Frozen: The story of Frostie the calf

Frostie calf CROPIan Wilmut is best known for his involvement with the team which cloned Dolly the sheep in 1996. However, his scientific career, which spans more than five decades, includes a variety of groundbreaking achievements and discoveries, which are being revealed as his papers are catalogued as part of the continuing ‘Towards Dolly’ and ‘The Making of Dolly’ projects.

Ian Wilmut initially wished to work as a farmer, but he ‘shuffled sideways into scientific research’*, as he puts it, and ultimately won a scholarship as an undergraduate at Nottingham University to work for two months under Chris Polge at  the Animal Research Station in Cambridge. His role was to help out generally with experiments, but he soon became fascinated by embryos, and returned to work with Polge once he graduated. Wilmut’s PhD, awarded in 1971, was on the freezing of boar semen. Copies of Wilmut’s published papers exist in the archive from 1969 onwards, and a glance through the papers which appeared over the next decade reveal Wilmut’s wide-ranging research on the effects of freezing, thawing and warming on embryos and spermatozoa in mice, sheep and cattle.

In 1973, Wilmut was the first scientist to successfully freeze a calf embryo (using liquid nitrogen), thaw it, and transfer it to a surrogate mother. This process led to the birth of a healthy red and white Hereford-Friesian cross calf, which Wilmut wryly named ‘Frostie’. Wilmut’s findings were published within a few weeks of Frostie’s birth in The Veterinary Record as ‘Experiments on the low-temperature preservation of cow embryos’ (June 30 1973, 686-690), and a copy of the reprint survives in the archives. Wilmut has remarked that this was ‘one of the fastest scientific publications ever’. It also led to some considerable interest from the world’s media, with Wilmut appearing on television and newspapers from as far away as New Zealand seizing upon the story. This media attention was a precursor to the storm which Wilmut, Keith Campbell and team would generate two decades later when Dolly the sheep was born. Wilmut’s discovery of the viability of frozen embryos to produce healthy offspring has since been used across many different species in agriculture and also for the conservation of rare breeds. The first human to be born from a frozen embryo was Zoe Leyland, born in Melbourne in 1984.

Wilmut’s work with Chris Polge equipped him with many of the techniques in reproductive physiology which would instruct his later work on cloning, nuclear transfer, stem cell and regenerative medicine in Edinburgh, where Wilmut moved in 1973. Throughout his career Wilmut has been inspired by the possibilities of advances in reproductive physiology and biotechnology for fertility treatments,practical applications to the farming industry and breakthroughs in treatments or cures for debilitating genetic diseases.

*All quotes taken from The Second Creation: the age of biological control by the scientists who cloned Dolly, I. Wilmut. K. Campbell and C. Tudge (London, 2000).
Clare Button
Project Archivist

Research and Refugees – Edinburgh genetics during the 1940s

George Clayton

Last Friday I delivered a talk on genetics in Edinburgh during the 1940s as part of the Scotland-wide Festival of Museums, for which Edinburgh University Library and Collections took the 1940s as its inspiration. This was of course a turbulent decade for the world in general, but not least for the science of genetics. In the four decades since the rediscovery of Mendel’s laws in 1900, scientists were gaining a greater understanding of the gene through the chromosome theory of inheritance and mutation studies, yet the discovery of the structure of DNA itself was yet to be discovered. The 1940s represented a crossroads for genetics, and Edinburgh was an important world player in its future.

Let us begin in the year 1939, when Edinburgh’s Institute of Animal Genetics hosted the prestigious 7th International Congress of Genetics. Originally scheduled for Moscow in 1937, the repressive Stalinist regime made this impossible. After some discussion, Edinburgh was chosen as the most appropriate location for the Congress, now rescheduled for the last week in August 1939. Over 40 Russian scientists were to give papers, alongside delegates from all over the world. However, it would not be plain sailing. Shortly before the Congress was due to begin, the director of the Institute Francis Crew received word that the Russians had been forbidden to attend, and the Congress programme had to frantically reshuffled. Things went from bad to worse once the Congress actually began, as war erupted across Europe and delegates from various countries began to return to their home countries while they could. Once the Congress was over, Crew, who was on the Territorial Reserve of officers, was mobilised, and posted to the command of the military hospital at Edinburgh Castle. He left the Institute in the hands of poultry geneticist Alan Greenwood.

