Practical Obstacles to "Therapeutic" Cloning
The idea of cloning human embryos for biomedical research (called by some "therapeutic cloning"), besides posing very grave moral problems, has become increasingly questionable on purely scientific grounds. Sample quotes from scientific sources:
"An academic panel investigating South Korean stem cell scientist Hwang Woo Suk concluded... that the embattled researcher's fraudulent experiments reach back further than previously known and encompass the most seminal of his so-called successes: the first creation of stem cells from cloned human embryos.
"The new determination that the results of those experiments were largely falsified and that Hwang never obtained stem cells from cloned embryos discredits what had appeared to be one of the biggest scientific breakthroughs of the decade. The deception means that the highly touted field of embryonic stem cell research is years behind where scientists thought it was."
A. Faiola and R. Weiss, "South Korean Panel Debunks Scientist's Stem Cell Claims," Washington Post, January 10, 2006, A9. http://www.washingtonpost.com/wp-dyn/content/article/2006/01/09/AR2006010901943.html
* * *
"Dr. Hwang Woo Suk, the South Korean researcher who claimed to have cloned human cells, fabricated evidence for all of that research, according to a report released today by a Seoul National University panel investigating his work....
"The Seoul panel said Dr. Hwang had accomplished only the first steps toward creating embryonic stem cell lines from people, and had failed to create any successful line, despite the many resources at his disposal. Those included skilled technicians and a bountiful supply of human eggs -- as many as 2,061 eggs from 129 women, an extraordinary number, given the pain and difficulty of extracting eggs from their donors....
"In practical terms... the panel's new finding is a sharp setback for therapeutic cloning, the much discussed goal of converting a patient's own cells into new tissue to treat a wide variety of degenerative diseases from diabetes to heart disease. The technique for cloning human cells, which seemed to have been achieved since March 2004, now turns out not to exist at all, forcing cloning researchers back to square one."
-N. Wade and C. Sang-Hun, "Human Cloning Was All Faked, Koreans Report," New York Times, January 10, 2006, A12. http://query.nytimes.com/gst/fullpage.html?sec=health&res=9904E3DF163FF933A25752C0A9609C8B63
* * *
"Scientists are surveying the wreckage left by the debacle involving stem-cell researcher Woo Suk Hwang after three co-authors on his landmark paper said that it could not be trusted. Researchers now face a long slog to rebuild the foundations of their field...
"[T]he complete loss of confidence in Hwang's work has set the field back by years. It has also taken away what seemed to be firm confirmation of the feasibility of using cloning to produce patient-matched stem cells.
"'We thought a fundamental question had been answered,' says Alison Murdoch of the University of Newcastle Upon Tyne, UK. 'Hwang's results shifted the research focus on to emulating his work. Now we may need to look again at that fundamental step.'....
"'We're back to knowing that animal cloning is possible but wondering whether it is possible in humans,' adds Kevin Eggan of Harvard University in Cambridge, Massachusetts. 'This is an enormous setback.'"
--Erica Check, "Where now for stem-cell cloners? Problems with landmark paper may set field back by years," Nature, (December 20, 2005), http://www.nature.com/news/2005/051219/pf/4381058a_pf.html
* * *
"Therapeutic cloning, also known as somatic cell nuclear transfer, will not be the route to successful stem-cell therapies, many scientists say. In fact, if therapeutic cloning were vital, it would make stem-cell therapies prohibitively expensive....
"'The value of nuclear transfer is not for cell therapy, it's to do molecular research to f igure out how genetic disease is manifest,' said Tom Okarma, CEO of Geron, a biotech company in Menlo Park, California, that has studied stem cells since 1995. 'When you inject nuclear transfer, (stem-cell therapy) becomes a dead end.'...
"'Not only would it be expensive, but logistically it could be impossible because you will have to have every single hospital in the world set up to do therapeutic cloning and prepared to do the different protocols,' said Jose Cibelli, a cloning researcher at Michigan State University in East Lansing.
"While immune rejection is a big hurdle for stem-cell therapies, excluding therapeutic cloning as the solution is a bit of a weight off researchers' shoulders. It means therapeutic cloning bans...might not throw a wrench in California's stem-cell initiative (or other states' plans), at least when it comes to deriving stem-cell therapies."
- Kristen Philipkoski, "Costly Cloning Isn't a Cure-All," Wired News (December 1, 2004), www.wired.com/news/medtech/0,1286,65883,00.html.
* * *
"A dose of reality needs to be injected into the excitement surrounding therapeutic cloning, senior stem-cell biologists have warned.
