Conquering Aging with Cloning
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West: The most difficult part, the nearly unthinkable has already been done. We know how to take a patient's cell, an old patient's skin cell, for example, back to the beginning of life, both in terms of its differentiated state and its replicative life span. That nearly miraculous event is now practical and achievable for human medicine. The concept of taking these resulting stem cells and turning them into heart muscle, bone, cartilage, skin or blood cells, is straightforward engineering. It's like saying that once we have electronics and we have the ability of making metal alloys and we understand basic Newtonian physics, we can go to the moon. It's simply a matter of engineering. In the same way, now that we have these technologies in our hands, like the ability to reprogram an old cell back to the beginning of life, applying them to medicine is simple engineering. It's a straightforward use of technology. This certainly doesn't mean that there aren't going to be many bumps in the road, a lot of hurdles in terms of regulatory approvals and finding the financial resources to move all of these projects forward, but it should be relatively straightforward engineering. We know how to get there.
LEF: Do you think there would be major problems getting, let's say, a cloned therapeutic cell line or cell type through the FDA approval process?
Ping Jiang, Department of Molecular Development, Advanced Cell Technology - Photo by Matthew Pace
West: Well, we don't really know. What we do have is a fair amount of input from the National Bioethics Advisory Commission; the position of Harold Varmus, Director of the NIH; and of course from the scientific community. There is broad support for the use of cloning technology to make stem cells and to apply these cells to the problems of the human condition. What is not clear is what would be the regulatory mechanisms from the Food and Drug Administration to allow these technologies to move forward. To my knowledge, that has not yet been directly addressed or answered by the FDA.
LEF: What would be the full impact of this sort of technology if it could be brought into full use?
West: Well about half of all health care expenditures in the United States, now upwards of 500 billion dollars a year, can be attributed to transplantation-related costs. And given an aging population, the numbers are expected to increase. It is important, of course, to point out that a lot of current health care expenditures are for conditions not treated by transplantation. A salient example would be diabetes. We don't have the ability to cure diabetes by replacing the beta cells that are lost and cause type 1 juvenile onset diabetes, so we give insulin instead, which is not a cure for the disease. As another example, Parkinson's disease is typically not treated by replacing the neurons that are lost and whose loss causes the disease, it is treated instead with L-DOPA. So what would be potentially useful would be to find a way of meeting this already significantly large need, representing upwards of half of all health care expenditures, with transplantable cells and tissues that are identical to the patient, and would not require immunosuppressive therapy. Therapeutic human cloning could enable us to meet this need.
LEF: Would replacement cells have to be human cells, or could they be cells from other species?
West: The whole field of xenotransplantation, obtaining tissue from other species, is increasingly promising with the recent cloning of the pig for instance. Cloning allows us to create sophisticated genetic modifications in animals, making those tissues potentially acceptable into patients. What therapeutic cloning, making tissues and organs directly from the patient's own cells, offers is perhaps the ultimate solution to the problem of transplant rejection. If we could make it easily available to a broad array of people, it has the potential to make xenotransplantation unnecessary. Why would you want a pig kidney if you could have your own kidney back?
LEF: Until the experiment is actually done, is it still possible to question whether genetically identical tissue would truly be immune from rejection? Might there be something during development that could trigger a later immune response?
West: Well, we do know, of course, the work performed nearly 40 years ago by Joseph Murray, who performed the first transplantation of tissue between identical twins. Those tissues were accepted long-term with no evidence of rejection. And, of course, a clone is essentially an identical twin, just separated in time.
LEF: One of the things that happens with aging is not just a wearing out of cells and tissues, but a change in the hormonal environment that affects tissue and cell function. One often-cited example is the diminution of the secretion of growth hormone with aging. This may be due to damaged cells in the base of the brain which could be replaced, but it may be due to some sort of aging clock. If it is the latter, do you see the possibility of cloning your own body cells with genetic modifications that could then be transplanted into the body to change that type of aging program?
West: Well, there certainly are such possibilities. The beauty of cloning technologies is that everything starts with a single cell. Whether it be a skin cell or a blood cell from the patient, from that single cell, stem cells would be created that would then be turned into whatever cell or even complex tissue the patient needed. Single cells can be genetically engineered in the laboratory. DNA can be added or even taken away from cells grown in a dish. The most sophisticated of these technologies are called gene targeting technologies, where we could actually go in and edit DNA in a living cell similar to the way words are altered on a word processing program in a computer. We could go in and change a given letter or indeed a whole paragraph of text. Technologies exist to do gene targeting in cultured cells, removing DNA, even changing DNA down to a single nucleotide. These technologies are relatively inefficient. Nevertheless, because we're cloning from a single cell, we could identify a cell in the dish that has undergone a specific type of genetic engineering and then create all resulting cells and tissues from it. What that means is, it could be possible in the future for us to genetically engineer a patient's cell to any desired degree of sophistication, including inserting genes from other species, eliminating genes, indeed engineering the very blueprint of life itself to any degree that we wish, and then creating any cell or tissue in the body, indeed even complex tissues, from that original cell. We can envision cells that self-assemble into intestines, for instance, complete in all of its architecture, all of the cells of that intestine being genetically engineered in a very sophisticated manner. This, or course, is a whole quantum leap forward from anything that is currently available. With the unlocking of the human genome, understanding the function of all of the human genes, the amount of creativity that can be brought to bear, the amount of engineering is mind boggling. We could conceivably make thousands of new inventions and new ways of treating diseases.
