Dollymania – Seven Days that Shook the World

Dolly the sheep

1997 was quite a significant year for the Roslin Institute with “’Dolly, the sheep, ‘…the first mammal cloned from a cell from an adult animal…generated an amazing amount of interest from the world’s media.” (Griffin, Harry. ‘Dollymania’, University of Edinburgh Journal, XXXVIII: 2, December 1997, GB237 Coll-1362/4/1476). And so, it’s been exciting to find articles in the offprints discussing her and the issues of cloning, biotechnology, ethics – Dr. Grahame Bulfield even wrote a report to Parliament on what this breakthrough means for science!

Harry Griffin, former Assistant Director (Science) at the Roslin Institute in 1997’s article, ‘Dollymania’ (cited above) provides an insider’s point of view of how Dolly was produced and the science and research involved. He writes,

Dolly was produced from cells that had been taken from the udder of a 6-year old Finn Dorset ewe and cultured for several weeks in the laboratory. Individual cells were then fused with unfertilised eggs from which the genetic material had been removed and 29 of these ‘reconstructed’ eggs – each now with a diploid nucleus from the adult animal – were implanted in surrogate Blackface ewes. One gave rise to a live lamb, Dolly, some 148 days later. Other cloned lambs were derived in the same way by nuclear transfer from cells taken from embryonic and foetal tissue.

On Monday, Dolly provided the lead story in most of the papers and Roslin Institute was besieged by reporters and TV crews from all over the world…. Dolly rapidly became the most photographed sheep of all time and was invited to appear on a chat show in the US. Astrologers asked for her date of birth and PPL’s share price rose sharply. President Bill Clinton called on his bioethics’ commission to report on the ethical implications within 90 days and Ian Wilmut was invited to testify to both the UK House of Commons and the US Congress…. Dolly Parton sad she was ‘honoured’ that we have named our progeny after her and that there is no such thing as ‘baaaaaed publicity’. Sadly, we also received a handful of requests to resurrect relatives and loved pets.

IMG_4284In the article, ‘Seven days that shook the world’ by Harry Griffin and Ian Wilmut in New Scientist, 22 March 1997 also describe the reality of the science of cloning in the face of intense media speculation and reportage.

Dr. Grahame Bulfield, former Director of the Roslin Institute, wrote several articles in 1997 on biotechnology, ethics, livestock and cloning. In some articles, he writes generally on the techniques of genetic engineering, genome analysis, and embryo manipulations and provides a biological context of these new technologies. (GB237 Coll-1362/4/1394 – 1400). He discusses Dolly more directly in the article, ‘Dit is pas het begin’ in the Dutch journal Natuur & Techniek, No. 8, 1997 (4/1376) IMG_4266and The Roslin Institute and Cloning an address to the Parliamentary and Scientific Committee in Science in Parliament, Vol. 54, No. 5, September/October 1997 (4/1400). In this particular article he writes specifically about Dolly:

As you know we have been thrown into the middle of public debate recently with a considerable amount of public interest and concern about “Dolly”. IMG_4275Over a period of about five days we had 3,000 telephone calls, 17 TV crews and we basically ground to a halt. We are perfectly aware now of the issues that are raised , and I don’t believe that a scientific organisation like ours can do anything buy try and be proactive in terms of communicating new biotechnology advances to the public and Government and ensuring the issues involved are widely debated.

A game of two halves

Halfsider singleOne of the photographs in the Alan Greenwood collection depicts a chicken. This is hardly unusual in itself, seeing as Greenwood was director of the Poultry Research Centre. However, a closer look reveals that this is no ordinary chicken: it is coloured and shaped differently on each side: in fact, it looks more like two separate chickens stitched together. This chicken is a ‘halfsider’. Halfsiders – also called bilateral gynandromorphs –  are birds whose colour, plumage, size and even gender is different on each side. Halfsiders are most commonly encountered in budgerigars, although they can occur in other birds too, including domestic chickens.