"Researchers fear that optimism generated by recent advances, including the award on 11 August of the first UK licence for research on the technique, has raised expectations of individualized cures for degenerative diseases. In reality, say those in the field, such a prospect remains distant at best....
"[T]he scientific hurdles that remain are immense. Cloning is tremendously inefficient, for example. When researchers at Seoul National University in South Korea produced the world's first human embryonic stem-cell line from a cloned embryo in February, they got through 242 eggs from 16 women. Until that success rate is improved, cures or treatments from therapeutic cloning will be impossible."
- J. Knight, "Biologists fear cloning hype will undermine stem-cell research," in 430 Nature (19 August 2004), p. 817.
* * *
Scottish cloning expert Ian Wilmut, on why cells from cloned human embryos are likely to be unnecessary for diseases of the central nervous system and useless for juvenile diabetes:
"In any treatment regime we must avoid immunological rejection of the transferred cells, but the immune response is likely to vary from one disease to another... [I]n the treatment of diseases within the central nervous system cells from cloned embryos seem likely to offer less advantage as fetal cells in the central nervous system appear not to be subject to rejection. Finally, several of the conditions that are mentioned as candidates for cell therapy are autoimmune diseases, including type 1 diabetes. In such cases transfer of immunologically identical cells to a patient is expected to induce the same rejection."
- I. Wilmut, "Human cells from cloned embryos in research and therapy," in 328 British Medical Journal (21 February 2004), pp. 415-6.
* * *
"The expression of several (imprinted and nonimprinted) genes differs substantially in cloned animals compared with conventionally bred counterparts.....
"Our conclusions have several implications for biotechnology. First, cells obtained by 'therapeutic cloning' will probably have the same life span as normal cells but may have abnormal gene expression caused by epigenetic errors."
- J. Fulka et al., "Do cloned mammals skip a reprogramming step?", 22 Nature Biotechnology (January 2004), pp. 25-6.
* * *
Twenty ethicists and scientists who strongly favor embryonic stem cell research, on why they have concluded that cloning by somatic cell nuclear transfer(SCNT) is "not practical at present" as a solution to the tissue rejection problem or the problem of access to cell therapies:
"Although SCNT might, in theory, solve the rejection-biological access problem, it can do so only one person at a time. The amount of time and money needed to create these uniquely cloned solutions makes it unlikely that SCNT will provide a practical, widespead solution to the biological access problem. Additionally, for the foreseeable future, research in this area will continue to be overshadowed by political and moral controversy."
- R. Faden et al., "Public Stem Cell Banks: Considerations of Justice in Stem Cell Research and Therapy," in Hastins Center Report, November-December 2003, pp.13-27 at p.15.
* * *
"Optimistically, --100 human oocytes would be required to generate customized ntES cell [nuclear transfer embryonic stem cell] lines for a single individual....human oocytes must be harvested from superovulated volunteers, who are reimbursed for their participation. Add to this the complexity of the clinical procedure, and the cost of a human oocyte is --$1,000-2,000 in the U.S. Thus, to generate a set of customized ntES cell lines for an individual, the budget for the human oocyte material alone would be --$100,000-200,000. This is a prohibitively high sum that will impede the widespread application of this technology in its present form....
"In the long run, efforts should be concentrated toward developing oocyte-independent systems... A major benefit of the complete elimination of oocytes and embryos from the concept of therapeutic cloning is that the ethical debate would vaporize instantaneously. In this way, scientific progress may provide a solution to ethical concerns."
- P. Mombaerts, "Therapeutic cloning in the mouse," 100 Proceedings of the National Academy of Sciences (September 30, 2003), pp. 11924-11925 at p. 11925, http://www.pnas.org/cgi/reprint/100/suppl_1/11924.pdf
* * *
The president and CEO of the world's leading biotechnology company in embryonic stem cell research, replying to a question about the impact of a possible ban on human cloning for research:
"The efficiency of making a stem cell line from an embryo made by nuclear transfer [cloning] is vanishingly small, and you're going back to the case-by-case, individualized-therapy story again, with enormous costs. The whole idea is to make this therapy internationally available, broadly. Nuclear-transfer procedures just are never going to get us there."
- Thomas Okarma, President and CEO of the Geron Corporation, quoted in E. Jonietz, "Cloning, Stem Cells, and Medicine's Future," Technology Review, June 2003, pp. 70-71 at p. 70.
* * *
"For all the handwringing by scientists, you might think that therapeutic cloning is on the verge of curing a disease or two. But that is not the case.... Despite optimistic statements about curing diseases, almost all researchers, when questioned, confess that such accomplishments are more dream than reality...