LEF: What about the cells that comprise our identity and our memories? Most cells are interchangeable, but in this case, a brand new cell or a group of cells would not contain the information originally there. How do you deal with that?
West: I think one of the strongest arguments for cloning, beyond the obvious issue of preventing tissue rejection, is the issue of identity. One can imagine in a world without human therapeutic cloning, engineering cow heart valves, pig kidneys and pig hearts. As you know, there are people walking around today with pig neurons in their brains for Parkinson's Disease. One can imagine ones' self as a patchwork of tissues from animals and nieces and nephews, and one wonders at some point, are we in a sense becoming someone else? The beauty of therapeutic cloning is that we are talking about replacing the body with its own genotype, with cells and tissues that have the same genetic blueprint that we were born with. Admittedly, inasmuch as we do genetic modifications or alterations of that blueprint, and as we seed the body with genetically engineered stem cells, which diffusely spread new cells throughout the tissues of our bodies, in a profound sense, we would be changing who we are. But I think therapeutic cloning offers the best approach to maintaining ones' identity in the face of a very clear need for cell and tissue transplantation.
LEF: That doesn't answer the question about those few cells that encode memory and identity.
West: As you know, cells within the brain are turning over to an unexpected degree as well. Stem cells planted in the brain can also distribute themselves throughout the brain. It is possible to imagine technologies that would seed new embryonic stem cells into the brain that would graft into existing tissue. What this would mean in terms of memory and the preservation of psychic identity remains to be determined. We simply don't know at this time.
LEF: Might the infusion of new cells rejuvenate cells that are dying, or aging or however you want to describe it?
West: We simply don't know. I think what we can be optimistic about is that these new technologies should play some role in helping us repair our aged bodies, heart disease, kidney disease or blood cell disorders. How profound a role it would be, and what role it could play in the brain, are currently unanswered questions.
LEF: Also, in the absence of brain diseases, people can maintain their identities and their memory pretty well, even when they may be about to die. There is also a recent paper in the Proceedings of the National Academy of Sciences (18) showing reversal of age-associated neuronal atrophy by growth factor gene therapy in aged monkeys, so the ability to generate patient-identical brain cells to carry transgenes into the brain for permanent growth factor therapy of cells that can't be replaced, for example, remains very important in light of this experiment. Perhaps there is no intrinsic need to replace identity-critical cells.
LEF: But what about problems? Are there any smoking guns out there? Are there any red flags that have been raised?
West: The one problem which concerns me to some extent is that there are opponents to this technology. The opponents say that they don't like two major things about the technology. The first is that we use the word "embryo" a lot. The second is that we use the word "cloning" way too much. I think this is more of a battle over words than substance.
ACT researchers can inject new life into old cells.
Photo by Matthew Pace
LEF: It may be that the problem is that the technology has rushed ahead of the lexicon. You may need to invent new, more precise terms to avoid these problems.
West: We have been labeled as part of a "culture of death" that wants to destroy primitive human beings for the benefit of existing human beings. I believe these opponents are people who have not carefully thought through the issues. When I have debated them and discussed the actual data, the science, they don't dispute them. What they do instead is revert to demagoguery. In one example, in a recent debate, one of my opponents referred to one of the movies in the "Raiders of the Lost Ark" trilogy, in which a voodoo priest thrusts his fist into the chest of a living man who is tied to a rack, wrenches from his chest his own beating heart, and holds it in front of his failing eyes as he dies. My opponent then said "Dr. West would say, this is the retrieval of stem cells for a humane and moral medical benefit."
But there is a very large difference between this and extracting cells from a microscopic ball of cells that has not individualized. To anyone who understands the facts, there is no individual and therefore no person or even any differentiated cells of any kind. Second, we are talking about saving lives, alleviating human suffering, allowing fathers to go back to their children and children to go back to their families. I think these technologies will be allowed to move forward, but it doesn't help to have people be demagogues and try to raise specters over "Brave New World" scenarios.
LEF: As soon as one person's life is saved, it will probably become a moot point.
West: It is parallel, in many respects, to the adversarial position many people had in regard to in vitro fertilization. The critics stated that it was a "Brave New World" scenario too. They accused the inventors of in vitro fertilization of "playing God," and said that science had gone too far, and that embryos created in the test tube would not have a soul and would be just hulks of human beings without personality. But when people saw Louise Brown, the dimpled babe in the arms of the smiling mother, I think many people thought, well, look, you know, maybe this technology isn't so bad after all and that, in fact, it's pro family.
LEF: Yes. But there are people who believe that life starts at conception, and that intervening even one cell beyond that is immoral and wrong.
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