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Mary Frances Lyon
MRC Harwell
Obituary
Mary Frances Lyon Geneticist who gave her name to the process of X-chromosome inactivation. Born in Norwich, UK, on May 15, 1925, she died in Drayton, UK, on Dec 25, 2014, aged 89 years. In 1961, working at what was then the MRC Radiobiology Unit (RBU) at Harwell in Oxfordshire, Mary Lyon put forward the contribution to genetics for which she is best known: the X-chromosome inactivation hypothesis. What’s distinctive about her particular claim to fame is that in one respect it’s likely to prove literally unforgettable because the process she postulated is also known by a term derived from her own surname: Lyonisation. What prompted her to formulate this hypothesis was the mottled appearance of female mice heterozygous for certain X-linked genes determining coat colour. How did this mottling come about, she wondered, and why did it occur predominantly in females? Her explanation was that during an early stage in embryonic development, one of the pair of X-chromosomes in each cell had been inactivated. Because this was a random event the colour genes that survived the process differed from cell to cell. The descendants of these cells would later generate equally random patches of colour in the animals’ fur. This process is not, of course, confined to mice or to colour genes. And it also has a relevance to human genetic disease. “It provided clinical geneticists with insights into the inheritance of haemophilia and Duchene muscular dystrophy,” says Professor Jo Peters who joined Lyon at the RBU in 1978 to work on biochemical genetics. “And it’s still very relevant today because X-chromosome inactivation was 768
one of the early examples of epigenetic gene regulation.” Inactivation, a complex and multilayered process, is still a flourishing research topic. Lyon’s career began in 1946 when she graduated from Cambridge University with a science degree, specialising in zoology. She started a PhD in genetics with R A Fisher, but finished it at Edinburgh University where there were more of the facilities she needed. By the time Lyon had completed her PhD the world was becoming evermore concerned with the consequences of radiation, and she joined a research group studying radiation mutagenesis headed by geneticist Toby Carter. In 1954, he moved to Harwell as Head of the Genetics Section; Lyon went with him, taking over his job in 1962, and remaining at Harwell for the rest of her life. X-inactivation was far from Lyon’s only preoccupation. “She contributed greatly to many topics including the part of the mouse genome known as the t-complex”, says Elizabeth Fisher, now Professor of Neurogenetics at University College London but in the 1980s a Harwell PhD student. The t-complex has a key role in fertility. “It was a real enigma because it was difficult to work out what was going on. At the time when Mary started to investigate it we didn’t have the molecular tools we have nowadays. She did remarkable work using simple genetic inheritance experiments.” Lyon also contributed to early work on stem cells, and was among the first to recognise the value of being able to preserve mouse embryos and gametes by freezing them. Fisher describes Lyon as having an incisive mind. “She could be intimidating, but only because she was head and shoulders above the rest of us in terms of her ability to think. She was kind, and had an interest in other people. But very reserved.” During the course of a conversation or an interview she was apt to lapse into a succession of silences to think through what she’d been told before she spoke again, which could be disconcerting for those unfamiliar with the habit. Peters agrees. “You had to decide what you wanted to ask her before you went in to see her. But she could be quite sociable, and she never refused an invitation to a party, though she seldom said much.” Lyon was respected, and held in affection by many of those who had worked for her. Lyon remained scientifically productive for many years after retirement, but the honours system never offered the reward that Fisher and others in the genetics community believe she deserved. The term Lyonisation may be her most evident memorial, but it’s not alone. The Genetics Society has created a Mary Lyon Medal awarded annually for outstanding research in genetics, and the UK’s Medical Research Centre established the Mary Lyon Centre for mouse functional genomics in 2004. So, using the more familiar spelling of the word, it could be said that for her long and illustrious career Lyon has been rightly lionised. She is survived by a sister and a brother.
Geoff Watts www.thelancet.com Vol 385 February 28, 2015
Obituary
Mary Frances Lyon Geneticist who gave her name to the process of X-chromosome inactivation. Born in Norwich, UK, on May 15, 1925, she died in Drayton, UK, on Dec 25, 2014, aged 89 years. In 1961, working at what was then the MRC Radiobiology Unit (RBU) at Harwell in Oxfordshire, Mary Lyon put forward the contribution to genetics for which she is best known: the X-chromosome inactivation hypothesis. What’s distinctive about her particular claim to fame is that in one respect it’s likely to prove literally unforgettable because the process she postulated is also known by a term derived from her own surname: Lyonisation. What prompted her to formulate this hypothesis was the mottled appearance of female mice heterozygous for certain X-linked genes determining coat colour. How did this mottling come about, she wondered, and why did it occur predominantly in females? Her explanation was that during an early stage in embryonic development, one of the pair of X-chromosomes in each cell had been inactivated. Because this was a random event the colour genes that survived the process differed from cell to cell. The descendants of these cells would later generate equally random patches of colour in the animals’ fur. This process is not, of course, confined to mice or to colour genes. And it also has a relevance to human genetic disease. “It provided clinical geneticists with insights into the inheritance of haemophilia and Duchene muscular dystrophy,” says Professor Jo Peters who joined Lyon at the RBU in 1978 to work on biochemical genetics. “And it’s still very relevant today because X-chromosome inactivation was 768
one of the early examples of epigenetic gene regulation.” Inactivation, a complex and multilayered process, is still a flourishing research topic. Lyon’s career began in 1946 when she graduated from Cambridge University with a science degree, specialising in zoology. She started a PhD in genetics with R A Fisher, but finished it at Edinburgh University where there were more of the facilities she needed. By the time Lyon had completed her PhD the world was becoming evermore concerned with the consequences of radiation, and she joined a research group studying radiation mutagenesis headed by geneticist Toby Carter. In 1954, he moved to Harwell as Head of the Genetics Section; Lyon went with him, taking over his job in 1962, and remaining at Harwell for the rest of her life. X-inactivation was far from Lyon’s only preoccupation. “She contributed greatly to many topics including the part of the mouse genome known as the t-complex”, says Elizabeth Fisher, now Professor of Neurogenetics at University College London but in the 1980s a Harwell PhD student. The t-complex has a key role in fertility. “It was a real enigma because it was difficult to work out what was going on. At the time when Mary started to investigate it we didn’t have the molecular tools we have nowadays. She did remarkable work using simple genetic inheritance experiments.” Lyon also contributed to early work on stem cells, and was among the first to recognise the value of being able to preserve mouse embryos and gametes by freezing them. Fisher describes Lyon as having an incisive mind. “She could be intimidating, but only because she was head and shoulders above the rest of us in terms of her ability to think. She was kind, and had an interest in other people. But very reserved.” During the course of a conversation or an interview she was apt to lapse into a succession of silences to think through what she’d been told before she spoke again, which could be disconcerting for those unfamiliar with the habit. Peters agrees. “You had to decide what you wanted to ask her before you went in to see her. But she could be quite sociable, and she never refused an invitation to a party, though she seldom said much.” Lyon was respected, and held in affection by many of those who had worked for her. Lyon remained scientifically productive for many years after retirement, but the honours system never offered the reward that Fisher and others in the genetics community believe she deserved. The term Lyonisation may be her most evident memorial, but it’s not alone. The Genetics Society has created a Mary Lyon Medal awarded annually for outstanding research in genetics, and the UK’s Medical Research Centre established the Mary Lyon Centre for mouse functional genomics in 2004. So, using the more familiar spelling of the word, it could be said that for her long and illustrious career Lyon has been rightly lionised. She is survived by a sister and a brother.
Geoff Watts www.thelancet.com Vol 385 February 28, 2015