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

By David Jay Brown

Michael D. West, Ph.D., is a geneticist, a stem cell pioneer, and an 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 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 cells 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 its 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 in 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.

Q: 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. Speaking from the standpoint of gerontology, the biggest mistake that I see medicine making today is in not adequately planning for the future, for what is called the “age wave” or the “graying of America.” The aging of America, and other industrialized countries, is the most profound demographic trend of our time. It’s going to greatly strain our resources to adequately care for the elderly. For the first time in the history of the United States, we face the risk that we will discriminate against a group of our citizens based on a biological characteristic—their age. We may have to simply say, “You’ve reached a certain age and we’re no longer going to provide medical services for you because we won’t be able to afford it.” That’s not the kind of country that I want to live in. I don’t think that’s the kind of country that those of us who are entering this age bracket want to live in either. 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.

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

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.

Q: 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.

Q: 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.

Q: 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 National Institutes of Health, Dr. Harold Varmus, has said that there is not a single area of medicine that these new technologies will not potentially impact. I think that’s probably an accurate statement, because they can potentially be made into anything.

Q: How long do you think it will be before we'll be able to use ES cells to grow any type of tissue or organ that we need?

Dr. West: I think it's going to be a spectrum of opportunities. Some things will be relatively easy to do, and then other things are going to be harder to do. I guess some of the early applications of ES cells may be things like cartilage for arthritis, and blood cells for leukemia or other blood disorders; maybe neurons for neurological disorders.

Q: Like Parkinson’s disease?

Dr. West: Parkinson’s disease, certainly, is a classic disease where you simply need those cells back. But any disease where there is a loss of cell or tissue function is a clear target for this sort of thing. There are all kinds of other possible applications. In heart disease, when you lose heart muscle, you need to replace it. A lot of arrhythmias could be treated this way. With just a little imagination, you can see there are literally thousands of applications. Until last year, we never had the ability to make any cell type in the laboratory. So it’s obviously a very exciting development.

Q: The discovery that the tips of our chromosomes—telomeres—become shorter with each somatic cell division may have important implications for our understanding of how we age. What sort of potential for extending human life do you foresee as being possible by preventing telomeres from being shortened during cell division?

Dr. West: We still do not know the real answer to that question. It’s amazing. I would put the blame for our lack of knowledge of this as simply the lack of funding that goes into aging research. As you know, Geron has been able to raise a fair amount of capital to promote aging research. Now, here at Advanced Cell Technology, we've been able to raise some money. The National Institute on Aging sponsors some research into aging.

But if you put all the biotech together, along with the federal government, it’s still a small fraction of what's spent on AIDS, and, of course, the budget on AIDS is too small. We probably spend more in a week bombing foreign countries than we ever spent on aging research. That's where I put the blame. We simply do not know. What we do know is that telomerase abolishes aging on a cellular level— what we call "cellular aging." So, for cells at least, we've solved the problem of aging. The lack of telomerase is what causes cells to age. When the immortalizing telomerase gene (hTERT), which directs the synthesis of telomerase, is turned off, cells become mortal.

Since we’re made of cells, this should have an application to human medicine. I would bet that it does, but we simply don’t know what percentage of human aging is caused by cellular aging. If you pinned me down on it, I would say somewhere between five and a hundred percent of human aging. I don’t know whether it’s closer to five or a hundred, but it's somewhere in that range. Recent studies point toward the higher end of that range. But even if it’s only five, it’s noteworthy that here we've tracked down the fundamental molecular cause of at least a part of human aging and have found a means of intervening in it and changing it. So even if it’s just a small piece of human aging, at least it's some advancement.

Q: Have you found that any genes trigger the release of endogenous enzymes that may be able to benefit us now through some type of supplementation?

Dr. West: No, I don't know of any. There are some genes that have been reported that induce telomerase, but none of them give us any clues as to any supplementation that would help—and that may be what you would expect. There are literally billions of people on the planet eating many different types of foods and supplementing their diet in many different ways. As of today, however, there's no known case of anyone who has dramatically affected their life span—maybe because there is no dietary means of fundamentally altering this biology.

The reason that we think this biology is in place is that it may be a powerful antitumor mechanism. Cancer is a runaway cell—a cell that's inappropriately growing without limits, like a runaway car that doesn't stop for stop signs. But all of the cells in our body can only divide a finite number of times. So the "car" has only an eighth of a tank of fuel. That way, if it becomes a runaway car, it can't go too far. Our bodies are actually littered with cells that have started to run away. If you look at your skin, you'll see little moles and splotches, which often represent some of the pigmented cells, where you can see the cells starting to run away in uncontrolled growth. But the mole, or the pigmented blotch on your skin, you'll notice, grows to a certain size and then stops.

