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Friday, Apr 26, 2024

The female scientist who changed human fertility forever

She was the first person to successfully fertilise a human egg in vitro, changing reproductive medicine forever – but few people know her name today.

In the textbook tale of scientific discovery, the researcher works late into the night, alone in their lab. Suddenly, genius strikes: an apple to the head, a lightning strike to a key, a contaminated petri dish. And eureka: discovery!

The Miriam Menkin story is a little different. One Tuesday in February 1944, the 43-year-old lab technician was up all night soothing her eight-month-old daughter – “an in vivo specimen”, she liked to say – who had just started teething. The next morning, Menkin went into her lab, just as she had every week for the past six years. Wednesdays were when she introduced a newly washed egg to a cloud of sperm solution in a glass dish and prayed that two would become one.

As a technician for Harvard fertility expert John Rock, Menkin’s goal was to fertilise an egg outside the human body. This was the first step in Rock’s plan to cure infertility, which remained a scientific mystery to doctors. He particularly wanted to help women who had healthy ovaries but damaged fallopian tubes – the cause of one-fifth of the infertility cases he saw in his clinic.

Usually, Menkin exposed the sperm and egg to each other for around 30 minutes. Not this time. Years later, she recalled what transpired to a reporter: “I was so exhausted and drowsy that, while watching under the microscope how the sperm were frolicking around the egg, I forgot to look at the clock until I suddenly realised that a whole hour had elapsed... In other words, I must admit that my success, after nearly six years of failure, was due – not to a stroke of genius – but simply to cat-napping on the job!"

On Friday, when she came back to the lab, she saw something miraculous: the cells had fused and were now dividing, giving her the world’s first glimpse of a human embryo fertilised in glass.

Menkin’s achievement would usher in a new era of reproductive technology – one in which infertile women became pregnant, children were conceived in tubes, and scientists peered into the earliest stages of life. In 1978, the world would meet its first in vitro baby, Louise Brown, conceived by what was by then known as IVF (in vitro fertilisation). Soon IVF was a big business: in 2017, IVF made up the majority of the 284,385 attempts at assisted reproduction in the US, resulting in 78,052 babies like Brown.

Despite the way she told the story, Menkin’s success was no accident. Like those other great moments of discovery, getting there took years of research, hard-won technical skills, and the patience to repeat the same experiment over and over again. She would go on to write or co-author 18 scientific papers, including two historic reports on that first success in the journal Science. But unlike her co-author Rock, she would not go on to become a household name.

History cannot agree on Menkin’s role. She has been called many things: technician, research assistant, biologist, Dr Menkin, Mrs, Miss. In a way, all are true. What can be said is that she was more than merely Rock’s assistant, says Teresa Woodruff, a professor of obstetrics and gynecology and head of the reproductive science department at Northwestern University’s Feinberg School of Medicine.

“I think she can be really thought of as co-equal with John Rock,” Woodruff says. “Not just a technician or a pair of hands, as people have argued, but actually the intellectual person doing the work.”

Margaret Marsh, a historian at Rutgers University, agrees. “Rock was basically a clinician,” she says. “She was a scientist, with a scientist’s mind, and a scientist’s precision, and a scientist’s belief in the importance of following protocols.”

Marsh delved into Menkin’s story for her 2008 biography of Rock, called The Fertility Doctor: John Rock And The Reproductive Revolution. But looking back, she says she regrets labeling her as only a research assistant. (Her newest book, The Pursuit of Parenthood, gives Menkin more credit.) “If I was doing this again, I would have said that she had a scientific mind,” she says. “She wasn’t just somebody’s gopher.”


Miracle worker

One day in 1900, an egg met a sperm, and fused. The pair split into two cells, then four, then eight. Nine months later, Miriam Friedman was born in Riga, Latvia, on 8 August 1901. When she was a toddler, the family immigrated to the United States, where her father brought in enough money as a doctor to provide her with a comfortable childhood and household help. She would later recall listening “spellbound” as he regaled her with tales of how science would soon come up with a cure for diabetes.

She had a promising start to her scientific career, graduating from Cornell University with a degree in histology and comparative anatomy in 1922. The next year she earned her master’s in zoology from Columbia University, and briefly taught biology and physics in New York.

But when she decided to follow in her father’s footsteps and enter medical school, she ran up against her first obstacle: she was rejected by two of the top medical schools in the country. “I don’t know why. I think it was mostly my personality,” she would later recall. In reality, it almost certainly had to do with her gender.

