Life Story & Education

Figure 1.

Early Life

Mary Lyon was born on May 15, 1925 in Norwich, England, the oldest of three siblings. Her parents were Clifford Lyon, a civil servant employed by the Inland Revenue, and Louise Lyon, a school teacher. Due to her father's job, Lyon's family frequently moved to various parts of the country, including Yorkshire and Birmingham. The outbreak of World War II led them to move to Woking, Surrey. It was during her time at King Edward VI grammar school in Birmingham that Lyon's interest with biology started as a result of winning a competition that awarded her a collection of books on nature and wildlife (Rastan 2015).

Academia

In 1943, Mary Lyon enrolled at Girton College, which was part of the University of Cambridge. There, she pursued a multidisciplinary curriculum that included zoology, physiology, and biochemistry. Although her primary focus was on zoology, she became increasingly interested by the emerging notion that genes played a fundamental role in shaping all aspects of embryological development (Rastan 2015).

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POSTSCRIPT

Admitting women to degrees would give them the right to participate in decision-making at the higher levels of these institutions and many men during the early 20th century were not keen to budge (McMurran and Tattersall 2017).

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Academia

Lyon was among the 500 women enrolled at Girton College, a stark contrast to the 5000 men attending the university. Although she pursued the same courses and completed identical exam materials as her male counterparts, women only received a "titular" degree instead of a regular degree, unlike their male counterparts. This gender disparity in degree recognition was a reflection of the gender norms in place during that era.

Lyon's experiences at Girton College laid the groundwork for her future contributions to genetics. After her time at Girton, she went on to pursue a Ph.D. in the emerging field of mouse genetics, setting the stage for her groundbreaking work on X-chromosome inactivation (Rastan 2015).

Ph.D - Initial Program

Mary F. Lyon began her Ph.D. program in the field of mouse genetics. Her Ph.D. studies started at the University of Cambridge in 1946, working with a renowned geneticist R. A. Fisher. Her research focused on the emerging field of mouse genetics, particularly studying coat colour mutations in mice. This period at Cambridge marked the beginning of her influential career in genetics. Lyon observed intriguing behaviours and characteristics in mice with the pallid mutation. Her curiosity about the underlying causes of these phenotypes led her to explore the genetic basis of these traits. Her supervisor R. A. Fisher, was not interested in developmental genetics, and Lyon, drawn to the relevance of mouse genetics and its possible connection to human studies. Which caused her to search for a new environment for her to continue her research (Rastan 2015).

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Ph.D - 2nd Program

In 1948, in search for improved histology facilities to finalize her doctoral studies, Lyon relocated to the Institute of Animal Genetics at the University of Edinburgh. This institute was under the leadership of C. H. Waddington, an embryologist whose work had a profound impact on Lyon. Conrad H. Waddington's return from his wartime post as a scientific advisor to the Royal Air Force presented Lyon with an opportunity to explore developmental genetics under his supervision. Lyon conducted her doctoral studies under the supervision of Douglas S. Falconer, who was a prominent geneticist and embryologist. She continued her research career, notably contributing to the understanding of X-chromosome inactivation and becoming a prominent figure in mouse genetics. Her work on pallid mice led her to observe that these mice exhibited a distinctive behavior of tipping their heads to one side. Lyon's investigations into the basis of this phenotype revealed that it was caused by the absence of otoliths in the inner ear. This research contributed to her understanding of the genetic basis of observable traits.

Medical Research Council

Lyon's Ph.D. work in Edinburgh laid the foundation for her subsequent research at the Medical Research Council (MRC) Radiobiology Unit at Harwell. There she continued to make significant contributions to the field of mouse genetics, particularly in the context of X chromosome inactivation. What made the Medical Research Council (MRC) so special was its commitment to gender equality in compensation. Waddington applied to MRC on her behalf which gained her postdoctoral funding that allowed Mary to continue her research in Edinburgh. During this period, she collaborated with Toby Carter to investigate the inherited genetic risks associated with exposure to ionizing radiation—a topic of that required much attention as a result of the aftermath of World War II. Due to the extensive demands for research on mice, the entire mouse group from University of Edinburgh relocated to the MRC Radiobiological Research Unit at Harwell in 1955, under the leadership of John Loutit. During the late 1950s, a significant focus of her research was on the unique chromosome translocations originating from the mutagenesis work in Edinburgh. Mary made notable contributions in this field along with Toby Carter, Tony Searle, and Charles Ford (Fisher 2015).

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X-Linked Work

Mary Lyon's early awareness of X-linked mouse mutants from her Edinburgh days led her to focus on mottled mutants at Harwell. These mutants exhibited females with patches of two different coat colours, while males either faced embryonic death or had a single coat colour. A spontaneous mottled male caught Mary's attention, becoming a key subject in her research. This mouse's breeding revealed that a mutation occurring during embryonic stages resulted in a mosaic of mutated and normal X chromosomes. This insight extended to his mottled daughters, showcasing two cell types: one with an active gene and one without (Gartler 2014).

