genome | Towards Dolly

M.M. Perry, R. Phillips, S. Dare-Delaney, M. Lyon, Edinburgh (1950s), from EUA IN1/ACU/A1/5/7

We were saddened to hear recently of the passing of Mary Lyon, a distinguished mouse geneticist. Born in 1925 in Norwich, Mary was best known for her X-chromosome inactivation hypothesis, which proposed that one of the two X chromosomes in every cell of female mammals is inactivated. Mary worked at the MRC Radiobiology Unit in Harwell from 1955 until her death, becoming head of the genetics division (later the Mammalian Genetics Unit) in 1995. What is perhaps not so well-known is that her early work took place in Edinburgh, at the Institute of Animal Genetics.

Mary began at the Institute in 1948 to continue her PhD on mouse genetics, which she had begun in Cambridge under R.A. Fisher. This was after studying zoology at Girton College, Cambridge (although, as women were not allowed to be official members of the University until 1948, Mary was only awarded a ‘titular degree’). The Institute of Animal Genetics, then under the directorship of C.H. Waddington, possessed superior histology facilities, which she needed for her work. Mary ended up staying for a further five years after her PhD, working with Toby Carter on a project funded by the Medical Research Council to study mutagenesis in mice (this was at a time, following the Second World War and atomic bombs in Japan, of great concerns about the effects of nucelar fallout in the atmosphere). In a 2010 interview, Mary Lyon stated that, out of her whole career, it was her time in Edinburgh that she enjoyed the most: ‘It was a very lively academic atmosphere…a big genetics lab and a lot of able and enthusiastic geneticists.’ The above photograph, from the Institute of Animal Genetics archives, shows Mary (far right) with (right to left) Institute Librarian Stella Dare-Delaney, Mary’s assistant Rita Phillips, and distinguished molecular geneticist and embryologist Margaret Perry.

Toby Carter’s Mutagenesis Unit moved south to Harwell in order to find more space in which to breed and keep mice, taking Mary with it, as well as Rita Phillips. Scientists working with Douglas Falconer in Edinburgh had been the first to discover X-linked mutants in mice. With this discovery in mind, Mary, noticed that female mice carrying X-linked coat colour mutations had mottled coats. Male mice which inherited a mottled coat (i.e. a mutant gene on their single X-chromosome) all died, but the females survived. This must mean that the female possessed one, inactivated, mutant gene on one X-chromosome, but a normal gene on the other chromosome, which was activated – therefore a female mouse needs only one X chromosome for normal development. This inactivation of one of the two X chromosomes in the cells of females is still called ‘Lyonisation’, and the discovery had profound implications for understanding the genetic basis of X-linked diseases such as Duchenne Muscular Dystrophy. Grahame Bulfield, later director of the Roslin Institute, first positioned the mouse muscular dystrophy mutant on the X-chromosome using Mary’s stock of mouse X-chromosome mutants.

Over the next six decades, Mary also made important studies of Chromosome 17 and ‘the t-complex’, which had significant bearings on the understanding of non-Mendelian inheritance (a departure from the expected one-to-one ratio due to the abnormal segregation of chromosome pairs). Mary’s work pioneered the use of the mouse as a model organism for advances in cell and developmental biology as well as molecular medicine, and laid the foundations for comprehending the human genome. She chaired the Committee on Standardised Genetic Nomenclature for Mice from 1975 to 1990, was made a foreign associate of the US National Academy of Sciences, and was a Fellow of the Royal Society (being the 28th woman to be elected such). In 2004, the Mary Lyon Centre opened at Harwell, a leading international centre for mouse genetics, and in 2014 the UK Genetics Society created the Mary Lyon medal.

Mary died on Christmas Day 2014, aged 89, ‘after drinking a glass of sherry, eating
her Christmas lunch and settling down in her favourite chair for a nap’.

