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LE Magazine March 2002

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THERAPEUTIC CLONING UNDER FIRE
An Interview with Michael D. West, PhD

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A year and a half ago, Michael West, PhD, President and CEO of Advanced Cell Technology (ACT), revealed his plan to use "therapeutic cloning" to attack aging in humans (Life Extension magazine, June 2000, pg. 40). At that time, there was relatively little opposition to Dr. West's idea (see "The Media Befriend De-Aged Clones," LEM, August 2000, pg. 57). But when he announced recently that ACT had taken the first step towards human therapeutic cloning, he was suddenly criticized by everyone from President Bush to the Pope. Further, a bill outlawing human cloning (including therapeutic cloning) had already been passed by the U.S. House of Representatives, and President Bush urged the Senate to approve the bill as soon as possible. In the face of this criticism, Dr. West has patiently and calmly stood by his guns. He was interviewed by telephone on Dec. 2 by Gregory M. Fahy, PhD and Saul Kent of the Life Extension Foundation about the latest scientific advances made by ACT and the furor and controversy over cloning.

Life Extension Foundation (LEF): Can you explain the advances you've made at ACT towards therapeutic cloning for humans and why this is such an important area of research?

Michael West (MW): The dream of cell biologists is to be able to take a body cell from a patient of any age back in time to an embryonic state. Embryonic stem cells have the unique ability to make virtually any type of cell that the patient would need. So their use in medicine could be very broad. One immediately thinks of making pancreatic islet cells for diabetes, heart muscle cells for heart disease, neurons for Parkinson's disease or spinal cord injury and so on. I believe we have found the "time machine." It is somatic cell nuclear transfer, otherwise known as cloning. The idea is quite simple. We would take a somatic cell from a patient and transfer it into an egg cell whose DNA had been removed. The egg cell would then act as the "time machine" by taking the patient's cell back to an embryonic state. Since the embryonic cell would be made through cloning, it would be immunologically identical to the patient's own cells and could then be transplanted into the patient without risk of rejection. The great hope is to be able to make young cells, tissues and organs for the treatment of aging and degenerative disease.

Do we think that's actually possible? The answer is "yes." As you know, we published back in 2000 that, in the cow, nuclear transfer can restore cellular life span and rebuild the telomere, the clock of cellular aging. That work was later replicated in a mouse model by Teru Wakayama, who was the first scientist to clone a mouse (Nature 2000; 407:318-9).

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I believe we have found the "time machine." It is somatic cell nuclear transfer, otherwise known as cloning. The idea is quite simple. We would take a somatic cell from a patient and transfer it into an egg cell whose DNA had been removed. The egg cell would then act as the "time machine" by taking the patient's cell back to an embryonic state. Since the embryonic cell would be made through cloning, it would be immunologically identical to the patient's own cells and could then be transplanted into the patient without risk of rejection.

In his experiment, Dr. Wakayama cloned a mouse, which he named Cumulina, after the cumulus cells that surround the egg. The donor nucleus had been taken from one of these cumulus cells. Then he cloned clones of Cumulina. And then clones of the clones of Cumulina. Every time he cloned these animals, the telomeres actually became slightly longer than they were originally. So Dr. Wakayama saw an effect on telomeres similar to what we saw in cows. (Editor's note: telomeres are regions of DNA at the ends of chromosomes that are partially lost when cells divide, which limits the number of times the cells can divide. They act as "clocks" of cellular aging.)

LEF: What did you publish in The Journal of Regenerative Medicine that caused all of the controversy (EBiomed: J. Regen. Med. 2001;2:25-31)?

MW: We published our initial experiments with human nuclear transfer for the purpose of therapeutic cloning. Now let me make something very clear at this point. We are building a technology to make cells for medical purposes, which we call "therapeutic cloning." We are not trying to clone humans, an application that is usually called "human reproductive cloning."

LEF: How does this differ from the results you reported a year and a half ago?

MW: This time we used human egg cells (oocytes), whereas in the past we were working with animal egg cells.

LEF: How far did you get in the work that was published?

MW: We made an encouraging first step. We saw the hallmark of what we call nuclear reprogramming, when a somatic (body) cell is taken back into an embryonic state. When the "time machine" works, the nucleus changes its morphology (its shape). It swells and takes on a particular appearance called a pronucleus.

When an egg is fertilized by a sperm, the sperm cell nucleus becomes a pronucleus. But if you effectively trick an egg into believing that a transplanted somatic cell nucleus is actually a sperm cell, then the nucleus will also become a pronucleus. What we saw was pronucleus formation after nuclear transfer, which in our experience is evidence that reprogramming is occurring within the nucleus.

LEF: So you accomplished the first step.

