Deriving Stem Cells From Skin, Not Embryos

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Scientists have discovered a way to turn normal human skin cells into stem cells. The discovery could bypass many of the ethical questions regarding the production and use of stem cells. Joe Palca, NPR science correspondent, answers questions about the recent breakthroughs in stem-cell research.

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NEAL CONAN, host:

This is TALK OF THE NATION. I'm Neal Conan in Washington.

News - now to the news of a stunning breakthrough in stem cell research. Two separate teams of scientists announced that they've turned ordinary cells, such as skin cells, into what are essentially embryonic stem cells without using human embryos or eggs. The new technique could resolve the impassioned ethical debate over the use of human embryonics. And if you have questions about the ethical, medical or scientific implications of this events, give us a call. Our number is 800-989-8255. E-mail is talk@npr.org.

NPR science correspondent Joe Palca joins us here in Studio 3A. Hey, Joe.

JOE PALCA: Hey, Neal.

CONAN: And how big a deal is this?

PALCA: I think it's really big. I talked with - it's interesting, the guy - you mentioned there were two teams that were doing this, one of the teams was led by a guy named Jamie - James Thompson, Jamie Thompson he goes by. In 1998, he was the person who published the recipe, essentially, for getting these embryonic stem cells from embryos. Big deal then, you know, this is the first time it happened. Now, he talks about - 10 years later, and he talks about this paper being just as big. It changes everything, I think, not immediately, not, you know, tomorrow, but as you said in the intro, this is a tremendously controversial issue. And if you can get to study these cells without destroying an embryo or without using a woman's egg to preprogram a nucleus - we can talk about that - is fantastic. It's amazing. It's great.

CONAN: Well, what in fact did they do? What was the breakthrough?

PALCA: Well, the breakthrough was - so what we're talking about is, you know, okay, so a skin cell is a skin cell because there's a program in the nucleus that says you're a skin cell now. Remember that every cell on our body has a complete set of all our genes, it's just that some are switched on and some are switched off. And the ones that are switched on in skin cells are the ones that the skin cell needs to be a skin cell.

CONAN: And that makes it different from being a blood cell or anything else.

PALCA: Yeah - that your skin suddenly doesn't start, you know, looking like an eyeball or a kidney or something like that. So what happens? Well, there was a time, once upon a time in its - you know, in its history that it was, that DNA could be anything. And so what these guys did was they looked at embryonic cells and they said, which cells are active - which genes are active in embryonic cells that aren't active and skin cells. And they came up with some candidates. And they said, what if we put these factors, these genes - it turns out there'll only be four of them, which is pretty astonishing - what if we put these four genes into a skin cell, what will that do? And it turns out, what it'll do is it'll trick the skin cell into thinking it's once again back in the stage where it was an embryo.

Now, here's where eggs come into that. It used to be that that tricking, that process of convincing a skin cell that it's no longer a skin cell but it's now ready to become an embryonic - embryonic stem cell, that tricking process used to be done with an egg, an egg from which you remove nucleus. But if you don't need the egg, ah, then you can do it with these four factors. And it used to be that embryonic stem cells came from the embryos, either the embryos that were created with egg and sperm - if you're starting with that kind of an embryo -or the embryo that was created through this so-called cloning technique where you use an egg which you've removed the nucleus from and you put your skin cell nucleus in. In any case, you don't have to wait until that stage. There is that state. That stage is gone. You've short-circuited the whole thing.

CONAN: And that's the heart of the ethical and, by extension, political debate over this.

PALCA: That's right. Nobody is objecting to people studying skin cells in the laboratory. And nobody is objecting to studying so-called adult stem cells, the stem cells that are in our bone marrow or the stem cells that are, you know, they found in fat cells. There's all sorts of stem cells. It's just the embryonic stem cells that's caused the political and, as you say, moral debate in this country.

CONAN: And part of this debate has been semantic, and that goes on into - there's implications for that in these new discoveries, too.

PALCA: Well, exactly, exactly. I mean, if you've got a cell that behaves like an embryonic stem cell but it didn't come from an embryo, is it an embryonic stem cell? Well, it is if you're going to define embryonic stem cells as having one set of meetings, and it isn't if it did.

And you know, the interesting thing is that the scientists in the last couple of years have realized, boy, we have a semantic problem because people are thinking embryos when we don't want them to think about it. So they're talking about changing the name to pluripotent stem cells.

