Reacción a "Serial mice cloning cannot be sustained indefinitely"
María del Carmen Navarro Maldonado
Senior Research Professor in the Department of Reproductive Biology, Division of Biological and Health Sciences, at the Autonomous Metropolitan University (Mexico)
What is novel is that we have maintained a lineage of more than 25 generations of cloned juvenile female mice over a period of 20 years, thereby detecting certain phenotypic and genetic abnormalities in the cloned individuals after the 26th generation, thus demonstrating that cloning cannot be sustained indefinitely.
All the results provide some evidence of certain phenotypic and genotypic abnormalities in cloned juvenile mice, for example:
- They reveal abnormalities in the spongiotrophoblast layer and areas of the labyrinth zone in placentas.
- A lack of effect of trichostatin (TSA – a histone deacetylase (HDAC) inhibitor) in improving the nuclear reprogramming of the somatic cells used to clone the mice, particularly from generation 26 onwards.
- Epigenetic alterations in certain histones and their acetylation.
- A reduced number of cells in cloned embryos, particularly in the inner cell mass.
- Lethal mutations in the oocytes of cloned mice, both nuclear and cytoplasmic.
- The accumulation of de novo mutations in cloned mice, particularly: single nucleotide variations, structural variants of the genome, the loss of an X chromosome and of heterozygosity in some chromosomes, and the translocation of some somatic chromosomes.
This is due to the absence of chromosomal recombination in clonal reproduction, which prevents natural selection and causes mutations to accumulate progressively across generations of clones.
The document explains that beyond the 25th generation, it is no longer advisable to clone juvenile mice.
I am unaware whether, as a member of the European Union, Spain prohibits cloning or to what extent. However, given that in Mexico it is permitted for research purposes, as well as for its application in animals for productive purposes and species conservation, my recommendation would be to permit it in the same way, but not in humans, until all the obstacles inherent in the reprogramming of the somatic donor cell nucleus have been overcome (for which it is essential to continue researching in other mammalian species). I would therefore recommend promoting its use for research, production and species conservation purposes in mammals until the problem is resolved, before deciding to apply it to humans.
As for recloning, I believe it would be worth evaluating it in species other than mice, to determine how many generations it could be sustained without affecting the genotype or phenotype of the cloned individual. I found the study very interesting.