"As it turns out, cloning is not even the first hurdle. Scientists often find it impossible even to extract and grow stem cells from a normal human blastocyst. 'Forget cloning, just to get human stem cells is not trivial,' Dr. Schultz said. 'They are difficult to generate and difficult to maintain.'...
"What about animal research? Can scientists take embryonic stem cells from mouse blastocysts, for example, and use them to cure diseases in mice? Not yet. ...
"It will take years and much federal money, many predict, before therapeutic cloning has a chance of succeeding. For now, Dr. Schultz said, the promise is all in the distant future."
- G. Kolata, "The Promise of Therapeutic Cloning," The New York Times, January 5, 2003, section 4, p. 7.
* * *
"The majority of cloned animals derived by nuclear transfer from somatic cell nuclei develop to the blastocyst stage but die after implantation. ... [W]e posited that cloned embryos derived from differentiated cell nuclei fail to establish a population of truly pluripotent embryonic cells because of faulty reactivation of key embryonic genes such as Oct4. ... When expression of Oct4 and 10 Oct4-related genes was analyzed in individual cumulus cell-derived cloned blastocysts, only 62% correctly expressed all tested genes."
- A. Bortvin et al., "Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei," 130 Development (2003), p. 1673.
* * *
"Leading stem-cell researcher Alan Trounson has abandoned his call for therapeutic cloning, saying scientific breakthroughs mean there is now no need for the controversial technique. ...
"Professor Trounson told The Age that the pace of change was so rapid in stem-cell technology that therapeutic cloning was now unnecessary.
"'My view is there are at least three or four other alternatives that are more attractive already,' he said....
"Professor Trounson said therapeutic cloning faced logistical problems, including the difficulty of obtaining large numbers of donor eggs and the fact the stem cells would be useful only to the donor, making the process time-consuming and expensive.
"New techniques, including those being developed in Australia, Britain and Japan, offered better options.
"'We know that the egg can reprogram a skin cell, for example,' Professor Trounson said....
"'I can't see why, then, you would argue for therapeutic cloning in the long term because it is so difficult to get eggs and you've got this issue of (destroying) embryos as well.'"
- T. Noble, "Stem-cell cloning not needed, says scientist," The Age (Australia), July 29, 2002, www.theage.com.au/text/articles/2002/07/28/1027818485322.htm
* * *
"Importantly, irrespective of the donor cell, clones display common abnormalities such as foetal and placental overgrowth. Indeed, gene expression analyses and extensive phenotypic characterization of cloned animals suggest that most, if not all, clones suffer from at least subtle abnormalities."
- K. Hochedlinger and R. Jaenisch, "Nuclear transplantation: lessons from frogs and mice," 14 Current Opinion in Cell Biology (2002), p. 741.
* * *
"Enthusiasm for therapeutic cloning was initially high. ...So to the casual observer, it may come as a surprise that many experts do not now expect therapeutic cloning to have a large clinical impact. Aside from problems with the supply of human egg cells, and ethical objections to any therapy that requires the destruction of human embryos, many researchers have come to doubt whether therapeutic cloning will ever be efficient enough to be commercially viable. 'It would be astronomically expensive,' says James Thomson of the University of Wisconsin in Madison, who led the team that first isolated ES [embryonic stem] cells from human blastocysts....
"Therapeutic cloning is almost certainly possible. ...But despite feverish efforts by groups world-wide, progress has been disappointing. ...
"Peter Mountford, chief scientific officer of Stem Cell Sciences, believes these problems can be overcome, and argues that it is too early to give up on therapeutic cloning – but his has become a minority view....
"Enthusiasm for therapeutic cloning may have dimmed, but regenerative medicine is still a hotbed of activity..."
- P. Aldhous, "Can they rebuild us?", 410 Nature (5 April 2001), pp. 622-5.
* * *
Discouraging words from the University of Wisconsin team led by Dr. James Thomson, the first researcher to isolate and culture human embryonic stem [ES] cells:
"Clearly...the generation of human embryos by nuclear reprogramming to create novel human ES cell lines would be exceptionally controversial. Furthermore, the poor availability of human oocytes, the low efficiency of the nuclear transfer procedure, and the long population-doubling time of human ES cells make it difficult to envision this becoming a routine clinical procedure even if ethical considerations were not a significant point of contention. By studying how oocyte cytoplasm mediates nuclear reprogramming in these animal models, it might be likely that nuclear reprogramming could be achieved by other methods, thereby obviating the need for human oocytes."
- J. Odorico et al., "Multilineage Differentiation from Human Embryonic Stem Cell Lines," 19 Stem Cells (2001), pp. 193-204 at p. 201.
February 23, 2006