egg to generate a zygote. The zygote (from here onwards also called an embryo) divides into two and then four identical cells. At this stage, the cells can be separated and allowed to develop into separate but identical blastocysts, which can then be implanted in a uterus. The limited developmental potential of the cells means that the procedure cannot be repeated, so embryo splitting can yield only two identical mice and probably no more than four identical humans.

The DNA in embryo splitting is contributed by germ cells from two individuals—the mother who contributed the egg and the father who contributed the sperm. Thus, the embryos, like those formed naturally or by standard IVF, have two parents. Their mitochondrial DNA is identical. Because this method of cloning is identical with the natural formation of monozygotic twins and, in rare cases, even quadruplets, it is not discussed in detail in this report.

Even if clones are genetically identical with one another, they will not be identical in physical or behavioral characteristics, because DNA is not the only determinant of these characteristics. A pair of clones will experience different environments and nutritional inputs while in the uterus, and they would be expected to be subject to different inputs from their parents, society, and life experience as they grow up. If clones derived from identical nuclear donors and identical mitocondrial donors are born at different times, as is the case when an adult is the donor of the somatic cell nucleus, the environmental and nutritional differences would be expected to be more pronounced than for monozygotic (identical) twins. And even monozygotic twins are not fully identical genetically or epigenetically because mutations, stochastic developmental variations, and varied imprinting effects (parent-specific chemical marks on the DNA) make different contributions to each twin [3; 4].

Additional differences may occur in clones that do not have identical mitochondria. Such clones arise if one individual contributes the nucleus and another the egg—or if nuclei from a single individual are transferred to eggs from multiple donors. The differences might be expected to show up in parts of the body that have high demands for energy—such as muscle, heart, eye, and brain—or in body systems that use mitochondrial control over cell death to determine cell numbers [5; 6].

Cloning of livestock [1] is a means of replicating an existing favorable combination of traits, such as efficient growth and high milk production,

Front Matter (R1-R22)

Executive Summary (1-18)

1. Introduction (19-23)

2. Cloning: Definitions and Applications (24-38)

3. Animal Cloning (39-60)

4. Assisted Reproductive Technology (61-73)

5. Human Reproductive Cloning: Proposed Activities and Regulatory Context (74-91)

6. Findings and Recommendations (92-100)

Appendix A: Panel and Staff Biographical Information (101-110)

Appendix B: Animal Reproductive Cloning Data Tables on Reproductive Cloning Efficiency and Defects (111-143)

Appendix C: Workshop Agenda and Speaker Biographical Information (144-153)

Appendix D: Bibliography (154-258)

Appendix E: Glossary (259-272)