CONAN: That's just because they hate radio broadcasters.

PALCA: Yes, because they wanted to do a peachick. No, they want to try to get people to stop thinking of them as having been derived from embryos. And now, that's what these new cells are called, induced pluripotent cells, because they don't come from embryos. They behave like embryonic stem cells, but they don't come from embryos.

CONAN: Mm-hmm. Now, there are a lot of questions about the implications. We talked about ethics and politics. There are more questions - and again, we invite you to join the conversation at 800-989-8255. But there are also another two more sets of questions. One of which has to do with science. Will this give biologists now an opportunity to figure out what the process is in the first place that from an original embryo allows some cells to understand, I'm supposed to be a blood cell now or I'm supposed to be a bone cell or a brain cell?

PALCA: Exactly. I think that's the thing that is for sure going to come out of this, not that they will understand it, but they'll get a better understanding. Because now, you know, you can't watch, you can't watch an embryo or - you can't watch something go from an egg and a sperm to a whole human being. You can only watch in little bits and pieces. And this is a way of studying, at least some of that process, in a test tube with cells that can - you know, it's really amazing. You know, if you see these cells, they start - by themselves -the embryonic stem cells, they start beating like a…

CONAN: Like a heart.

PALCA: …a heart cell. You'd think, what happened here? Something happened from the time that they were just a blob of cells on a plate to a bunch of things that start beating. It's really remarkable. How does that happen? Well, there's obviously genes that are switched on and factors that are released and cells talk to one another. Now, it's all a place you can study in.

CONAN: There is also, again, a question I guess about medical applications about this. All along everybody has thought these embryonic stem cells - if you'll allow me to use that terminology - would have enormous potential to cure all kinds of diseases. We think of Parkinson's, for example.

PALCA: Right. I mean, the trouble - okay, so if you want to give somebody new brain cells because their dopaminergic neurons in the substantia nigra are destroyed. So it's hard to get brain cells. I mean, people don't want to give them up, you know, if they've got them.

But what if you had embryonic stem cells that, let's say, I can make from you and I could coax those embryonic stem cells instead of turning into a cardiac cell, a heart cell, they could turn into a brain cell, give them back to you, put them back. That's the theory. I mean, it seems so obvious in a way. I mean, if something's damaged or destroyed, put it back and it will work again, especially if they're from you.

CONAN: Easier said than done.

PALCA: Easier said than done. That's exactly right. Because it's not that simple, cells don't always take up residence. If they do take up residence, what's to stop them from growing odd infinitum? I mean, that's another problem. These cells grow and that's fine, and then you want them to stop, and maybe we don't know what the stop signals are, and all of a sudden, you know, you've got too many of them and what do you do then?

So there's - it's, you know, it's like there's a lot of questions. It's easy to draw this up on a blackboard, and that's why in the media, this has been very compelling, you know. We can replace these cells and they will make you into something. Well, it's easy to say, but the actual getting it done is turning out to be quite difficult.

CONAN: E-mail question from Jim(ph) in Sonoma, California. Can the same process be used to alter any other cells than skin cells - heart cells or heart therapy brain cells for stroke?

PALCA: Well, yes. I think the question is, is it - can you - first of all, what you have to think about is first, when we're taking a skin cell and turning it back into an embryonic cell and then turning it into a heart cell or a brain cell. So it doesn't really matter what cell you start with. And so the question is: Does it have to be a skin cell or could it be a hair cell or could it be a, you know, a cell from the inside of your cheek. The answer is right now, it seems these factors can transform any adult cell back into an embryonic cell. Then you go forward again. So you go back to being an embryonic cell, then - or pluripotent - then you go forward and transform the cells that you've created -this mass of pluripotent cells - into whatever cell type you need: the heart cell, the brain cell, the liver cell.

CONAN: 800-989-8255. Let's get Tom(ph) on the line. Tom calling from Berkeley, California.

TOM (Caller): Yeah. I was - thanks for taking my call. And I was curious, given that many of the diseases that they're talking about treating are actually genetic. How does starting from a skin cell of somebody that is genetically defective already actually fix anything?

PALCA: Tom, my opinion is - great question - there is some genetic defect that caused the problem in the first place. The idea is - again, and this is all drawing it up on a chalkboard - it seems to be that if you can find the genetic defect that's causing the problem in the cells, maybe you can correct it at a cellular level and then put healthy cells back in.

