LE: Let’s consider the merits of telomerase therapy vs. stem cell therapy. After capturing telomerase technology for Geron, you left Geron and went full tilt into stem cell research. Explain why.
MW: If we age because our cells have a built-in clock that controls how many times our cells can divide, and if we are right that the telomere is the clock that triggers this aging, then telomerase would be a key to rewinding that clock, potentially making old cells young. Telomerase could be introduced into the body, essentially making old tissues young, and maybe old people young. There are multiple assumptions involved in each step of this approach but, in the best of all scenarios, if all these things went our way, we would still need one more piece of the puzzle, a means of introducing telomerase into the cells of a human being. I knew by the mid-1990s that this means—gene therapy—a problematic technology. I wasn’t convinced that we were going to be able in the near term to deliver telomerase into the body effectively.
We knew that we could potentially perform telomerase therapy on cells in a cell culture dish, so I began thinking about how we could introduce these cultured cells into the body. Stem cells turn into multiple cell types, and I thought that perhaps we can find very primitive stem cells that could be introduced into the human body where they would spread and interweave themselves into the tissues as rejuvenated cells. As I thought about this tree of cellular life, I came to realize that there must be a human cell at the base of the tree of cellular life that leads to all the cells in the body. It then occurred to me that perhaps we don’t need telomerase at all because the base of the tree of cellular life can also become a sperm or egg cell. Perhaps the embryonic stem cell is a naturally immortal and young cell, the reason that babies are born young, and therefore it might be able to make young cells in a lab dish. That was the genesis of my efforts to isolate the embryonic stem cell.
LE: In the human body, there are cells that divide and cells that don’t divide. Gerontologists usually think the non-dividing cells suffer the most from aging. But, since those cells don’t turn over, how are embryonic stem cells going to be able to replace them?
MW: I believe a telomerase-type therapy may rejuvenate only the proliferative capacity of cells that divide in the body and therefore prevent age-related changes in just those cells. For cells that don’t divide, we believe we can make any desired replacement cell in the body—such as a heart muscle cell or a neuron found in the brain—from embryonic stem cells. The resulting cells should be, as far as we know, truly young. Through transplantation, through various routes of entry, these cells could be introduced back into the body to provide physiological support to the aging person.
I don’t mean to make it sound overly simple, but we can now imagine, through therapeutic clo-ning, a means of repairing or replacing any cell or tissue in the human body. Perhaps it’s not unlike the early 1960s when engineers and scientists believed we had the technology to carry a man to the moon. When we will be able to deliver new therapies to extend the human life span and improve the quality of human life entirely depends on how many hands are put to work on this project and how many hours of research we can do every year. At this point, I’m sorry to report that we’re moving forward at a snail’s pace. But the good news is, momentum is increasing every month, and I’m hopeful that some of the fruits of this technology will be available in our lifetime.
LE: Do you have human embryonic stem cells? You published a scientific paper* showing that you could grow cloned human embryos to a certain stage, but not far enough to obtain human embryonic stem cells. Where do you stand today?
MW: I have presented, in meetings, some progress toward making stem cells from egg cells alone, through a related technology called “parthenogenesis.” We’ve made continual progress in embryonic stem cell technology and feel more optimistic than ever about the relative ease of turning back the clock of aged cells. We think the cellular time machine is a practical means of making young cells available to individuals. I don’t have any doubt of its ability to work. But, again, I would emphasize that to turn this little cellular time machine into a therapy to actually rebuild the aging heart or immune system will require many years of hard work.
LE: Have you had any religious or ethical feedback about using parthenogenesis as an alternative to therapeutic cloning?
MW: Shortly after we published our work on cloned human embryos, we were planning to publish a paper in the journal Science, showing that we had successfully made “parthenotes,” or embryos made by parthe-nogenesis (a word whose roots parthenos and genesis mean “virgin birth” to reflect that only the DNA from the egg cell is involved). My belief was that if religious groups were upset about us cloning human embryos, they would see it as the most flagrant of all insults that scientists had created a “virgin birth” in the laboratory. True, we did it with monkey cells, but the implications for humans were clear.
To my surprise, some of our opponents argued that because parthenotes do not lead to a live birth when they occur naturally in the body, they could not be human beings. They had no objection to the procedure, and actually thought it was a good idea. It goes to show you that religious positions are not as predictable as one would think. Some have even argued that because parthenogenesis is a solution to the problem of making autologous cells—that is, cells identical to the patient’s cells (at least for women)—that we should use parthenogenesis and ban therapeutic cloning. I’ve tried to make the case that, first, we should let all flowers bloom, and second, some of us are men, and we get sick and grow old, too.
