Working with Robert Edwards at the dawn of IVF

I first encountered Professor Sir Robert Edwards – Bob – when I was studying physiology at Cambridge University in 1967. Unlike most of the lecturers, Bob had a dynamic style of teaching. He would stride up and down in front of the class, gesturing wildly and sometimes looking for notes that he had crammed into his pockets. I was excited by his enthusiasm for his topic, and decided then and there to become a reproductive physiologist.

Bob's basic themes were that we knew too little about human reproduction, and that infertility was a major problem that needed attention. In those days, the focus was on female infertility, but the only realistic treatment (resection and reanastomosis) wasn't very successful. In his lectures, Bob proposed a radical idea – removing eggs from the infertile patient, fertilising them in vitro, and returning the resulting embryos to the uterus.

I did not know it at the time, but Bob had worked for several years to mature eggs in vitro, first with animals and later with human material. For the latter, he was given portions of ovaries that had been removed for medical reasons at a local hospital. He had tried several times to fertilise human eggs in vitro without success, and so while he was enthusiastically discussing his IVF approach to human infertility, he knew that it was going to be difficult. It is a tribute to his vision and determination that he was not deterred.

In the summer of 1967, I became a graduate student in the famous Marshall Laboratory in Cambridge. Bob was working there in a tiny laboratory with his two graduate students, Martin Johnson and Richard Gardner. My supervisor was Professor CR 'Bunny' Austin, who in 1951 had been one of the discoverers of sperm capacitation (a process that sperm cells must undergo before they are capable of fertilising egg cells). That discovery laid the foundation for IVF in all species, and so it was serendipitous that Bob, Bunny and I were all in the same small space in 1967.

I was working on a project under Bunny's supervision, namely sperm capacitation in the hamster. It was Bob who had suggested that topic to me and to Bunny, no doubt hoping that some nugget of information from my efforts might be helpful to his attempts at human IVF. It was also Bob who persuaded Bunny to take me on as his PhD student, sight unseen.

I spent my first year in the Marshall Laboratory trying to duplicate the successful IVF in hamsters that had been reported by Min Chueh Chang and Ryuzo Yanagimachi, in 1963 and in 1964. Without a consistently successful IVF system, I could not begin to study the changes undergone by sperm cells during capacitation.

After a year of frustratingly variable results, it dawned on me that the pH of the culture medium was critically important. When extracellular pH was high, virtually all of the eggs were fertilised. As I have discussed elsewhere, I believe this was the first report that mammalian fertilisation is pH-dependent.

In view of this information, I formulated a culture medium. When Bob learned of my success with hamster gametes, he suggested applying my culture medium to support fertilisation of in vitro matured human eggs.

We started working together in the summer of 1968, and continued into autumn. As before, Bob obtained human ovarian fragments from which he extracted immature eggs and matured them in vitro. Then we inseminated the eggs in the culture medium.

We believed (thanks to Bunny's work) that human sperm cells needed capacitation, but we had no idea how long that process took. As a result, we inseminated batches of eggs and then waited for two, four or six hours, before examining the eggs to see if they were fertilised. That usually meant inseminating the eggs in the early evening, then going home for dinner and returning at night to check the results.

On one occasion, we found that the huge gates across the entrance to the laboratories were locked for the night. Bob was fond of telling the story that it was my fault, because I had forgotten my keys. To the best of my recollection, lowly graduate students such as myself were not entrusted with keys to those gates, and it was Bob who had forgotten his keys.

In any case, we had to boost ourselves over the high iron gates to get into our laboratory. I don't remember whether that was the very night that we observed the first human IVF, but it is nice to think so. I wonder what would have happened to our work if the police had caught us breaking in?

Typically, Bob and I would take turns to examine the precious human eggs, one at a time, at varying intervals after insemination. This was laborious. Human sperm cells are tiny compared to hamster sperm cells, and it took a lot of searching in the egg cytoplasm under high magnification to convince ourselves that there was no sperm penetration.

After several fruitless inspections, one evening Bob was getting frustrated and said: 'Barry, you do the next one.' So I had the privilege of examining the egg that proved to be the first one with evidence of sperm penetration. Within the egg cytoplasm was a hairlike structure that could only be a sperm tail, and at one end was a clearly recognisable expanding sperm nucleus.

I remember sitting there at the microscope for just a few seconds, then turning to Bob and saying: 'There it is!' Bob rushed over, took one look, turned to me with a big grin, and said: 'Barry, we've done it.'

When Bob thought we had enough data, he wrote and submitted two manuscripts. All this time Bob had been collaborating with Dr Patrick Steptoe to obtain in vivo matured eggs for IVF, and so Patrick was credited as an author on both papers – as was I. With classic understatement, the abstract of the first paper to be published read: 'Human egg cells have been matured and fertilised by spermatozoa in vitro. There may be certain clinical and scientific uses for human eggs fertilised by this procedure.'

I have not forgotten the excitement of our discovery. Nor have I forgotten that Bob made me the first author on our second paper, even though he actually wrote the paper and I was just a graduate student. This gesture is typical of Bob's generosity to his colleagues, as countless others will no doubt attest.

When our work was published, Bob was asked to go to London for a press conference. He asked me to go too, but Bunny advised me not to get involved in the media frenzy and to concentrate on my studies.

That turned out to be good advice. Soon, our laboratory was invaded by hordes of journalists, all clamouring for interviews with Bob. In those days, television cameras were huge boxes on tripods, while giant cables snaking down five flights of stairs connected them to 'outside broadcast' vans parked outside the building.

The intrusion was highly resented by some of the other professors in the building. I think some of them also resented the fact that Bob was getting publicity for doing something of practical importance.

It should not be forgotten that other laboratories around the world were also working on IVF, but it was Bob who argued most forcefully for IVF to be accepted. He did this for years, at public and scientific meetings and in scholarly articles, until the birth of Louise Brown in 1978 (see BioNews 1304).

It was my great privilege to work with Bob during those exhilarating months of 1968, and to have had my name associated with his ever since. Bob epitomises the socially conscious, visionary scientist. The legacy of his work speaks for itself.

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A version of this article was originally published in the programme for the conference 'In Vitro Human Embryos: Interdisciplinary Reflections on the First Four Decades', held in Cambridge in 2009 and supported by Wellcome.