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Remembering Mary Lyon and her impact on mouse genetics

Dr Mary Lyon, an important figure in the field of mouse genetics, died in December. Here Katherine Nightingale looks back on her career, from a ‘titular’ degree to her impact on generations of scientists, via a discovery in the early 1960s which explained a fundamental difference between men and women in the inheritance of disease.

A portrait of Mary Lyon by artist Dr Lizzie Burns

A portrait of Mary Lyon by artist Dr Lizzie Burns (Image copyright: Dr Lizzie Burns)

It’s not often that the MRC names a building after a scientist, even with our roll-call of scientific greats. But at MRC Harwell in Oxfordshire, the MRC Mary Lyon Centre teems with life — murine life that is. Opened in 2004, the centre is a national facility for mouse genetics where genetically modified mice are produced, cared for and studied.

Mary Lyon, who died on Christmas day 2014 aged 89, worked with mice throughout her scientific career, becoming one of the foremost geneticists of the 20th century through her research on mice with mutated genes. She made her most famous discovery, named ‘lyonisation’ in her honour, during her time at MRC Harwell.  

Mary discovered lyonisation, or X-chromosome inactivation, in 1961 by studying the mottled patterns on the coats of a particular strain of mouse. Females have two X chromosomes and males an X and a Y. Using a series of mouse breeding experiments and observations Mary suggested that early in the development of female mammals, each cell inactivates one of its X chromosomes. This is a random process, meaning that in some cells one X chromosome is active and in others it is silenced.

This has important medical implications. Some diseases, such as Duchenne muscular dystrophy and haemophilia, are caused by mutations on the X chromosome. Because women have two X chromosomes they are often protected from X-linked disease, while men are affected. However, because of X-inactivation women who are carriers of these diseases can display symptoms.

Mary in 2010

Mary in 2010 (Image: Jane Gitschier on Wikimedia Commons under CC BY 2.5)

A deep thinker

“Mary had a remarkable ability to process complex data and produce absolutely new insights of profound importance. She was a quiet person, and clearly a deep thinker, but someone who laughed a lot,” says Prof Lizzy Fisher, leader of the Mammalian Neurogenetics Group at the MRC Prion Unit, who carried out her PhD research at MRC Harwell.

Mary was born in Norwich in 1925 to schoolteacher Louise (nee Kirby) and civil servant Clifford Lyon. Her family moved around a lot in her childhood, and it was at grammar school in Birmingham that she developed her interest in science after winning a set of books on nature in an essay prize.

She went on to be one of just 500 women allowed to study at Cambridge University alongside 5,000 men — though women weren’t technically members of the university. Despite attending the same lectures and practical courses as the men, she received a ‘titular’ rather than official degree in zoology, physiology and biochemistry.

But though this was clearly a challenging time to be a woman at university, the timing turned out well in other ways. Graduating in 1946, the Second World War had not only changed the place of women in society, but had also restricted the numbers of men in universities, actually increasing the postgraduate opportunities for Mary.

She began a PhD at Cambridge in 1946 but later moved to Edinburgh to access better facilities for mouse genetics such as mouse breeding and histology. Post-war worries about atomic radiation meant that after her PhD she spent five years in Edinburgh doing MRC-funded work researching the effects of radiation on mice. Her work there involved studying mutant mice with names like twirler (a mouse with no sense of balance due to inner ear problems) and ataxia (a mouse which had trouble walking).

A younger Mary Lyon at MRC Harwell

A younger Mary Lyon at MRC Harwell

The move to Harwell

At Harwell, the MRC was funding work looking at radiation and cancer, and in 1954 Mary moved to the MRC Radiobiological Research Unit. As well as assessing the types of genetic damage caused by radiation, Mary pursued the study of the mouse mutants themselves, often in her spare time.

She also had the foresight to recognise the importance of cataloguing and archiving mouse strains by cryopreservation. Harwell’s extensive collection of frozen mouse embryos would not be the important international resource it is today with her work.

She was Head of Genetics from 1962 to 1986, and, though she had to retire in 1990 due to age restrictions, she continued to work at Harwell a few days a week until just a couple of years ago.

“Mary was a very clear thinker and careful experimentalist who made a massive contribution to genetics. She was quiet, serious and mild mannered. However she was a tenacious fighter on scientific matters on which she felt strongly and she didn’t suffer fools gladly. She could also be very kind and helpful,” says Prof Jo Peters of the MRC Mammalian Genetics Unit.

Her list of prizes and honours is long. She was made a Fellow of the Royal Society in 1973 and received the society’s Royal Medal, along with the Wolf Prize in Medicine and the Pearl Meister Greengard Prize. She was also elected a foreign member of the National Academy of Sciences, reflecting the high regard in which she was held worldwide. In 2014 the UK Genetics Society established the Mary Lyon Medal in her honour.

“I wish she had had more general recognition, outside the scientific community, including through the British honours system, but somehow, quietly, this did not happen in her lifetime,” says Lizzy.

Why she never received the Nobel Prize or was made a Dame is a mystery to many. But Dame or not, she was one of the greats of British science.

Katherine Nightingale

More information

The Gift of Observation: An Interview with Mary Lyon, PLOS Genetics

Mary Lyon obituary, Guardian website

The Lyon Queen – Dead, But Never Forgotten, Huffington Post

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