Mary Lyon's research advanced the understanding of X-linked inherited diseases such as haemophilia. Photograph: Adrian Ford<\/p>\n
Mary Lyon, who has died aged 89, was one of the foremost geneticists of the 20th century. She used the mouse as a powerful genetic tool to gain fundamental and profound insights into mammalian genetics and the genetic bases of disease. <\/p>\n
Perhaps her greatest achievement was to propose in 1961 the theory of X chromosome inactivation, in which she suggested that one of the two X chromosomes in the cells of female mammals is randomly inactivated during early development. This process is now sometimes referred to as Lyonisation, and the theory has had a fundamental impact on research into mammalian genetics and human medical genetics. <\/p>\n
Marys work greatly advanced the understanding of X-linked inherited diseases, including Duchenne muscular dystrophy and haemophilia, and explained why women who are carriers of these diseases can display symptoms. It was an early example of an epigenetic phenomenon, whereby changes in the expression of genes are caused not by alterations in the DNA itself but by non-genetic factors. The theory of X chromosome inactivation provided a compelling insight into the mechanisms of genetic regulation and Marys discovery still resonates with contemporary research into how genes are regulated as we develop and grow. <\/p>\n
Born in Norwich, to Louise (nee Kirby), a schoolteacher, and Clifford Lyon, a civil servant working for the Inland Revenue, Mary was the eldest of three children. Because of her fathers job, the family moved around the country, to Yorkshire, then Birmingham, and, at the outbreak of the second world war, to Woking, Surrey. It was the prize that Mary won for an essay competition at King Edward VI grammar school in Birmingham, a set of books on wild flowers, birds and trees, that first sparked her interest in biology. <\/p>\n
In 1943, she went on to read zoology, physiology and biochemistry at Girton College, Cambridge. Zoology was her main subject, but she became interested in the concept that genes underlie all embryological development, a relatively new idea at the time. Before 1948 women were not official members of the university, so Mary graduated in 1946 with a titular degree. <\/p>\n
She began a PhD in genetics with the eminent geneticist and statistician Sir Ronald Fisher at Cambridge, but completed her research under the supervision of Douglas Falconer in Edinburgh, where she had access to better facilities. On completion of her PhD in 1950, she was offered a position in the group of Toby Carter at Edinburgh to conduct research into the genetic hazards of radiation. <\/p>\n
In 1954, Carters group and Mary moved to the Medical Research Council Radiobiological Research Unit at Harwell, Oxfordshire. Reflecting wider concerns about the need to understand the mechanisms of radiation damage in the atomic era, a genetics division was established at MRC Harwell under the leadership of Carter, to assess genetic risks based on the incidence and types of genetic damage caused by radiation.Mary and her colleagues made significant contributions to our understanding of mutagenesis mechanisms. However, given Marys fascination with the genetic variants and anomalies that mutagenesis can produce, it seems inevitable now that she would establish an interest in the mouse mutants arising from these radiation studies. <\/p>\n
It was her curiosity and fascination with the humble mouse and the extraordinary collection of mouse variants generated at Harwell that led her to the many discoveries that transformed our understanding of mammalian genetics. She recognised the advantages to biomedical science of cryopreservation of mouse mutants and strains; and the archive of frozen mouse embryos at Harwell, which provides such an important repository for biomedical science worldwide, is testament to her foresight. <\/p>\n
Mary took over the stewardship of the genetics division from Carter in 1962. She stepped down in the mid-1980s, and officially retired in 1990, but continued to come to the unit several times a week to do academic work and to attend scientific lectures right up to 2012. <\/p>\n
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