Nature

Building on her understanding of female mice requiring only one X chromosome for normal development and having sex chromatin in their nuclei, Mary delved into the work of Susumo Ohno. His discovery that sex chromatin was a condensed X chromosome prompted Mary's analysis of the mottled mouse, leading to the publication of her X inactivation hypothesis in Nature in 1961. This groundbreaking concept (now known as lyonization), proposed random inactivation of one X chromosome in early female embryo development. However, it faced skepticism, notably from geneticist Hans Gruneberg, who doubted the presence of patches of inactivated cells (Fisher 2015).

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1950's & Beyond

Mary edited the Mouse News Letter (MNL) from 1956 to 1970, fostering collaboration among postwar UK and USA mouse geneticists. Despite her numerous contributions, Mary's modesty and reluctance to seek recognition meant she did not receive all the honours she deserved. She was elected a Fellow of the Royal Society (FRS) in 1973 and a Foreign Associate of the US National Academy of Sciences in 1979 (Rastan 2015).

In the 1980s, Mary contributed to human and mouse homology maps, laying the groundwork for the Human Genome Sequencing Project. Her research at Harwell spanned various areas of mouse genetics, including the complex, embryo freezing for mouse stock preservation (with David Whittingham), and early work on mouse preimplantation embryos' X inactivation timing (with Richard Gardner) (Gartler 2014).

Personal Traits

Mary Lyon's quiet demeanor concealed an intellectual colossus with an extraordinary mind and memory. Her contributions were commemorated with the naming of the Mary Lyon Medal by the UK Genetics Society. Mary Lyon passed away peacefully on Christmas Day in 2014, leaving a void in the scientific community (Fischer 2015).

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Timeline of Accolades

Click here to view references for this page

Fisher, E. M. C. et. al. 2015. Mary Frances Lyon (1925-2014) Obituary. CELL. [accessed December 1, 2023]. 160(4), 577–578. https://doi-org.login.ezproxy.library.ualberta.ca/1

Gartler SM. 2014. A brief history of dosage compensation. Journal of Genetics. [accessed 2023 Nov 6]. 93; 591–595. https://doi-org.login.ezproxy.library.ualberta.ca/10.1007/s12041-014-0360-50.1016/j.cell.2015.01.039

McMurran SL, Tattersall JJ. 2017. Fostering academic and mathematical excellence at Girton College 1870–1940. In: Beery, J., Greenwald, S., Jensen-Vallin, J., Mast, M., editors. Women in mathematics, vol.10. Gewerbestrasse (CH): Springer; [accessed 2023 5 November]. p. 3-37. https://doi.org/10.1007/978-3-319-66694-5_1

Rastan S. 2015. Mary F. Lyon (1925–2014). Nature [accessed 2023 Oct 30]. 518; 36. https://doi.org/10.1038/518036a

Rastan S. 2015. Obituary: Mary F Lyon (1925–2014). Reproductive BioMedicine Online. [accessed 2023 Oct 30]. 30(6):566-567. https://doi.org/10.1016/j.rbmo.2015.02.007

Unknown. 2015. Mary F. Lyon. Journal of Genetics. [accessed December 1, 2023]. 94(4):561-562. https://search-ebscohost-com.login.ezproxy.library.ualberta.ca/login.aspx?direct=true&db=a9h&AN=112050795&site=eds-live&scope=site.

Photo References

Header photo courtesy of:

Figure 1 : Rastan S. 2015. Mary F. Lyon (1925–2014). Nature [accessed 2023 Oct 30]. 518; 36. https://doi.org/10.1038/518036a

Figure 2 : Button C. 2015 Feb 6. Mary Lyon (1925-2014) - Edinburgh connections. Towards Dolly: Edinburgh, Roslin and the Birth of Modern Genetics. University of Edinburgh; [accessed 2023 Nov 7]. https://libraryblogs.is.ed.ac.uk/towardsdolly/2015/02/06/mary-lyon-1925-2014-edinburgh-connections/

Figure 3 : The Royal Society. 2016 October 4. SCIENTIFIC MEETING : X-chromosome inactivation: a tribute to Mary Lyon. [accessed 2023 Dec 1]. https://royalsociety.org/science-events-and-lectures/2016/10/x-chromosome-inactivation/

Figure 4 : Independent. 2015 February 19. Mary Lyon: Groundbreaking scientist whose research led to a leap in our understanding of mammalian genetics. [accessed 2023 Dec 1]. https://www.independent.co.uk/news/obituaries/mary-lyon-groundbreaking-scientist-whose-research-led-to-a-leap-in-our-understanding-of-mammalian-genetics-10056466.html

Figure 5, 6, 7, 8, 9, 10: 2015. Mary F. Lyon. Journal of Genetics. [accessed December 1, 2023]. 94(4):561-562. https://search-ebscohost-com.login.ezproxy.library.ualberta.ca/login.aspx?direct=true&db=a9h&AN=112050795&site=eds-live&scope=site.

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