Cloning Robert Streiffer, Ph. D. April 26, 2005

1. CloningRobert Streiffer, Ph. D.April 26, 2005 Department of Philosophy, School of Letters and Sciences Department of Medical History and Bioethics, Medical School Department of Medical Sciences, School of Veterinary Medicine University of Wisconsin, Madison rstreiffer@wisc.edu; http://philosophy.wisc.edu/streiffer/

2. What is cloning? • Cloning is the process of making genetically identical duplicates. • For some time now, we have been able to clone: • DNA: Cloning DNA is called molecular cloning. This is used to produce large quantities of identical DNA for genetic research, genetic testing, and genetic engineering. • Cells: Cloning cells is called cellular cloning. This is used to produce large quantities of identical cells for use in research, testing, and therapy. • Plants: Plants that are clones of one another are said to be of the same “variety.” This is used to reproduce plants with valuable genetic traits. • Animals: Animals can be cloned using embryo twinning, parthenogenesis, or nuclear transplantation.

3. Embryo Twinning • “The technique of dividing and transferring embryos makes it possible to accelerate the rate at which prize livestock can be reproduced and produce genetic twins. These in turn make possible comparative tests, in which one twin is treated with a certain substance and the other serves as a control.”

4. Tetra • In January 2000, researchers at the Oregon Health Sciences University reported that they had produced Tetra. • They took a 8 cell embryo, divided it into 4, 2 cell embryos, and implanted them. • Only Tetra survived.

5. Embryo Twinning In Humans • In 1993, Jerry Hall and Robert Stillman at George Washington University applied this technique to 17 2-cell human embryos that were already genetically abnormal to the point of being unsalvageable. The embryos survived to the 32 cell stage. • Stated aim was to explore whether this technique could be used to increase the success rates of IVF.

6. Nuclear Transfer Cloning • An egg has its nucleus removed and replaced with the nucleus of an embryonic or fetal cell, prior to the cell’s differentiation (viz., prior to its becoming a specialized kind of cell such as a skin cell). • The resulting egg can then be implanted into an animal’s womb and brought to term, with almost all of its DNA derived from the donor. • Most research was done to determine when and how cells shifted from being “totipotent” to being more specialized. Did they lose DNA, or did the DNA remain but gets inactivated? If the latter, could it be reactivated?

7. Nuclear Transfer Cloning • 1952 : Nuclear transfer first demonstrated in frogs. Source of nuclei was a very early frog embryo. • 1956: Nuclear transfer demonstrated in toads. Source of the nuclei was a tadpole. • 1989-90: Nuclear transfer first demonstrated in mammals (rabbits, sheep, cows) by nuclear transfer from very early embryos.

8. Dolly • In 1996, Ian Wilmut cloned Dolly from an adult sheep, demonstrating somatic cell nuclear transfer cloning. • Dolly died when she was 6 years old of a respiratory problem common among sheep.

9. Sexual Reproduction vs. SCNT Source: Genetic Science Learning Center, University of Utah

10. Somatic Cell Nuclear Transfer Source: Advanced Cell Technologies

11. CopyCat • In February 2002, researchers from Texas A & M reported the live birth of a cloned tabby. • Researchers are interested in using cloned cats in AIDS research, since feline AIDS is a good model for human AIDS.

12. Pet Services • Below are Baba Ganoush and Tabouli, both clones of Tahini, created by Genetic Savings & Clone, Inc. • Cost: $50,000. • They say they can even clone a dead animal, so long as they get the relevant tissue sample within five days of the animal’s death. • GSC offer a money-back guarantee for both health and resemblance*. • Plan to start cloning dogs in 2005.

13. Noah • Researchers at Advanced Cell Technologies reported that they had cloned Noah, a baby bull guar. • Guars are endangered species, and Noah was gestated inside of a cow. • Noah was born alive, but died within 48 hours of dysentery. ACT denied that the death was related to the cloning procedure itself.