The phenomenon which produces halfsiders is is actually part of a larger phenomenon of ‘mosaicism’. Mosaics are organisms of a ‘patchwork’ phenotype and/or genotype generally only found in domesticated species (although a wild gynandromorphic Northern Cardinal was discovered on the east coast of America in 2009). F.A.E Crew at the Institute of Animal Genetics was one of the first geneticists to write on gynandromorphy in birds, with Greenwood and colleagues continuing to study it at the Poultry Research Centre.

Halfsiders are so interesting for genetics because they contradict the  theory that sexual development in birds and mammals follows the same course, with the embryonic cells being ‘unisex’, the gender being determined at around seven weeks by signals sent by hormones. However, chicken cells apparently ‘know’ which sex they are at the time of fertilisation, and scientists have had to propose an entirely separate model for avian sexual development.

Early explanations for how halfsiders happen usually posited gene mutation or embryo damage in the early stages of cell division, or else the loss of a chromosome.. However, a study in 2010 (Zhao, McBride et al) found that halfsider chickens are in fact nearly perfect male:female chimeras comprised of normal female cells (with ZW chromosomes) on one side and normal male cells (with ZZ chromosomes) on the other side. Therefore, halfsiders appear to result from an abnormal ovum containing two pronuclei, fertilised by two sperm, which then results in both a Z and W chromosome–containing nucleus. As the cells develop, and are subject to exactly the same hormones, they respond according to their own chromosomes rather than signals being given out by the gonads, as with mammalian development. This in essence means that the two ‘halves’ develop entirely separately, at the same time.

Although the phenomenon producing halfsiders is genetic in origin, it is not heritable and so cannot be intentionally bred (in any case, gynandromorphs are nearly always sterile). It is estimated that 1 in 10,000 domestic chickens is a gynandromorph.

FAE Crew’s Off-Prints (1814-1940)

In addition to the off-prints of the various past organizations that made up the Roslin Institute, we have FAE Crew’s collection.  The majority of the off-prints in his collection, found in 39 bound volumes, were written by other authors such as Conrad Hal Waddington, Leonard Darwin, and Alan Greenwood among others and some of the articles were even previously owned by Arthur Darbishire. The non-Crew authored material dates between 1814 and 1936 and Crew’s articles date between the years of 1930 to 1940 and he organized the bound off-prints into series: Fowl (18 volumes- GB 237 Coll-1496/1-18); Birds (2 volumes – GB 237 Coll-1496/19-20); Pigeons (2 volumes -GB 237 Coll-1496/21-22); Genetics General (9 volumes – GB 237 Coll-1496/23-31); and General Biology (8 volumes – GB 237 Coll-1496/32-39). There is a wealth of fascinating articles found in this collection – especially in the Genetics General and General  Biology volumes which show Crew’s wide-ranging interests  including animal genetics, human genetics, eugenics, evolution (both scientific and philosophical), teaching medical students and ethics. A few particular highlights are Major Leonard Darwin’s article Organic Evolution: Outstanding Difficulties and Possible Explanation,  Cambridge University Press, 1921; Darwin

Condemned for Teaching Lies: the following is a speech prepared by William Jennings Bryan for delivery in closing argument for the State in the Evolution Case at Dayton, Tennessee, July 21, 1925;WJ Bryan

and H. Muller’s Lenin’s Doctrines in Relation to Genetics, Academy of Sciences, USSR, 1934.Lenin

In addition to the articles collected by Crew for his research, there is a box of un-bound off-prints authored by Crew himself (GB 237 Coll-1496/40/1-70).  IMG_4260These articles span the years between 1930 and 1940 and discuss such topics as: animal breeding, sterilisation, eugenics, heredity versus environment and other genetic based topics. The last article in the collection is quite interesting since it’s Crew’s thoughts on war when he was a Lieutenant-Colonel in the British Army, Crew and warThe war and ourselves in the Journal of the British Army Medical Corps, 1940 (GB 237 Coll-1496/40/74).

This material, the collected offprints of other scientists, offers a fascinating insight into the research interests of FAE Crew by showing his diverse interests which helped to inform his work as seen in the same collection in his self-authored papers.