IVF Pioneer Robert Edwards died today (April 10, 2013).

April 10, 2013Carole No Comments »

One of the biggest, if not the biggest, pioneer in IVF died today. Sir Robert Edwards died in his sleep today after a long illness. He was 87 years old. Here is a BBC article announcing his death.  This article about his early academic life which led, ultimately, to the clinical offering of IVF and the birth of the first “test-tube baby” Louise Brown in 1978 is a fascinating account compiled by Martin H. Johnson in collaboration with the Edward’s family. What I take away from this article is that the path to clinical IVF was a rocky one with frequent setbacks. Although many view IVF as a widely accepted clinical procedure today, it wasn’t always so.

Highlights of IVF as viewed through the career of Robert Edwards (summarized from the paper by Martin H Johnson, entitled Robert Edwards: the path towards IVF)

1925: Born in Yorkshire, England to a working class family. Passed special exam to attend Manchester Central Boy’s High School.

1945: Began university education but was interrupted by WWII

1951: Continued at University College of North Wales at Bangor, initially for agriculture, but then switched to more appealing Zoology. Surprisingly, he graduated with only a pass, without honors, which was very personally upsetting at the time.

1951: Was accepted at Edinburgh in a post-grad Diploma course in Animal Genetics; began intra-disciplinary research in Developmental Biology in the mouse model. Published 14 papers here, largely on sperm-related topics. Egg biology was more difficult to research due to lack of research material- namely mouse eggs. He mastered superovulation of the mouse in order to get sufficient eggs for his research. Superovulation with gonadotropins is critical to  IVF so this basic work was one of the stepping stones to human IVF.  During his time at Edinburgh, the work he did resulted in 38 papers, so many that some were not even published until 1963.

1957-1958: Worked at the California Institute of Technology in the US studying sperm-egg interactions. He became interested in reproductive immunology, particularly how the mother’s uterus was able to accept rather than reject an embryo that was half foreign (due to 50% paternal contribution).  Although he considered this time a “holiday” of sort, he published 23 papers from work he did in this area.

1958: Returned to the UK to work on the science of immuno-contraception, but was ultimately more interested in the mysteries of the egg, egg maturation and fertilization. He was interested how the egg could have problems during meiosis called non-disjunction events or lagging chromosomes which could result in an abnormal number of chromosomes (aneuploidy). Aneuploidy is a significant issue for older women and interferes with successful IVF outcomes.

1960-1962:  Edwards worked with a gynecologist to get ovarian biopsy tissue, recovered eggs for the tissue and noted that they seemed to spontaneously mature in vitro when released from the follicle. This phenomenon of spontaneous maturation, although encouraged by administration of hCG a few days before retrieval,  allows eggs to be combined with sperm after only a few hours post-retrieval.  Although encouraging, his work on human IVF using human eggs from ovarian tissue was banned by the director of the Institute, abruptly ending his progress toward clinical IVF for a time.

1965-1966: He published papers in which he showed that he could derive embryonic stem cells(ESC)  from rabbit embryos by dissecting the intercellular cell mass and growing the cells in vitro. This work was largely ignored for the better part of 20 years until two other researchers (Evans and Kaufman) demonstrated that ESC’s could be derived from mouse embryos in 1981. Edwards was a little too advanced in his ESC production and so his seminal ESC work failed to be appreciated for over twenty years.

1963: Moved to Cambridge as a Ford Foundation Research Fellow. For the next several years, he continued his efforts to understand egg maturation and the kinetics of chromosomal sorting that occur during meiosis. Mishaps with chromosomal sorting result in aneuploidy. He developed the “production line theory” of egg maturation to explain the increased occurrence of aneuploidy with increasing maternal age. In 1965, he reached out to Howard and Georgeanna Jones, IVF pioneers who opened the first US IVF Clinic and who provided him with sufficient human eggs to confirm his egg maturation theories in the human. This also started a long-lasting collaboration between Edwards and the Jones’s.

In this interesting interview with the now-deceased Howard Jones, he discusses his belief that he and Edwards may have actually fertilized a human egg in 1965 while Howard was still at John Hopkins, but they weren’t sure because they could not detect a sperm tail, just two pronuclei. Today we know that two nuclei is considered ample evidence of fertilization in humans. An intact sperm tail is rarely observed. (In 1979, a year after Louise Brown’s birth in England, Georgeanna and Howard Jones “retired” from John Hopkins and opened up the first US IVF clinic, the Jones Institute at Eastern Virginia Medical School.)

Wednesday 28 February 1968: Robert Edwards met Edward Steptoe, who had been a Consultant Obstetrician with a specialty in surgical laparoscopy at Oldham General Hospital since 1951. Steptoe’s interest in human IVF was treated with hostility by his colleagues and Edward’s was initially “warned off” contacting Steptoe. The earliest IVF egg retrievals were performed not with minimal invasive ultrasound-guided needle aspiration as is used today  but by opening up the abdomen. It was this surgical skill for egg removal for IVF that interested Edwards. Likewise, Steptoe found in Edwards, a life-long colleague, who shared his interest in human IVF. Together they would achieve the birth of the first IVF baby, Louise Brown, born in 1978,  ten years after this first meeting.

Another scientific problem holding back Edwards and Steptoe’s ambitions for human IVF was the problem of sperm capacitation. Sperm need to be exposed to the female reproductive tract fluids to become “capacitated”, the final step in sperm maturation so they are capable of fertilizing an egg. This sperm capacitation problem was solved when Robert Edwards encountered the work of Barry Bavister, who had just solved the problem of in-vitro capacitation in hamster sperm, by showing he could increase sperm fertilizing ability, simply by increasing the pH of the media.

December 1968:  Edwards, Bavister and Steptoe, submitted their landmark paper to the journal Nature, describing human IVF for the first time.  Previous papers by others had claimed success but this Nature paper was definitive.

1971: His 1968 IVF success was met with public distrust due to hostile media coverage of human IVF in Britain and his request for research funding was denied in the UK. Perhaps this was the first, but certainly not the last time that IVF research would be killed due to societal backlash, both in the UK and the US.

Edwards battled negative public perception of IVF and professional hostility from his colleagues for the better part of a decade. Some of his  colleagues considered human IVF a form of human experimentation, without merit. Treatment of infertility was not considered a societal good because human overpopulation was considered the overriding social ill and research to develop better population control was considered more worthy scientific work.

July 25, 1978: Louise Brown was born, and the social tide against human IVF began to turn. It is hard to deny the joy of new parents who have overcome infertility through the intervention of IVF. It was a long hard road for Edwards to see his life’s work culminate in joy for that first IVF patient. He was awarded the nobel prize in 2010 for his IVF work.

Robert Edward’s scientific work left a lasting mark on the world- for the better. Thank you, Sir Edwards.

 

 

 

 

 

 

© 2013, Carole. All rights reserved.

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