Edinburgh Research Explorer Dolly at Roslin Citation for published version: Myelnikov, D & Garcia Sancho Sanchez, M (ed.) 2017, Dolly at Roslin: A Collective Memory Event. University of Edinburgh, Edinburgh. Link: Link to publication record in Edinburgh Research Explorer General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 07. Oct. 2021 Dolly at Roslin A Collective Memory Event Alan Archibald Robin Lovell-Badge Angelika Schnieke John Bracken Jim McWhir Bruce Whitelaw Alan Colman Bill Ritchie Ian Wilmut Harry Griffin Helen Sang Edited by Dmitriy Myelnikov and Miguel García-Sancho With a foreword by Grahame Bulfield Dolly at Roslin A Collective Memory Event Old College, University of Edinburgh • 19 April 2016 Alan Archibald Robin Lovell-Badge Angelika Schnieke John Bracken Jim McWhir Bruce Whitelaw Alan Colman Bill Ritchie Ian Wilmut Harry Griffin Helen Sang Edited by Dmitriy Myelnikov and Miguel García-Sancho With a foreword by Grahame Bulfield © University of Edinburgh, 2017 Science, Technology and Innovation Studies University of Edinburgh Old Surgeons’ Hall High School Yards Edinburgh eh1 1lz United Kingdon isbn 978-1-5272-0503-1 Designed by Dmitriy Myelnikov Contents Foreword ii Introduction iv Timeline of key events ix Participants x 1. Roslin, PPL, and the pharming programme 1 2. Dolly and her flock 9 3. Funding Dolly 24 4. Species choice 30 5. Dolly’s legacy 33 Notes 42 Acknowledgements 45 Foreword Grahame BuLfIeld Director of Roslin Institute, 1988–2002 The publication of the research paper in 1997 on the cloning of the first animal from an adult cell – Dolly the sheep – caused a scientific and media storm. The scientific breakthrough, long thought to be impossible, was achieved by a small team from Roslin Institute led by Ian Wilmut together with colleagues from its spin off company PPL Therapeutics. This is a transcript of a Collective Memory Event held on the 19th April 2016 with members of the team and other colleagues closely involved. Of course, al- though 1997 is seen as the date of the publication of the research, its origins lie much earlier, not only with the birth of Dolly in 1996, the cloning of Megan and Morag from embryo cells in 1995, but also with the long standing interest of Ian Wilmut and his group in the potential totipotency of somatic cells and in the derivation of stem cells. Indeed, I first heard in detail of Ian’s research objectives in December 1988, a few days after I became Head of Roslin,i nearly a decade be- fore the publication. The question I was most asked at the time was ‘why is Roslin doing this re- search?’ It appeared strange, if not incomprehensible, for a small agriculturally- oriented Institute in Scotland to be working on such a challenging topic, which seemed, at first glance, to have no practical relevance. In the late 1980s and early 1990s, the molecular biology revolution was sweeping through biological re- search. The first genetically modified / transgenic animal (a mouse) had been pro- duced and the beginnings of the genomics revolution were in place. Roslin, like many other biological research institutes, decided it had to adopt these technolo- gies, especially as no one else was doing so in farm animals, which is where Ros- lin’s expertise lay. Transgenic sheep had been produced in Roslin and a company, PPL Therapeutics, ii was established to exploit the technology, although prima- rily in producing pharmaceuticals rather than for animal breeding. Fortunately as a government sponsored Institute, Roslin (in collaboration with John Innes Institute) managed to persuade their parent organisation and main funder, the BBSRC,iii to establish decade-long research programmes in transgenics and stem cells, and in gene mapping and genomics. For routine use in animal breeding, there were problems with transgenic tech- nology, especially that it was too inefficient. Less than one per cent of injected eggs produced viable transgenic offspring and almost all commercially important traits in farm animals are controlled by many genes, whose number, identity and characteristics are all unknown.iv It was to improve transgenic technology that Ian Wilmut proposed using nuclear transfer from somatic cells; the programme was funded under the new BBSRC initiative and Keith Campbell was appointed as the post-doc on the project. The first cells targeted were from a stable embryo cell line isolated by Jim McWhir, and produced Megan and Morag, the first cloned sheep, in 1995. Next year, the group’s main aims were to repeat the experiment with embryo cells but also foetal fibroblasts, which they thought to be the most suitable cells for manipulation. It was only because extra sheep were available and a