Cloning: Techniques and Applications in Human Health (2000)

Since 1997, when scientists revealed that they had cloned a sheep, Dolly, cloning, the creation of a fully developed, essentially identical twin animal from a cell of a donor individual, has attracted huge interest from academic, industrial, medical, political, and religious sectors. Since what is possible for sheep has also proven possible for other large animals, there have been intense debates on the ethical and legal issues related to the prospect of cloning humans. This review focuses on how cloning is accomplished in mammals and the variety of possible applications of cloning, with an emphasis on uses related to human health. WHY DOLLYMANIA? Dolly caused such a fuss because she was a fully developed animal cloned from a body cell of an adult mammal. There were lambs, Megan and Morag, cloned a year before Dolly, but they came from embryonic cells (Campbell et al., I996) and created nothing akin to the worldwide Dollymania that arose after announcement of Dolly's birth by scientists at the Roslin Institute in Edinburgh, Scotland, and their colleagues at the related biopharmaceutical company, PPL. Dolly was not just a mammal like usshe came from an adult cell (Wilmut et al.,1997). Dolly told us that it is probably possible to clone anyone, including a human, regardless of age, even if the person is dead-as long as a living cell can be found. Scientists and laypeople alike were unsettled. Scientists were unsettled because they had long thought that earlier cloning successes were related to the unusual regenerative capacity of amphibian and embryonic cells. The birth of Dolly turned this notion upside down and opened a whole new area of scientific research with important new applications for the benefit of humankind. However, laypeople and scientists alike also were unsettled because the issues related to mammalian cloning, especially human cloning, had not been carefully thought out, and there were essentially no guidelines. The following pages provide a brief introduction of the technology of cloning and an overview of its potential applications in science and medicine. HOW TO CLONE AN ANIMAL Cloning Megan, Morag, and then Dolly was accomplished by transfer, a technique similar to that used in cloning tadpoles in the 1970s. Nuclear transfer can be summarized in a sentence: Insert a donor cell or its genetic material into an unfertilized egg (oocyte) from which the genetic material has been removed, activate it, then place the embryo into a surrogate mother for development to term. However, the procedure is actually a complex one that is confounded by the idiosyncrasies of reproduction in different species. Dolly's birth is a tribute to a long line of biologists who have been studying the details of embryonic development for a century and exploring cloning for nearly half of that time. The essential elements of the nuclear transfer technique developed and successfully employed by Ian Wilmut, Keith Campbell, and their colleagues (Wilmut et al., i997; Campbell et al.,1996) are illustrated in Figure r. The figure legend provides some additional detail related to individual steps, and slight variations on this method have been described, but the basic technique has now been used to clone a variety of different mammalian species, including mice (Wakayama et al., 1998), goats (Baguisi et al., 1999), and cattle (Kubota et al., 2000). The original experiment in sheep was relatively inefficient. Dolly was a 1-in-277 success story: Of 277 reconstructed oocytes, 29 embryos apparently developed properly, but only one (approximately 3 percent of transferred embryos) led to a live birth. However, the procedure in other species such as mice and cows is more efficient, with approximately 20 to 30 percent of reconstructed embryos developing to live animals (Wakayama et al., 1998; Kubota et al., 2000). This frequency of success is not much different from that for in vitro fertilization of oocytes with sperm or conventional mating. …