KB Home Guard transport

The King’s Buildings Home Guard Transport Unit

During the lean five years which followed, the Institute did its bit for the war effort. The land adjoining the Institute building was used for allotments for growing animal feed and planting vegetables. All male staff joined the ARP or Home Guard as well as the Watch and Ward parties for the protection of University buildings, while the women were involved in First Aid work. The annual report for 1940-41 records that everyone was given ‘a daily dose of halibut liver oil to reduce the incidence of winter colds’! Genetics teaching and research continued as much as possible by a skeleton staff, including Charlotte Auerbach, who would make a major scientific discovery during this period.

Lotte Auerbach, Wadd birthday album

Charlotte Auerbach

Charlotte (‘Lotte’ to her friends) Auerbach was from a scientific German Jewish family, and had sought refuge in Edinburgh after being dismissed from her teaching job in Berlin under Hitler’s anti-Semitic laws. Once established at Crew’s Institute, she had begun a developmental study of the legs of Drosophila, the fruit fly. But the arrival at the Institute of Hermann Joseph Muller in 1937 changed Auerbach’s career forever. Muller was the outstanding scientist of his generation: he had been part of Thomas Hunt Morgan’s famous ‘Fly Room’ at Columbia University in the 1910s, helping to formulate the groundbreaking chromosome theory; Muller’s later discovery that X-rays cause mutation, gained him the Nobel Prize in Physiology or Medicine. But he arrived in Edinburgh a broken man after undergoing political and racial persecution in America, Germany and the Soviet Union. Muller had a radical effect on the staff and students at the Institute, and he quickly interested Charlotte Auerbach in mutation studies.

In 1940, the year Muller returned to America, Auerbach and her colleague J.M. Robson were tasked with conducting research into mustard gas. They were not told the true nature of the work, which had been commissioned by the Chemical Defence Establishment of the War Office. Auerbach reported sustaining horrific injuries to her skin from working with the gas with inadequate apparatus, but it shortly became clear that the results were astonishing for the science of genetics. Mustard gas caused mutations in similar ways to X-rays. Although this important discovery had to be kept confidential until after the war, Auerbach would be awarded the prestigious Keith Prize from the Royal Society of Edinburgh for the work.

Waddington portrait

Conrad Hal Waddington

Once the war ended, it was assumed that Crew would return to the Institute and that research would continue much as before. However, Crew felt he had been left behind by recent advances in genetics, and decided to transfer to the Chair of Public Health and Social Medicine at the University. Around the same time, the government were looking to move scientific research into areas of agricultural interest, following the acute food shortage crisis of the war years. It was decided to establish a National Animal Breeding and Genetics Research Organisation (NABGRO, later ABRO), and Edinburgh’s strong track record in genetics, animal breeding research and veterinary medicine made it the obvious choice. Conrad Hal Waddington, a developmental biologist and embryologist, was appointed director of the new Genetics Section of NABGRO, which moved to occupy the more-or-less empty Institute building. Alan Greenwood moved to become director of the newly-formed Poultry Research Centre, next door to the Institute.

Staff socialising at the Institute of Animal Genetics, c. 1955

Staff socialising at the Institute of Animal Genetics, c. 1955

ABRO’s work was to be split between research into fundamental work on genetics and the applied science of animal breeding and livestock improvement. However, conflict soon arose between the experimental geneticists and the animal breeders, which was not helped by the rather bizarre initial arrangement of Waddington, his staff and their families living together under one roof, taking their meals communally and driving to work together every day. As might be imagined, there were some scandals and arguments, and eventually the arrangement disintegrated and administrative shifts took place to accommodate the rift.

