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8	National Academy of Sciences, Guidelines for Human Embryonic Stem Cell Research (2005), p. 29
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13	"Clone - 1" Clone - 1) An exact genetic replica of a DNA molecule, cell, tissue, organ, or entire plant or animal. 2) An organism that has the same nuclear genome as another organism. Cloning - The production of a clone. (For the purpose of this report, generating an individual animal or person that derives its nuclear genes from a diploid cell taken from an embryo, fetus, or born individual of the same species.) Embryo - A group of cells arising from the egg that has the potential to develop into a complete organism. In medical terms, embryo usually refers to the developing human from fertilization (the zygote stage) until the end of the eighth week of gestation when the beginnings of the major organ systems have been established. Scientific and Medical Aspects of Human Reproductive Cloning (2002), p. 261-262. "While use of the term embryo can be polarizing, it can also promote clarity, even where some feel it has too great a political, emotional or social "charge." Thus, for the purposes of this report, we have chosen to use the term cloned embryo to describe the product of nuclear transplantation." ... For purposes of this workshop, the term "reproductive cloning" will refer to human cloning (i.e., nuclear transplantation) for the purpose of initiating a pregnancy and producing a baby. The term "research cloning" will refer to human cloning for the purpose of conducting biomedical research on stem cell derived from cloned embryos." Regulating Human Cloning, A report on the workshop held March 11, 2003, by the American Association for the Advancement of Science. p. 4, p. 11-12
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17	"Clones may need to be..." Clones may need to be gestated to “harvest” already-differentiated tissues R Lanza et al.; “Generation of histocompatible tissue using nuclear transplantation,” Nature Biotechnology 20, 689-696; July 2002 R Lanza et al., “Regeneration of the infarcted heart with stem cells derived by nuclear transplantation,” Circulation Research 94, 820-827, April 2004 *R Lanza et al., “Long-term bovine hematopoietic engraftment with clone-derived stem cells”, Cloning and Stem Cells 7, 95-106, July 2005
18	"Clones may need to be..." Clones may need to be gestated to “harvest”already-differentiated tissues R Lanza et al.; “Generation of histocompatible tissue using nuclear transplantation,” Nature Biotechnology 20, 689-696; July 2002 R Lanza et al., “Regeneration of the infarcted heart with stem cells derived by nuclear transplantation,” Circulation Research 94, 820-827, April 2004 *R Lanza et al., “Long-term bovine hematopoietic engraftment with clone-derived stem cells”, Cloning and Stem Cells 7, 95-106, July 2005
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23	"“Therapeutic cloning”—unlikely..." “Therapeutic cloning”—unlikely chance of clinical success “[T]he 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 [therapeutic cloning] becoming a routine clinical procedure…” Odorico JS, Kaufman DS, Thomson JA, “Multilineage differentiation from human embryonic stem cell lines,” Stem Cells 19, 193-204; 2001 “However, it is unlikely that large numbers of mature human oocytes would be available for the production of ES cells, particularly if hundreds are required to produce each ES line. The technical capability for nuclear transfer would also need to be widely available and this is unlikely. 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 ES cells derived by nuclear transfer. …it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation.” Alan O.Trounson, “The derivation and potential use of human embryonic stem cells”, Reproduction, Fertility, and Development 13, 523-532; 2001 Thomas Okarma, CEO, Geron Corporation says: “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.” Denise Gellene, “Clone Profit? Unlikely”, Los Angeles Times, 10 May 2002
24	"Transplant rejection still likely using..." Transplant rejection still likely using cells from cloned embryos “Robert Lanza, chief scientist at Advanced Cell Technology in Worcester, Mass., an ardent advocate for both embryonic stem cell studies and therapeutic cloning, agreed that in the course of the political debate, the need for cloning to overcome immune system rejection has been overstated. ‘It’s not all or nothing. You can move ahead.’” San Francisco Chronicle, Monday, March 18, 2002 Page E – 1 “There is no question in my mind that the possibility exists that if you are doing an egg donor, and nuclear transfer into an egg, that there possibly exists that that cell -- that the embryonic stem cells derived from that could be rejected. Absolutely.” Dr. John Gearhart, Johns Hopkins, 25 April 2002 meeting of 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.” He concluded, “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, Stanford, 13 February 2002 meeting of the President’s Council on Bioethics
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30	"Promises" Promises, Premises, and Published Data… Claims thus far unsubstantiated for embryonic stem cells Current or potential embryonic stem cell problems: Difficult to establish and maintain Difficulty in obtaining pure cultures in the dish Potential for tumor formation and tissue destruction Questions regarding functional differentiation Hansson M et al., “Artifactual insulin release from differentiated embryonic stem cells”, Diabetes 53, 2603-2609, October 2004 Sipione S et al., “Insulin expressing cells from differentiated embryonic stem cells are not beta cells”, Diabetologia 47, 499-508, 2004 (published online 14 Feb 2004) Rajagopal J et al.; “Insulin staining of ES cell progeny from insulin uptake”; Science 299, 363; 17 Jan 2003 Zhang YM et al.; “Stem cell-derived cardiomyocytes demonstrate arrhythmic potential”; Circulation 106, 1294-1299; 3 September 2002 Problem of immune rejection Swijnenburg R-J et al., Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium, Circulation 112, I-166-I-172, 30 August 2005 Genomic instability Maitra A et al., Genomic alterations in cultured human embryonic stem cells, Nature Genetics online 4 Sept 2005 Cowan CA et al., “Derivation of embryonic stem-cell lines from human blastocysts”, New England Journal of Medicine 350, 1353-1356, 25 March 2004 Draper JS et al., “Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells”, Nature Biotechnology 22, 53-54; January 2004 *Humpherys D et al.; “Epigenetic instability in ES cells and cloned mice”; Science 293, 95-97; 6 July 2001 Few and modest results in animals, no clinical treatments Ethically contentious
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34	"Current Clinical Trials of Adult..." Current Clinical Trials of Adult Stem Cells Cancers—Lymphomas, multiple myeloma, leukemias, breast cancer, neuroblastoma, renal cell carcinoma, ovarian cancer Autoimmune diseases—multiple sclerosis, systemic lupus, rheumatoid arthritis, scleroderma, scleromyxedema, Crohn’s disease Anemias (incl. sickle cell anemia) Immunodeficiencies—including human gene therapy Bone/cartilage deformities—children with osteogenesis imperfecta Corneal scarring-generation of new corneas to restore sight Stroke—neural cell implants in clinical trials Repairing cardiac tissue after heart attack—bone marrow or muscle stem cells from patient Parkinson’s—retinal stem cells, patient’s own neural stem cells, injected growth factors Growth of new blood vessels—e.g., preventing gangrene Gastrointestinal epithelia—regenerate damaged ulcerous tissue Skin—grafts grown from hair follicle stem cells, after plucking a few hairs from patient Wound healing—bone marrow stem cells stimulated skin healing Spinal cord injury—clinical trials currently in Portugal, Italy, S. Korea Liver failure—clinical trials in U.K.
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