A Sample of the Roslin Institute’s Cloning Research Post-Dolly: 1998 and 2007

Dolly and Bonnie

As mentioned in a previous post, Dolly, the sheep caused a media sensation in 1997 as the first cloned animal using a nuclear transfer process  and so, I thought it would be interesting to highlight several articles that I came across on Dolly and cloning at the Roslin Institute in 1998 and then again in 2006. I wondered what cloning research had developed over the years since Dolly, the sheep’s birth in 1996 and surprisingly, or not, the articles I came across (that evoked Dolly) dealt with the issue of eating cloned animal meat and the ethical debate of cloning humans for medical purposes.

Note:  these four articles are just a sampling of the articles produced by the Roslin geneticists on the  issues, debates and research surrounding Dolly, nuclear transfer, animal and human genetics, cloning purposes (medical, agricultural, genetic conservation, etc..) to illustrate what way being discussed at the time. For more articles on these subject, please consult the Roslin Institute off-prints for 1998 and 2006 at GB237 Coll-1362/4/.

Update on DollyIn the 1998 Roslin off-print bound volumes, I found Harry Griffiths report, ‘Update on Dolly and nuclear transfer’ in the Roslin Institute, Edinburgh: Annual Report April 1, 97-March 31 (GB 237 Coll-1362/4/1848) and Sir Ian Wilmut’s article, ‘Cloning for Medicine’ in Scientific American, December 1998 (GB 237 Coll-1362/4/1897). Griffiths report describes Dolly’s creation by the Roslin geneticists and notes that their breakthrough caused several other groups to ‘take advantage of public interest in cloning to advertise their successes …. Calves cloned from adult animals were reported from Japan and from New Zealand.’ The New Zealand clone was from ‘the last surviving animal of a rare breed’  which highlighted the use of cloning to preserve endangered species. He continues with discussing Intellectual Property issues in relation to Professor Yanagimachi and his colleagues at the University of Hawai’i ‘Honolulu Cloning Technique’ and closes with a couple of paragraphs on human cloning. He notes the UK Human Genetics Advisory Commission and the Human Fertilisation and Embryology Authority’s report ‘Cloning  issues in Reproduction, Science and Medicine’ from 7 December, 1998 which recommends that ‘there should be a continued ban on all ‘reproductive  cloning’ – the cloning of babies – but gives cautious support  to the cloning of human cells for therapeutic purposes.’

IMG_4359Wilmut’s article in Scientific American reports on the how biomedical researchers are developing ways to use genetically modified mammals for medical purposes.  He mentions the sheep, Megan and Morag who were the first mammals cloned from cultured cells. A technique that allows cloned sheep to carry human genes and such animals produce milk that can be processed to create therapeutic human proteins. The sheep, Polly, is a transgenic clone of a Dorset sheep and ‘a gene for a human protein, factor IX, was added to the cell that provided the lamb’s genetic heritage, so Poly has the human gene.

In the 2006 Roslin off-print bound volumes, I found two fascinating articles:– Sir Ian Wilmut’s  ‘Human cells from cloned embryos in research and therapy’ in BMJ Vol. 328, February 2004 and J. Sark, et al.’s  ‘Dolly for dinner? Assessing commercial and regulatory trends in cloned livestock’ in Nature Biotechnology, Vol. 25, No. 1, January 2007.

IMG_4371Sir Ian Wilmut’s article ‘Human cells from cloned embryos in research and therapy’ in BMJ Vol. 328, February 2004 is one of the more contemporary papers in the collection that discusses stem cell technology and human cloning issues. He cites studies of human genetic diseases and how cloned cells ‘will create new opportunities to study genetic disease in which the gene(s) involved has not been identified’, specifically describing work with motor-neurone diseases. Then, Wilmut notes how stem cells could be used in treatments for a variety of degenerative diseases, i.e. cardiovascular disease, spinal cord injury, Parkinson’s disease and Type I diabetes. Finally Wilmut discusses the differences in regulation of nuclear transfer and human cloning in various countries, noting that in the United Kingdom, ‘project to derive cells from cloned embryos may be approved by the regulatory authority for the study of serious diseases. By contrast human reproductive cloning would be illegal.’

