Genetic modification of animals through cross breeding and selection has probably been practiced since wild animals were first domesticated, but became more intensive beginning ~200 years ago with the creation of defined breeds with specialised phenotypes. This generality applies both to agriculturally important species, such as chickens and cattle, and to companion animals, such as cats and dogs. It also applies to plants. In the 20th century, new technologies designed to improve agricultural productivity, perhaps best illustrated by the development of artificial insemination and sperm cryopreservation for the dairy industry, as well as improved nutrition and veterinary care, all fueled by generous government support of agricultural research, accelerated progress towards providing low-cost, safe, and nutritious food for a burgeoning world population. Progress in some cases has been quite remarkable, especially in milk and meat production. The report by Palmiter, Brinster and colleagues in 1982, that mice harboring a transgene for growth hormone under the control of a metallothionein gene promoter grew faster than control siblings, raised the spectre of using relatively simple, one-step gene insertions, rather than cross-breeding and selection, to improve the production of milk, meat, and fibre, and enhance animal health quickly and directly. Although agronomy and horticulture have been able to benefit greatly from applying genetic modification to plants, there has been only very slow application of transgenesis to animal agriculture and aquaculture. The main goal of my talk will be to illustrate some of the difficulties, both scientific and social, that have been encountered in bringing genetic modification and related technologies, such as cloning, into mainstream agriculture. I shall also discuss the competitive advantage held by rodents over alternative animal models in biomedical sciences but argue that the latter still have an important role to play in this regard. A final topic will be to review the potential value of pluripotent stem cells for introducing genetic change in domestic species and for testing the efficacy and safety of grafts derived from pluripotent stem cells before human clinical trials.
An episomal DNA vector platform for the persistent genetic modification of pluripotent stem cells and their differentiated progeny
