Therapeutic Cloning of Stem Cells   

Stem Cell Therapy
Patient Application
FAQ
Contact
Locations
Our Scientific Articles
News
Videos
Research
Stem Cell Primer
Introduction
What are Stem Cells?
Bank Account Analogy
Key Terms
Types of Stem Cells
Types Compared
History
Regulation
Therapeutic Cloning
Successful Treatments
Regeneration
Conclusions
Glossary
Bibliography
FAQ
 


Therapeutic Cloning: An Unnecessary Risk

Characteristics, and a Comparison with Adult Stem Cell Research

Proponents of therapeutic cloning claim that this technique may offer a new mode of treatment in the repair and regeneration of tissue and organs. Especially in the field of organ transplantation, where immune rejection is common, therapeutic cloning is often seen as a way of eliminating this problem of immune rejection. Critics, however, claim that this view is incorrect, and that immune rejection still exists in therapeutic cloning, along with a myriad of other complexities and problems.

In therapeutic cloning, stem cells are created from a donor for the main purpose of providing tissue (such as for organ repair), in the event that the donor might need such treatment at a future date. The way in which this is done is as follows.

A somatic (adult) cell from the donor is transferred into an enucleated egg (an egg from which the nucleus has been removed), yielding a single celled cloned embryo. When the egg has developed into a blastocyst, the inner cell mass is then removed and cultured into embryonic stem cells, which are grown to produce the desired, healthy, "therapeutic" cells (such as nerve cells, muscle cells, organ tissue, etc.). These new cells are then transplanted back into the patient (who is presumed to be the same as the donor of the original somatic cell, in order to avoid immune rejection).

A single cell, cultured in a dish by itself, will divide to form a population of identical cells, known as cell clones. The resulting cloned embryo is therefore genetically identical to the donor. Until very recently, this characteristic of identical genetic matching has been considered the primary advantage of "therapeutic" cloning. Now, however, there is evidence to prove otherwise.

Other names for therapeutic cloning include Somatic Cell Nuclear Transfer (SCNT, which gave rise to Dolly the sheep), and Cell Replacement through Nuclear Transfer (CRNT). Whichever name is used, therapeutic cloning requires the deliberate creation and disaggregation (destruction, in other words) of a human embryo.

It is possible, however, that the cloning may be used for reproductive purposes instead of for "therapeutic" purposes. For example, from an adult female, the DNA may be removed from a harvested egg (thus "enucleating" the egg). Skin cells may then be removed from an adult male, and the DNA of these cells may be transferred into the nucleus of the woman's unfertilized egg, to produce an early stage embryo with the donor's DNA. From this cloned embryo, human embryonic stem cells (hESCs) may be grown in the laboratory, and then implanted into a surrogate woman who ultimately gives birth to a clone of the man from whom the skin cells were derived. This is how Dolly the sheep was produced. Although "reproductive cloning" and "therapeutic cloning" have different objectives, the means by which they are conducted, and the controversies surrounding such means, are inseparably linked.

According to Dr. Robert Lanza, "It is true that the techniques developed in CRNT research can prepare the way scientifically and technically for efforts at reproductive cloning." (Robert Lanza et al., "The ethical validity of using nuclear transfer in human transplantation", JAMA, 284, 3175 - 3179, 12/27/2000). Needless to say, reproductive cloning is already widely recognized to be an ethical can of worms.

Ethical controversies aside, however, David A. Prentice, Ph.D., of the Department of Life Sciences at Indiana State University, adds that cloning is unsafe both for the clone and for the surrogate mother. He points out that even apparently healthy clones have abnormalities in gene expression. "A review of all the world's cloned animals suggests that every one of them is genetically and physically defective," he says. He also cites Ian Wilmut, who points out that, "There is abundant evidence that cloning can and does go wrong and there is no justification for believing that this will not happen in humans." (Quoted in "Gene defects emerge in all animal clones", Sunday Times of London, 4/28/02).

The success rate of reproductive cloning is extremely low, as 277 nuclear transfers were required to enucleated the eggs from which Dolly the sheep was created. It has been pointed out that even when animals are successfully cloned, every one of them, without exception, suffers from numerous genetic abnormalities. Even Dolly the sheep was "born" with incomplete epigenetic reprogramming (the heritable erasure and remarking of genes that determines either normal or abnormal development). Currently, the highest efficiency rate of SCNT cloning in any species is 7% (with pigs), and in most species the success rate is below 1%. However, even when successful, from 10,000 genes that were analyzed in cloned mice, approximately 400 of these genes were found to express genetic abnormalities.

