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Scientists Convert Mouse Skin Cells to Stem Cells

June 7, 2007 at 6:25 PM EST
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JEFFREY BROWN: In Washington today, the House of Representatives debated and voted on funding for stem cell research. At the same time, there was important news published in two science journals about a potential breakthrough in the field.

The basic finding: Scientists took skin cells from mice and added viruses containing four specific genes. That caused the skin cells to be reprogrammed to behave like embryonic stem cells, which could then be used to treat diseased tissue and organs.

To walk us through both the science and the politics, we’re joined by Kenneth Miller, a cell biologist and professor at Brown University — for the record, he’s also one of the advisers to the NewsHour’s Science Unit — and Rick Weiss, a science reporter for the Washington Post.

Well, starting with you, Professor Miller, explain this a bit more, this new method to us. How does it work?

KENNETH MILLER, Cell Biologist: Well, it works in a very simple way. About a year ago, a Japanese laboratory at Kyoto University analyzed the genes that were active in embryonic stem cells. And by a very careful process of elimination, they determined that there were four essential genes whose activation was required to keep stem cells in a state where they could develop into other cell types.

What they then did, and two other laboratories did, as well, is to take these four genes, take ordinary skin fibroblast cells from a mouse, ordinary adult cells, and, by some very clever genetic engineering, get these genes into the cells. Once those genes were put in the cells, and the cells containing them were identified, and those genes were activated, they then grew those cells for a while, and they discovered a couple of things.

First of all, they discovered that the cells formed colonies that looked like embryonic stem cells. Then they analyzed their genetics and discovered that the right genes were turned on and the right genes were turned off to act like stem cells. And, finally, they put them to what you might call the acid test, which is to see whether or not these cells could develop into all the issues in the body and, in one case, in one laboratory experiment, actually become fully functional adult organisms, and these cells passed every single test.

JEFFREY BROWN: So what are the potential benefits here? What would it be used for?

KENNETH MILLER: Well, there’s nothing to be used for right now. This is still a highly experimental technique. You might refer to it as proof of concept. And what I mean by proof of concept is the concept is that unlocking the developmental potential of a cell doesn’t require an embryo. It doesn’t require an embryonic cell.

All it requires is understanding the signals that turn cells on to the proper developmental pathway to produce the tissues in the body, and these experiments are proof of concept. So, in effect, a door is now opened to researchers everywhere to run in and exploit this idea and try to find a way to develop genuine therapies from this scientific breakthrough.

JEFFREY BROWN: So, Rick Weiss, the news here that flashed around the world was that here is a potential way to avoid the ethical issue that has been so rife in this debate.

RICK WEISS, Science Reporter, Washington Post: Right. I mean, the whole problem with embryonic stem cell research, since embryonic stem cells were first discovered back in ’98, has been that the only way to get them is to destroy human embryos, which is really crossing a moral and ethical line for a lot of people in this country. This presents the possibility of just turning ordinary cells into human embryonic stem cells, essentially getting around that whole ethical dilemma and letting the field go forward.

What the discovery means for humans

Kenneth Miller
Brown University
This is very exciting to everyone in the field of science, and I think this should be exciting to members of the general public, as well -- this is an entirely new opening.

JEFFREY BROWN: And Professor Miller talked about how we're in early stages here. And let me start with you on this. The question is how to make it work for humans. What are the limitations here? And what are the restrictions so far?

RICK WEISS: Right. Well, there are some limits, and we'll see which way it cuts. There's two major categories of problems that scientists are talking about. One of them is that the way they got these important four genes to turn on is by inserting viruses into these cells that know how to do that.

The problem is, these viruses can also cause cancer. And, in fact, some of the animals in these experiments did end up getting cancer. So they're going to have to find a different way to get these genes turned on if they want to do this in people. And there are actually alternatives being worked on right now that look quite promising, so that's good.

The other thing is that the four genes that are crucial for making a mouse cell into an embryonic stem cell are not necessarily the same four genes that you need to turn a human skin cell into a human embryonic stem cell. And until scientists can really clarify which genes they want to turn on and off, this still remains something undone for humans.

JEFFREY BROWN: Professor Miller, what would you add to that? I mean, what would you add to that, and how long are we talking about before we'd know how promising it is?