MW: Yes. And we got the reconstructed embryos, as we call them, to begin dividing. In this experiment, we only got up to a total of six cells.

LEF: What happened afterwards?

MW: Further development was blocked, meaning that the embryos stopped dividing.

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LEF: When that happened, was there any change you could detect, which might explain why they were blocked?

MW: In our experience, based on the other species we've worked with, cloning is largely trial and error, because we don't know how it works, ultimately. It's magic, it's a black box. And so what you do is fine tune this or that variable, the concentration of particular chemicals in the media, or the timing of events, until it works. However, you know you're getting close if you see pronucleus formation and some cell division. So the first few rounds of cell division we saw in our human experiments were encouraging.

LEF: Did you measure the telomere length in the human embryos you produced?

MW: No.

LEF: Critics have said that you didn't get very far at all because your embryos stopped dividing at the 6-cell stage.

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Human cells dividing - 2 days old

MW: I don't understand the critics here. I think what this reflects, frankly, is that this is a very emotional area. It's a lot like the Wright brothers' first flight. When they got their plane to fly 120 feet, their critics said that the Wright Brother's plane had only managed to cover 120 feet, but the Wright brothers were thrilled that they had managed to fly at all.

LEF: Did you expect the extent of publicity you've gotten?

MW: No. We decided to publish our findings in The Journal of Regenerative Medicine because it's an Internet journal and we knew we could get it out there rapidly. U.S. News and World Report (Dec. 3, 2001, Vol.131, No. 23) was doing an in-depth story on us. They released their article within minutes of our publication in the journal, which took an obscure scientific publication and put it in an international spotlight.

LEF: Isn't it true that when you transferred nuclei from somatic human cells into cow eggs a couple of years ago, you created more developed embryos than you have with human eggs?

MW: It's true that we induced these embryos to develop to the blastocyst stage, but we've done thousands of inter-species nuclear transfers. It's a very inefficient process compared to using cells from the same species, but since we've done a lot more human-to-cow transfers, this explains our greater success with this procedure. It's important to point out that access to human oocytes is far more problematic than to cow eggs. It took us months to work out the right way to do this with human egg donors. Obviously, a lot needed to be done to protect these women who were doing such a great service for humanity in donating their cells. We needed to be sure that it was safe for them. We needed to work out a whole battery of physical and psychiatric exams and other procedures.

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Bovine embryo from the tip of a hypo needle pictured next to a human hair. ACT's cloned human embryo is approximately the same size as this bovine embryo.

LEF: When you were first doing the human nucleus/cow egg experiments, did you get results similar to your initial human nucleus/human egg results in the early stages? And did you later overcome the problems to get more advanced development?

MW: As of today, our cross-species nuclear transfer procedure using a cow's egg cell and a human somatic cell is not yet efficient enough to meet our standards. We are still working on this and are hopeful for success. An alternative to human egg cells would make the therapies much less expensive.

LEF: Do you have greater efficiency with human-to-human transfers?

MW: It's too early to say. We're still fine-tuning, learning from our mistakes, and we're not even close yet to optimum conditions.

LEF: Could you identify the steps that need to be taken to develop therapeutic cloning and give us an estimate of how long it might take to achieve those steps?

MW: The first step will be to optimize the conditions for the cellular "time machine," according to the therapy we want to develop. We will then turn our attention to an animal model of disease and work to show we have a new therapy that is safe and effective. Once we've demonstrated the value of the therapy in animals, we will ask the FDA for permission to begin human clinical trials. All of this could take 7-10 years or longer, depending upon the disease.

LEF: Let's get to the opposition to your work and how that's led to the House bill which is going to be discussed in the Senate shortly.

MW: Well, what we have is, potentially, a solution to this age-old problem of transplantation, the ability to offer patients the cells they need, even biologically young cells, without the fear of rejection. Our opponents are objecting to this, I would argue, largely, out of fear of a brave new world scenario. A lot of people are afraid of the word "cloning." I can understand this. I mean, we've had a long stream of science fiction movies (including a new movie called "Attack of the Clones") which paint a very scary picture of cloning.

The second problem is that the pro-life community has picked up on this as a pro-life issue, which I think is unfortunate and short-sighted. Why? No serious ethicist or embryologist believes that a pre-implantation embryo is a human being. We are not talking about creating a pregnancy. We are talking about making a microscopic ball of cells with no body cells of any kind. These cells have not even individualized. They don't make a final decision as to whether they'll make one or two persons (identical twins) until after they've been implanted in a uterus and passed the stage called "primitive streak." Because there are no body cells of any kind, and the cells have not yet individualized, they are not a person yet, by definition. Saying that a pre-implantation embryo is a human being and arguing that therapeutic cloning is, therefore, unethical is simply not based on fact.


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