Dr. Prentice offers some further alarming statistics on the success rates (or the lack thereof) of cloning in animals:

  • Dolly the sheep, the first cloned animal: 1 live birth out of 277 cloned embryos. Success rate = 0.4%.
  • Cloned mice: 5 live births out of 613. Success rate = 0.8%
  • Cloned pigs: 5 live births out of 72 cloned embryos implanted. Success rate = 7%.
  • Cloned goats: 3 live births out of 85 cloned embryos implanted. Success rate = 3.5%.
  • Cloned cattle: 30 live births out of 496 cloned embryos implanted. Success rate = 6%.
  • Cloned cat: 1 live birth out of 188 cloned embryos. Success rate = 0.5%.
  • Cloned gaur: 1 live birth out of 692 cloned embryos. Success rate = 0.1%.
  • Cloned rabbits: 6 live births out of 1852 cloned embryos. Success rate = 0.3%.

One of the risks for the surrogate mother presented by cloning is what is known as "large offspring syndrome", in which the cloned embryo develops into an abnormally, and dangerously, large fetus by the time of birth. But there are also many other ways in which cloning places women at risk. For example, in order to treat all of the 17 million people in the U.S. who suffer from diabetes, Dr. Prentice has made some sobering calculations. Allowing for 10 eggs harvested per donor, and allowing for a generous 20% cloning efficiency to achieve the blastocyst stage, as well as a generous 10% efficiency at initiating the embryonic stem cell culture, a minimum of 850 million eggs would be required, which translates into 85 million women of childbearing age who would be required as donors. This would be more than one-third the population of the United States, who would be needed as egg donors for the treatment of a group of people roughly one-sixteenth as large in population size.

While high dose hormone therapy and surgery have been developed to obtain eggs in large numbers, such techniques nevertheless pose significant health risks by jeopardizing the donor's immediate health and future reproductive success. Additionally, the possibility for commercial exploitation puts economically disadvantaged women in particular jeopardy.

Overall, Dr. Prentice concludes, therapeutic cloning may be judged as unsuccessful. Transplantation remains one of its many problems, and Dr. Prentice cites W.M. Rideout as having stated, "Our results raise the provocative possibility that even genetically matched cells derived by therapeutic cloning may still face barriers to effective transplantation for some disorders." (W.M. Rideout et al., "Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy," an online publication in Cell, 3/8/2002).

It has been proposed by a number of researchers that cloning is not able to provide the claimed medical treatments, and Drs. James Thomson and Alan Trounson add that there is a very low chance of success in the clinical use of therapeutic cloning. (Dr. James Thomson, "Multilineage differentiation from human embryonic stem cell lines", Stem Cells, 2001; Dr. Alan Trounson, "The derivation and potential use of human embryonic stem cells", Reproduction, Fertility and Development, 2001). Additionally, Dr. Irving Weissman of Stanford University, and Dr. John Gearhart have both stated before the President's Council on Bioethics that transplant rejection will still occur, even though the cells from the cloned embryos are considered "genetically identical" to the donor. (Dr. Irving Weissman, 2/13/2002, before the President's Council on Bioethics; Dr. John Gearhart, 4/25/2002, before the President's Council on Bioethics). Dr. Thomas Okarma, CEO of Geron Corporation, has pointed out that cloning is not commercially viable, stating that, "The odds favoring success are vanishingly small, and the costs are daunting. It would take thousands of [human] eggs on an assembly line to produce a custom therapy for a single person. The process is a nonstarter, commercially." (Quoted by Denise Gellene in, "Clone Profit? Unlikely", Los Angeles Times, 5/10/2002). Corroborating such a view, Drs. Odorico, Kaufman and Thomas have written, "The poor availability of human oocytes, the low efficiency of the nuclear transfer procedure, and the long population doubling time of human embryonic stem cells make it difficult to envision this becoming a routine clinical procedure." (Odorico JS, Kaufman DS, Thomson JA, "Multilineage differentiation from human embryonic stem cell lines," Stem Cells, 2001).

Dr. Prentice adds, however, that it is unlikely that large numbers of mature human oocytes would actually be available for the production of embryonic stem cells, particularly if hundreds are required to produce each embryonic stem cell line. "The technical capability for nuclear transfer would also need to be widely available, and this is unlikely," he says. Dr. Alan Trounson adds,

"In addition, epigenetic remnants of the somatic cell used as the nuclear donor can cause major functional problems in development, which must remain a concern for embryonic stem cells derived by nuclear transfer. Although it is possible to customize embryonic stem cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing embryonic stem cells compatible for transplantation." (Alan O. Trounson, "The derivation and potential use of human embryonic stem cells," Reproduction, Fertility and Development, 2001).