KENNETH MILLER: I know a lot better than to predict a timeline for future advances. And I think even two or three years ago, no one would have predicted that this line of research would open up.

But I think it's fair to say that we are far away from anything that's directly applicable at a clinic. You're not going to be able to go in next week or next year and order up some stem cells produced in this way to replace a faulty heart valve or fix your liver.

But I think what is clear -- and this is very exciting to everyone in the field of science, and I think this should be exciting to members of the general public, as well -- this is an entirely new opening. And, in effect, what this has done is sort of take the study of stem cells out of the hands of those who would clone cells -- or I shouldn't say that -- but no longer have it restricted to those who would have to clone cells or get eggs donated in order to do the research and put it in the hands of every laboratory that can simply do cell and molecular biology with cells taken from adult cells.

And what that's going to do, in terms of research, I would suspect is get a lot more laboratories, a lot more investigators involved, a lot more new ideas, and I think this is a very good day for science.

Explaining the genetic breakthrough

Rick Weiss
The Washington Post
The bill goes to the president and would allow federally funded scientists, those at the National Institutes of Health, for example, to, for the first time, start doing research on cells from embryos.

JEFFREY BROWN: I don't know if there's a brief layman's way to do this, but this notion of reprogramming those cells and finding the right genes, is it known how that works?

KENNETH MILLER: Oh, boy, that's the -- the answer to that question is going to win you several Nobel Prizes.

JEFFREY BROWN: Not me, but somebody maybe.

KENNETH MILLER: It's going to win somebody several Nobel Prizes, but the essence of it is pretty simple, and that is that all of the cells in our body, with one group of exceptions, are at a dead end. In other words, when we pass away, none of those cells are going to survive us, with one possible exception, and those are the cells in our germ line, our reproductive cells, in the testes or in the ovaries.

Those are the cells that can undergo a process of reprogramming where, in effect, the nuclei of those cells are basically told, "Get ready to form an entirely new individual." The whole idea of doing cloning by using early embryos is to somehow capitalize on the trick, whatever it is, that must exist in the cell of an egg that tells the nucleus in that cell, "Hey, it's time for you to get busy and make a new organism."

What would be much better scientifically is not just to take a cell and ram it into an egg, but understand what those instructions are. Now, we don't understand them fully yet. But the papers published today tell us that we have taken one giant step closer to getting exactly that understanding of what the instructions are that say, "Hey, make a new individual."

JEFFREY BROWN: All right. Now, in the meantime, Rick Weiss, as we said, Congress has looked at this again today. Tell us briefly what was on the table in today's vote?

RICK WEISS: All right. Well, this is as big a political story as the scientific story. Today, the House passed legislation that would loosen President Bush's restrictions on human embryonic stem cell research. These restrictions have been in place since 2001.

They've been a matter of great frustration to scientists and proponents of this research. They have kept the federal scientific workforce pretty much out of this field or limited them to a very small number of stem cells they're allowed to work on.

With this legislation passed by the House today -- which has already been passed by the Senate -- the bill goes to the president and would allow federally funded scientists, those at the National Institutes of Health, for example, to, for the first time, start doing research on cells from embryos that are being discarded at fertility clinics, which are right now out-of-bounds for them, and really expand the amount of material they have to work with, instead of forcing them to work on these 20 or so colonies that have been available to them for the last six years, which are quite old and not as ideal as they'd like them to be.

Clashing political perspectives

Rick Weiss
The Washington Post
Do you want to wait until we've got this really under control and can do it without crossing the line that some people consider to be going too far? Or, in the meanwhile, do you pursue multiple paths, try to figure it out as best as you can?

JEFFREY BROWN: Now, both sides today referred to the new research in their arguments. Let's listen to a couple of excerpts from today's debate. First we have Jeb Hensarling, a Republican from Texas, followed by Rahm Emanuel, a Democrat from Illinois. Let's listen.

REP. JEB HENSARLING (R), Texas: What this debate is about, Mr. Speaker, is whether or not, going forward, should taxpayer funds be used to destroy what many consider to be human life, for research purposes? And this is especially, especially highlighted when we know that there are ethical alternatives and promising alternatives, such as adult stem cells, umbilical blood cord, embryonic fluid, and today banner headlines all around the nation about the promise now of skin cells. Let's fund stem cell research, but let's fund it ethically.