Waddington set about recruiting as many promising research workers as he could, including some of his old army contacts from his days in Operational Research and Coastal Command. One scientist who joined the Institute at this time, Toby Carter, had been in the RAF at the time of the fall of Singapore, and had commanded the only boat to escape towards Java.  A diploma course in genetics was established, and laboratory space increased apace. By 1951, Waddington’s staff numbered 90 and the Institute grew to become the largest genetics department in the UK and one of the largest in the world.

By the time the 1950s arrived, molecular biology was on the horizon, paving the way towards advances in genomics and biotechnology which we see today. Edinburgh has consistently remained at the forefront of these advances, but it is interesting to reflect that early organisations such as the Institute of Animal Genetics and ABRO paved the way, and that the 1940s was a hugely important decade for this evolution.

Clare Button
Project Archivist

William Bateson’s Books in the Roslin Collection at the University of Edinburgh

In 1908, biologist William Bateson (1861-1926) became Britain’s first professor of genetics at the University of Cambridge. He was known for his interest in studying inheritance traits and Mendel’s research and was the first to translate his works into English. With Reginald Crundall Punnett, Bateson published a series of breeding experiments that extended Mendel’s theory to animals and showed, contrary to Mendel, certain features were consistently inherited together which was termed linkage.

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We are lucky enough to have seven books in the Roslin Rare Book Collection that belonged to William Bateson. They are :  Instruction sur la maniere d’elever et de perfectionner la bonne espece des betes a laine de Flandre, 1763; Browne, D J, The American Poultry Yard, 1863; Dixon, Reverend Edmund Saul, Ornamental and Domestic Poultry, 1848 (showing the title page and flyleaf with Bateson’s signature); Dickson, Walter B., Poultry: their breeding, rearing, diseases, and general management, 1847; Croad, AC, The Langshan Fowl, it’s history and characteristics, 1889; Poli, A and G Magri, Il bestiame bovino in Italia, 1884; and ; Nathusius, Hermann, Vortrage über Viehsucht,1872.

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As it is apparent from this small selection of books, Bateson’s interests were fairly diverse. He went on to accept the Directorship of the John Innes Horticultural Institute at Merton, England in 1910 and many of the books in the Roslin Collection contain the library stamp from this organisation, but whether it was Bateson acquiring these books or another scientist, it is unclear.  That Bateson’s books are found in the Roslin Collection highlights thelinks between the research scientists were conducting in both Cambridge and Edinburgh in the early/mid 20th century.

Beautiful Books Breeding in the Roslin Rare Books Collection

The Roslin Collection comprises a surprisingly wide-range of material from archival papers, the bound collection of scientific offprints and glass slides. It also includes 71 books on agriculture, animal breeding and genetics. The span of topics and time is remarkable – the earliest book in the collection is a book on Italian horse breeding from 1573 Roslin Il Caualerizzoup to a book on Scottish photography from 1999!  These books were used by scientists at the Institute of Animal Genetics Library, Edinburgh; Animal Breeding Research Organization and Animal Breeding Research Department, University of Edinburgh; University of Edinburgh Agricultural Department, Poultry Research Centre, the Commonwealth Breeding Organization, Imperial Bureau of Animal Breeding and Genetics and Roslin including Professor Robert Wallace and FAE Crew. Some books contain beautiful fold-out illustrations and may have some annotations.