As Dr. Irving Weissman of Stanford University stated in his testimony before the President's Council on Bioethics,

"I should say that when you put the nucleus in from a somatic cell, the mitochondria still come from the host. And in mouse studies it is clear that those genetic differences can lead to a mild but certainly effective transplant rejection, and so immunosuppression, mild though it is, will be required for that." (Dr. Irving Weissman, 2/13/02, before the President's Council on Bioethics).

Dr. Alan Trounson, the Australian embryonic stem cell expert and a globally recognized leader in the field, has stated that cloning has now become "unnecessary and obsolete". He says that stem cell research has advanced so rapidly, just in the past few months alone, that therapeutic cloning is now unnecessary. "My view," he states, "is that there are at least three or four other alternatives that are more attractive already." In light of this realization, he has abandoned his own work in therapeutic cloning, turning his attention instead to the more promising field of stem cell research.

Emphasizing the point that therapeutic cloning faces too many "logistical problems," and that other techniques show "greater promise" and offer "better options," Dr. Trounson adds, "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." ("Stem cell cloning not needed, says scientist", The Age [Melbourne], 7/29/2002; "Stem cell research outpaces cloning", The Australian, 7/29/2002; "Therapeutic cloning no longer necessary: expert", AAP Newsfeed, 7/29/2002).

Many experts are now extolling the promise of regenerative medicine through stem cells, instead of through therapeutic cloning. Even the previously assumed multipotency and monopotency of adult stem cells is now being challenged by more recent data, which have demonstrated that some adult stem cells are capable of exhibiting pluripotency. The versatility of adult stem cells is thus much greater than originally thought.

Arguments against human cloning include:

  • There is no evidence that cloning is necessary or useful for medical treatments.

  • Cloning research will divert resources away from other, more worthy areas of research, and delay cures.

  • Banning only implantation (reproductive cloning) is unenforceable.

  • Cloning creates a class of human beings who exist only as a means to achieve the ends of others.

  • Cloning risks the health, safety and possible exploitation of women.

  • Cloning may possibly lead to the commodification and commercialization of human life.

  • Cloning is the "gateway" to genetic manipulation and control of human beings.

Additionally, a report issued in February of 2004 from South Korea highlights the difficult logistics of human cloning. The report describes the first successful attempt to create a hES cell line by SCNT. Researchers at the South Korea Seoul National University, in a study led by Dr. Hwang Woo Suk, were the first to successfully clone a human embryo, for purposes of growing "customized" stem cells for replacement tissue in the treatment of disease. Sixteen (unpaid) women voluneteers had been recruited for participation in the study, and they were then given hormone injections to induce superovulation, which resulted in the production of 242 eggs that were used to produce the single hES cell line. Each volunteer also donated some cells directly from one of her ovaries. From the cumulus cells surrounding the developing oocyte (the immature egg cell), the nuclei were transplanted to the egg of the same individual, using the same process as that used in the cloning of animals. Donor and recipient were therefore the same, presumably eliminating the risk of immunological rejection. However, only one-fourth of the SCNT eggs successfully reached the blastocyst stage (at which point the inner cell mass was harvested to create hES cells), despite the fact that additional chemicals were used to "jump start" the cellular division. From a total of 30 blastocysts, 20 inner cell masses were harvested, but only one ES cell line was successfully obtained. The cells in this ES cell line are genetically identical to the donor, and began forming muscle, bone and other tissues in test tubes and when implanted into mice. The results were published in the U.S. Journal Science.

Citizen's rights activists and bioethicists complained of the lack of transparency surrounding the recruitment of the egg donors, and they raised questions over how rigorously Hwang and his colleagues had followed the ethical guidelines imposed upon their research. A further complication is the fact that it is not yet fully understood how to control the direction of hESC growth, so researchers are still trying to determine the specific types of tissue into which the cells will grow, a goal which continues to remain elusive.

Even Alan Colman, one of the experts on Dolly the sheep, was quoted as saying, "I do not welcome this." Cloned embryos, if transferred into a woman's uterus, could, theoretically, grow into cloned babies. The bioethics of such research has triggered debate among scientists and politicians worldwide.

It was noted, however, that attempts by the South Koreans to clone male cells failed. Even beyond the ethical questions, there still remain concerns that therapeutic cloning is too inefficient and too expensive.

In summary, therapeutic cloning may correctly be viewed as unsafe, unethical, and unnecessary.

The greatest hope for clinical regenerative medicine may therefore be found in postnatal and adult stem cell research.


 
 

Copyright © 2004, 2005, 2006, 2007, 2008 Cell Medicine   Disclaimer   Terms and Conditions   3/19/2024