The University of Edinburgh’s remembrance of Mary Lyon can be read here: http://www.ed.ac.uk/news/staff/obituaries/2015/mary-lyon-030215

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Project Archivist

Sources:

– ‘The Gift of Observation: An Interview with Mary Lyon’, Jane Gitschier (2010), http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000813
– ‘Mary F. Lyon (1925-2014): Grande dame of mouse genetics’, Sohaila Rastan, Nature, 518, (05 February 2015)

Glass slide, which probably once belonged to James Cossar Ewart, showing the tsetse fly (Coll-1434/3139)

It was announced last week that scientists have deciphered the genetic code of the tsetse fly, which offers hope of eradicating one of Africa’s most deadly diseases. The fly, which is only found in Africa, carries parasitic micro-organisms which cause sleeping sickness (trypanosomiasis) in humans by attacking their circadian rhythms (biological clock) and can be fatal if left untreated. As well as the threat to people, the tsetse can have equally devastating effects on animals, particularly livestock, causing infertility, weight loss and decrease in milk production. By also rendering animals too weak to plough, the consequences for farmers can be catastrophic. Since the parasite can evade mammals’ immune systems, vaccines are useless, and control of the tsetse is currently only achievable through radiation, pesticides or trapping.

James Cossar Ewart with one of his zebras in Penicuik, outside Edinburgh, c.1900 (GB 237 Coll-14/4/6)

James Cossar Ewart with one of his zebras in Penicuik, outside Edinburgh, c.1900 (Coll-14/4/6)

Concerns about the tsetse fly in Africa date from far before such advances in genetics could hope to help. There are several letters in James Cossar Ewart’s archives which give an insight into how the problem was being dealt with over a century ago. As you may remember from other posts, Ewart, Professor of Natural History at the University of Edinburgh from 1882 to 1927, famously conducted cross-breeding experiments with zebras and horses on his home farm in Penicuik. It is perhaps not too surprising then, that zebras featured in Ewart’s thoughts about the tsetse fly…

Ewart’s letters show that between 1903 and 1909 he was corresponding with various individuals involved in the administration of East Africa (which was then a protectorate of the British Empire), where the tsetse fly was a great problem, particularly where animals such as horses – which were invaluable for transport – were being infected. Ewart believed his zebras could be the solution, if it could be shown that they were immune to the disease the fly carried. (Ewart had already been researching the potential of zebras and zebra hybrids as alternative pack and transportation animals in military, mining and agricultural contexts around the world). However, in June 1903, a letter from Ewart’s regular correspondent, the German animal dealer and trainer Carl Hagenbeck, regretfully informed Ewart that three zebras had died in Berlin after being infected. However, hope was not lost; a month later, Alice Balfour (sister of the 1st Earl of Balfour) wrote to Ewart wondering whether cross-breeding infected zebras with healthy horses might lead to an immune hybrid strain being created. As a matter of fact, zebras are indeed immune to the bite of the tsetse, with some theories holding that zebras have evolved stripes to confuse the flies and deter attack. In 1909, the author, soldier and hunter Lieutenant-Colonel John Henry Patterson wrote to Ewart stating that it was a shame zebras were not easily domesticated, as East Africa sorely needed animal transport immune from ‘the fly’.

Glass slide, which probably once belonged to James Cossar Ewart, showing the distribution of the tsetse fly across Africa (GB 237 Coll-1434/2058)

Glass slide, which probably once belonged to James Cossar Ewart, showing the distribution of the tsetse fly across Africa (Coll-1434/2058)

We don’t know from Ewart’s correspondence whether zebras did end up being used in East Africa, although they have remained useful to the present day – in 2010, for instance, it was announced that cattle in East Africa were being scented with zebra odour in order to deter the tsetse!

These letters offer an insight into ways of tackling the tsetse problem through species selection and cross-breeding before scientific advancement enabled the full sequencing of the tsetse genome.

See the catalogue of James Cossar Ewart’s paper here:
http://www.archives.lib.ed.ac.uk/towardsdolly/cs/viewcat.pl?id=GB-237-Coll-14&view=basic

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Project Archivist

Towards Dolly

Edinburgh, Roslin and the Birth of Modern Genetics

Tag Archives: genome

Mary Lyon (1925-2014) – Edinburgh connections

New Strides, Old Stripes: Zebras and the tsetse fly