At the time, few elite medical schools accepted women, and those that did imposed strict quotas. Cornell sought to restrict female students lest the school “be overwhelmed by women applicants,” as one dean put it in 1917. Others only began accepting women during the war years – including Harvard, which would welcome its first class of women in 1945. (During the college’s debate over the "woman question", one faculty member argued that letting in female students would violate “the fundamental biological law that the primary function of women is to bear and raise children”, writes Mary Roth Walsh in Doctors Wanted: No Women Need Apply.)

Instead, she married a medical student at Harvard, Valy Menkin. Miriam Menkin worked as a secretary to help put her husband through his studies, going so far as to get another bachelor’s in secretarial studies from Simmons College. She took advantage of her proximity to academia, taking courses in bacteriology and embryology, and assisting her husband with experiments in the lab. It was there that she met Gregory Pincus, the Harvard biologist who would go on to become, with Rock, the co-developer of the contraceptive pill.

Pincus had risen to notoriety as the Frankensteinian scientist who had created “fatherless rabbits” fertilised in a dish, which were raised to a healthy, hopping adulthood. He tasked Menkin with extracting two key hormones from the pituitary gland, which she was to inject into the uteruses of female rabbits to make them ovulate extra eggs. Menkin executed this task skillfully, but her time in the lab would be short-lived. In 1937, Pincus was denied tenure and returned to England, and Menkin likely lost her job as a result.

John Rock soon emerged on the scene as the fertility specialist who wanted to take Pincus’s animal insights into clinical research. “What a boon for the barren women with closed tubes!” he wrote in an unsigned editorial in the New England Journal of Medicine. Menkin applied to work in his lab and was accepted. “She was smart, tenacious, and meticulous – a perfect fit for Rock,” says Marsh. “He was brilliant, intuitive, and driven to seek answers, but he had little patience for the tedium of the laboratory.”

Fortunately for Rock, the tedium of the laboratory was where Miriam thrived.

Every Tuesday at 08:00, Menkin hovered outside the operating room in the basement of the Free Hospital for Women, a charity hospital in Brookline, Massachusetts, for low-income women. If she was lucky, Rock would hand her a tiny piece of an ovary he had just removed from a patient – often a follicle “the size of a small hazelnut”, she recalled. She would take the sample and dash up the four flights of stairs to her lab. There, she would slice open the follicle and hunt for the precious egg inside.

This was no easy feat. Though it’s one of the largest cells in the body, the human egg is still smaller than the full stop at the end of this sentence. Most people need a magnifying glass to see one; even then, it’s just a dark speck. To Menkin, it was a universe. She could pinpoint an egg with her naked eye, and could even tell by looking whether it was deformed or normal. With pride, she dubbed herself Rock’s “egg chaser”.

Week after week, Menkin followed the same routine: chase eggs on Tuesday, mix with sperm on Wednesday, pray on Thursday, look into the microscope on Friday. Every Friday, when she looked in the incubator, all she saw was one cell – an unfertilised egg – and a bunch of dead sperm. She did this 138 times. Over six years.

Until that fateful Friday in February 1944, when she opened the incubator door, and screamed for Rock. “As usual he was at the other end of town in the hospital getting a real baby for a mother,” she recalled later, in a talk to a classroom of schoolchildren. “We telephoned him… When he saw what was in the dish, he became pale as a ghost.”

As the lab filled up with onlookers – “everybody came running in to look at the youngest human baby that had ever been seen” – Menkin kept the egg in her view. She was “afraid to let out of my sight that precious object, which had been an unfulfilled dream for six years,” she wrote for her talk. To preserve it, she had to add fluid to the dish, drop by drop. For hours she worked the egg, eating her sandwich with one hand, dropping fluid with the other, long into the night.

That first egg would escape her – “the first miscarriage in a test tube,” she remembered ruefully. But she would repeat the achievement thrice more, creating another two-cell zygote and two three-cell zygotes. She fixed them in glass, stained red and blue, and sent them off to the Carnegie Institute of Washington, in Baltimore. Those specimens were “our pride and joy,” Menkin said, because they proved “without a doubt – we had the egg.” By the time they arrived, Rock and Menkin were receiving hundreds of letters from infertile women asking if science could cure them.

Menkin was now poised to become a reproductive scientist who would push the frontiers of fertility even further. Next she planned to grow an egg to four cells, then eight, and then – who knows?

But then something happened that neither she nor Rock could have anticipated: her husband lost his job. As his wife and mother of his children, she was left to follow him to Duke University, North Carolina, where IVF was considered a scandal – and, to at least one doctor, “rape in vitro”. (Read more about how sex and reproduction have changed – and where they might go in future).

Without Menkin’s skills, IVF research in Boston ground to a halt. None of Rock’s assistants would definitively succeed in fertilising an egg in vitro ever again.


