Lessons from reproductive technology research.

A plethora of assisted reproductive technologies (ARTs) have come into routine use over the past half century. Some of these procedures were used much earlier experimentally. For example, Spallanzani performed artificial insemination in the dog in the late 1700s, and Heape did successful embryo transfer in the rabbit in 1890. Truly revolutionary tools and concepts important for ART occur at approximately half-decade intervals, for example, recombinant DNA procedures, transgenic technology, somatic cell nuclear transplantation, the polymerase chain reaction, and microRNAs. Similarly, obvious technologies sometimes take decades to come into practical use, such as sexing sperm and in vitro fertilization. I have categorized ARTs into five somewhat arbitrary categories in terms of perceived difficulty and feasibility: (a) when the seemingly possible turns out to be (essentially) impossible, e.g., homozygous, uniparental females; (b) when the seemingly impossible becomes possible, e.g., cryopreservation of embryos and transgenesis; (c) when the seemingly difficult turns out to be relatively easy, e.g., cryopreservation of sperm; (d) when the seemingly easy turns out to be difficult in key species, e.g., in vitro fertilization; and (e) when the seemingly difficult remains difficult, e.g., making true embryonic stem cells. The adage that "it is easy when you know how" applies repeatedly. The boundaries between what appears impossible/possible and difficult/easy change constantly owing to new tools and insights, one of the more important lessons learned. ARTs frequently are synergistic with each other. For example, somatic cell nuclear transplantation has made many kinds of experiments feasible that otherwise were impractical. Another example is that sexing sperm is useless for application without artificial insemination or in vitro fertilization. ARTs frequently are perceived as neat tricks and stimulate further thinking. This is useful for both teaching and research.