Reproductive Cloning - Harms to the Mother and Harms to the Clone

A human clone can't be created by methods available today. The process of cloning mice is now fairly well-established. African wildcats have been successfully cloned by Dr. Betsy Dresser, Director of the Audubon Center for Research of Endangered Species. Research on primate cloning, done at the Oregon National Primate Research Center, has led to the creation of cloned rhesus monkey embryos. The results were reported in November 2007 in Nature, and described the derivation of embryonic stem cells from the cloned blastocysts. This was a significant breakthrough in the field of reproductive medicine. Yet work on cloning itself has not proceeded any further than the ability to produce cloned early embryos in rhesus monkeys.

The practical challenges to human reproductive cloning are huge. Additionally, of course, there are formidable ethical challenges. On the practical side, all the potential obstacles relate to the fact that cloned embryos are not the same as embryos created by sexual reproduction. These latter "standard" embryos are the products of two haploid sets of chromosomes. Millions of years of evolutionary refinement have developed the processes by which an embryo is formed. Embryos created by somatic cell nuclear transfer (SCNT) break this process. At present cloned embryos are created by brute force. SCNT in its initial iteration used a jolt of electricity to fuse the injected donor nucleus with the cytoplasm of its enucleated egg host. Researchers are now using more refined methods - involving various chemical cocktails - to cause the two disparate components to fuse and begin the process of development.

The list of developmental processes that are broken by SCNT is long. Embryologic development involves deep and complex events. The circumstances may be relatively well understood, but the biochemical mechanisms are at best poorly described and at worst completely unknown. For example, the processes by which the egg cytoplasm reprograms the sperm DNA's set of epigenetic marks are completely unknown. In cloning the egg cytoplasm must reprogram a diploid set of chromosomes, twice as many as the haploid number contained in the sperm. Also, somatic chromosomes contain epigenetic marks that vary significantly from those of sperm chromosomes. The sperm's configuration has been modified extensively during the process of sperm production, i.e., gametogenesis. The effects on the developing embryo of these several contrasts in epigenetic management are completely unknown at present.

Privately funded researchers, imagining themselves to be free of ethical constraints, might push ahead and force the issue without waiting for new findings to emerge from legitimate science. The consequences for the mother-to-be, gestating a cloned embryo in her womb, could be disastrous, even fatal. If a live birth is obtained, that child's health could be at risk for his entire life.

David Lemberg, M.S. in Bioethics, Albany Medical College, May 2010
Consultant, Author, Speaker. Research interests - health care and health care policy, reproductive technologies, genetics and genomics, K-12 science education
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Reproductive Cloning - Benefit Or Curse?

The announcement in February 1997 of the birth of Dolly the sheep (1) startled the scientific world and shocked the public. Dolly was a clone - a complete genetic copy of her parent. Cloning a mammal from an adult cell had always been thought impossible. There had been speculation regarding the possibility of reprogramming an adult cell from its differentiated state to a primitive state of totipotency. But this seemed more the realm of science fiction than science.

There was a great outcry from many public sectors, including religious figures, ethicists, and politicians. Many people believed that cloning humans would be the final outrageous outcome of the very slippery slope created by the advent of Dolly, who in fact was a friendly, mild-mannered sheep. Many religious leaders believed that human cloning would be an abomination and cloning itself should be outlawed. The debate over cloning persists and is very much in the news.

The notion of human cloning immediately brings to mind well-known works of literature and film. In the dystopia of Aldous Huxley's Brave New World clones are created in vats and used to populate all segments of society. In the 2005 film The Island human clones are created to supply spare parts for wealthy individuals. The clones are fully functioning adults with hopes, wishes, and dreams. But they have no rights and are killed when needed by their respective hosts. The masses of soldiers in Star Wars represent the archetype of everything that is bad about clones. These clones are produced in huge quantities, apparently have no wills of their own, and are used for political purposes and warfare. The Star Wars Clone Wars are the fevered nightmare of opponents to human cloning.

But reproductive cloning could provide a profound benefit to families and individuals. In the United States at least 8% of women have had a medical office visit related to infertility. (2) More than 2 million men in the U.S. have been diagnosed with male infertility. More than 100,000 in vitro fertilization procedures are done in the U.S. each year. Many of these procedures are done with donated eggs and/or donated sperm.

Reproductive cloning would allow a couple to have a child genetically related to both parents. For example, the father would provide the cell to be cloned. The mother would provide the egg which would be fertilized with the nucleus of the father's reprogrammed cell. Similarly, reproductive cloning would allow single-sex couples to have a child genetically related to one or both partners, depending on the circumstances.

Clinical reproductive cloning will not be available, if ever, for many years. Much research needs to be done. The ethical, legal, and social questions regarding reproductive cloning are profound. As a society we need to continue to debate the issues and explore possibilities and alternatives. We need to do these things in advance of scientific developments.

