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Researchers Report Cloning Advance For Producing Stem Cells


This is SCIENCE FRIDAY, I'm Ira Flatow. This week, scientists at the Oregon Health and Science University, OHSU, announced a breakthrough in cloning of a human embryo. They took adult cells, put the cells into specially prepared human eggs and created genetically identical embryos. It's something lots of stem cell researchers have been trying to do for years without success.

How did they get it to work, and what happens next? Will the technique be used to treat disease? We have other ways of creating stem cells, ways that don't involve creating embryos. What makes this different, and what are the ethical questions we need to consider? That's what we'll be talking about, our number 1-800-989-8255. Let me introduce my guests.

George Daley is a professor at Harvard Medical School and director of the Stem Cell Transplantation Program at Boston Children's Hospital. Josephine Johnston is a research scholar at the Hastings Center, that's a bioethics think tank based in Garrison, New York. Welcome to the program Dr. Johnston, Dr. Daley.

GEORGE Q. DALEY: Good to be here.

Thank you very much.

FLATOW: Dr. Daley, let me ask you: Is this a real breakthrough in the true sense?

DALEY: Oh, it definitely is. I mean, technically this has been a challenge that dozens of labs have really been working hard at across the world for, say, 10 or 15 years, and this is really the first time that it's worked in humans.

FLATOW: Give us a little bit of an inside baseball, a few details of what they did.

DALEY: They fundamentally used the same technique that was used by Campbell and Wilmette to make Dolly the Sheep in 1997. But instead of going all the way to making a baby, which is not anything anyone wants to propose, they copied cells. What that really involved was taking an egg from a woman who was paid to donate that egg, removing the DNA from the egg and replacing it with the DNA from a donor cell.

They did it both from a kind of generic fibroblast but also from the donor cells of a patient with a particular disease. What that does then is it actually starts the process of early human development, there's a small embryo created from which one can harvest stem cells. So they made patient-derived stem cells that would have been identical to that individual with the disease.

FLATOW: Did it go as far as the cell to actually develop stem cells in it?

DALEY: Yes, so they - their breakthrough was being able to reproduce the sort of early stage blastocyst, you know, this earliest stage of human development, when we're really a small cluster of cells, a couple hundred cells at most, but those are the substrates for deriving these master cells, these embryonic stem cells that can be any tissue in the human body.

FLATOW: And theoretically, then, there was no father to this embryo, it was just a mother's egg?

DALEY: Well yes, I mean, the mother's egg is involved, but fundamentally we're talking about the DNA, in the case of the patient, the DNA is a combination of that patient's mother and father. I mean, it's the identical nucleus and DNA from the patient.

FLATOW: Now I heard in the technique there was involved using caffeine. What was that about?


DALEY: Yeah, the Starbucks experiment, in a sense. Well, one of the challenges that many groups have faced, than when you manipulate the egg, when you stick an eye needle into it to pull out its chromosomes, that tends to shock the egg and activate it, and it tends to start to develop. Caffeine, we know, actually inhibits some of the enzymes that are involved in activating the egg.

And so by adding caffeine to the culture, the mix, the sort of broth in which these cells are grown, they could stick the needle in without starting this process. So it was an important contribution to getting this all to work.

FLATOW: Dr. Johnston, as a bioethicist, what are some of the possible landmines here?

JOSEPHINE JOHNSTON: Well, we're back to a situation where we're talking about the creation of an embryo, which will then be destroyed for research purposes, which of course is still controversial in the United States and in other countries. And because of the nature of this particular experiment, it reopens the debate about reproductive cloning and whether this technology takes us a step further towards, or closer towards being able to do reproductive cloning.

One of the other issues that is, you know, still debated to some extent is the involvement of egg donors in research and the compensation that is provided to them. So there are at least - those are at least a few of the unresolved debates that this particular study sort of reignites.

FLATOW: Does it matter that these are not fertilized eggs?

JOHNSTON: So, does it matter for...

FLATOW: People who are concerned about...

JOHNSTON: So I think this question of whether or not this kind of embryo is - morally has the same status as an embryo that was created by fertilization is an unresolved question. A lot of people are opposed to the destruction of embryos created by fertilization, and now we have one created by cloning, and the question is is it the same kind of thing in terms of its status?

And that's not a question I can answer for - it's a very contentious, about which a lot of people have different feelings about what is a human embryo and what is its moral status, and what can we do with it.

FLATOW: George Daley, we have another type of technology to get these types of cells, don't we, without creating embryos?

DALEY: Yes, in fact it was the subject of this past year's Nobel Prize. Shinya Yamanaka, a Japanese scientist, taught us that if you take just a couple of genes that are normally expressed in embryo-derived stem cells and transfer those genes into let's say a skin cell from a particular patient, you can reset the skin cell back to its embryonic state. These are called induced pluripotent stem cells, or IPS cells.

