Cesare Galli
Session: Genetic determinism and eugenics
Title: Somatic cell nuclear transfer in animals: lessons for the future

Talking about cloning immediately people’s mind goes to think about copying machines and believe that each cloned animal is a photocopy of the original or of its twins clones. Early studies in monozygotic twins already indicated that this is not the case and each individual is the result of complex interactions between its genes and its gene’s products (its proteins) and the environment albeit a strong resemblance for morphology and physiology but less for character and behaviour. In technical terms a cloned animal is a genomic copy of the original donor, this means that it has the same genetic make up (except possible mutations). However gene function is controlled by the interaction between genes, proteins, enzymes, and the possible outcome is very variable depending on the number of factors determining it, as well as being unpredictable and often random. Given the complexities of the interactions each individual including cloned individuals is unique.
Epigenetic mechanisms, whereby chemical modifications of the chromatin or of the associated proteins determine the structure, are the main source of this diversity between genetically identical individuals both in physiological and pathological conditions. A classical example of these mechanisms is the chromosome X inactivation in female embryos, that is a random phenomenon, even in female cloned embryos. As a consequence which X chromosome will be functioning in which tissue in the derived individual, is unpredictable. This was clearly demonstrated in the first cloned kitten, a female, a two coat colour animal that was cloned from a tabby female (3 colours one of which is X linked). Also cloned cattle display a coat colour that for reasons other than epigenetics, is never identical to the original or between the clones themselves. Behavioural studies in cloned pigs and evidence in cattle also indicate that animals are never identical and therefore even amongst clones each animal is an individual.
The pre-implantation development of a cloned embryo is not different from that of a normal embryo. However because of the inadequate epigenetic reprogramming of the cell genome the ability of cloned embryos to develop to term into a fully functioning individual, after transfer into the uterus, is ten fold lower than a normal embryo. This indicates that it is much more complex to generate a cloned individual than a cloned embryo embryo.
Embryo derived cell lines (embryonic stem cells) can be derived from both cloned and normal embryos at apparently the same efficiency at least in animals. These cells in both cases retain the ability to differentiate in many cell types but because of their inadequate epigenetic status, then potential to differentiate and safety should be carefully investigated before any attempt of therapeutical applications.
The evidence from somatic cell nuclear transfer is that a cloned embryo can generate stem cells but it is less likely to generate and individual, moreover using the same genome the resulting animal is far from being genetically determined.

Talking about cloning immediately people’s mind goes to think about copying machines and believe that each cloned animal is a photocopy of the original or of its twins clones. Early studies in monozygotic twins already indicated that this is not the case and each individual is the result of complex interactions between its genes and its gene’s products (its proteins) and the environment albeit a strong resemblance for morphology and physiology but less for character and behaviour. In technical terms a cloned animal is a genomic copy of the original donor, this means that it has the same genetic make up (except possible mutations). However gene function is controlled by the interaction between genes, proteins, enzymes, and the possible outcome is very variable depending on the number of factors determining it, as well as being unpredictable and often random. Given the complexities of the interactions each individual including cloned individuals is unique.
Epigenetic mechanisms, whereby chemical modifications of the chromatin or of the associated proteins determine the structure, are the main source of this diversity between genetically identical individuals both in physiological and pathological conditions. A classical example of these mechanisms is the chromosome X inactivation in female embryos, that is a random phenomenon, even in female cloned embryos. As a consequence which X chromosome will be functioning in which tissue in the derived individual, is unpredictable. This was clearly demonstrated in the first cloned kitten, a female, a two coat colour animal that was cloned from a tabby female (3 colours one of which is X linked). Also cloned cattle display a coat colour that for reasons other than epigenetics, is never identical to the original or between the clones themselves. Behavioural studies in cloned pigs and evidence in cattle also indicate that animals are never identical and therefore even amongst clones each animal is an individual.
The pre-implantation development of a cloned embryo is not different from that of a normal embryo. However because of the inadequate epigenetic reprogramming of the cell genome the ability of cloned embryos to develop to term into a fully functioning individual, after transfer into the uterus, is ten fold lower than a normal embryo. This indicates that it is much more complex to generate a cloned individual than a cloned embryo embryo.
Embryo derived cell lines (embryonic stem cells) can be derived from both cloned and normal embryos at apparently the same efficiency at least in animals. These cells in both cases retain the ability to differentiate in many cell types but because of their inadequate epigenetic status, then potential to differentiate and safety should be carefully investigated before any attempt of therapeutical applications.
The evidence from somatic cell nuclear transfer is that a cloned embryo can generate stem cells but it is less likely to generate and individual, moreover using the same genome the resulting animal is far from being genetically determined.