9 January 1998

How Dolly helps progress

With media attention

focusing on the prospect of

cloning humans, the original

reasons for producing Dolly

the sheep have tended to be

lost. Roslin Institutes

John Woolliams reflects on

the scope that the Dolly

technology provides for the

livestock industry and for

the preservation of

genetic diversity

DOLLY was derived from cells taken from the udder of a six-year-old Finn Dorset ewe which were then allowed to grow and multiply in the laboratory. A few of these cells were fused with unfertilised eggs from which the nucleus had been removed and 29 of these reconstructed eggs – each with a nucleus form the original adult ewe – were then implanted into surrogate Blackface ewes. One gave rise to a live lamb, Dolly, some 148 days later. Other cloned lambs had been from cells taken from embryonic and foetal tissue.

The major aim of the experiment was practical – to develop cell culture systems from which it was possible to derive live animals. The existence of Dolly and the other cloned sheep at Roslin have clearly shown this is now possible in farm animals.

However, it will be the biotechnology industry that will use this new technology first since it provides a better way for molecular biologists to genetically engineer livestock. Transgenic sheep and cattle are already used to produce valuable human proteins in their milk and transgenic pigs are being developed as donors of organs in human transplantation.

The new nuclear transfer techniques will be more reliable and allow molecular biologists to remove or replace genes as well as simply add them as at present.

The nuclear transfer techniques developed at Roslin can also be used to deliver what is the popular image of cloning, that is to produce – at least in principle – unlimited numbers of genetically identical animals. Previous experience with artificial insemination and multiple ovulation/embryo transfer suggest that it may be at least 10-20 years before this could become a routine procedure in livestock production. There are major practical hurdles to overcome. We first need to show the techniques can be used in cattle and pigs since it is probably only in these species that the benefits are likely to justify the cost. Non-surgical means of transferring embryos would need to be developed to keep the procedures on the farm as simple as possible. Success rates would have to be dramatically improved, and this particular objective is being pursued at Roslin with the help of a new MAFF grant.

Use in breeding

Genetic progress is dependent on exploiting genetic variation and cloning would have only limited use within breeding programmes. Some commercially important traits are greatly influenced by environment and, as a result, it is often difficult to accurately assess the genetic merit of an individual animal.

Mastitis and laminitis in dairy cattle are examples where it might be beneficial to clone several copies of an elite animal in order to more accurately assess her susceptibility to these conditions. With carcass traits, there may advantage in providing two clones, with one identical twin being killed for carcass evaluation and the other being retained for breeding if the analysis was favourable.

Rapid progress

The main advantage of cloning would not be within selection programmes but in the more rapid dissemination of genetic progress from elite herds to the commercial farmer. At present this is achieved through AI which supplies only half the genes – and by limited use of embryo transfer. This process is not that efficient and recent estimates in dairy cattle suggest the average cow is some 10 years behind the best. With cloning, it would be possible to remove this difference.

Farmers who could afford it would receive embryos that would be clones of the most productive cows of elite herds and in doing they could so lift the performance of their herds to that of the very best within one generation. This would be a one-off gain, since from then on the rate of genetic progress would return to that of the elite herds.

In this scenario, breeding companies would sell embryos in much the same way as they now sell semen. There would be scope to choose cloned embryos from high genetic merit beef bulls or dairy cows from catalogues that describe the genetic merit for a series of economically important traits, including fertility, health and longevity.

They could choose the sex of the embryo (male for beef, female for milk) and would be guaranteed a genotype of proven performance in either low or high input systems. The cloned embryo would be delivered to the farm in much the same way as semen straws are today, perhaps from breeding companies based overseas.

Protecting diversity

Loss of genetic diversity could be avoided by systems that ensured that breeding companies produced a limited number of clones of each genotype and restricted the number of each clone that could be sold to any one farmer. Although some farmers herds might consist entirely of cloned animals, the fact that they were clones of different elite animals may actually increase genetic diversity on some farms.

Many of the problems of using clones have already been encountered by foresters. Overall, the benefits of careful use of cloning trees are judged to be greater than the risks and many new plantations around the world are now being planted with clones.

Whether cloning of livestock will become a commercial reality will depend on the expected economic returns and further research is needed if these are to be estimated accurately. Genetic models are already available to quantify the possible benefits, but further work is needed to be able to quantify risk.

Genetic conservation

Although cloning is associated in most peoples minds with a loss of genetic diversity, the techniques that were used to produce Dolly will provide new methods for genetic conservation.

With increasing commercial pressures, many indigenous breeds adapted to local conditions are under threat from imported breeds that are being reared in intensive farming systems. Local breeds may contain valuable genes that confer heat tolerance or disease resistance and there is an urgent need to prevent their extinction.

Current methods of conservation involve storage of frozen semen or embryos but are time consuming and costly. As a result the future of only a small proportion of the endangered breeds is being addressed.

New techniques developed at Roslin may soon provide much simpler and more effective means of conserving breeds. Blood samples, skin biopsies or even hair follicles might be suitable sources of cells that could be sampled easily, grown briefly in the laboratory, and then frozen in liquid nitrogen for long term storage.

The technology used at Roslin to develop Dolly, the cloned sheep, offers new opportunities for progress in the livestock industry.

Roslins John Woolliams… techniques to produce Dolly will provide effective new methods for genetic conservation of stock.