An astonishing journey into reproductive genetics since the 1950’s

Abstract

-Training in genetics in Edinburgh in the 1950s led to a PhD on the developmental biology of mouse embryos with unusual chromosomal complements. Fundamental aspects of reproduction under study included ovulation induction, oocyte maturation and embryonic growth to blastocysts. It led to the introduction of embryo stem cells, preimplantation genetic diagnosis, the exact timing of human oocyte maturation in vitro and studies on fertilising human eggs in vitro to alleviate human infertility. My work was helped by studies on sperm capacitation and the physiology of fertilization in domestic and laboratory species by Thibault, Dauzier, Austin, Chang, Yanagimachi and others. I met Charles Thibault at a meeting in Cambridge U.K. where he criticised the work of Moricard, and then frequently on lecture circuits. Impressed by his grandeur but not his doubts about human IVF, Steptoe and I initiated human embryo transfers and the birth of Louise Brown. Details of her pregnancy had to be confidential to reduce the risks of abortion associated with the intrusion of numerous newsmen chasing the story. I was compelled to withold this information at a meeting in Paris in the late 1960s when I had to leave early to return to UK. This omission annoyed Thibault and led to our celebrated quarrel. I felt he failed to appreciate the complexity, the implications of this pregnancy and an astonishing future. So much was at stake, including IVF, stem cells and preimplantation diagnosis to help millions of patients. Some months later, our dispute was ended even if somewhat formally. Nevertheless it is a pleasure to recall how we shared so much in common. I still admire him as an inspiration to many colleagues and students, and a father figure in French agricultural research. human / embryo / reproductive genetics / stem cells / in vitro fertilizationI am honoured to be at this meeting to salute the life of Charles Thibault since I knew him over a period of 40 or 50 years. Ours was not an entirely smooth relationship, but I think we both had mutual respect for each other. I also believe we each recognized a worthy opponent or colleague when difficult times arrived. In a sense, although I never formally told him this, it was his work, and that of Chang [1], and of Austin [2], on the capacitation of spermatozoa which set me off on my travels into human IVF.

Virtues and limitations of the preimplantation mouse embryo as a model system

“…Mouse embryos are frequently used in the development of ART that will ultimately be applied to human embryos. Notably, the mouse has played an important role in the development of IVF [33], the development of culture systems [10] and embryo cryopreservation [34], and the reader is referred to these reviews for more detailed discussion of these areas. Mouse embryos continue to play a role in the development of new assisted reproductive techniques; once demonstrated to be safe and effective in the mouse, these techniques can be applied to embryos from other species, a strategy that is recommended but not always followed [35].…”

Robert Edwards: the path to IVF

“…Edwards saw that to understand development involved engaging in an interdisciplinary mix, not just of embryology and reproduction, the conventional view at the time, but also of genetics. Given the scientific and social emphasis on genetics over the last 40 or so years, it is important to understand how advanced this view was in the 1950s, when genetic knowledge was still rudimentary and largely alien to the established developmental and reproductive biologists of the day, as Edwards himself was later to recall (Edwards, 2005). For example, it was in the 1950s that DNA was established as the molecular carrier of genetic information (Watson and Crick, 1953a,b; Franklin and Gosling, 1953; Wilkins et al, 1953), that it was first demonstrated that each cell of the body carried a full set of DNA/genes (Gurdon, 1962a,b; Gurdon et al, 1958) and that genes were selectively expressed as mRNA to generate different cell phenotypes (Weinberg, 2001).…”

“…Paul was then the acknowledged master of tissue culture in the UK and had got wind of some experiments that Edwards had been doing on the side at NIMR attempting to generate stem cells from rabbit embryo cultures (Edwards, 2005). The objective of this strategy was to use these stem cells to study early developmental mechanisms, either in vitro , or in vivo after their incorporation into embryos.…”

“…He had previously visited Cambridge at least once, as ‘a recently graduated PhD’ in the late 1950s for a conference on Reproduction held in Trinity College (Figure 5), where he recalls meeting some of the big names in the subject, including John Hammond, Alan Parkes, MC Chang, Thaddeus Mann, Rene Moricard, Bunny Austin and Charles Thibault (Edwards, 2005). Although Edwards was to remain in Cambridge for the rest of his career, in 1963 his reactions to the place were mixed.…”

Subfertility overview

“…94 Edwards believed this development would be useful in 'certain clinical and scientific uses for human eggs fertilized by this procedure'. In 1969, Robert Edwards and his colleagues reported successful in vitro maturation and fertilization of human oocytes.…”