embryos in the lab -- 3/6/24

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Today's selection-- from Dance of Life by Magdalena Zernicka-Goetz and Roger Highfield. Work with embryos outside of the body first started in 1944:

“The advances that led to human embryos developing in the laboratory date back to the mid-twentieth century. The first report of a human egg fertilized outside the body was made in 1944 by John Rock, working with Miriam Menkin. This seminal study suggested that a pregnancy resulting from IVF was possible in humans. However, it took another fifteen years, until 1959, when Min Chueh Chang at the Worcester Foundation for Experimental Biology in Shrewsbury, Massachusetts, had the first success in generating an offspring after IVF in mammals. Chang achieved births after IVF in a rabbit by fertilizing eggs in vitro from a black rabbit with sperm from a black male and transferring the embryos to a white female resulting in black young.

“One of the central figures in the story of the first human IVF pregnancy was the English physiologist Robert Edwards, who initially had studied mice and then became interested in human egg maturation and chromosomal abnormalities.

“To find a supply of human eggs for his work at Cambridge, Edwards was introduced to Molly Rose, a gynecologist at the Edgware General Hospital, London, who would provide him with biopsied ovarian samples for the next ten years.  He was keen to find ways to treat women with blocked fallopian tubes, which prevent eggs from traveling from the ovaries to the womb where they can be fertilized. While some doctors were investigating tubal surgery, Edwards thought that IVF offered a powerful new way to treat infertility. 

“In 1968, Edwards met obstetrician and gynecologist Patrick Steptoe, who had been pioneering the use of the laparoscope in gynecological ‘keyhole surgery,’ and they decided to collaborate. They stimulated egg production by giving patients hormones before harvesting their eggs for fertilization. Then one day Edwards tried to culture fertilized human eggs in a medium developed for hamster experiments by Barry Bavister, a student working down the corridor from him at Cambridge. And it worked. After dinner, they inspected Bavister's medium and saw many different stages of human embryo development. Edwards would later refer to this as ‘that fabulous night.’ In December 1968, Edwards, together with Bavister and Steptoe, submitted a paper to Nature that described the first successful IVF in humans. (Even then, he was aware of the wider implications and in 1971 aired the legal and ethical issues raised by IVF.) 

“The first IVF pregnancy would not be reported in the United Kingdom, however, but in Australia in 1973 by a team at Monash University and the University of Melbourne. This attempt resulted 

In early miscarriage. Two years later, the Cambridge team reported an ectopic pregnancy following IVF. By 1977, Edwards and Steptoe had endured five years of failure. Their funding application was at first rejected, asking for primate experiments to be done first, as is the case for most grant applications proposing bold ideas. Because they could now predict when ovulation was imminent, thanks to a test developed in Japan, Edwards and Steptoe decided to abandon the cocktail of drugs used to stimulate egg production, placing their faith in the less productive natural cycle instead.

“At that time, Lesley and John Brown were desperate for a child and felt there must be an operation to fix a blocked fallopian tube. Lesley was referred to Steptoe. ‘He told us that until then it hadn't worked,’ said Lesley, ‘but I didn't want to hear that.’ Steptoe and his team made a renewed attempt on Lesley and two other women in November 1977. ‘They found one solitary egg and that was Louise,’ she recalled. By then, Steptoe and Edwards had decided to halve the period that the embryo was allowed to develop to just eight cells before transfer to her mother. The resulting pregnancy caused a sensation. 

This image shows intracytoplasmic sperm injection, the most commonly used IVF technique.

“In July 1978, Lesley Brown developed mild preeclampsia, a condition that could affect the pregnancy. Steptoe decided to wait no longer and, with an obstetrician and gynecologist, John Webster, prepared to deliver her baby by caesarean. Shortly before midnight on July 25, 1978, Louise Joy Brown entered the world. The day after that second fabulous night, the story of the first IVF baby was worldwide news. Louise was the ‘Baby of the Century.’

“The birth eased the concerns of scientists and paved the way for more success and for the Medical Research Council to support IVF. But would Edwards have been allowed to do his research under today's legal machinery and guidelines? The answer might well be no. Behind every one of his experiments was a couple willing to take risks associated with an invasive procedure because they so wanted a child, while his peer group was deeply skeptical of his motives, even fearful that his experiments would end in disaster by creating embryos with abnormalities. 

This pioneering IVF effort depended on many more people than Steptoe and Edwards. There was the goodwill of nursing staff led by Muriel Harris, operating room superintendent at the Oldham Royal Infirmary and at Oldham and District General Hospital, along with Jean Purdy, whom Edwards had recruited in 1968 as a technical assistant and who had helped with the research. Decades later, Edwards would refer to Purdy when he said: ‘There were three original pioneers in IVF and not just two.’

“It is also important to pay tribute to all the women who subjected themselves to experimental IVF. Over ten years, notebooks on their experiments recorded data for 282 anonymous women, 457 attempted egg retrievals, 331 attempted fertilizations, and 221 embryos. This effort only resulted in five pregnancies and two successful births. These women should be remembered today, when IVF remains far from easy even though it has become routine.”

author:	Magdalena Zernicka-Goetz , Roger Highfield
title:	The Dance of Life: The New Science of How a Single Cell Becomes a Human Being
publisher:	Basic Books
pages:	127-130