LE: Near the end of your book you mention some very exciting coming applications of therapeutic cloning that could rapidly and profoundly modify human aging and even human lifespan. These involve the use of therapeutic cloning to produce primitive bone marrow and endothelial stem cells.
MW: This, I hope, is how we will make some dramatic changes in how we age in our lifetime. Imagine taking a cell from you or me, transporting it back in time to young embryonic stem cells, differentiating them into primitive blood stem cells, and releasing them into the bloodstream to repopulate the blood with young immune cells. Another very pro-mising new possibility is to introduce into the bone marrow cloned young endothelial precursor cells that can then spread throughout our vascular tree to “re-plumb” the cardiovascular system with brand new cells. There’s an old saying, “We’re as old as our arteries,” and some of the most serious complications of aging are related to the cardiovascular system. Even more recent and promising is the possibility that these same cells introduced into the bone marrow could leave the vascular system to actually regenerate damaged heart muscle and skeletal muscle.
Those are the areas we’re now targeting. Our hope is that we may be able, at least to a limited extent, to apply these cellular technologies to create the first substantial intervention in clinical geriatrics, a profound new technology to help people in a meaningful way to combat the ravages of aging.
LE: Since cardiovascular disease is the leading cause of mortality in the aging population, these approaches alone might actually be able to add five or ten years to the human life span, and might eliminate vascular dementias and many strokes on top of that. But you also mention that this same approach might be turned into a way to combat the other major killer disease of aging, cancer.
MW: I believe that if we extend the human life span, we will expand the problem of cancer. Cancer represents chaos at work, and the longer human cells are around, the more prone they are to becoming damaged in a way that leads to the runaway process of cell proliferation we call cancer. One promising application of these technologies in cancer would be to engineer these vascular precursor cells in the bone marrow in such a way that when they are recruited to a growing tumor mass, they carry with them certain genetic mod-ifications that allow us to target them for destruction. This would, in effect, “give a tumor a stroke.”
LE: In the preface of your book, you say, “I believe this book is, in itself, a mere preface to a much larger story still in the making.” What do you see as the next chapter in this story?
MW: I believe that the evolution of human life is proof that life has evolved in the struggle against entropy to form an immortal machine called the immortal cell, the cell that led to you and me, which scientists call the germ-line. What I believe the future holds for medical research is a nearly infinite pipeline of young cells extracted from the immortal, regenerative power of the human germ-line, countless numbers of cells of any kind that could be used to repair the human body from the ravages of age. Equally profound is that with our understanding of DNA, the blue-print of human life, we can now combine the power of these immortal cells with our knowledge of the genome. Meaning that we will be able to turn back the clock of old human cells, and then genetically engineer them in any way desired. Because the immortal cell lasts indefinitely, there is no limit to the number of genetic changes that might be made. These technologies, when all assembled together, present an awesome prospect.
This also could lead to use of the technology that I do not advocate, germ-line genetic engineering. Here I’m making the distinction between somatic cell engineering, which is engineering cells within the body for the benefit of the existing individual, and the cloning of people with genetically engineered cells to make brand-new people with genes designed to enhance those people. This is going beyond trying to help people who are sick, to the engineering of human beings for the purpose of making “super people.” To prove such a technology is safe would take a lifetime of study and become very costly. We’ll be debating such new issues of medical ethics, science, religion and public policy for the next century.
LE: Is there a final message you would like to leave with our readers?
MW: I would encourage readers to think through and study these issues, and if, after due consid-eration, they believe these discoveries can be used to advance medical therapies, to take the time and trouble to write their members of Congress to lend their support to therapeutic cloning and to oppose any ban. There are many people in Congress who would like to vote on our side in this important debate but need to know they have the support of their constituents.
To find your Senators, call the U.S. Capitol switchboard at 1-202-225-3121. To discuss these issues with your Senators, you can be connected to their offices directly. You can also find out how to contact your Senators by logging on to www.senate.gov.
Dr. Michael D. West is CEO of Advanced Cell Technology. In 1990 he founded Geron, the first prominent biotechnology company to focus on human aging, where he served as a director and vice president until 1998.
Dr. Gregory M. Fahy received his Ph.D. in pharmacology from the Medical College of Georgia in 1977 and has worked as a research scientist and research director in the life extension sciences ever since. He is now the Chief Scientific Officer of 21st Century Medicine, a member of the Board of Directors of the American Aging Association, and a member of the Editorial Board of the Journal of Anti-Aging Medicine.
* Cibelli JB, Kiessling AA, Cunniff K, Richards C, Lanza R, West MD. Somatic cell nuclear transfer in humans: pronuclear and early embryonic development. e-biomed: The Journal of Regenerative Medicine 2001 Nov 26; 2: 25-31.