Nuclear transfer in the rhesus monkey: opportunities and challenges.

Abstract

CLONING IN PRIMATES is of exceptional importance, and carries ethical, legal, and social implications perhaps even beyond that of cloning in other mammals. This chapter will focus on the cloning of non-human primates. There are two reasons for perfecting cloning in nonhuman primates. First, if reproductive cloning were to generate identical primates (that is, identical study and control groups), biomedical research would be accelerated because fewer primate studies would still produce faster and more accurate preclinical data than at present. The second reason is to learn if embryonic stem cell derivation after nuclear transfer (NT-ESC) can be reliably performed. Needless to say, this latter application might well extrapolate from nonhuman primates to humans. However, that extrapolation carries a weighty burden, since once successful, the technique might be used by practitioners without proper scientific or medical expertise who suggest that nuclear transfer for human reproductive purposes might be appropriate within the next several years or decades. The reasons never to attempt to clone a human have been made clear (Schatten et al., 2003). Unless and until safety questions are fully addressed by demonstrating that primates derived by somatic cell nucleus transfer display normal longevity and completely normal behavior, we adhere to the position that human cloning is unsafe, unethical, and ought to be illegal everywhere on Earth. However, reproductive cloning of nonhuman primates may well accelerate medical research. The rationale behind the study of in-bred mouse strains is that each and every gene is in precisely the same position on each and every chromosome in each and every mouse (except for the sex chromosome differences between males and females). Because all primates are fully diverse, large numbers of nonhuman primates are investigated in preclinical studies, and enormous numbers of patient subjects are enrolled in clinical trials, to ensure that genetic diversity does not confound the ultimate results and interpretations. Consequently, genetically identical nonhuman primates might well permit faster, better, and less expensive investigations— and perhaps most importantly, the use of fewer primates in preclinical research. While rodents are always the ideal mammal for fundamental discoveries, there are many human conditions, diseases, and disorders that cannot be adequately studied in rodents. These include reproductive issues since only Old World primates (monkeys, apes, and humans) have monthly cycles, Y-chromosome deleted regions that cause male infertility (e.g., DAZ, AZF), and the complex neuroendocrine regulations of reproduction. Primates also are unique in their immune fundamentals, lacking the alpha 1,3-galactosyltransferase on the cell surfaces (hence the utility of double-knock-out “humanized” pigs). Also, diseases caused by elongated triplet nucleotide repeats (TNRs)—like Huntington’s and Fragile X—are not yet modeled in rodents. Furthermore, it is important to remember that it is the phenotype that investigators are interested in, not the genotype. Finally, nonhuman primates have the same high