REP. RAHM EMANUEL (D), Illinois: It is ironic that every time we vote on this legislation, all of a sudden there is a major scientific discovery that basically says, "You don't have to do stem cell research." The truth is, you don't base your research on one report in a medical journal. You provide leadership.

And if you go back to the 1950s, we had a polio epidemic in this country. It was killing thousands of people, leaving people terminally paralyzed. With funding from Washington, we found a cure for polio. Politics did not lead the way; medical research led the way, and America led its leadership there.

JEFFREY BROWN: So, Rick Weiss, Republicans are hearing an argument that we've heard for many years, but now they're saying, "Hey, wait a minute, there's new information out here."

RICK WEISS: Right, and there will always be more and more evidence that we don't need to use human embryos to do this. I think Dr. Miller said it right: We are learning to control these things gradually.

The question is, do you want to wait until we've got this really under control and can do it without crossing the line that some people consider to be going too far? Or, in the meanwhile, do you pursue multiple paths, try to figure it out as best as you can?

And the tough thing here is that, in the end, it's not a question of science or even of politics. It's a matter of personal belief. Do you think that these frozen embryos that are going to be thrown out from fertility clinics amount to an entity of moral standing that deserves protection? Or is this basically the same as any cell culture that you'd work with in the lab, and should you have access to it, to answer some pressing biomedical questions?

A "fertile area for scientists"

Kenneth Miller
Brown University
In order to do the same trick in human cells -- which we would all love to do -- we are going to have to learn the secrets of the human embryonic stem cells.

JEFFREY BROWN: And so, Professor Miller, Democrats today and scientists who do this research are saying, "Let's go ahead on everything."

KENNETH MILLER: Yes. And I think what you see today, the results of this work, is the result of research advancing on many fronts. And there's just two points I want to make, and that is, however the debate in Congress goes, the issue is not whether or not embryonic stem cell research will go forward. It will go forward. Right now, it goes forward at great pace funded by private funds, by pharmaceutical companies, and by various state initiatives, and it goes forward in nearly every country in the industrialized world. So it's going to happen.

JEFFREY BROWN: I wanted to ask you, because, you know, we keep talking on the program, and we keep seeing this debate about research, but there is research going on, correct?

KENNETH MILLER: Absolutely.

JEFFREY BROWN: How much? Just give us some ballpark sense. Is it a very fertile area for scientists?

KENNETH MILLER: It is -- no pun intended -- an extremely fertile area for scientists, but there's no question that the NIH, the National Institutes of Health, funding and review mechanism is the best mechanism we've ever had for oversight and accountability in science, and we're not using it for embryonic stem cell research.

There's another point that's really worth making about the breakthrough today, and that is the only way that the laboratory in Kyoto fixed upon those four genes as candidates for reactivating the skin cells was by studying embryonic stem cells in mice. In order to do the same trick in human cells -- which we would all love to do -- we are going to have to learn the secrets of the human embryonic stem cells. And, ironically, it is by allowing that research to go forward in the short run that in the long run will make it unnecessary to destroy embryos for therapeutic and research purposes.

JEFFREY BROWN: Rick Weiss, you watch this debate, though, in Washington, where the politics are first for many people.

RICK WEISS: Right. And politically, you know, it's quite obvious where this is going right now. The bill will go to the president's desk. He will veto the bill, as he has done once before. Congress has passed this legislation before. And in terms of the political momentum to loosen Bush's restrictions, the proponents will be back to square one again.

They have promised that they will do everything they can to get this legislation passed one way or another, perhaps by tacking it on to some other must-pass legislation. If nothing else, they're going to dog the Republicans and the conservatives with this until 2008 and make it an election issue. Are you for or against human embryonic stem cell research?

JEFFREY BROWN: So this will go forward into the election, is at least what the proponents want to do?

RICK WEISS: Absolutely, that you can expect to see this coming up more and more, whether there's more research findings like this or not.

JEFFREY BROWN: All right, Rick Weiss, Kenneth Miller, thank you both very much.

KENNETH MILLER: Thank you.