In 1911, a group of four scientists set out in relatively luxury to the summit of Pikes Peak, a mountain outside Colorado Springs at 4,300 m above sea level. That group included biologist John Scott Haldane, who wanted to collect more data to study the effects of high altitude on the human respiratory system. Arriving at the summit by train, Haldane’s team spent five weeks there in a comfortable hotel with meticulous experiments. They examined the alveolar partial pressure of oxygen and carbon dioxide in the expedition participants during the altitude acclimatization and during the entire stay. They also took measurements of the concentration of hemoglobin and the oxygen capacity of the blood.

Meanwhile, another ace, albeit less well-known, climbed the mountains around Colorado, albeit in much less luxury. This biologist, Mabel FitzGerald, gathered data from the miners and other residents of the many small towns she passed through on how altitude affects blood oxygen levels at increasing altitudes. Your research should go a long way towards finding out how our bodies react to changing oxygen levels. Her contributions outside the sphere of competence in which she was active have long been overlooked.

Mabel Purefoy FitzGerald was born in 1872 in the family home in Preston Candover, Hampshire, where she lived with her four sisters and two brothers. But in 1895, at the age of 22, her world changed dramatically. Both of her parents died unexpectedly of illness and Mabel lived with her grandmother and sisters in the Purefoy family home – Shalstone in Buckinghamshire, England. During her year-long stay in Shalstone, FitzGerald’s interest in physiology and medicine was piqued – she often went on rounds with the village doctor.

She was the first student to enter Oxford Medical School

After a year the sisters all moved to Oxford and found themselves at 12 Crick Road. Her neighbor at number 11 would have had a huge impact on FitzGerald’s life and career: JS Haldane himself. While it’s nice to think the neighbors were linked by their shared love of biology, it’s unlikely they would have met then says Martha Tissot van Patot. Tissot van Patot, a physiologist and writer based in Colorado, USA, has spent the last 10 years learning more about FitzGerald’s life and research, and is writing her biography.

Her interest in medicine was already confirmed and FitzGerald began a pursuit of education that never stopped. Back then, women weren’t allowed to graduate from Oxford University, but they were allowed to attend lectures. And that’s what FitzGerald did. In 1896/97 she studied chemistry and biology and then enrolled in a physiology course in 1897. She was the first student to enter Oxford Medical School. FitzGerald’s desire to study medicine and get a degree has been a driving force in her career. At Oxford, she completed more than 1500 hours in the medical curriculum and completed a three-year clinical training with William Osler, Regius Professor of Medicine. But her failure to graduate didn’t mean she was out of influence at Oxford. She did so well on the physiology exams that Francis Gotch, a physiology professor, changed the rules to allow women to officially take the exams.

At the same time, FitzGerald started her scientific career with Gotch and the histologist Gustav Mann. FitzGerald’s expertise in staining and histology, which she acquired in Mann’s laboratories, was critical to her subsequent success, says Tissot van Patot. FitzGerald’s collaboration with Mann resulted in her first single-author article, a trend that has continued throughout her career. “You made her the sole author of your papers,” comments Tissot van Patot of FitzGerald’s mentors and colleagues.

FitzGerald traveled alone, carrying her gear on a mule, and slowly climbed the mountain

After a brief research stay in Copenhagen, Denmark, FitzGerald returned to Oxford in 1905 and began working with her former neighbor, Haldane. They researched the role of carbon dioxide in the airways. In 1907 she applied at the suggestion of Osler to the Rockefeller Institute in New York City and became a research assistant there. In the USA she tried again, unsuccessfully, to be admitted to medical school. Despite many attempts, she would never succeed in her search.

When she returned to Oxford, Haldane invited her to join the Pikes Peak Expedition in 1911. The team made their way to Colorado, but it was decided that it would not be safe for a lonely woman to join a group of four unaccompanied men on a high mountain.

FitzGerald and started working with her former neighbor Haldane in 1905In 1911, the team made their way to Colorado, but it was decided that it would not be safe for a lonely unaccompanied woman to join a group of four men on a high mountain.