So it's a sort of a gene therapy, but gene therapy done in the cell culture before it goes back into the patient. So you make the cells healthy. Because the idea is, if it's just a single cell that's damaged, if you can put in healthy ones, genetically…

TOM: You to single out genes…

CONAN: Single type of cell.

PALCA: Single type of cell, yeah. Most of these diseases that they think are amenable to cell-based therapies are the kinds of diseases where only a single type of cell is damaged. So, you know, if it's - I've always wondered that, yes. The successes that people have had with cell-based therapies like for Parkinson's - and it isn't the artificial kind of Parkinson's where a drug damages all the cells at once, but in the progressive, you know, you've got some sort of progressive disease problem, the cells die because the disease hasn't been cured. It's a great question.

CONAN: Hmm. Tom, thanks very much for the call. Appreciate it.

We're talking with NPR science correspondent Joe Palca about news you may have seen on the front page of your paper this morning, about two sets of scientists who made breakthroughs in stem cell research. If you've got questions about that, give us a call: 800-989-8255. E-mail: talk@npr.org. There are ethical, medical and scientific implications for this research.

You're listening to TALK OF THE NATION coming to you from NPR News.

And let's see if we can get - this is Stuart(ph). Stuart with us from Ann Arbor, Michigan.

STUART (Caller): Yes. A fairly simple question. About a year ago in Scientific American, there was an article saying that cancer was basically rogue stem cells going other places and developing. It seems like this therapy which uses a bit of cancer-ish stuff to make it might be another entree into working at cancer, in how it works and how it starts and what it is.

PALCA: Oh, absolutely. I think if I know the article you're describing, it's the fact that cancer - there was a description that some cancers have at their root a kind of a cancer stem cell that it didn't matter what you did to all the other cells in a tumor if you didn't actually get rid of the cancer stem cells, the cancer would continue to grow.

But you're absolutely right. I mean, there's a funny connection between stem cells which can grow and grow and grow and grow. That's one of their definitions. They can replenish themselves without end because you'll never - the body never knows when they might need them, so they replenish themselves. And cancer which is, of course, cells that replenish themselves when you don't want them to. And so there's an interesting connection there. And I think a lot of cancer biologists and stem cell biologists have been cross-fertilizing - if I can use that word in this context - their various fields as they figure out what's going on in the basic biology here.

CONAN: Thanks, Stuart.

STUART: Thank you.

CONAN: So long.

Let's go now to - this is Jim(ph) in Ann Arbor, Michigan.

JIM (Caller): Hello.

CONAN: Hi.

JIM: Hi. I just want to make the comment that I was delighted to hear the advancement. I very much oppose destruction of embryos for the sake of any kind of research, and I think this is a good thing that if we can come up with these cells without it. In my view, and in fact, most of the - all of the advancements that have helped anybody so far have been with non-embryonic cells.

And those of us on this side of the fence, I think, for a long has been clamoring that the terminologies be clarified a little bit here, because so and so says George Bush is against stem cell research, Obama's for stem cell research, and meanwhile, I think we like to say, well, what kind of stem cell, which ones are you talking about. Because, really, people are talking about embryonic stem cell research, and most - everybody does not oppose the other varieties - cord blood, adult, and so on and so forth.

So anyway, a little more long moment than I should've…

(Soundbite of laughter)

JIM: Overall, I think it's a good thing.

PALCA: Well, I - yeah.

CONAN: Thanks, Jim.

PALCA: I was just going to say that it is true. And this is one of the arguments. I don't think - from the way I've talked to people, nobody is happy at the idea that you have to use - nobody who is doing this was happy with, even the people who didn't have a moral objection to it, you know. The embryos that are being discarded, this is the big - there's a big - there's tens -hundreds of thousands of embryos sitting in cold storage that aren't going to be used.

Even though they're - many of them are going to be discarded, they're not probably going to be adopted even though that's what some people would like to see happen. Even though people are okay with them being used for research, some people, nobody is thrilled about the prospect. They were created in the hope that they would turn into life and when they don't there's got to be a certain level of sadness. Now, may be not a great level, but some level. And I think that's really what's one of the issues that's - I think everybody's going to be glad that that's an issue that could go away.

CONAN: Embryo, of course, one of the loaded terms in this debate. Another one we've not brought up though is clone.

PALCA: Mm-hmm.

CONAN: How does this relate to cloning?

