The wonderful world of cloning

Since the world's most famous cloned sheep was unveiled to a gob-smacked science community, the race has been on to build on the work.

Groups around the world have since validated the research, creating clones of cattle, mice and even a cat. But the Holy Grail for agricultural cloning researchers now lies in the fundamentals of the science.

How is it, they want to know, that a cell can be reprogrammed to revert to a undifferentiated stem cell suitable for use in nuclear transfer to create a cloned mammal?

A non-exhaustive list of some of the leading international research groups working in agricultural cloning includes:

Geron, US Geron licenses out its nuclear transfer and gene targeting technologies for agricultural applications such as the production of unlimited numbers of genetically identical animals with superior commercial qualities across the beef, dairy, pig and chicken industries. The company has a research collaboration with the Roslin Institute to produce more efficient nuclear transfer procedures. Other current partners and collaborators include the University of California at San Francisco, AviGenics, Origen Therapeutics, Australia's Clone International, Nexia Biotechnologies, Viragen, ProLinia, and New Zealand's AgResearch.

Texas A&M University, US In 1999, researchers at Texas A&M created what was believed to be the first calf cloned from an adult bull, following up the work in 2000 with the first calf cloned to be resistant to disease. In 2001, the group, led by scientist Mark Westhusin, cloned goats and pigs, making the centre the first in the world to clone three species of animal. This year the team moved beyond agricultural applications by unveiling a cloned cat named "cc", believed to the first successfully cloned companion animal.

Roslin Institute, Scotland No introductions needed here. The Roslin Institute achieved world fame in 1997 when it became the first in the world to clone a sheep through somatic cell nuclear transfer. Dolly became the benchmark, with scientists worldwide clamouring to do even better and ethicists concerned over the new step towards potential human clones. In 2001 the institute published a paper in Nature Biotechnology reporting that it had produced a lamb with one copy of the prion gene deleted - the first time a gene had been deleted in a mammal other than a mouse - but that had to be put down after 12 days because of an untreatable cardiopulmonary defect. It also reported last year that it had cloned a pig using the same techniques it had used to create Dolly. Both projects were done in collaboration with Geron.

PPL Therapeutics, Scotland The company was involved with the Roslin Institute in the creation of Dolly and has since developed a gene targeting system to enable the introduction of DNA at specific sites in livestock chromosomes. PPL's main cloning interests lie in the potential of transgenic livestock to help produce medical treatments. This year the company announced it had combined its DNA technology with nuclear transfer to create five "knock-out" piglets in a step towards xenotransplantation.

Kinki University, Japan About 20 different Japanese groups are funded to do research into agricultural cloning, underlining the priority placed on the technology in that country. Leading the field is Dr Yukio Tsunoda of Kinki University, Nara, who entered the history books in 1998 by becoming the first to clone a cow. Using entrails discarded at a slaughterhouse, Tsunoda collected cumulus cells and cells from the fallopian tubes and put them into 25 empty cow eggs. Ultimately, eight calves were born with four dying soon after birth, with the researchers suggesting the technology could prove as efficient as in vitro fertilisation.

National Institute of Agricultural Research (INRA), France The developmental biology and biotechnology unit of INRA's Juoy-en-Josas Research Centre is focused on early embryonic development of domestic animals, with cloning work concentrated on mice, rabbits and cattle. The lab, led by Prof Jean-Paul Renard, is currently examining cloning and the organisation of a "functional somatic nucleus" in cattle.

University of Hawaii In 1998, a University of Hawaii group led by Ryuzo Yanagimachi successfully produced 22 cloned mice - seven of which were clones of clones. The development, published in the journal Nature, marked the first reproducible cloning of a mammal from adult cells.