Clear direction

In her talk to the schoolchildren, Miriam marvelled at the process by which egg meets sperm in vivo. “When you think how small this egg is, does it not seem amazing that once it is liberated from the follicle, and falls into the comparatively tremendous body cavity, that it does not get lost?” she wondered. “How does such a tiny thing, a little speck, find its way to the place where it is supposed to be going?”

In the case of the egg, marvelous changes in the female body propel it forward. The mass of webbed fingers that coalesce at the head of the fallopian tube stiffens, fills with blood, and draws the egg into the tube; there, tiny hairs called cilia draw the egg further down toward the uterus.

In Menkin’s case, two factors led her back to fertility research: sheer persistence and a bit of luck.

Everywhere her husband’s job took her, she sought out opportunities to chase down eggs and lab space. She knocked on doors of prominent reproductive researchers and asked Rock to write her introductions. “It took someone who was very … persistent to be able to approach people out of the blue and say ‘Hey, I used to work with John Rock, could I have some lab time?’” says Sarah Rodriguez, a historian at Northwestern University who has written on Menkin’s contributions to reproductive science. “That takes a certain amount of – if not boldness – at least confidence and desire.”

But in 1945, Menkin wrote to Rock from North Carolina that “the prospects here as far as doing any ova work are still somewhat discouraging”. Unable to get into the lab, she nevertheless continued to collaborate with Rock remotely. In 1948, the pair published the full report on their first IVF achievement in the pages of Science, with Menkin as first author.

But she soon faced new limitations in pursuing IVF. For years, she had put off getting a divorce from Valy, who withheld funds from her and often threatened her with violence in front of the children, Lucy and Gabriel. “I believed it would create too much of a trauma,” she wrote in a letter dated September 1948. “The stigma of divorce would be especially hard on Gabriel.”

But when her husband’s behaviour continued to worsen, she decided to leave. “I do not wish to commit suicide by this slow process,” she wrote the following month. She secured a lawyer, filed for divorce, and gained custody of Lucy.

As a single mother, she now found herself scrimping to make ends meet. Adding to her responsibilities, Lucy, who had epilepsy, was often ill and required trips to psychiatrists and doctors. When Menkin was offered unpaid opportunities to use researchers’ labs on nights and weekends, she often found it impossible to do so.

In the early 1950s, Menkin moved back to Boston to enroll Lucy in a school for children with special needs. She was reunited with Rock in the lab – but much had changed in the past decade. Now the reproductive task of the hour was not to make more babies, but to prevent more babies from being born. Rock had his own lab, and his primary mission was to develop a convenient method of contraception, an undertaking that would lead to the historic approval of the pill for contraceptive use in 1960. (Read about the strange truth behind the pill).

As Rock moved closer to his ultimate goal, Miriam worked behind the scenes as his “literary assistant”. She looked into research topics ranging from Japanese sperm freezing to horse infertility (One query garnered this response: “Dear Mizzy, With all the troubles in the world I am delighted that you are so interested in infertile horses!”). She co-authored papers investigating whether women’s periods could be stabilised by light, and whether a heating jockstrap could render men temporarily infertile.

Though these later papers seem far afield of her original goal, Menkin was contributing to the same endpoint. Like Rock, she probed the mysteries of reproduction, stretching the limits of what science knew. She, too, felt for those “barren women”, and was proud to contribute to a technology that might someday help them become mothers. But personally, she would have no interest in using IVF. “I would never do it because I would think it wasn’t right,” she once told a reporter. “You’d be taking too much of a chance … you could create a monster.”

Rather, her real passion was solving the scientific riddle of fertilisation outside the womb. For her, in vitro work represented the chance to be a part of a larger scientific project, the fulfillment of a career derailed.

It’s hard to know what Miriam Menkin could have achieved if her life had gone differently – if she hadn’t married Valy, or if she’d received her PhD. What can be said is that her era and circumstances forced her into a particular box. Even at her scientific zenith, her narrative became the story of an addle-minded new mother who happened upon a breakthrough. But one has only to look at her careful notes, her rigorous protocols, and her well-researched bibliographies to see that here was a scientist in her own right.


Missed Genius

Ask people to imagine a scientist, and many of us will picture the same thing – a heterosexual white male. Historically, a number of challenges have made it much more difficult for those who don’t fit that stereotype to enter fields like science, math or engineering.

There are, however, many individuals from diverse backgrounds who have shaped our understanding of life and the Universe, but whose stories have gone untold – until now. With our new BBC Future column, we are celebrating the “missed geniuses” who made the world what it is today.

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