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Scientists publishing in Cell attempt the cloning of macaque monkeys using somatic cell nuclear transfer.
Dr William Ritchie, embryologist on the team that cloned Dolly the sheep at the Roslin Institute, University of Edinburgh; now retired, said:
“The method used for these experiments is similar to that used to clone Dolly except that a machine was used to locate the chromosomes before removal of the nuclear material (a dye which attaches to the DNA was used to help remove the chromosomes in the case of Dolly). A part of a disabled virus was used to fuse the cell containing the nucleus to the enucleated oocyte (the fusion of the two cells was achieved by using an electric current for Dolly). Various chemicals were used to make the cloning more effective in this case. These differences are updates to the method used to clone Dolly.
“The animals which survived were cloned from cells taken from a foetus and the animals which did not survive were taken from the cumulus cells surrounding the oocyte of an adult animal. Perhaps a different adult cell type would have given different results. Although the adult cells did not result in viable young this is another species which has been successfully cloned.”
Prof. Robin Lovell-Badge, Group Leader, The Francis Crick Institute, said:
“Although many mammals have now been cloned via transfer of the nucleus of a differentiated (somatic) cell into an enucleated egg (oocyte), the process is very inefficient, with many embryos failing at different stages of development, or newborn animals dying. This suggests that there are sets of genes that are difficult to reprogramme from their state in the original somatic cell (with respect to being active or inactive) to behave as if they were in an embryonic state capable of allowing development to term. (These are referred to as reprogramming resistant regions, or RRRs in the paper.) A variety of methods have been tried to facilitate the reprogramming, such as using small molecules to help open up genes that have been locked tight by ‘epigenetic’ mechanisms. These have been found to improve rates of obtaining cloned early embryos and liveborn animals, although the efficiencies of the latter are still poor. (All it takes is for one essential gene to fail to be reprogrammed for the later embryo or newborn to be compromised.)
“Previous experiments using the cloning methods with macaques have shown that it is possible to have reasonable rates of early embryo development, and to establish Embryonic Stem cell lines from such embryos, which can then be differentiated into a broad diversity of cell types. However, there were no published reports of live born macaques following transfer of cloned embryos into recipient females. In this paper, by combining several methods to boost reprogramming efficiency, the authors were able to obtain two apparently healthy offspring from 79 cloned embryos that transferred, when using fetal fibroblast cells as the nucleus donor. When they used an adult cell type, the cumulus cells that surround the egg at ovulation, they also had two newborn animals, but this was out of 181 transferred and both failed to survive for long. It is known that the genetic material in some cell types is easier to reprogramme than in others, where there is the tendency for more specialised cells to have their programme of gene activity locked tighter.
“While they succeeded in obtaining cloned macaques, the numbers are too low to make many conclusions, except that it remains a very inefficient and hazardous procedure. Because they are non-human primates, macaques are obviously evolutionary much closer to humans than other animals typically used in research, and the aim of the work was to use the cloning methods to allow production of genetically identical macaques to use in biomedical research, where confounding factors of genetic variability could otherwise complicate experiments. However, with only two produced it would have been far simpler to just split a normal early embryo into two, to obtain identical twins. The work in this paper is not a stepping-stone to establishing methods for obtaining live born human clones. This clearly remains a very foolish thing to attempt, it would be far too inefficient, far too unsafe, and it is also pointless. Clones may be genetically identical, but we are far from only being a product of our genes.”
Prof. Darren Griffin, Professor of Genetics, University of Kent, said:
“The first report of cloning of a non-human primate will undoubtedly raise a series of ethical concerns, with critics evoking the slippery slope argument of this being one step closer to human cloning. The benefits of this approach however are clear. A primate model that can be generated with a known and uniform genetic background would undoubtedly be very useful in the study, understanding and ultimately treatment, of human diseases, especially those with a genetic element. Careful consideration now needs to be given to the ethical framework under which such experiments can, and should, operate. Primate research is already highly regulated and thus it seems likely that the process will not be widely used, and only when there are not feasible alternatives. Cautious optimism is my personal response to this study. The study itself is very impressive technically. From reading the paper it appears to have been performed carefully and robustly. One concern however is that the clones made from adult fibroblast cells did not survive more than a few days. If this work is continue, the reasons for this loss need to be investigated more thoroughly.”
* ‘Cloning of macaque monkeys by somatic cell nuclear transfer’ by Zhen Liu et al. published in Cell on Wednesday 24 January 2018.
Declared interests
Dr William Ritchie: “Technical Director of Monash Biomed Private Limited, a company based in India making glass micro tools for the IVF industry and science.”
Prof. Robin Lovell-Badge: “I have no conflict of interest to declare.”
Prof. Darren Griffin: “No COI.”