To give you an idea of the scope of the collection:

Corte, Claudio, Il Cauallerizzo de Claudio Corte da Pauia, 1573; Instruction sur la maniere d’elever et de perfectionner la bonne espece des betes a laine de Flandre, 1763; Buc’hoz, Traité Economique et physique des oiseaux de basse-cour, 1775; Hunter, A., Georgical Essays, 1777; Bakewell and Culley, Letters from Robert Bakewell to George Culley, 1777; Great Britain Board of Agriculture, Communications to the Board of Agriculture, vol. 1-7,1797-1813; Salle-Pigny, F.A., Essai sur l’education et l’amelioration des betes a laine…, 1811; Desaive, Maximillian, Les Animaux Domestiques, 1842; Low, David, The Breeds of the Domestic Animals of the British Islands Vol. 1 & 2, 1842; Dickson, Walter B., Poultry: their breeding, rearing, diseases, and general management, 1847; Dixon, Reverend Edmund Saul, Ornamental and Domestic Poultry, 1848; Dickson, James, The Breeding and Economy of Livestock…, 1851; Youatt, William, The Dog, 1852; Doyle, Martin (ed), The Illustrated Book of Domestic Poultry, 1854; Wegener, J.F. Wilhelm, Das Hühner- Buch, 1861; Brown, D J, The American Poultry Yard, 1863; Charnace, Le Cte Guy de, Etudes sur les animaux domestiques, 1864; Youatt, William, Sheep, 1869; Bates, Thomas, The History of Improved Short-Horn or Durham cattle …, 1871; Nathusius, Hermann, Vortrage über Viehsucht,1872; Coleman, J, The Cattle of Great Britain: being a series of articles on the various breeds…vol.1 & 2, 1875; La Pere de Roo, Monagraphie des Poules, 1882; Tegetemeir, WB, Pigeons: their structure, varieties, habits, and management, 1883; Poli, A and G Magri, Il bestiame bovino in Italia, 1884; McMurtrie, William, Report upon an examination of Wools and other Animal Fibres, 1886; Croad, AC, The Langshan Fowl, it’s history and characteristics, 1889; Wright, L, The Practical Poultry Keeper, 1890; Tegetmeier, WB, Poultry for the Table and Market…, 1893; Gordon, DJ, The Murray Merino, 1895-96; Theobald, Fred V., The Parasitic Diseases of Poultry, 1896; Felch, IK, Poultry Culture. How to Raise, Manage, Mage and Judge, 1898; Hearnshaw, Roger R, The Rosecomb Bantam, 1901; Weir, Harrison, Our Poultry and All About Them, Vol. 1 & 2, 1902; Parlin, S W, The American Trotter, 1905; Axe, Professor J Wortley, The Horse: its treatment in health and disease, Vol. 1-9, 1905; Davenport, CB, Inheritance in Poultry, 1906; Gunn, WD, Cattle of Southern India, 1909; Committee of Inquiry on Grouse Disease, The grouse in health and in disease Vol. 1 & 2, 1911; Hewlett, K, Breeds of Indian Cattle, Bombay Presidency, 1912; Lewis, Harry R, Productive Poultry Husbandry, 1913; Bateson, W, Mendel’s Principles of Heredity, 1930; Punnett, RC, Notes on Old Poultry Books, 1930; Houlton, Charles, Cage-bird hybrids : containing full directions for the selection, breeding, exhibition and general management of canary mules and British bird hybrids, 1930; Prentice, E Parmale, The History of Channel Island Cattle: Gurnseys and Jerseys, 1930; Hays, FA and Klein, GT, Poultry Breeding Applied, 1943; Odlum, George M, An Analysis of the Manningford Herd of British Friesians, 1945; Heiman, Victor (editor), Kasco Poultry Guide, 1950; Schlyger, Hühnerrassesn, c1951; Hartley and Hook, Optical Chick Sexing, 1954; Tyler, Cyril, Wilhelm von Nathusius 1821-1899 on Avian Eggshells, 1964; Marsden, Aloysius, The effects of environmental temperature on energy intake and egg production in the fowl, 1981; Ford, Donald, Millennium Images of Scotland, 1999; Bayon, HP, Diseases of Poultry: their prevention and treatment, n.d.

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This collection of books provide a valuable resource for the collection as it offers an insight into what the scientists were reading and researching over the years. Over then next few weeks I’ll be highlighting some of the gems of the collection!