Instead, FitzGerald went on her own part of the expedition – to measure the effects on the human body at medium altitudes. This was arguably a far less secure option. She traveled alone, carrying her gear on mules, and slowly climbed the mountain, through a series of mining towns. “It’s so brave,” says Tammie Bishop, a lecturer in hypoxia at Oxford University. FitzGerald’s trip was in stark contrast to the men’s team, who got on the train and stayed in a hotel.

The Pikes Peak Expedition was instrumental in shaping our understanding of how the body reacts to changes in oxygen. Up until that point, Bishop says, scientists thought the way the body responded to oxygen was a fixed process and wouldn’t change at lower oxygen levels. The Pikes Peak team, building on Haldane’s work and others, changed that thinking.

In her studies, FitzGerald examined fully acclimatized people in different degrees between sea level and Pikes Peak summit. It showed that with increasing altitude – and decreasing oxygen content – the hemoglobin values ​​of the people she examined increased accordingly. There was also an increase in breathing and, with it, a decrease in carbon dioxide. And all of the studies showed differences between men and women.

She found that her own carbon dioxide partial pressure did not change with small changes in altitude, but her hemoglobin level rose. In his inaugural lecture by JS Haldane in Oxford in 2019, oxygen sensor expert Peter Ratcliffe said: “That really should have been the indication that oxygen was probably being measured”. “It doesn’t quite hit the nail on the head,” says Bishop, but adds that FitzGerald’s 1913 publication of its results was the first evidence that the body is able to sense oxygen. Ratcliffe and his colleagues then uncovered and exposed the process behind it, says Bishop.

Although she is the only author, it is still referred to as Haldane’s work

In 2019, Ratcliffe, along with William Kaelin and Gregg Semenza, received the Nobel Prize in Physiology or Medicine for the discovery of the molecular mechanisms behind oxygen sensing in cells and how animals react to changes in oxygen via these signaling pathways. FitzGerald, while working on this ascent to Pikes Peak, almost came to the conclusion that an oxygen sensing mechanism was involved.

The four male Pikes Peak scientists published their results on their return. It took FitzGerald a little longer to write her experiments, but when she did, another single author article was published in 1913. Despite these independent publications, her contributions tended to be lumped together with those of Haldane, says Tissot van Patot. “Everyone knew Haldane. Everyone knew she was working with Haldane. Although she is the only author, it is still referred to as Haldane’s work, ”says Tissot van Patot. “It was society. That’s what she buried. ‘

But for researchers in the field of hypoxia and oxygen sensing, FitzGerald remains part of the story. “Mabel is a hero to many in this area,” says Nobel Prize winner Ratcliffe. ‘Your work has been misunderstood for a long time and is still not recognized by many.’ And Ratcliffe’s own remarkable scientific story itself begins with it: “It can be said that Mabel FitzGerald’s work was one of the first to describe the sensitivity of altitude adjustment (and therefore low oxygen levels) at various levels. It was this sensitivity, later reflected in erythropoietin’s response to minor disturbances in blood oxygen, that led me to the field, ”he says.

After receiving the Nobel Prize, Ratcliffe made sure to commemorate FitzGerald’s work. He included the Pikes Peak single author paper in his Nobel Speech to show it to the Stockholm audience. And he also donated Haldane’s barometer, which FitzGerald used to take measurements at Pike’s Peak, to the Nobel Museum.

FitzGerald’s research interests were much broader than those of the Pikes Peak Expedition, and she published a total of 12 articles. The last of these papers was published in 1915. Even after 1915 she remained an active scientist. In 1915 she was appointed as a clinical pathologist at the University of Edinburgh, she also became a lecturer in bacteriology at the Royal College of Surgeons. Tissot van Patot says she continued taking classes into her 60s. However, she was never admitted to full medical school and returned to Oxford in the late 1930s.

FitzGerald died in 1973 at the age of 101. When she turned 100 a year earlier, her birthday presents included a telegram from the Queen, an Honorary MA from Oxford, and membership of the Physiological Society. Those last two presents may have come a little late. After all, she has been a member of the American Physiological Society for 60 years. In a 1999 biographical article by Oxford physiologist Robert Torrance, he claims that these gestures were born out of a sense of guilt: “Oxford and England felt quite guilty about them: they ignored them.”

Katharine Sanderson is a freelance journalist based in Cornwall, United Kingdom

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