14. Nuclear Transfer Piglet Clones • Research on producing pigs using nuclear transfer. Required between 115-164 transfers per arm to produce 4 healthy cloned piglet and 5 additional pregnancies Researcher say that the techniques “should allow the use of genetic modification procedures to produce tissues and organs from cloned pigs with reduced immunogenicity for use in xenotransplantation.”

15. SCNT in Humans • On February 12, 2004, Science Magazine published a report by South Korean scientists, led by Woo Suk Hwang and Shin Yong Moon. • The report indicated that they had successfully completed “the derivation of a pluripotent embryonic stem cell line (SCNT-hES-1) from a cloned human blastocyst.” • So, they successfully cloned a human being, and then derived human embryonic stem cells from the resulting embryo.

16. More Details about Hwang and Moon’s Work • Used 16 female volunteers for eggs. The volunteers were put through an informed consent process, and they received no payment. • Retrieved 242 oocytes (immature eggs) by hyper-stimulating the volunteers with hormones and then extracting the oocytes using microsurgery. • 176 of those oocytes had DNA inserted into them, where the DNA had been removed from cumulus cells from the egg donor herself, and put in culture. This is called “somatic cell nuclear transfer (SCNT). • 30 of those oocytes reached the blastocyst stage. • 20 inner cell masses were derived from those 30 oocytes • From those inner cell masses, they were able to establish 1 human embryonic stem cell line. http://www.sciencemag.org/cgi/content/abstract/1094515

17. SCNT in Primates • In October 2004, Gerald Schattan of the University of Pittsburgh, Pennsylvania, reported that he had used the improved techniques developed by Hwang and Moon to clone monkeys. • He transferred the cloned embryos into female monkeys, but none of them survived more than a month. • Nonetheless, this is the closest anyone has come to cloning an adult primate.

18. Therapeutic vs. Reproductive Cloning Source: “Stem Cells: A Primer,” NIH

19. TherapeuticCloning

20. Applications of Therapeutic Cloning • Would allow the production of embryos with specific genetic traits for us in research on that trait. • Would allow the production of embryos from which stem cells could be derived. Those stem cells would be immunologically compatible with the donor of the nucleus.

21. Ethical Issues with Therapeutic Cloning • Requires destroying an embryo (no different from deriving new HES cell lines in this respect). • Requires creating an embryo with the intent of destroying it for someone else’s benefit. • Separates fertilization from reproductive intent.

22. Potential Applications of Reproductive Cloning • Would allow infertile parents to have a child that is genetically related to one of them • Would allow a couple in which one partner has a dominant genetically transmitted disease to have a child genetically related to one of them without risk of the disease’s being transmitted • Would allow a person to make a delayed twin from whom compatible organs or tissues could be obtained for transplantation (c.f., Nashes, Ayala) • Would allow people to clone someone special, e.g., a child who had died • Would allow the cloning of people of great talents

23. Pro: Rights • The Right to Reproductive Freedom: Includes the right to use assisted reproductive technologies without interference by the government or others when made available by a willing provider

24. Pro: Individual Benefits • Human cloning would provide a new means to relieve the infertility some persons now experience. • Human cloning would enable couples in which one party risks transmitting a serious hereditary disease to an offspring to reproduce without doing so. • Human cloning would enable a later twin to obtain needed organs or tissues for transplantation . • Human cloning would enable individuals to clone someone who had special meaning to them.

25. Pro: Social Benefits • Human cloning would enable the duplication of individuals with exemplary qualities. • Human cloning and research on human cloning might make possible important advances in scientific and medical knowledge.

26. Con: Rights • The right to have a unique identity • The right to an open future (or to ignorance about one’s future)

27. Con: Individual Harms • Human cloning would produce psychological distress and harm to the later twin. • Human cloning procedures would carry unacceptable safety risks to the clone. • 0.1 percent to 3 percent success rate • Accumulation of genetic mutations • Large offspring syndrome

28. Mice Fetus • The pup and placenta on the left display normal growth. The pup and placenta on the right was derived by nuclear transfer of ES cells, and displays common overgrowth phenotype seen in cloned mice. This animal did not survive.

