Who is Frances Ashcroft?

28/03/2012

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In 1984, Frances Ashcroft discovered a protein (a tiny pore called an ion channel) that acted as the link between blood-glucose levels and insulin secretion. As a result, people with a rare inherited form of diabetes can now relieve their symptoms simply by taking an existing drug in pill form, rather than by daily insulin injections. The drug has improved their blood glucose control and so reduced the risk of diabetic complications, such as blindness and kidney disease. She is now studying why 25% of patients with this disease also have neurological problems, and continues to explore what goes wrong with insulin secretion in type 2 diabetes, which affects 336 million people worldwide.

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THE EXHILARATION OF DISCOVERY

Science has always been an all-consuming passion for Frances Ashcroft. ‘To make a discovery, to know that you are the person who’s seen something for the very first time, is the most exciting thing in the world’, she says. ‘It is really extraordinarily exhilarating. When that’s happened to you once or twice, you are hooked for life. And that exhilaration sustains you throughout the long years of work in the lab.’

Frances Ashcroft insists that credit be shared with the many lab members and colleagues she has worked with over the years. ‘Science is a team effort’, she says, ‘and no-one walks alone’. Nevertheless, she alone was responsible for the discovery that made it all possible 25 years ago, when she found the ion channel that is the missing link between glucose and insulin secretion. Glucose stimulates insulin release by closing this channel (a tiny pore in the cell membrane). Another breakthrough came in 1995, when Professor Ashcroft and others elucidated the DNA sequence that codes for the channel. This enabled them to screen the DNA of people with diabetes for mutations (variants) in the channel genes. Then in 2003, her friend and colleague, Professor Andrew Hattersley, found a mutation in the channel gene in a patient with a rare inherited form of diabetes that develops within the first few months of life. Ashcroft’s team showed the mutant channel was no longer closed by glucose, thus explaining the patient’s diabetes. Importantly, they also found that the channel could still be closed by sulphonylurea drugs. At that time, people born with diabetes were treated with insulin injections, as their symptoms suggested they had an unusually earlyonset form of type 1 diabetes (a disease in which the beta-cells are destroyed by the body itself and life-long insulin is essential). The work of the Ashcroft and Hattersley teams suggested that instead such patients could be treated with sulphonylurea drugs, which by shutting their open channels would stimulate insulin secretion from their own beta-cells. Over 90 percent of people with neonatal diabetes have now switched to sulphonylureas. This has resulted in improved blood glucose control and a better quality of life for hundreds of patients.

: Frances Ashcroft (2012 L’Oréal-UNESCO Laureate)

A PILL THAT CHANGES LIVES

Meeting some of the people her work has helped has been very special for her. ‘It’s been an incredibly rewarding and emotional experience’, she says. ‘I do science out of curiosity – from a desire to find out how things work. If you work in a medically related field, as I do, you always hope that your work might ultimately benefit patients, but you never imagine that will happen in your own lifetime. I have been incredibly lucky that it has done so.’

ASK QUESTIONS!

Professor Ashcroft’s career as a scientist had its roots in an idyllic childhood in rural Dorset, on the southwest coast of England, where she ‘roamed wild around the woods and fields’. Her interest in natural history was piqued by the enchanting moment – still fresh in her mind – when she came upon beautiful bright-pink orchids growing wild in the fields. A girl who later scolded her for picking them ended up becoming her best friend, and they spent their schooldays hunting for wild orchids, bird watching and sailing (still favourite activities). ‘We inspired each other,’ says Professor Ashcroft. At school, she took an interest in biology and chemistry (physics was not an option, ‘because it was a girl’s school’).

Studying at Cambridge University later was a ‘liberation’ because her tendency to ask questions constantly was encouraged rather than frowned upon. ‘Suddenly, this was where I belonged.’ She received enthusiastic support from her PhD supervisor, John Treherne, a scientist who wrote novels and other books, setting an example for Frances Ashcroft: her own bestselling book for the general reader, Life at the Extremes (published in 2001), investigates how life forms survive in extreme conditions.

Professor Ashcroft has not lost the great sense of curiosity that first drew her into the world of nature and science. When she was one of many people asked to write about an individual from any time period she would like to dine with, she was shocked that the other respondents chose famous people from the past. ‘I want to have dinner with people from the future,’ she says, ‘who can tell me what goes wrong in type 2 diabetes and what’s happening in the future.’

Comments

Jacqui Furneaux - Activity (optional) 25/06/2012

I have just heard Francis on Radio 4 and looked her up as I was so moved by her enthusiasm, humility and joy of discovery. How inspiring on a Monday morning!