(1) Wilmut I, et al: Viable offspring derived from fetal and adult mammalian cells. Nature 385:810-813, 1997

(2) CDC

David Lemberg, M.S. in Bioethics, Albany Medical College, May 2010
Consultant, Author, Speaker. Research interests - health care and health care policy, reproductive technologies, genetics and genomics, K-12 science education
Executive Producer, SCIENCE AND SOCIETY, http://scienceandsociety.net
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Beneficence - The Bioethics of Human Cloning

Human cloning (HC) could provide great benefit to families and individuals who have lost the hope of ever having children to whom they have a genetic bond. HC could also substantially benefit those who have lost loved ones through disease or accident. Also, HC could provide cures for those suffering an incurable disease. Thus, there is considerable ethical justification for going forward with research in this contentious field.

HC could make it possible for infertile couples to have genetically related children in a wide set of circumstances. Many solutions already exist for couples who are able to provide neither viable sperm nor viable eggs. These couples may choose from a range of assisted reproductive technologies and sperm/egg donor options. But the children who are born via current methods of have no genetic connection to either parent.

With human cloning, sperm are not necessary and eggs do not need to be capable of fertilization by a sperm. Adult somatic cells (usually skin cells) serve as sperm substitutes. The nucleus is removed from the adult somatic cell and injected into an enucleated egg. The egg is manipulated by physical or chemical means to launch its fertilization program. Embryo creation occurs in the laboratory, bypassing defective physiologic systems of the mother, father, or both which have caused fertilization and development to fail in the past.

HC can result in the birth of a child who is genetically related to the mother and/or the father for couples who are both infertile. If both members of a male same-sex couple are infertile, HC would enable the birth of a child who is genetically related to one father. If both members of a female same-sex couple are infertile, HC would make it possible for them to have a child who is genetically related to both parents. HC significantly expands the capability of assisted reproductive techniques.

Additionally with the availability of HC, tragic circumstances can be mitigated to a certain extent. If a child is fatally killed in a car crash or dies after sustaining a head injury in football or ice hockey, parents would be able to clone the child using DNA from a somatic cell. The new child would not necessarily be identical to the deceased child in terms of personality, interests, and abilities, but he would be a genetic copy and that fact might ameliorate a great deal of the parents' pain and suffering.

A third scenario involves cloning a child with a potentially fatal disease. The clone would be a histocompatible match and be able to provide replacement tissue for her older sibling.

In these diverse situations HC would confer substantial, lifelong benefits to all parties involved in the rearing of a child who is a clone. The parents, the child herself, extended family, friends, and the community all would all benefit from this breakthrough technology.

David Lemberg, M.S. in Bioethics, Albany Medical College, May 2010
Consultant, Author, Speaker. Research interests - health care and health care policy, reproductive technologies, genetics and genomics, K-12 science education
Executive Producer, SCIENCE AND SOCIETY, http://scienceandsociety.net
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Cloning - New Threat to the Human Race?

Is a clone an example of the species that was cloned? Or does the clone represent a new species, one very similar to the original but different nonetheless? As we've learned during the last 25 years, subtle distinctions in the genome are responsible for substantial variation. For example, the similarity between the human genome and the mouse genome is approximately 85%. The human genome and the chimpanzee genome share 98% commonality. The genome of Home sapiens sapiens - the current version of human beings - and the genome of Homo neanderthalensis have only a 0.5% difference in structure. But no one would mistake a 2010 resident of New York City, Johannesburg, or Hong Kong for a Neanderthal man.

Complex systems are critically sensitive to small changes in initial conditions. This deep concept, encapsulated by the descriptive "butterfly effect", was made famous by Michael Crichton's character Dr. Ian Malcolm in Jurassic Park. As he explains chaos theory to Dr. Ellie Sattler, a paleobotanist, Malcolm notes that a butterfly flapping its wings in the Amazon rain forest can cause a tornado in the American Midwest. The butterfly effect is a key component of most, if not all, physiologic processes.

It is notoriously difficult to predict the exact manner in which a complex system will respond to a specific small change in initial conditions. For example, turning on one specific gene - a small change, in the context of the 20,000 or so genes in human DNA - may cause a cell to overdo its job, underperform, die, or become cancerous. Any of these states may result in local pathology, a low level of disease, chronic disease, or death of the individual.

The field of embryology and development involves deeply complex systems. The mechanisms of development are beginning to be understood after 100 years of investigation. In embryology, cells respond to chemical signals generated by processes occurring in other locations. Their responses affect activities elsewhere. Many of these processes are random, based on molecular interactions, and if too much randomness is present normal development will fail. For example, small perturbations can disturb the process and result in the death of the developing embryo, as evidenced by the fact that up to 75% of embryos fail to mature successfully.

Cloning, achieved by somatic cell nuclear transfer, effects substantial alterations in the process of reproduction. The vast majority of these alterations are unknown and their effects can only be guessed at. Any single alteration could cause profound changes in the physiology of any clone that survived the mechanisms of development. But many changes in initial conditions are introduced during cloning, not only one. The clone may walk and talk like a human and we may believe she is human, but the true nature of the cloned organism will only be revealed over time. It is not guaranteed that a human-appearing clone will turn out to be human at all.

David Lemberg, M.S. in Bioethics, Albany Medical College, May 2010

Consultant, Author, Speaker. Research interests - health care and health care policy, reproductive technologies, genetics and genomics, K-12 science education.

Executive Producer, SCIENCE AND SOCIETY, http://scienceandsociety.net.

Twitter - http://twitter.com/david_lemberg.

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