We believe that this is a reflection of the mortality of cells—that they have a finite life span. If there were a simple dietary means of unlocking a replicative immortality, it might allow those cells to just continue to grow. So the repression of telomerase may be an antitumor mechanism. Now that's not the same as to say that telomerase would induce cancer. The ability to refuel the gas tank of a car doesn’t make it a runaway car. But it may be that allowing all the cells in our body to be immortal would raise the risk of cancer. Over the eons, natural selection has tended to “mortalize” the body, since in ancient times we rarely lived very long anyway. The average human being lived maybe 20 years in ancient times. So why would you need your cells to divide forever, when cancer or being eaten by a lion was much more of a risk?

Q: Can you talk a little about the cloning research at Advanced Cell Technology?

Dr. West: What we’ve been working on here more recently is nuclear transfer or cloning. Having ES cells is great, but they’re not you—they’re somebody else.

Q: I thought the whole idea was to use your own DNA?

Dr. West: Right, that’s what the nuclear transfer idea is. The ES cells that exist today came from embryos made during in vitro fertilization. That’s from taking a sperm and an egg and then making this little microscopic ball of cells we call a blastocyst. This contains the ES cells that can become anything. They’re sort of like a raw material for life in some respects. They can be grown in a dish and made into the cells and tissues in the dish. But those cells that exist today are not you. Your body will reject cells that are not your own.

So any cells or tissues that are made from an ES cell that's not your own, your body would reject. But your body doesn't have any ES cells—they're long gone. So what we're working on is a cloning technology to make ES cells for you. We just scrape some cells off your skin and put them back into an egg cell whose DNA has been removed. What you then get is this little ball of cells—ES cells that have your DNA. So what you're doing there is cloning, but you're not making an embryo that would be put in a woman. That would lead to a cloned copy of yourself. Rather, we’re proposing cloning stem cells.

You’re just making cells, not people. That’s called “therapeutic cloning,” as distinct from “reproductive cloning.” So we’re trying to make that work. The wonderful thing about this—which isn’t widely known—is that we've actually shown that you can take an old cell that’s at the end of its life span, and if you put it into an egg cell, it’s like taking the cell back in a time machine. The cell is actually made young again.

Dolly, the sheep that was cloned, was made from an adult animal but was obviously born young. In the same way that she wasn’t prematurely old (despite starting out as an old cell), we’ve shown that we can take old cells in a dish, and when we do this cloning technique, the cells we get are young: they have their whole life span ahead of them again. We believe that somehow, that step of putting the cell back into an egg cell winds the clock up again and takes the cell back to the beginning of life. So, theoretically, it looks as though we should be able to take a very old person and make new, young, transplantable tissue for that person, just like their own tissue when they were born.

Q: And give them a new heart?

Dr. West: Potentially. Under certain conditions, we’ve observed ES cells actually forming complex tissues, such as intestines.

Q: I read in Science that a dog’s bladder had been engineered.

Dr. West: That bladder was made using tissue engineering, which is a little different: it was manufactured. But the ES cells will actually form complex tissues themselves. They self-assemble into tissues like intestine that are obviously young. No matter how you think humans age, here is a technique that will allow us to create young, transplantable tissue. We honestly believe that we will be able to make new liver tissue, or maybe even young whole organs that are composed of your own cells, to replace the old worn-out ones. It’s a long-term project, and it’s years away from being available for most applications. But it’s an exciting prospect.

Q: What are your thoughts about the rate at which our understanding of ES cells is progressing?

Dr. West: I’m happy to say that the field is advancing at a fast pace, despite the fact that there’s been very little federal funding for the research, and this is largely a result of just simple scientific ingenuity. I’m aware of numerous remarkable advances that have taken place in field, and we’re actually ahead, I would say, of where I thought we would be as of today. Of course, we could be much further if the federal government were funding this research. As you know, the state of California voted for the allocation of three billion dollars to fund precisely this area of research—called Proposition 71—and it’s anticipated that the funding will eventually materialize. So, despite the fact that we have not had a lot of federal funding, which is the normal way medical research is undertaken, I’m happy to say we’ve made some rather remarkable progress.