29. Cloned Lamb • The lamb on the left is a clone, and is abnormally large. Researcher suspect it is due not to a defect in the DNA itself, but rather in the imprinting of genes, the marking of genes so that expression patterns of the maternal and paternal genes differ.

30. Con: Social Harms • Human cloning would lessen the worth of individuals and diminish respect for human life. • Human cloning might be used by commercial interests for financial gain. • Human cloning might be used by governments or other groups for immoral or exploitative purposes.

31. The Legislative Situation in the U.S. • Ban all cloning (e.g., the Brownback Amendment): • (1) HUMAN CLONING - The term `human cloning' means human asexual reproduction, accomplished by introducing nuclear material from one or more human somatic cells into a fertilized or unfertilized oocyte whose nuclear material has been removed or inactivated so as to produce a living organism (at any stage of development) that is genetically virtually identical to an existing or previously existing human organism

32. The Legislative Situation in the U.S. • (a) IN GENERAL - It shall be unlawful for any person or entity, public or private, in or affecting interstate commerce, knowingly-- • (1) to perform or attempt to perform human cloning; • (2) to participate in an attempt to perform human cloning; • (3) to ship or receive for any purpose an embryo produced by human cloning or any product derived from such embryo. • (b) IMPORTATION - It shall be unlawful for any person or entity, public or private, knowingly to import for any purpose an embryo produced by human cloning, or any product derived from such embryo. • (c) PENALTIES – up to 10 years imprisonment, between $1,000,000 and twice any gross financial gains

33. The Legislative Situation in the U.S. • Ban only reproductive cloning (e.g., Senator Specter): • (1) HUMAN CLONING - The term `human cloning' means implanting or attempting to implant the product of nuclear transplantation into a uterus or the functional equivalent of a uterus.

34. President Bush to the Senate • “Allowing cloning would be taking a significant step towards a society in which human beings are grown for spare body parts, and children are engineered to custom specifications; and that’s not acceptable.” • “Research cloning would contradict the most fundamental principle of medical ethics, that no human life should be exploited or extinguished for the benefit of another.” • “Yet a law permitting research cloning, while forbidding the birth of a cloned child, would require the destruction of nascent human life.” • “Anything other than a total ban on human cloning would be virtually impossible to enforce.” • Therapeutic cloning “would create a massive national market for eggs and egg donors, and exploitation of women’s bodies that we cannot and must not allow.”

35. The FDA • The FDA, which has jurisdiction over all biologics used to treat medical conditions, has asserted jurisdiction over reproductive cloning, and has said that it is illegal to try to attempt it at the present time.

36. The United Nations November 18, 2004 United Nations (AP)In a victory for advocates of stem cell research, U.N. diplomats on Thursday gave up trying to craft a treaty to outlaw human cloning, and will probably settle for a less powerful document that won't seek a worldwide ban, officials said.Member nations had been split between two treaty proposals for a year. One group, led by the United States, sought to ban all human cloning, while the other, led by European countries, wanted to ban reproductive cloning but allow cloning for research.In the end, both sides realized they wouldn't get enough support for a treaty to achieve worldwide ratification, said Marc Pecsteen, a Belgian diplomat in the thick of the talks. Instead, they were leaning toward a nonbinding declaration that would include language ambiguous enough to please both sides.

37. Kass: The Wisdom of Repugnance • Even if we cannot fully articulate satisfactory reasons for thinking that cloning is wrong, the emotional reaction we feel when we contemplate it is sufficient to know that it is wrong (17-19). • Moreover, the fact that it is wrong provides us with sufficient justification for a political ban on reproductive cloning (50-51) • And it will probably justify a ban on therapeutic cloning as well, since the only way to have an effective ban on reproductive cloning is to ban therapeutic cloning also (53).