Dolly for DinnerThen, in 2007, the article by and J. Sark, et al’s ‘Dolly for dinner? Assessing commercial and regulatory trends in cloned livestock’ in Nature Biotechnology, ‘reviews the state of the art in cloning technologies; emerging food-related commercial products; the current state of regulatory and trading frameworks, particularly in the EU and the United states and the potential for public controversy.’

As you can see by these four examples there are a range of issues and concerns that have been discussed over the years. While advances are made in cloning and genetic modification, there are still ethical debates to be had and more research to be done. In reading over these and other similar articles in the Roslin off-prints, I enjoyed learning about the different uses of transgenic animals.

Dolly, Polly, Molly, Megan and Morag

Dolly and press Murdo MacleodHere on the ‘Towards Dolly’ team we couldn’t let the 05 July go by without celebrating our namesake, who was born on this day in 1996. To most people, Dolly the sheep (1996-2003) needs no introduction. The first mammal to be cloned from adult cells, Dolly was produced at the Roslin Institute, Edinburgh as part of research into producing medicines in the milk of farm animals. The creation of Dolly met with public acclaim and outcry, fuelling the continuing debates surrounding the ethics of cloning. Most people know the basics about Dolly (including, of course, how she acquired her name), but here are a few facts that may surprise:

Dolly’s birth was kept under wraps for seven months

Dolly’s birth was announced to the world in Nature (385, 753-844) on 27 February 1997, when Dolly was already seven months old. (This time delay was so that the research could be properly prepared for presentation.) Although the journal featured ‘Dolly’ on the front cover, the ‘announcement’ was couched in somewhat muted terms: ‘Viable offspring derived from fetal and adult mammalian cells.’ It is only towards the close of the article that the phrase ‘The lamb born after nuclear transfer from a mammary gland cell is, to our knowledge, the first mammal to develop from a cell derived from an adult tissue’ suggests the importance of the event. Even so, few people at Roslin realised what the strength and duration of public interest in Dolly would be.

 Clones pre-Dolly

Of course, there are naturally occurring clones in nature, such as in bacteria. In terms of laboratory cloning, transgenic frogs, mice and cows have been available from the 1980s onwards. The difference with Dolly was that it is so much more difficult to clone from an adult cell. Dolly was the only live lamb to emerge from 277 attempts.

Ever heard of Megan and Morag?

Megan and Morag were identical twin sheep cloned from the same embryo and were the first mammals to have been successfully cloned from differentiated cells. They were born at the Roslin Institute in July 1995. Although Megan and Morag never got the same level of publicity as Dolly was to have, there was a lot more resting on their birth. Crucially, Megan and Morag demonstrated that viable sheep can be produced by nuclear transfer from cells which have been cultured in vitro. The technical breakthrough which produced them made Dolly the sheep possible.

Polly and Molly the sheep

Since Dolly, other sheep have since been cloned from adult cells, as have cats, rabbits, horses, donkeys, pigs, goats and cattle. In 1997, two ewes were born at Roslin which were the first mammals to have been successfully cloned from an adult somatic cell (like Dolly) and to be transgenic at the same time. Scientists used cells into which a new gene had been inserted so that the animals produced a therapeutic protein in their blood. Polly and Molly built on the work that had been done with Dolly to demonstrate the therapeutic potentials of recombitant DNA technology combined with animal cloning.

Read more about Dolly and the work of the Roslin Institute here: http://www.roslin.ed.ac.uk/public-interest/dolly-the-sheep/

Over the next two years, I will be cataloguing the papers of Professor Sir Ian Wilmut (part of the team who cloned Dolly), Professor Grahame Bulfield (former Director of Roslin) and the Roslin Institute itself as part of the second phase of our Wellcome Trust-funded project. I look forward to discovering more about Dolly the sheep as well as the work of the Roslin Institute from its inception in 1993 until the early 21st century.

 Photograph reproduced with kind permission of Murdo Macleod.