“STUPENDOUS” and “mind-boggling” were just two reactions to the birth of Dolly, the first mammal cloned from an adult cell, 10 years ago this week. Suddenly, the idea of herds of identical prize bulls, or sheep producing medicines for humans in their milk, seemed wholly plausible. Then there was therapeutic cloning, which would provide genetically matched human tissue to patch up even the most seriously ill patient.A decade on, much of that excitement has vanished and cloning is in the doldrums. Creating genetic replicas of animals has proved so difficult that it is only used when large profits beckon, and therapeutic cloning has not got off the starting blocks. So is that it? Were those high hopes just an illusion?
The field has obviously not been helped by the controversy it stirred up. Thoughts of cloned humans and discarded embryos generated moral, religious and political outrage. In the US, restrictions on federal funding for stem-cell research have stunted development. Then, last year, the exposure of South Korean researcher Woo Suk Hwang as a fraud set the field back several years. Cloning has also turned out to be more difficult than anyone originally thought (see “Therapeutic cloning set back by hype and fraud”). As well as being technically challenging it faces fundamental problems such as a shortage of human eggs, which unless solved will limit what can ever be achieved.
Such issues have persuaded some researchers to rethink their ideas of therapeutic cloning. The process depends on nuclear transfer, in which the nucleus of an egg is replaced by that from a patient’s cell. The egg is encouraged to divide until it forms a blastocyst, from which embryonic stem cells can be collected. These ESCs, which have the same genes as the patient, can in theory transform into any of the body’s cell types. It is an elegant idea, and should eventually be achievable in people - though with Hwang’s work discredited only one group has reported creating a human blastocyst, and that died before ESCs could be collected.
The scarcity of human eggs has, however, convinced some that individualised therapeutic cloning is a non-starter. They talk instead of setting up ESC banks from normal, fertilised embryos. Though the match provided by these cell banks is not perfect, it should be close enough for most individuals.
If hopes for cloning are being lowered, prospects remain bright for stem-cell research in general, much of which does not depend on cloning. There have been successes in transforming ESCs into everything from insulin-producing cells for diabetics to heart-muscle cells for treating heart-attack patients. The Californian company Geron has plans to treat spinal injury with cells created from human ESCs. Using unmatched tissue in the central nervous system should not be a major problem because immune reactions there tend to be weaker than elsewhere in the body. Geron also believes the cells themselves may be resistant to attack by the immune system.
Another approach is to use the adult stem cells we all carry inside us. Researchers have recently found sites in the eyes and heart, for example, where stem cells collect, and efforts are now under way to use these cells to regenerate corneas and heart muscle.
Even the signalling chemicals that guide stem cell development may be of value as therapies. This week, researchers at the US National Institute of Neurological Disorders and Stroke report in Nature that injecting the right proteins into the brains of rats with stroke-like damage encourages adult stem cells to develop into cells capable of repairing the injuries (DOI: 10.1038/nature04940).
That is not to say that stem-cell researchers have all the answers. Far from it. The field is rife with anecdotal evidence and short on controlled studies. Identifying stem cells can be difficult, and the very existence of some types is still in question. We do not understand how some stem cells repair damaged tissue, nor can we always guide ESCs down particular developmental pathways.
Nevertheless, there are many encouraging avenues to explore and no obvious show-stoppers. Though little of this burgeoning field stems directly from the work on Dolly, her influence should not be downplayed. Dolly’s creation sparked imaginations and changed people’s ideas of what biology is capable of. That may be her lasting legacy.