mammals, including humans, and at the present time, we do not know whether attempts at human cloning would reveal fewer, more, or different abnormalities.

FINDINGS

3-1. In general, the efficiency of reproductive cloning in animals remains extremely low despite several years of experimentation.

3-2. Animal cloning results in a wide variety of abnormalities, including greater than normal size (both during gestation and after birth), greater early- and late-gestation fetal morbidity and mortality, greater postnatal mortality, and various developmental defects in the immune, cardiovascular, and possibly nervous systems. (Subtle behavioral and mental defects might be undetectable in animal models.) In addition to the risks inherent in the overproduction of oocytes from egg donors, increased maternal morbidity and mortality are to be expected.

3-3. The most likely reasons for the abnormalities are failures in reprogramming in the adult nucleus used for reproductive cloning, so that it fails to turn on all the appropriate embryo-specific genes at the right times, and errors in imprinting.

3-4. Before human reproductive cloning is feasible, a great deal more research is necessary, including studies of cloning in nonhuman primates. Research focused on gaining an understanding of all aspects of reprogramming and imprinting, determining which steps in the reproductive cloning technique contribute to the overall low efficiency, and determining how these problems can be overcome would be most useful.

REFERENCES

1. SOLTER D. Mammalian cloning: advances and limitations. Nat Rev Genet 2000 Dec, 1(3):199-207.

2. LEWIS IM, MUNSIE MJ, FRENCH AJ, DANIELS R, TROUNSON AO. The cloning cycle: From amphibia to mammals and back. Reprod Med Rev 2001, 9(1):3-33.

3. WILMUT I, SCHNIEKE AE, MCWHIR J, KIND AJ, CAMPBELL KH. Viable offspring derived from fetal and adult mammalian cells. Nature 1997 Feb 27, 385(6619):810-3.

4. SCHNIEKE AE, KIND AJ, RITCHIE WA, MYCOCK K, SCOTT AR, RITCHIE M, WILMUT I, COLMAN A, CAMPBELL KH. Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 1997 Dec 19, 278(5346):2130-3.

5. MCCREATH KJ, HOWCROFT J, CAMPBELL KH, COLMAN A, SCHNIEKE AE, KIND AJ. Production of gene-targeted sheep by nuclear transfer from cultured somatic cells. Nature 2000 Jun 29, 405(6790):1066-9.



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