38. Kass: Objections • “Any attempt to clone a human being would constitute an unethical experiment upon the resulting child-to-be.” (31-33) • “Cloning creates serious issues of identity and individuality.” (33-38), and these issues are not undermined by the falsity of genetic determinism (34-36) • “Human cloning would also represent a giant step towards turning begetting into making, procreation into manufacture (literally, something “handmade”), a process already begun with in vitro fertilization and genetic testing of embryos,” (38-40) and this arrangement is “profoundly dehumanizing” (39) • Cloning “would enshrine and aggravate a profound and mischievous misunderstanding of the meaning of having children and of the parent-child relationship.” (40-42)

39. Tribe: Response to Kass • Kass proposes to ban human cloning on the grounds that it is “incompatible with what the opponent of [cloning] deems the essence of human nature or of the human condition,” (226) • Such a justification “takes the form of an irreducible appeal to human nature, whether or not divinely ordained, as the normative source of the case for legal prohibition.” (227). • “[S]uch arguments would almost invariably rest on, and if acted upon would reinforce, the notion that it is unnatural, and intrinsically wrong, to sever the conventional links between heterosexual unions sanctified by tradition and the creation and upbringing of new life”

40. Tribe: Response to Kass • The cost of justifying a ban on such grounds “is the very considerable one of creating a class of potential outcasts—persons whose very existence the society has chosen, through its legal system, to label as a misfortune and, in essence, to condemn.” (229) • And this is “not costless for lesbians, gay men, persons gay or straight with genetically transmittable diseases, and others whose sexual or other orientations or capacities draw them into unconventional patterns of intimate relationship—and unconventional modes of linking erotic attachment, romantic attachment, genetic replication, gestational mothering, and the joys and responsibilities of parenting.” (231)

41. A “Savior Sibling” Case Study • From Jeff Kahn, head of Center for Bioethics at the University of Minnesota • What is pre-implantation genetic diagnosis (PGD)? • Create embryos using in-vitro fertilization (IVF) • Biopsy at the 8-cell stage (blastocyst), ~2-3 days • Remove one cell, leaving the rest intact • Perform genetic tests on DNA from the single cell

42. Fanconi Anemia • Recessive genetic disease • 2 carriers (heterozygous) mate, offspring: • ¼ = unaffected • ½ = unaffected carrier • ¼ = affected • Affected children • Limb deformities • Mildly reduced IQ • Leukemia by 6-7 years old • Require hematopoetic stem cell transplant to survive (bone marrow or umbilical cord blood) • Stem cell donors must be HLA (Human Lymphocyte Antigen) matched • Sibs, other family members, pools of adult donors, cord blood banks

43. Nash Case Background • Molly (6 yo) affected by Fanconi Anemia (FA) • Nashes hope to have more (unaffected) children • Consider natural conception followed by prenatal testing; then learn of PGD • Seek IVF in Denver, and PGD in Chicago • 2 stage PGD: FA -; HLA matched to Molly • 5 cycles to get 1 matched embryo • Adam born early August 2000 (Denver) • Cord blood flown to Univ. of Minn; stem cell transplant late Sept. 2000 + 100 days • Molly and family return to Denver Jan. 2001

44. The Nashes

45. Do Characteristics Chosen Matter? • Does it matter that PDG was done to avoid a child carrying a disease • Does the disease matter? • Does it matter that PDG was also done in this case to select for a non-disease trait (HLA compatibility) • And does it matter that it was a trait that was selected for the benefit of someone else? • What if it were physical or behavioral characteristics?

46. Does Parental Motivation matter? • Why do people have children? • Intrinsic value • Carry on legacy • Siblings for other children • By accident • Tax deduction • More hands to work the farm • Are there wrong reasons? • Is saving a sick child’s life a good reason, a bad reason, or a reason of the wrong kind?

47. Immanuel Kant • A Kantian Prohibition on treating others merely as a means would rule out: • PGD, use cord blood, put baby up for adoption • PGD, abortion at 21+ weeks, harvest cells from tissue • Bearing a child for his or her vital organs.