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The bumpy road to human in vitro fertilization

Nature Medicine volume 7, pages 1091–1094 (2001)Cite this article

My first ideas of human in vitro fertilization (IVF) arose with my PhD in Edinburgh University in the early 1950s. Supervised by Alan Beatty, my research was based on his work on altering chromosomal complements in mouse embryos. All went very well, as haploid, triploid, tetraploid and more-bizarre embryos emerged1, and I learned about mouse meiosis, fertilization, embryos, blastocysts and chromosomes as well as immense amounts of reproductive physiology. The arrival of Alan Gates in Edinburgh relieved my midnight labors. Also working with Alan Beatty, he brought the Organon preparations of gonadotrophins which induced immature mice to ovulate many eggs and mate with adult males. Transfer of their embryos to adult mice produced fully normal offspring in huge numbers.

Science in Edinburgh was incredibly fruitful. Another PhD student, Ruth Fowler (later my wife), and I decided to test these Organon hormones on adult mice. They again induced estrus and timed oocyte maturation, with erratic numbers of ovulated oocytes, fertilization, cleavage, implantation and fetal growth to full term2. Julio Sirlin and I3 applied radioactive tracers to spermatogenesis, oogenesis and embryology, labeling DNA, RNA and proteins. My professor, Conrad Waddington, discussed ethics and genetics with senior churchmen, which proved invaluable for me, as ethics would feature immensely in my future work on human conception. After a year at the California Institute of Technology with Albert Tyler, a welcome from Alan Parkes and Bunny Austin to the National Institute for Medical Research, London, in 1958, shifted me from pure science to biomedicine. Emphasis on immunology gradually decreased as visiting lecturers described their work. Margaret Jackson ran a sperm donation program in Devon. Only 5 feet tall, her heart was double the normal size as she stoutly defended her work against a barrage of critical ethical questions. What could I do for patients? Literally nothing until human eggs were fertilized in vitro. Carl Gemzell in Sweden began treating infertile acyclic women with extracts of human anterior pituitaries4 but, as in mice, oocyte numbers were erratic, so very high-order multiple pregnancies were established alongside patients with singletons or twins. Later, some of his patients died from Creutzfeldt–Jacob disease transmitted by those pituitaries, showing how clinical matters can go badly wrong. Donini et al.5 extracted follicle-stimulating hormone from human menopausal urine and Bruno Lunenfeld6 applied it clinically, so pituitary glands were no longer needed.

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Figure 1: Initial work in introducing human IVF.
Figure 2: Reverend Gordon Dunstan talking with Robert Edwards some time in the 1980s.
Figure 3
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  1. Reproductive BioMedicine Online Duck End Farm, Dry Drayton, Cambridge, UK

    Robert G. Edwards

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Edwards, R. The bumpy road to human in vitro fertilization. Nat Med 7, 1091–1094 (2001). https://doi.org/10.1038/nm1001-1091

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