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Michael West

The Technology of Immortality:
An Interview with Dr. Michael West

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By David Jay Brown

Michael D. West, Ph.D., is a geneticist, stem cell pioneer, and entrepreneur. He has extensive academic and business experience in age-related degenerative diseases, telomerase molecular biology, and human embryonic stem (ES) cell research. Dr. West founded the first biotechnology company focused on controlling the aging process in human cells, and he has spent the last twenty years researching the cellular and molecular mechanisms of human aging. He is the founder of Geron Corporation, a biotechnology firm in Menlo Park, California, and is currently the president and Chief Scientific Officer of Advanced Cell Technology (ACT) in Alameda, California. Geron funded the research that isolated human embryonic stem (ES) cells, and ACT is at the forefront of therapeutic cloning. ACT cloned the first human embryos for the purpose of advancing therapeutic research.

Human embryonic stem (ES) cells–the primal cells that give rise to essentially all cell types in the body–are now routinely grown in culture. This breakthrough technology is opening the door to an astonishing array of potential medical applications. ES cells can differentiate into all types of tissue and can be used to grow new organs. With ES cells scientists can literally grow new heart or new kidney cells, or perhaps soon, whole organs. Since ES cells can be made using one’s own DNA, the body will accept the new tissue as its own. Although ES cell therapy is still in it’s infancy, our understanding about ES cells is advancing rapidly and their therapeutic potential looks more promising every day.

Dr. West received his M.S. in Biology from Andrews University in 1982, and he earned his Ph.D. from the Baylor College of Medicine in 1989, concentrating on the biology of cellular aging. Dr. West’s research into the cellular and molecular mechanisms of human aging during the early 1990s led to his founding Geron. From 1990 to 1998, Dr. West was a Director and Vice President at Geron, where he initiated and managed research programs in telomerase therapy. Telomerase is an enzyme which allows cells to divide indefinitely. Inhibiting the production of telomerase in cancer cells kills them, and turning on telomerase production in healthy cells makes them essentially immortal. Dr. West also organized and managed the program at Geron from 1995 to 1998 which, in collaboration with Dr. James Thomson and Dr. John Gearhart, led to the first isolation of human embryonic stem and human embryonic germ cells.

Dr. West’s current biotechnology company, ACT, is applying human ES cell technology in the emerging field of regenerative medicine. ACT’s research is focused on the use of stem cell therapy in treating age-related disease and nuclear transfer technology, which allows for the production of stem cells to be genetically matched to the patient. They own or license over three hundred patents and patent applications related to the field of stem cell therapy, and a library of stem cells for acute clinical applications. In November 2001, researchers at ACT announced that they had cloned the first human embryos for the purpose of advancing therapeutic research. The results were limited in success. Although this process was carried out with eight eggs, only three began dividing, and only one was able to divide into six cells before stopping. Nonetheless, this was a dramatic demonstration that human cloning is indeed possible.

Dr. West currently serves as Chairman of the Board, President, and Chief Scientific Officer of ACT, and is Adjunct Professor of Bioengineering at the University of California, Berkeley. He is also the author of the book The Immortal Cell, and the story of Dr. West’s quest to solve the mystery of human aging is chronicled Stephen Hall’s book Merchants of Immortality.

When I spoke with Dr. West I got a strong sense that he is truly excited by his research. We spoke about the potential therapeutic uses of ES cells, telomerase therapy, and the future of biotechnology.

David: What do you think are some of the biggest problems with modern medicine and what do you think needs to be done to help correct the situation?

Dr. West: I’m a gerontologist, and speaking from the standpoint of gerontology, the biggest mistake that I see medicine making today is in not adequately planning for the future, in what’s called the “age wave” or the “graying of America.” The aging of America and other industrialized countries is the greatest, or let’s say the most profound demographic trend of our time, and it’s going to greatly strain our resources to adequately care for the elderly. The risk we face is that, for the first time in the history of the United States, we will discriminate against a group of our citizens based on a biological characteristic–being their age–and simply say, “You’ve reached a certain age and we’re no longer going to provide medical services to you, because we won’t be able to afford it.” That’s not the kind of country I want to live in, or, I don’t think, for those of us who are entering that age bracket. I don’t think it’s the kind of future that we want to see, so it’s not an exaggeration to say that we have a crisis of epidemic proportions here with the aging population and its associated healthcare costs.

David: How did you get involved in embryonic stem cell research?

Dr. West: It goes back to the fundamental interest that I’ve had in the cellular basis of what’s called the “immortality of species.” As you know, life continues generation after generation, in an apparently immortal fashion. This is because germ-line cells (our sex cells) come from the previous generation of germ-line cells, and there’s an immortal lineage of these cells that connects the generations of all living beings on the planet. That lineage of cells is immortal in the sense that they have no dead ancestors and have survived all of the insults of life–free radical damage, cosmic rays, and everything else that can injure living things.

These cells have survived all those sources of injury and, according to some estimates, have been evolving for over four billion years as a continuous life form. Of course, this immortal lineage of cells that connects the generations, and causes babies to be born young, is of great interest to gerontologists. This is because the cells that make up the rest of our body–what’s called the somatic lineages of cells–clearly do not share in the immortality of the germ line. Our goal has been to learn from the immortality of the germ line and transfer these characteristics to somatic cells.

Telomerase was the first attempt to do that. Telomerase is an enzyme, a critical piece of which is a protein made by a gene commonly called the “telomerase gene.” The actual name for it is human telomerase reverse transcriptase, or hTERT for short. But that particular gene is turned “off” (it’s inactivated) in mortal cells that age, and it’s turned “on” (activated) in cells that are immortal. The gene is turned “on” in our germ-line cells and is turned “off” in most somatic cells.

David: And, unfortunately, our bodies are basically composed of somatic cells.

Dr. West: Yes. You probably know that back around 1992, we began trying to track down the telomerase gene, and we eventually managed to clone it. Having done that, we found that telomerase is useful for preventing somatic cells from aging. There are clearly cells in our body that don’t age, simply because they don’t divide. Heart muscle cells and neurons in the brain are two examples. It could be that they age as a consequence of other cells that are aging.

For instance, heart muscle cells do not divide and therefore do not age. But damage to heart muscle can occur due to a heart attack, arrhythmias, or other heart disease. Damage to the heart muscle could also be the result of the aging of cells of other biological structures, such as the cells that make up the vessels to the heart, or some other cells that have a finite life span and upon which the heart muscle is dependent for healthy functioning. When that tissue becomes diseased and the blood vessel can no longer feed the heart muscle, the heart muscle is damaged secondarily. But however you think about it, the point is that there are aging or damaged cells and tissues in our body that need to be replaced.

The ES cell research is an attempt to find a novel way of treating age-related disease. It’s essentially a transplant therapy, replacing damaged cells and tissues, by going back to this immortal germ line. These ES cells are so primitive that they are still in the immortal germ line. So when you make a somatic cell from an ES cell, the cells that result are born young, as a baby is born young. We are creating a technology to replace damaged cells and tissues with young cells as a therapy for aging.

David: Are ES cells currently being used to help repair damaged tissue?

Dr. West: No. It’s a brand-new technology. It’s so new that the first report of isolated ES cells is only a few years old.

David: What are some of the future applications that you foresee?

Dr. West: The ES cell is, as we say, “totipotent,” which literally means “total power.” These cells have the ability of becoming any cell or tissue type in the body, so the applications are endless. The Director of the

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