A scientist in the extremes

May 5, 2000

Frances Ashcroft's quest for knowledge has carried her from the ocean depths to Mount Kilimanjaro's heights -a trip that nearly killed her. But whatever the means, it is the science that fuels her passion. Alison Goddard reports

Story-teller, artist's inspiration and professor of physiology at the University of Oxford, multitalented Frances Ashcroft leads a hectic life. She is writing a book, she is staging an art exhibition at the university museum and she is one of the driving forces behind the university's centre for gene function, which last month gained a Pounds 10 million grant from the Wellcome Trust. Then there is her highly respected research work on insulin secretion - she became a fellow of the Royal Society last year - and her teaching duties.

For the past two years, Ashcroft has spent Sundays - her day off - and the Christmas and Easter holidays writing Life at the Extremes.

Meanwhile, she teaches undergraduates at Oxford, explaining the science by telling stories "about individual people and the extraordinary things that happen to them".

She discovered her talent for story-telling a few years ago after the Wellcome Trust ran a competition for a life scientist to write a book for the general reader. She decided to enter, principally for the Pounds 25,000 prize. "That's a hell of a lot of money. Academics aren't terribly well paid and this was definitely bribery," she says.

Ashcroft did not win the prize, but the editors at HarperCollins liked her idea so much they commissioned the book anyway. Its chapters deal with what happens to people when they climb to high altitudes, dive to great depths, and cope with heat and extreme cold. Each chapter begins with a personal story about how Ashcroft encountered that extreme.

To illustrate what happens at high altitude, Ashcroft tells the tale of the time she ascended Mount Kilimanjaro in Tanzania. Ashcroft scaled the mountain too rapidly and began to experience mountain sickness: "I collapsed at the top of the crater rim, my head feeling as if knives were being driven through it, my vision swimming with dots."

Gasping for air and experiencing hallucinations, Ashcroft was forced back down the mountain. She was lucky - the previous week, two people had died of mountain sickness on the same trek.

The stories include the tale of Mabel Fitzgerald, 19th-century scientist whose life, had she been born 70 years later, might have mirrored Ashcroft's.

"Mabel Fitzgerald and some male colleagues went from Oxford to climb Pike's Peak in Colorado," Ashcroft says. "Their aim was to measure the effect of altitude on red blood cells and to look at the oxygen-to-carbon dioxide concentrations in the lungs.

"There was a little hut on the summit and all the men stayed there but Mabel was banned - I don't know whether it was because they couldn't bear to have a woman in the same place - and she was banished on a mule to lower levels to take blood samples from the people who lived there."

Fitzgerald and her colleagues found that people living at high altitudes had more red blood cells, which carry oxygen, than those at lower altitudes. The team also gained an insight into the maximum height to which human beings can ascend.

The higher a mountaineer climbs, the less oxygen there is in the air. The climber starts breathing more rapidly to get more oxygen but also breathes out more carbon dioxide and the carbon dioxide concentration in the blood falls. Concentration of carbon dioxide in the blood determines the rate at which a climber breathes. As it falls, the climber loses the desire to breathe.

"The question is, how low can the carbon dioxide levels in your blood fall before it stops you from breathing?" Ashcroft says. "They didn't go to the top of Everest but if you extrapolate their data points, the data predicted that people should not be able to survive on the top of Everest. In fact, we now know that they can survive on top of Everest. It is a salutary lesson about how science works: you must not extrapolate beyond your data points."

Fitzgerald published a series of papers on the altitude experiments before vanishing from scientific life - in those days it was unusual for women to become university lecturers or laboratory heads.

Ashcroft is still concerned that there are not enough female scientists. Last year, when she was elected the 8,000th fellow of the Royal Society, she realised there were not many other women members. She is particularly pleased to be working with another woman on the creation of a new centre for gene function at Oxford. It will be directed by Ashcroft and Kay Davis, professor of genetics at the university - "Two women. It's very exciting," she says.

The building will be one of the few scientific institutes in the United Kingdom to be run by women. The idea behind the centre is that within the next few years scientists will know the sequence of the genes that make up the whole of the human genome and researchers will then start to study systematically what the genes do.

The aim is to bring people who work in many different disciplines - geneticists, physiologists, statisticians and mathematicians - together in one place so they can interact, and it is now the university's chief priority in the life sciences.

Ashcroft's own research focuses on insulin secretion. After a meal, a person's blood-sugar level increases, which stimulates the release of insulin, a hormone that promotes uptake of blood sugar by the muscles. She is trying to understand how blood sugar causes insulin to be released.

In particular, her work focuses on the role of ion channels in the pancreas, the gland that secretes insulin. The membranes of the pancreatic beta-cells contain proteins that act as channels, allowing calcium ions and potassium ions to flow into and out of the cells. Ashcroft has a grant from the Wellcome Trust, worth more than Pounds 1 million over three years, to pursue this work.

"Potassium channels play a key role in insulin secretion," she says. "When they are shut, that allows the calcium channels to open and calcium ions to come in and stimulate insulin secretion. When they are open, the calcium channels remain closed and insulin is not released."

The work is linked with gene function because, in many cases, faults in the function of ion channels have a genetic basis. Some patients have a genetic mutation that causes them always to have the channels closed, so they are always releasing insulin. Genetic faults with ion channels account for other illnesses, too. "There are many types of ion channel, and mutations or defects in the genes that code for these ion channel proteins have been found to cause large numbers of diseases," Ashcroft says.

But these varied ion channels have also inspired artistic work. This month, Ashcroft has an exhibition, "Points of View: Visualising Insulin Secretion", with the artist Benedict Rubbra, showing at the Oxford University Museum of Natural History. "Ben came to the lab and worked with me for a week. We talked about insulin secretion and he built a three-dimensional model in wood and card, which he painted," she says.

Rubbra's huge oil paintings depicting the open and closed ion channels will be displayed alongside text describing the scientific processes at work, scientific images, Rubbra's three-dimensional models and a discussion of the different ways in which artists and scientists view the world.

The collaboration is not the only joint venture through which Ashcroft has tried to boost public understanding of science. She received funding to produce a television documentary on colour vision with film producer Mike Dibbs and the independent production company Mentorn Barraclough Carey. But the project is in need of more funding.

But while writing a popular science book, staging an art exhibition and planning a television documentary are important to Ashcroft, they are not her main interest.

"I am excited by the science," she says. "I have always tried to find out what the next answer is. I am interested in the public understanding of science, but the science itself is much more important to me."

Frances Ashcroft's Life at the Extremes (HarperCollins) will be published in July.

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