PALCA: Well, as - so it was cloning that proved - cloning in the first place, that proved that you could reprogram the nucleus of a somatic cell because…

CONAN: That's Dolly the sheep.

PALCA: …that's what Dolly the sheep was. It was a mammary gland cell that they used an egg to reprogram so that it could actually direct the development of an entire animal. So we didn't know any of these was possible, even until that breakthrough occurred. The difference has always been that the scientists have said, we don't want to create animals. We want to use this reprogramming technique to study cells.

Well, now, there's a reprogramming technique that does involve cloning, or if you prefer somatic cell nuclear transfer. Because again, in nomenclature, scientists realized, oh my gosh, if we're going to call this cloning, people are going to jump all over us because nobody wants to have a cloned human being. But if we call it somatic cell nuclear transfer to create pluripotent stem cells, well, A, people won't know what we're talking about, but B, you know, we're describing it accurately and we're getting away from the words embryo and clone.

CONAN: Joe, thanks very much. We appreciate the explanation. NPR science correspondent Joe Palca here with us in Studio 3A. Happy Thanksgiving, Joe.

PALCA: Thanks, you too.

CONAN: We'll be here tomorrow to bring you the latest on this year's must-have gadgets for the techie on your list. Plus, it's never too early advice from an expert on hanging your holiday lights. If you're headed towards grandmother's house over the river and through the woods, drive carefully everybody. We'll see you tomorrow.

I'm Neal Conan. It's the TALK OF THE NATION from NPR News.

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Scientists Produce Embryonic Stem Cells from Skin

Genetic modifications in skin cells.

Genetic modifications in skin cells (above) induced the cells into what scientists call a pluripotent state — a condition that is essentially the same as that of embryonic stem cells. Junying Yu/University of Wisconsin-Madison hide caption

itoggle caption Junying Yu/University of Wisconsin-Madison

Two teams of scientists have independently discovered a way to turn ordinary human skin cells into stem cells with the same characteristics as those derived from human embryos, a breakthrough that could open the door for advanced medical therapies.

If the work holds true to its promise, it would largely bypass ethical issues that have dogged research on human embryonic stem cells. It could also allow scientists to tailor the cells to specific individuals, eliminating the possibility of rejection.

The crux of the discovery, published online Tuesday by the journals Cell and Science, is a "direct reprogramming" technique that adds a cocktail of four genetic factors to run-of-the-mill human skin cells.

The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the Science paper is from a team led by Junying Yu, working in the lab of stem-cell pioneer James Thomson of the University of Wisconsin-Madison.

The discovery builds on work presented in 2006 by Yamanaka in which the same technique was demonstrated for skin cells from mice.

The two teams have been able to isolate cells that look and behave like embryonic stem cells. The researchers caution that there are still many steps to take before the cells are useful for human therapies.

Yamanaka said he knew that the real payoff would be if his work on mouse cells could be translated to human cells.

"We started working on human cells more than a year ago, but in the beginning, the four factors didn't work," he told NPR.

He said it was unclear whether the cells he produced from skin were identical to embryonic stem cells, but "all I can say is they are very similar."

While Yamanaka was working on mice to find the critical factors for transforming skin cells to embryonic stem cells, Thomson was already working on human cells. His team also reports four factors that can transform skin cells, but two of them are different from those Yamanaka found.

"It does seem that there are multiple paths to the same outcome," Thomson said. "How divergent those paths are remains to seen."

Thomson, 48, made headlines in 1998 when he announced that his team had isolated human embryonic stem cells.

Since then, the research has pitted groups that question the ethics of harvesting stem cells from human embryos against those that hope the line of research could result in important medical breakthroughs. The latest announcement from the Japanese and American teams could skirt the controversy.

"It changes everything in that these are not cells derived from embryos anymore," Thomson told NPR. But "we are back at the starting point now. These biologically ... appear to be the same as embryonic stem cells, and we still have to figure out how to differentiate them into useful things."

The whole idea of stem-cell based therapies is that the stem cells could be used to replace or repair cells damaged or destroyed by disease or injury, such as new heart cells for people who have had heart attacks or new neurons for patients with Alzheimer's disease.

"This is a huge deal," said Jose Cibelli, a researcher at Michigan State University.

"Anybody can do this procedure. It's a very simple recipe," he said. "A combination of three or four genes, and in a couple of weeks, you go from a skin cell to an embryonic stem cell. It's remarkable."

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