And IPS cells look to all of us to be virtually identical to embryo-derived stem cells. They have, you know, tremendous potential for teaching us about disease and maybe one day for actually treating disease. Now in reality, though, when we look very carefully at the molecular details of the IPS cells, there are still some lingering questions as to whether they are identical to the embryo-derived cells.

We did an experiment a few years ago in mice where we very carefully compared these IPS cells to embryo-derived stem cells and to this new type of stem cell, the ones derived by cloning or nuclear transfer. And in that experiment it looked like the cloned stem cells had very subtle advantages. They were slightly more similar to the natural stem cells.

And whether that's going to be relevant in the human context to studying disease or treating disease, we don't know. But this new breakthrough, this human nuclear transfer stem cell, now gives us the ability to make that ultimate comparison. So from a scientific point of view, this is in fact an important contribution.

FLATOW: There is another difference in that you are inserting the nucleus, the DNA, into the cytoplasm, right, of the...

DALEY: Yes, this is a very important point, as well. So one of the real advantages of nuclear transfer, if you will, is to potentially treat a range of diseases that are called mitochondrial disorders. Now in the egg, the - obviously the DNA encodes for most of the genes, but there are these little factories, these sort of power plants of the cell, called mitochondria, which are small structures that live outside of the nucleus.

They are inherited from the mother in her cytoplasm. Now if you have defective mitochondria, you can have a range of diseases called Kearns-Sayre syndrome or Pearson's syndrome. These can be devastating diseases. They can be associated with eye muscle abnormalities or muscle weakness or bone marrow failure. We've seen kids here at the Children's Hospital who die of these diseases.

Nuclear transfer actually allows you to generate an egg or an early embryo, which has the DNA of the parents but has replaced any defective mitochondria with healthy mitochondria. So this general strategy of nuclear transfer does have a legitimate medical application in the treatment of mitochondrial diseases.

But I want to go on record as saying that there's a clear, bright line between legitimate scientific applications of nuclear transfer, of cloning, and that is to make stem cell, that is different from what I would say is an illegitimate and unsafe application, which would be in reproduction, in making babies.

I don't think any legitimate scientist wants to take this technology forward to making babies, but to make cells and to study cells is of great medical value.

FLATOW: Dr. Johnston?

JOHNSTON: Well, I think that Dr. Daley is right in pointing out that there is a significant, significant consensus against the use of this technology for reproductive cloning in the scientific community. And that's reflected also in some state laws in the U.S. and also some laws in other countries that have distinguished between reproductive uses and research and therapeutic uses of this technology.

I would say that I don't think we've had a really significant public debate about reproductive cloning and what would - why we would ever want to do it and what any reasons might be for doing it. It's fairly widely assumed to be a negative use, and many people are opposed to it.

We don't have a national law on that, but a number of states that have put money into stem cell research have gone - have passed laws at a state level that permit therapeutic uses of this technology but ban reproductive uses. So it is a very popular and important distinction.

FLATOW: But do you suspect someone might do it someplace, somewhere?

DALEY: Well, you know, it's...

FLATOW: I mean, we had Dolly the Sheep.

DALEY: We don't know what is going to be practiced, and in fact there was one published attempt some years ago of the use of nuclear transfer to create a cloned embryo and to do a transfer to create a pregnancy. That was done offshore. The Food and Drug Administration is on record as saying that it would fall within their jurisdiction if this type of approach were practiced for human fertility.

FLATOW: OK, let me interrupt you. We'll get - we have to take a break. We'll talk lots more about that, our number 1-800-989-8255, talking with Josephine Johnston and George Daley on SCIENCE FRIDAY. I'm Ira Flatow, this is SCIENCE FRIDAY from NPR.


FLATOW: This is SCIENCE FRIDAY; I'm Ira Flatow. We're talking this hour about the breakthrough announced this week in cloning of a human embryo with my guests, we were talking about this, George Daley of Boston Children's Hospital, Josephine Johnston of The Hastings Center.

When I rudely interrupted you, Dr. Daley, you were talking about whether you think anybody would ever actually go down the full Dolly path and clone a human, and you said this is under FDA regulation, and that it probably, most likely, for sure, the FDA would not permit this. But I'm thinking of somewhere around the other parts of the world, where there is no tight regulation of this.

DALEY: And that's true, and I think there is - there is one published account of an attempt. I mean, I think the question that's raised is, you know, does there need to be, you know, a new law, and I'm making the point that the Food and Drug Administration already has jurisdiction and would step in and prevent this.

