By Philip Cohen in Honolulu IT IS lunch time at the University of Hawaii in Honolulu, and Ryuzo Yanagimachi is encouraging a visiting reporter to eat his own words. “This year, a magazine predicted who was likely to clone the next adult animal,” he says. “You know, my lab didn’t even make that list.” True, the article to which he refers (“Clone Watching”, New Scientist, 9 May, p 35) gave no clue that Yanagimachi and his colleagues would, within two months, unveil dozens of cloned mice. But New Scientist wasn’t alone in overlooking the potential of this Hawaiian lab—initially, even Yanagimachi wasn’t let into the secret. To understand the background to the scientific coup of the year, it helps to visit Yanagimachi’s base. On a campus where offices with a view of the forbidding volcanic walls of Diamond Head Crater must be highly coveted, Yanagimachi has for decades inhabited a windowless suite. If he is oblivious to his surroundings, it is because he is so focused on his science, says Tony Perry, a researcher in his lab. It isn’t unusual for Yanagimachi, now 70, to work 12 hours a day, seven days a week. “He works hard, knows everything, and is incredibly supportive,” says Perry. Yanagimachi was best known for his work on IVF in animals. But when Dolly the sheep made her debut, Teruhito Wakayama, one of Yanagimachi’s postdocs, seized his chance to work on an idea that had fascinated him since reading science fiction as a boy in Japan. “I used to dream about cloning,” he says. Everyone working for Yanagimachi has to work three days a week on their main project, but can explore other interests in the remaining time. Wakayama’s main challenge was to create mice from freeze-dried sperm. Cloning became his hobby. At first, he said little to Yanagimachi. Cloning an adult animal involves reprogramming the genes from one of its cells. Mice were thought to be difficult because their genes become active early on in embryonic development, giving little time to achieve the necessary reprogramming. Without time for elaborate preparations, Wakayama used the materials at hand. For his donor cells, he used the cumulus cells which coat the surface of the egg. He was used to injecting sperm heads into eggs. So rather than fusing donor cells with eggs stripped of their chromosomes, like other groups, he injected only the nuclei of the donor cells. Wakayama implanted the resulting embryos in surrogate mothers. Yanagimachi first found out about the project in August 1997, when Wakayama dragged him to a microscope. “I saw a healthy mouse fetus with a beating heart,” Yanagimachi remembers. The lab’s focus shifted overnight. The fruit of their labour came on 3 October 1997 when Cumulina, the first cloned mouse, was born. Wakayama’s original choice of cells turned out to be a lucky break. About 2 per cent of cumulus cells yielded clones, while the researchers were unable to produce full-term embryos from Sertoli cells, which nourish developing sperm, and neurons. The team has since produced more than 80 cloned mice—some of them clones of clones of clones of clones. This is the most important breakthrough in cloning since Ian Wilmut’s team at the Roslin Institute near Edinburgh produced Dolly. But until Cumulina’s arrival, the prospects for ever again cloning another adult animal had seemed remote. In January, Norton Zinder of Rockefeller University in New York spoke for many when he speculated that Dolly was cloned from a contaminating fetal cell, rather than adult tissue. Those dark days of doubt now seem like a distant memory. Researchers in Japan and New Zealand both claim to have cloned adult cows and a genetic analysis appears to confirm that Dolly was cloned from an adult. Investors are keenly aware of the progress being made, says Simon Best, chief executive of Roslin Biomed, a company set up to develop biomedical applications from Wilmut’s work. “Each time a new group clones an animal, I predict they’ll be able to set up a company the next day,” he says. Not surprisingly, researchers are beginning to clash over patent rights to cloning technology. One exciting area would be to combine cloning with another of the big biological announcements of 1998, the isolation of human embryonic stem cells. Adult cells would be cloned to create an embryo, from which stem cells could be extracted to grow tissues for transplants. And as New Scientist revealed in July, this need not involve the creation of a viable human embryo, if the egg cells used in the cloning process were from cows. Cumulina’s other legacy will be a boon for basic science. Because so much is already known about mouse genes and because mice reproduce so quickly, the Hawaiian researchers could rapidly address some puzzling questions. When animals are cloned from adult cells, do they age more rapidly? Why is the success rate of cloning still so low? How do long dormant genes get revived during cloning?