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Conquering Aging with Cloning
(page 4 of 4)
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Bovine fibroblast cells extracted from cow cartilage - Photo by Matthew Pace |
West: There is nothing in the Bible that you could bring as evidence that life begins with a fertilized egg. It is more an aesthetic preference, the sense that life should begin with a compassionate and loving act of making love, not with some stranger inserting a sperm head through the zona pelucida into an oocyte (egg cell) under a microscope and culturing in a CO2 incubator.
What I think we need to do as a society is to grow up. We are living in an age where it is in our power to do good, to alleviate human suffering, and we need to be mature and use our discoveries to make the world a better place.
LEF: A lot of people have been conceived from rapes, so even when it is done in the "natural" way, it isn't always a product of love.
West: Fair enough. You know, I think the ultimate act of love here is recognizing and responding to the needs of the thousands of people who need kidneys, livers or hearts, yet all too often are left to die while waiting for such tissues.
The Bible says, "to him that knows to do good and does it not, to him it is sin." I don't mean to be necessarily referring to the Bible as my authority, but I think it is important that if we know how to do something good, that we do it and that we do it quickly. One of the criticisms that was made is that the NIH has been proactive, and Health and Human Services and the President have been supportive, but that NIH hasn't actually spent the money to move embryonic stem cell research forward because of pro-life opposition. Every day that goes by, there are more people dying. We published a letter in Science advocating that funding move forward on this technology, and we had some 60 Nobel Prize winners signing that letter (19).
LEF: Well, even if the government doesn't support it, it is moving forward anyway. You are moving forward with it, and other companies are moving forward with it.
West: Yes, the private sector is moving, but you know, Advanced Cell Technology has only a couple of dozen people, and there are hundreds of cell types in the body, so we literally need thousands of researchers working on these new technologies, not dozens.
LEF: You said the President has been supportive, but the President was also somewhat alarmed by your announcement in 1998 that you or your colleagues had transferred a human cell nucleus into the enucleated egg cell of a cow. People were very worried about crossing the line between species and so forth. In fact, with therapeutic human cloning to treat aging, getting the donor cell is not a problem, but the recipient cell, the egg cell, has to be obtained somewhere, and getting it from human beings may be difficult. What is your plan to deal with that? Are you contemplating using bovine egg cells for therapeutic human cloning and, if so, are there mitochondrial or other problems or other problems that you would be concerned about?
West: We share, I think, the present concern about mixing DNA across species. There have been reports over the last few years of the transfer of whole human chromosomes into animals such as mice, and there are, I think, ethical concerns about what kind of life forms we might create. What we are talking about doing in cloning across species, with human cells and cow egg cells, is not mixing species. The President simply misinterpreted the discussion. The New York Times article he read talked about "minotaurs and mermaids," but what we are proposing is different. Rather than getting human egg cells, which as you point out they are to obtain, we propose using cow egg cells, which are widely available from slaughter houses at a dollar or two per egg, and removing the genetic information from the cow's egg cell, so that we put a human cell into it, we would provide the genetic information from the human nuclear DNA and mitochondrial DNA, which would then completely transform the resulting cells into human cells. We do not believe that any animal DNA would remain, either mitochondrial or nuclear.
LEF: You think that the original mitochondria from the cow would die off?
West: Yes, we do.
LEF: Because they wouldn't have sufficient genetic support from the human nuclear and mitochondrial genes to keep going?
West: Exactly.
LEF: So part of the beauty of injecting an entire cell into the egg of the cow is that all of the human mitochondria go along.
West: Yes. As far as the cow egg cell proteins are concerned. As you know, protein does not make one a cow. Drinking cow's milk does not make you a cow. DNA, the blueprint of life, confers those characteristics, and we're not talking about mixing DNA across species. That was the debate of the 1970s, the recombinant DNA debate, where scientists actually put a moratorium on their own research, because they were mixing, in a very profound way, DNA across species. Those concerns have been addressed, and recombinant DNA is now routine. I think you would be hard pressed to find examples where that technology has done harm, but you can find thousands of examples where recombinant DNA technology has saved lives.
