicist work together in the same building day by day.

So, I think ethics is very, very important.

Yeah, I knew that you were very, very interested in sensitive the ethical issues from the very beginning.

So when your mouse paper came out, George W Bush vetoed for the second time a congressional, legislation that would have allowed for more federal funding for human embryonic stem cell research.

And when he vetoed it, he said, there's research coming out of Japan that you can make, stem cells out of skin cells.

He didn't say in the mouse, but he said, you know, you could do that.

So he's more committed to vetoing this.

And I told you about that.

We were in a meeting in Australia.

I told you that George W Bush said that.

And, so we decided to write a commentary together where you have to, along with you.

Rudolph Yang at MIT, come out holding at Harvard, the four of us, for the commentary.

That said, just because you have a cell technology doesn't mean that you can stop human embryos stem cell research.

They have to develop together, and you have to compare the two.

And it was for scientific and ethical reasons.

There's there's a need to sort of, you know, keep, for safety reasons, to keep, both areas of research active.

So you are a part of that.

And that was actually one of the most cited papers that year.

And then shortly after that, the human work started to come out.

And so, yeah, I agree.

I mean, I think that that the approach of going forward in these new frontier areas with ethics and science is extremely important, and they have to be intertwined.

I'm going to turn to questions now.

I'm sure many have come in.

What were, some of the best and worst advice you received in your career?

Best and worst.

Best.

And, so, the best advice.

Was from my mentor.

And when, I, got the unexpected result when I was, graduate student.

And also when I was a postdoc, I got very unexpected result.

And in each cases, my mentor, they encouraged me to work on continue working on that unexpected results.

Because of their encouragement, I was able to, continue my research, which actually eventually resulted in the generation of viper cells.

So that was the best advice.

Worst advice.

So it's very difficult.

But, further, when we try to, when we started this project, trying to generate IPA cells, many, many of my colleagues, they tried to talk out of this project, doctor America, this is too risky.

You should stop this.

So, that may have been the worst advice, but, very reasonable advice.

And so I thought I should encourage young people, young scientists, to take risks because I learned from my own experience.

But now I am very old, and I need to, teach many young scientists.

And I'm responsible for many, young scientists for their future.

I end up ended up stopping trying to stop the, this project.

So it's much easier said than done.

Some very many people want to know.

Could you tell a little bit more the story behind how you narrowed it down to just those four factors?

Okay.

We we initially had, 24 candidates.

And, when my colleague, cousin, he mixed all the 24 factors and put them all together into mouse fibroblast and it worked.

We, we observed emergence of some SL like cell population.

So then we need to narrow down from 24 divided by two required.

Well, we we had no idea how many out of 24 were required.

So it was, very difficult task, but, once again, Castle did, very nice experiment.

Instead of testing all the combination, combination of two.

Combination three.

Combination four.

Combination five.

It's an enormous number.

He just took one factor out of 24 and, tried the remaining 23 factors.

So only 24 combination and just one experiment.

We found out those four factors.

Essential because when he removed one of those four factors, the remaining 23 factors could not do the job.

So, it does the a very, smart, but very nice experiment that he did.

Here's a good question.

Have you ever lost your motivation to do research, and if so, how did you get your motivation back?

I think this is coming from a young researcher.

Because there are no old researchers that, like, lost motivation.

So, when I was a student or a postdoc, I mainly worked by myself at that time, it was very difficult because, once again, science is failure almost every day.

The result is not good.

And I was working by myself mainly.

So at that time it was kind of difficult to maintain my motivation.

But, once we started working as a group, it is much easier, because we can talk to each other, we can help with each other.

So working as a team is probably important to maintain motivation.

And now, after, reporting epistles, not only our colleagues, but we have, opportunity to meet many patients or, from family members of patients.

They, have a huge motivation every day, and they are amazing.

We know, because the kids are, suffering from intractable diseases.

So you today, they're having a hard time, but, they often tells us, doctor America, please take care of yourself.

So it's really, moving.

You know, they're having a hard time, but instead of taking care of themselves, they they, worrying about, health, they say don't work too, too hard.

So, those, conversation with patients and their family members is the biggest motivation right now.

Do you see differences in how, your area of research is conducted in Japan versus the US?

Well, in terms of science itself, it's very similar, but, the funding is very different in Japan.

We rely on heavily on, the government funding from the Japanese government.

But here, of course, funding from NIH is important, but we have many other sources, funding from each state and more importantly, funding from private sectors, fundraising.

So, I think the situation here is, much better than in, in Japan.

What do you think is the next big thing in stem cell research?

So I hope, many applications, more than ten applications using IPS cells, now in clinical trials.

So I really hope in the next five years, ten years, many of them will be, where to go?

More general.

Will be approved by the government, by FDA or, PMD in Japan so that many, patients can, have those new therapies.

So that's the biggest hope right now.

Can IPS cell research cure baldness?

I'm asking for a friend.

Well, it's very important for me and probably for you.

But, it's not life threatening.

So, you know, I think you're going to get a lot of volunteers for that clinical, but that many groups are working on that.

Yeah, actually, it's, they're making, very surprising progresses.

So I'm hoping.

There might be a Nobel Prize in that one, too.

Last question here.

What do you think are important qualities to be a good scientist?

What are the important qualities?

Okay, I would say, curiosity, I think that's the number one.

It's not your score at school.

And, whether you can enjoy failures, whether you can learn from failures, I think it's it's very important we, to be a scientist.

Well, I'm going to close this out by just recalling my favorite memory that I have with you.

So it was back to that original meeting in Norway.

I come down in the morning to go for a run, and you were stretching in the lobby, and you said you want to go for a run together.

So we went for a run.

We were in completely unfamiliar territory.

It was beautiful.

But the fog was coming off the ground.

You were in the woods and we didn't know where we were.

We were assigned to.

We go left to, we go right, where should we go next?

And we're running together.

And I thought, this is this is ideal science and ethics going together and, and exploring something new.

Thank you so much for joining us here today.

It was pleasure, everyone.

Shinya Yamanaka.

Kiri.

That's fine.

Thank you very much.