And so my concern is that any new law, as it's been debated in the past in the U.S. Congress, has tended to conflate the legitimate scientific applications of nuclear transfer, the so-called therapeutic cloning, and the illegitimate reproductive aspect. I'm worried that the politicization of this issue would end up with a law that would outlaw all sorts of nuclear transfer research, and that would be, I think - have a very, very negative effect on the science, which is extremely valuable and should continue.

FLATOW: Dr. Johnston, does it matter ethically that the women were paid for using their eggs?

JOHNSTON: Well, this is something that's - about which there's a significant debate. So I personally have come forward towards the end of believing that it is permissible to pay participants in research for their participation, and I don't see why would treat egg donors any differently in that regard than we treat other people who are involved in research and often compensated for their time.

So I don't see that as inherently trouble. I will point out, of course, that egg donation carries risks with it, and so we want to be very careful that we understand those risks and that they're clearly communicated and that they are balanced against the benefits of the research.

FLATOW: Let me go to one call from Ron(ph) in Manchester, New Hampshire. Hi Ron.

RON: Hi, amazing topic, and I (unintelligible), correct me if I'm wrong. My understanding is a major difference between a regular somatic cell and a cell derived - you know, an embryo derived the conventional way has to do with the telomeres on the chromosomes, that, you know, the gonadal tissues that give rise to the reproductive cells can clip the telomeres and make them young.

But like, if you start with an adult cell, and the cell - the chromosomes have already aged, and they have these longer telomeres, you know, one would think that would be a major difference between these embryos and conventionally derived embryos.

DALEY: Yeah, so telomeres are like the little plastic at the end of your shoelace that keeps it from fraying. The telomeres are on the ends of each of the human chromosomes, and they end in the cells of the gonads and let's say the sperm and the egg, they tend to be kind of rejuvenated with each cycle of life.

The cloning process, as with the reprogramming process that Yamanaka taught us about, actually re-grows the telomeres. So we believe that the stem cells that arise from the process are in a way rejuvenated, and so we wouldn't have to worry about the aging of these chromosomes by deterioration of telomeres. So the stem cells really function very well.

FLATOW: If you then created new body parts or use them therapeutically, the stem cells, and they had rejuvenated telomeres, would - does it mean that those body parts are younger?

DALEY: Well, I mean, to say that all aging has to do with the deterioration of the telomeres is a - you know, that's simplistic. Aging is a very complex process that affects lots of aspects of the cells. But if you're just looking at telomeres, when we make stem cells in a Petri dish and tissues from them, they have been rejuvenated at the level of their telomeres. So yes, they would be healthier and younger, if you will.



JOHNSTON: One thing that the caller raises in my mind is that we have had some experience with cloning in animals, reproductive cloning, and there have been - it seems that there are medical problems with the offspring. And so what the caller's question made me think about the fact that even if the cells, the stem cells that we get out of the cloned embryos are medically useful and helpful, it's not clear that any reproductive use of those embryos would result in healthy children, which is one of the reasons why there is so much concern about reproductive cloning and why that would represent a significant ethical question about whether it could be done safely, if it would be done at all.

DALEY: Yeah, I would echo that. We have had experience with cloning over a dozen different mammals, from mice to pigs to cats, dogs, cows and the like, and, you know, where you can tell, these cloned animals have had significant medical problems: shortened life spans; problems with obesity and the like.

And so for that reason I don't think any scientists are comfortable thinking that you're going to use these embryos in reproduction.

FLATOW: One question for you before we go. If you were going to use them therapeutically, as you're speaking, would there be any advantage - let's say a woman needs some therapeutic use of these stem cells - would there be any advantage in taking an egg from the same person that you would take the skin cells to produce the stem cells from?

DALEY: Well you ask an interesting question. I mean whether or not there's any immunogeneticy or an immune response to proteins of the mitochondria, and there is some evidence that that can be - so your question is - yeah, there might be some advantages, but we have the IPS approach.

So if I took a skin biopsy from that woman and reprogrammed her skin cells, I'd be bringing along with it not only her nuclear DNA but her mitochondria, and they would be identical to her. So the real question is: Does a cloned cell have any scientific advantage or medical value that we don't already get from IPS cells?

JOHNSTON: And it's an important question. I happen to think IPS cells are much more flexible and easier to use and will ultimately be the dominant platform, but we have to do the comparison, and we have to answer the questions.

FLATOW: Well, thank you very much for taking time to talk with us about this very interesting subject, George Daley, professor at Harvard Med School, director of the Stem Cell Transplantation Program at Boston Children's Hospital; Josephine Johnston, research scholar at The Hastings Center, that's a bioethics think tank based in Garrison, New York. Thank you both.

DALEY: Thank you for your interest.

JOHNSTON: Thank you very much.

FLATOW: You're welcome. Transcript provided by NPR, Copyright NPR.