Editor's note: The following essay is reprinted with permission from The Conversation UK, an online publication covering the latest research.
By Ian Wilmut, University of Edinburgh
It is unlikely that a mammoth could be cloned in the way we created Dolly the sheep, as has been proposed following the discovery of mammoth bones in northern Siberia. However, the idea prompts us to consider the feasibility of other avenues. Even if the Dolly method is not possible, there are other ways in which it would be biologically interesting to work with viable mammoth cells if they can be found.
In order for a Dolly-like clone to be born it is necessary to have females of a closely related species to provide unfertilised eggs, and, if cloned embryos are produced, to carry the pregnancies. Cloning depends on having two cells. One is an egg recovered from an animal around the time when usually she would be mated.
In reality there would be a need for not just one, but several hundred or even several thousand eggs to allow an opportunity to optimise the cloning techniques. The cloning procedure is very inefficient. After all, after several years of research with sheep eggs, Dolly was the only one to develop from 277 cloned embryos. In species in which research has continued, the typical success rate is still only around 5% at best.
In this case the suggestion is to use eggs from elephants. Because there is a danger of elephants becoming extinct it is clearly not appropriate to try to obtain 500 eggs from elephants. But there is an alternative.
There is a considerable similarity in the mechanisms that regulate function of the ovaries in different mammals. It has been shown that maturation of elephant eggs is stimulated if ovarian tissue from elephants is transplanted into mice.
In this way it might be possible to obtain a considerable number of elephant eggs over a period of time if ovarian tissue is obtained from elephants that die.
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Cells from mammoths are required to provide the genetic information to control development. The suggestion is to recover cells from the marrow of bones emerging from the frozen north of Siberia. However, these cells will degenerate rapidly at the temperature of melting snow and ice. This means that cells in the bones may well become useless for this capacity as they thaw.
The chances of cells being viable would be increased if bones could be recovered from the lowest possible temperature rather than waiting until they emerge from snow. The cells can then be warmed rapidly. Alternatively, the nuclei could be transferred directly into eggs.
The very first stages of embryo development are controlled by proteins that are in the egg when it is shed by the ovary. One for example has a critical role in cell division. Together these proteins have an extraordinary ability to repair damaged nuclei so it may not be strictly necessary for the cells to be viable. It would be best if the mammoth nucleus could be introduced into an egg immediately, by injection of the contents of the damaged cell into the egg.
Research in 2008 found that when nuclei from freeze-dried sheep cells were transferred into eggs, some of the cloned embryos developed for a few days, but not to term. This was a very clear indication of the ability of the egg to repair damaged nuclei. However, freeze-dried cells are likely to be more stable than those that have been frozen with liquid still present. In the case of the mammoth, the cells would likely be killed by large ice crystals formed from the liquid.