Q: What do you think are the primary causes of aging?

Dr. West: I’ve believed for some time that aging has multiple facets and components, but it is not as complex or difficult to understand as many people have proposed. In the early days, for many people diabetes looked to be a very complex disease. You have sugar in your urine. You have problems in your eye, retinal disease. You get ulcers on your skin, heart disease, and you have all these complications associated with the disease. It looks very complicated and difficult to solve. Well, we now know, of course, that diabetes is caused by the simple loss of a single protein—insulin—and the regulation of that insulin. That is the sole cause, and all those other complicated manifestations of the disease are now largely explainable, likened back to that single cause.

Diseases like progeria and Werner’s Syndrome are what we frequently refer to as premature aging syndromes. Although not exactly like human aging, they are very similar in many ways. You see grey hair, wrinkled skin, cataracts, coronary disease, osteoporosis—and many of these manifestations of aging we know are caused by a single genetic mutation. So what I believe is the case is that much of what we call human aging is due to the damage of DNA. In particular, I’m an advocate of the idea that much of that damage is at the telomeric region of the DNA. I think that in the future we will look back to these days, and we’ll see this as time when we came to understand that at least much of what we call human aging is due to damage to the DNA, that that’s a large percent of human aging.

I mentioned earlier that it’s somewhere between five and ninety-five percent of human aging, and that recent data suggests that telomeres are more up toward the higher end of that percent, closer to the ninety-five percent. There are studies now in rodents, where human telomeres are inserted into those rodents. The Werner mutation has been put into those rodents and now, for the first time, rodents tend to age like humans. They have age-related diseases like humans. That strongly suggests that we’re beginning to understand some of the fundamental biology of human aging. Scientists are quick to point out that I’m not saying a hundred percent of human aging, but much of what we call human aging.

Q: What are your thoughts about the future of Western medicine in general, and what sort of new medical breakthroughs do you foresee coming over the horizon?

Dr. West: I believe in science and in the scientific method. Despite what I notice as being a widespread distrust of traditional scientific medicine, I believe that scientific medicine is going to deliver beyond anyone’s expectations in the coming decade. I can’t express the amount of enthusiasm I have over new developments like embryonic stem cells, and the rapid increase in power in our ability to work with DNA and see all the molecular biology. As I’m speaking to you here just now, I have in front of me a spreadsheet with forty thousand genes on the vertical axis and many of the cell lines that we’re working with on the horizontal axis. In a matter of seconds, I can tell you the expression level of any gene in any of these cell lines.

The analytical abilities that I now have allow me to do research at somewhere between a hundred and a thousandfold faster than I could ten years ago. This helps me to answer fundamental questions. I’m interested in the collagen gene, the gene that makes the protein from which a lot of skin tissue is composed. If I want to know what the collagen gene does as embryonic stem cells differentiate, I can have that answer in about five seconds now. That would have taken me weeks or months worth of work in the past. So the rapidity at which we answer fundamental scientific questions today is so much faster that we wonder how we were even able to answer scientific questions like this in the past. Without the public knowing it, medical research has so dramatically changed from what it was ten years ago that it’s just hard to even compare.

Q: What are you currently working on?

Dr. West: Regenerative medicine. I’m interested in the immortality of the germ line cells and learning lessons from them. I’m also interested in using nuclear transfer and other techniques to wind back the clock of aging and make young cells for old people. The medical toolbox that gerontologists of the future will bring to the patient, and to the problems of aging, will have several tools in it. There’s not going to be one tool that fixes it all. So, in some cases, we’re going to need to put young cells into old people that can rebuild tissues and restore function lost as a result of age. There are going to be some approaches where regenerative medicine, as it’s been dubbed, is applied, and there’ll probably be some approaches where traditional drugs are applied. So there will be several tools in the toolbox.

David Jay Brown is the author of four volumes of interviews with leading-edge thinkers, Mavericks of the Mind, Voices from the Edge, Conversations on the Edge of the Apocalypse, and Mavericks of Medicine. (Mavericks of Medicine will be published by Smart Publications as a book in late 2006.) He is also the author of two science fiction novels, Brainchild and Virus. David holds a master’s degree in psychobiology from New York University, and was responsible for the California-based research in two of British biologist Rupert Sheldrake’s bestselling books on unexplained phenomena in science: Dogs That Know When Their Owners Are Coming Home and The Sense of Being Stared At. To find out more about David’s work visit his award-winning web site: www.mavericksofthemind.com