suitable mammary cell line had been produced at PPL, that the team had adult cells that could be used to produce Dolly. This Collective Memory Event brings together most of the scientists involved in the experiments: Ian Wilmut who led the team, Bill Ritchie who carried out the embryo manipulations and John Bracken who cared for the animals, together with scientists from PPL Therapeutics, Alan Colman, its Research Director, and ii Angelica Schnieke who produced the mammary cell line. They are joined by oth- er Roslin colleagues: Harry Griffin who was at the time Assistant Director of Sci- ence (and later Director); Alan Archibald, leading Roslin’s genomics programme; Bruce Whitelaw leading mammalian transgenics; and Helen Sang leading poultry transgenics. The event was chaired by Robin Lovell-Badge, a leading figure in transgenesis who was also a member of the Roslin Governing Council at the time when these events took place. These are then the genuine voices of what hap- pened at Roslin in the mid-1990s and their recollections make a fascinating story of not only the scientific research but also the complex interactions that took place. It is only so very sad that John Clark and Keith Campbell, so much leading players in these events, were no longer with us and able to take part. The cloning of Dolly was in some ways a diversion from what Roslin was trying to achieve; later experiments did in fact produce cloned animals from manipulated foetal fibroblasts cells with working human genes and capable of producing pharmaceuticals, but this success got lost in the furore of Dolly’s arrival. Although the farm animal genomics programmes have now identified many genes controlling commercially important traits, the political climate has strongly inhibited the use of GM technology in practical animal breeding. The Dolly publication also generated much public, media and government in- terest. Roslin was overwhelmed with TV crews and request for interviews; myself and Ian Wilmut were called to a special meeting of the House of Commons Select Committee on Science and Technology that was squeezed in a few weeks later, just before the 1997 General Election. The ethics of the technology were debated at the Human Genetics Advisory Commission in the UK and at by various bod- ies in the EU, USA and the rest of the world. One positive side of all this atten- tion was that Roslin’s policy of openness about its research (mainly executed by Harry Griffin) turned out to be very successful and Roslin became seen as a ‘safe pair of hands’; we were asked for our opinion by the media and Government on many biotechnology issues, not all in our area of expertise. This interest contin- ues up to the present. In 1998 Roslin established a second company, Roslin BioMed, with £6 M of funding from the 3i Venture Capital Group, in order to develop the cloning tech- nology. It was the multimillion pound sale of Roslin Biomed to the Californian biotech company, Geron, that stimulated more political interest. Roslin affairs were examined by the National Audit Office; myself and Harry Griffin had to at- tend the House of Commons Public Accounts Committee to explain and justify our actions. The money Roslin received from the sale to Geron was put into a Foundation, which continues to fund research at Roslin. The story of ‘Dolly the Sheep’ is one of a formidable piece of research with a seemingly impossible objective, outstanding success from the persistence and skill of an excellent team of scientists, to its explosion into the public domain which engulfed those involved, producing many lessons, not only of science strategy, but also of the role of scientists in their interaction with commercial companies, the Government and the public; the voices of those involved add much to the story. i. I have used the name Roslin Institute throughout this foreword, but although its origins go back to 1919, the Institute only adopted its current name in 1993. ii. PPL Therapeutics Ltd. was founded in 1987 as Caledonian Transgenics, but was soon re- named Pharmaceutical Proteins, Limited, and eventually, PPL. iii. The Biotechnology and Biological Sciences Research Council (BBSRC), the ‘owners’ of Ros- lin Institute at this time, was only founded in 1994, although its origins go back to the forma- tion of the Agricultural Research Council in the 1930s. iv. A solution to the gene identity problem came from the genomics programmes. iii Introduction Dmitriy MyeLnIkov & MigueL GarcÍA-SAncho Science, Technology & Innovation Studies, The University of Edinburgh Born on 5 July 1996, Dolly the sheep was the first animal to be cloned from an adult cell, and became the most iconic member of her species.