LEF: Can you project a credible timetable for advances in this field? Please also address the issue of what is the best way of accelerating this timetable.
West: The easiest products of cloning are simply cloned animals. Improving the genetics of agricultural animals, cloning search and rescue dogs with improved genetic traits, and so forth.
LEF: What about human therapeutic cloning?
West: On the human therapeutic front, it is likely that the early products are going again to be human therapeutic protein drugs made in cloned transgenic animals. We are now making human medicines in the milk of cloned and genetically engineered cows for instance, such as human serum albumin.
LEF: Is that the main current business of ACT?
West: It's part of our near-term business. Human therapeutic cloning is clearly a long-term project. I think the earliest clinical trials of human cells made by human therapeutic cloning are likely 5-10 years from now at the earliest.
LEF: What are the main bottlenecks? Manpower?
West: Certainly. The major determinant of where we'll be five years from now or ten years from now, really will be a matter of how many people can be put to work on the project.
LEF: You mentioned that Advanced Cell Technology is a very small company. What plans do you have to get investment capital to speed the rate at which your company can proceed in this direction?
West: The first step toward that took place in December of last year, 1999, when we acquired Advanced Cell Technology from its parent, Avian Farms, in Waterville, Maine. We acquired Advanced Cell Technology in a new holding company, called ACT Group, so that we could pursue private financing for the company according to the more traditional model with private rounds of funding, leading to an IPO. For now, ACT remains a privately held company.
LEF: In order for these technologies to be applied in humans, you are going to have to get them through Human Subjects Committees, and you are going to have to have physicians who are willing to infuse the cells into their patients. Can you anticipate what the concerns might be on the part of the physicians?
West: Well, one of the concerns about using an animal egg cell is that we are introducing a potential source of contamination into the equation.
LEF: You mean xenoviruses (viruses transmitted from non-humans to humans) or something like that?
West: Yes. That's one of our reasons for exploring the use of the bovine oocyte, because cows can be cloned so easily by us. It will be possible, we believe, to make oocytes from a herd of genetically identical cloned cows to be used in therapy. Then, at least, we would know, in a very precise manner, the background from which these cells came. I think that would be one of the major concerns. I guess the second concern would likely be dealing with undifferentiated, totipotent cells. Because these cells can become anything, a few of them contaminating the graft could have a rather disastrous effect. You know these cells will self-assemble even into things like teeth, whole teeth. A friend of mine once said that it certainly wouldn't be good if you were transplanting cardiocytes into a heart and a tooth developed in the heart wall, because then the patient would "eat his heart out."
LEF: That's too much!
West: As I said earlier, these are issues of engineering, and we believe there are straightforward means of addressing the issues of potential animal viruses and/or contaminating cells entering the equation. We know how to address those issues.
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ACT's laboratory, where pioneering work to develop cloning techniques to combat aging and disease continues.
Photo by Matthew Pace |
LEF: Will therapeutic cloning be expensive?
West: We have a real concern about two issues: cost and having time to treat the patient. Cost is one of the reasons we are looking for an alternate source for the egg cells. The nuclear transfer procedure is actually not that labor-intensive, and the cost of materials is small, but the egg cell expense potentially could be large if you had to use human egg cells.
LEF: Right.
West: The second issue is the time to treat the patient. This procedure requires time. The nuclear transfer to create the stem cells will take a couple of weeks. The creation of specialized cells and tissues will take about seven additional weeks. So what we envision for chronic long-term disease, such as Parkinson's Disease, heart failure, kidney failure, and so on, is plenty time to create cells and tissues to help the patient.
LEF: Right, they are not going to die suddenly in the middle of the preparation process.
West: But when it comes to acute conditions, it's a different story. For example, with skin burns the patients come in and need immediate treatment. In the future we will likely have cells taken from people and reprogrammed, back to a totipotent state as well as young differentiated cells and tissues kept frozen in waiting for sudden trauma needs.
