Keith H. Campbell (1954–2012) Creator of Dolly, the First Mammal Cloned from an Adult Body Cell

OBITUARY COMMENT Keith H. Campbell (1954–2012) Creator of Dolly, the first mammal cloned from an adult body cell.

eith Campbell was the inspiration company PPL Therapeutics, which was to become head of embryology at PPL behind Dolly the sheep, the first collaborating with the Roslin Institute, was Therapeutics, where he led work on cloning mammal to be cloned from an using the sheep cells for experiments on pigs. In 1999, he became professor of animal Kadult body cell. He died on 5 October at drug development. development at the University of Notting- the age of 58. A few days later, the Nobel I always wonder who was most surprised ham, UK, where he continued to work on committee recognized the importance when, after being transferred into a ewe, one nuclear reprogramming and cloning tech- of the field by awarding the 2012 medi- of the embryos derived from the nucleus of niques. (PPL Therapeutics was sold when cine prize to John Gurdon and Shinya it ran into financial problems in 2003, Yamanaka for their achievements in largely because of the difficulty of using reprogramming cells. animal cloning to develop pharmaceuti- In 1995, Campbell — then at the cal products.) Roslin Institute near Edinburgh, UK Despite the tremendous media stir MURDO MACLEOD — conceived of a method to generate a prompted by Dolly’s birth, animal clon- pair of cloned lambs, Morag and Megan, ing has never really come of age as a from a cell taken from a sheep embryo. commercially useful biotechnology. In his opinion, these were “the first ani- This is mainly because, in most species, mals produced from differentiated cells epigenetic marks (experience-depend- because these cells had differentiated ent molecular alterations that alter how in culture”. It took Dolly, however, to genes behave, but not their sequence), convince the scientific community that carried over in the introduced chroma- differentiated mammalian body cells tin, cause embryonic losses and post- — which had already become special- natal abnormalities. Yet somatic cell ized for a particular function — could cloning has proved a very useful tool in be reprogrammed to produce an entire mouse developmental and cell biology, organism. and has made significant contributions In the mid-1990s, the consensus to stem-cell biology. In 2008, Campbell among cell biologists was that clones and Wilmut were jointly awarded half of could not be produced from cells that the prestigious Shaw Prize in Life Science had become specialized. Decades ear- and Medicine, with Yamanaka winning lier, Gurdon, a British developmental the other half. biologist, had managed to produce adult Keith was acutely aware that the frogs by transferring the nuclei of tad- cloning method he had pioneered drew pole cells into eggs stripped of their own strong opposition from some, including nuclei. But reprogramming differentiated a mammary-gland cell developed into an conservative religious groups and members mammalian embryonic cells or adult body apparently normal lamb: the ewe, the farm of the Green Party. He defended his work, cells was thought unlikely to work. hands or the research team? Wilmut cer- saying that it was important for the progress Campbell’s breakthrough was realizing tainly was surprised. I think Campbell was of biology and possibly medicine, but he was that he could reprogram the nuclear infor- optimistic that even adult cells could be strongly opposed to human reproductive mation in a donor cell if he coordinated the reprogrammed. cloning. cell cycles of the donor embryo cell and the Campbell was born in 1954 in Birming- A great companion and argumentative recipient egg. By depriving the cells in his ham, UK, and grew up there and in the in a delightful way, Keith was a strong sup- laboratory cultures of nutrient-rich serum, Scottish city of Perth. He graduated from porter of his colleagues and a proud father he forced them to enter a quiescent state. Queen Elizabeth College, London, in 1978 of his daughters Claire and Lauren. It was When cell division was reactivated, the with a bachelor’s degree in microbiology. perfectly in keeping with his wry humour cell cycles were aligned. By transferring After various jobs, including a locum posi- that he named Dolly the sheep after the the nucleus of an embryo cell into an egg tion as chief medical laboratory technolo- singer Dolly Parton, and told The New York cell from which the chromatin had been gist in South Yemen, he started a PhD in Times in 1997 that sex “will always be the removed, and then activating that nuclear 1980 at the University of Sussex, UK. It was preferred way of having children”. Cloning, material, he created Morag and Megan. at Queen Elizabeth College and as a post- he said, is “far too expensive and a lot less Wanting to track down exactly when the graduate student studying frog-egg matura- fun than the original method”. ■ developmental potential of embryonic cells tion that Campbell developed his interest in was lost, Campbell and Ian Wilmut, the Ros- the control of cell division and in the factors Alan Trounson is at the California Institute lin Institute’s group leader, asked their col- that direct the behaviour of cell nuclei. After for Regenerative Medicine, San Francisco, league James McWhir for some adult cells. postdoctoral positions at the universities of California 94107, USA. He became a close McWhir gave them some sheep mammary- Edinburgh and Dundee, Campbell joined friend of Keith Campbell after meeting him gland cells that happened to be in the freezer. the Roslin Institute in 1991. in 1993. The Edinburgh-based biotechnology Campbell left the institute in 1997 e-mail: [email protected]