Mary Frances Lyon (1925–2014)

Mary Frances Lyon Mary Lyon was one of the most notable geneticists of the 20th century. She is renowned for her discovery of X inactivation, an early example of epigenetic gene regulation, but she alsomade fundamental contributions to the entire field of genetics. Mary was born on May 15, 1925 in Norwich, in the rural east of the United Kingdom. She was the first child of Clifford James Lyon, a civil servant, and Louise Frances Lyon (nee Kirby), a former school teacher. When she was 10, Mary’s family, which by then included a younger brother and sister, moved to Birmingham. There, she attended King Edward VI High School for Girls and began her scientific career, like so many of us, through an inspirational teacher who made lessons interesting: Mary Udall, whom Mary described as having ‘‘a clear analytical mind.’’ Mary was fascinated by physics and chemistry, but the prize she received from an essay competition, four books on nature study, ultimately led to her becoming a world-class biologist. The Second World War helped change the status of women, and Mary decided to take the unusual step of reading natural sciences at the University of Cambridge (Girton College), where women took the same coursework as men but at that time were awarded only titular degrees. She focused on zoology and became interested in experimental embryology, graduating in 1946 with her titular degree. Rather unusually, she went on to Ph.D studies with R.A. Fisher, the Balfour Chair of Genetics at Cambridge, who founded much of the field of statistics and developed analysis methods for early gene linkage studies. R.A. Fisher was in his fifties—brilliant, eccentric, and difficult. He threw out many who joined his lab, but he led Mary directly to her lifelong study of mouse genetics. At the time, there was no systematic method of mapping mouse genes. With 20 mouse chromosomes, Fisher decided that, if he crossed all possible combinations of his 21 visible mouse mutants, he would likely detect a new linkage. Students were each given a line of mice carrying five mutations, and Mary took on line 18, which included the ‘‘pallid’’ mutation. Already an insightful experimentalist, Mary was unconvinced that her mouse-crossing experiments would give her enough data for a Ph.D, but she noticed that pallid mice tended to tip their heads to one side. She found that they were missing otoliths in the inner ear and went on to investigate the effects of penetrance and to work out how otolith absence correlated with postural reflexes. Meanwhile, Mary was reading books by Conrad Waddington, known as the father of epigenetics, and became aware of the novel idea that embryonic development depends on genes—at a time when the exact nature of a gene was unknown. R.A. Fisher was not interested in developmental genetics, and Mary needed facilities for histology; so as Waddington had returned from his wartime post (scientific advisor to the Royal Air Force) to become Professor of Animal Genetics at the University of Edinburgh, Mary moved to his department and to a new supervisor, Douglas Falconer. Waddington and Falconer were important influences on Mary; she chose to stay in mouse genetics due to the relevance to human studies. Waddington applied to the Medical Research Council (MRC)—which unlike other funders awarded equal pay for women—and gained postdoctoral funding for Mary to