LEF: So, for example, if somebody is planning ahead, they might have the therapeutic human cloning process begun, let's say, when they are 50, so that when they are 75 have a sudden heart attack, or their doctor tells them they are in danger of a sudden heart attack, they'll have a young healthy copy of their own heart sitting in a bank some place waiting for them (20).
West: I think that's likely where we will be headed in the future. We do that now with things that matter far less to us, like our car. We have parts in waiting. We have a spare tire in the trunk.
LEF: We sure do. Meanwhile, we'll be waiting for news of more progress in this field. Congratulations on your major accomplishment, and thank you for a very informative interview.
References
1. Lanza, R.P., Cibelli, J.B., Blackwell, C., et al., Telomere restoration and extension of cell lifespan in animals cloned from senescent somatic cells, Science, April 28, 2000.
2. Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., and Campbell, K.H.S., Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810-813, 1997.
3. Pennisi, E., Breakthrough of the year, the lamb that roared, Science 278, 2038-2039, 1997.
4. Lanza, R.P., Cibelli, J.B., and West, M.D. Prospects for the use of nuclear transfer in human transplantation, Nature Biotechnology, 17: 1171-1174, 1999.
5. Lanza, R.P., Cibelli, J.B., and West, M.D. Human therapeutic cloning, Nature Medicine, 5:975?977, 1999.
6. Colman, A., and Kind, A. Therapeutic cloning: concepts and practicalities. Trends Biotechnol. 18: 192-196, 2000.
7. Stice, S.L., Robl, J.M., Ponce de Leon, F.A., et al., Cloning: New breakthroughs leading to commercial opportunities, Theriogenology, 49:129?138, 1998.
8. Zawada, W.M., Cibelli, J.B., Choi, P.K., et al., Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats, Nature Medicine, 4: 569?574, 1998.
9. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., et al., Embryonic stem cell lines derived from human blastocysts, Science 282: 1145-1147, 1998.
10. Shamblott, M.J., Axelman, J., Wang, S., et al., Derivation of pluripotent stem cells from cultured human primordial germ cells, Proc. Nat'l. Acad. Sci. USA 95: 13726-13731, 1998.
11. Cornelius, J.G., Tchernev, V., Kao, K.J., and Peck, A.B., In vitro-generation of islets in long-term cultures of pluripotent stem cells from adult mouse pancreas. Horm. Metab. Res. 29: 271-277, 1997.
12. Ramiya, V.K., Maraist, M., Arfors, K.E., Schatz, D.A., Peck, A.B., and Cornelius, J.G., Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nature Medicine 6: 278-282, 2000.
13. Shiels, P.G., Kind, A.J., Campbell, K.H., Waddington, D., Wilmut, I., Colman, A., and Schnieke, A.E., Analysis of telomere lengths in cloned sheep. Nature 27: 316-317, 1999.
14. Cibelli, J.B., Stice, S.L., Golueke, P.J., et al. Cloned transgenic calves produced from nonquiescent fetal fibroblasts, Science, 280:1256?1258, 1998.
15. Stice, S.L., Cibelli, J., Robl, J., Golueke, P., Ponce de Leon, F.A., Jerry, D.J., Cloning using donor nuclei from proliferating somatic cells, U.S. Patent 5,945,577, issued August 31, 1999.
16. Pittenger, M.F., Mackay, A.M., Beck, S.C., et al., Multilineage potential of adult human mesenchymal stem cells, Science 284: 143-147, 1999.
17. Horwitz, E.M., Prockop, D.J., Fitzpatrick, L.A., et al., Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine 5: 309-313, 1999.
18. Smith, D.E., Roberts, J., Gage, F.H., and Tuszynski, M.H., Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy. Proc. Nat'l. Acad. Sci. USA 96: 10893-10898, 1999.
19. Lanza, R.P., Arrow, K.J., Baltimore, D., et al. (73 scientists, 67 of them Nobel laureates), Science over politics, Science 283: 1849?50, 1999; see also Editor's note on page 1850.
20. Fahy, G.M. Organ cryopreservation. In: Advances in Anti-Aging Medicine, Vol. 1 (R.M. Klatz, Ed.), Mary Ann Liebert, New York, 1996, pp. 249-255.
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