Transgenic animals: a new era in developmental biology and medicine.

In the relatively short period since its development, the technique for the production of transgenic animals by pronuclear microinjection, as established by Gordon et al. (1980), has resulted in studies that have clearly had a profound effect on our basic understanding of mammalian development and genetics, and upon our outlook for genetic engineering. The question now is: What remains to be done? Clearly, a greater understanding of the mechanism of integration could lead to more efficient transfer of genes and lessen the problem of rearrangement of host DNA. A better characterization of enhancers and their mode(s) of action would allow design of molecules with highly specific patterns of gene expression, as well as novel distributions of expression. When these goals are met, it may well become scientifically feasible to transfer genes into the human germline. Whether such an undertaking is advisable or even desirable is an issue requiring open discussion, but it is an issue that is clearly distinct from the question of technical feasibility. The most rational approach to this profound question lies in the continued pursuit of knowledge relating to transgenic technology, rather than self-imposed ignorance. Even if never used as a medical therapy, transfer of genes into the germline will reveal what is certainly one of nature's greatest secrets: the nature of the interaction of genes in the development of a multicellular eukaryotic organism. Through the contributions to this volume and in the years ahead, we will find ourselves in a position to unravel the details of the awesome and fascinating phenomenon that is mammalian development.