Therapeutic cloning and other alternatives

Luis María Gonzalo Sanz.
Full Professor of Anatomy and Embryology.
article published in the Revista de Medicina de la Universidad de Navarra.

Cloning is a topic that has aroused great interest not only among doctors and biologists, but also among all those concerned with scientific advances and ethical issues. This interest grew considerably when the news of the birth of the female lamb Dolly appeared in Nature in February 1997. Wilmut's team in Edinburgh succeeded in cloning her using the nucleus of a cell from the udder of an adult sheep. The novelty and significance of this news was that the cell used for cloning was from an adult animal. Cloning of mammals had been achieved somewhat earlier, but using embryonic cells.

What was the significance of this development?

It demonstrated that adult cell nuclei could be reprogrammed, which for those who aspired to human reproductive cloning was a window of hope. Hence, lesbian and gay groups were the first to be interested: they would be able to have daughters and sons respectively without having to resort to the other sex, and they would also be a faithful copy of each other.

How is this possible?

Cloning in the narrow sense in which the term is now used is the asexual production of individuals with the same genetic constitution as the parent. This requires two cells: an oocyte and a somatic (i.e. diploid) cell. The oocyte must be enucleated (its nucleus removed) and will serve as an inducer of modifications in the nucleus transferred to it and of its successive divisions. The nucleus is taken from the somatic cell and transferred to the enucleated oocyte: it provides the chromosomal endowment for the new being.

The main induction of the oocyte on the nucleus transferred into it is its reprogramming: making the genes silenced by the effect of cell differentiation active again. The zygote thus obtained begins to divide and when it reaches the blastula stage, it is implanted in the uterus of a suitably prepared animal of the same species.

Technical and biological difficulties

These seemingly simple operations require a great deal of technical expertise, and yet the number of failures is enormous. Wilmut and his team, for example, obtained the lamb Dolly after 433 attempts, Dominko cloned 302 monkeys and only 35 implantations were obtained and in no case did they reach birth; something similar happened in other animals such as cows, goats, mice, etc. If we take this to our species it would mean eliminating hundreds of human embryos to get one to be born normally. For this reason, and above all for ethical reasons, all countries and scientists involved in this topic have banned human reproductive cloning.

Therapeutic human cloning

The ban on human reproductive cloning seems reasonable, but is the same true for therapeutic cloning?

Therapeutic cloning only differs from reproductive cloning in its purpose: it seeks to obtain tissues and organs suitable for transplantation without rejection, not new human beings. Nor would implantation in the uterus of a surrogate mother be necessary, as the development could be carried out in vitro. However, this procedure of development considerably limits the growth of the blastodermal sheets and the tissues derived from them. The reason for this is that, as they do not develop a circulatory system, their nutrition is carried out by imbibition, which is only sufficient if the thickness of the tissue or cell layer is small. It would of course be impossible for complete organs such as the liver or pancreas to develop. In addition to these technical limitations, there are also the ethical ones, since here too human embryos are used which have to be sacrificed so that other humans can improve their ailments. In this respect it is good to recall the statement of the Pontifical Council for the Family committee (12/8/00) "every embryo must be treated and considered as a human person".

For its part, the European Parliament in plenary session spoke out against therapeutic human cloning on the grounds that it is contrary to respect for human dignity and that there are other means of dealing with serious illnesses. Some have argued that waste embryos "which were not used in in vitro fertilisation and which, after 5 years, can be destroyed" could be used. This argument has two weaknesses: the first is ethical: embryos, even if they are waste, are still human. The other is biological: the blastomeres, which is the ontogenetic stage in which these embryos are found, cannot be cloned at the moment and possibly not in the future either.

Other alternatives to therapeutic cloning

If therapeutic cloning does not present a bright prospect, what other alternatives are offered as viable?

Among the alternatives, the most promising is that of stem cells. Stem cells are found not only in embryonic and foetal tissues, but also in the adult individual. Stem cells are pluripotent (they can give rise to several cell lines), can multiply and then differentiate. For the time being, haematopoietic stem cells have been used with very good results in cases of bone marrow aplasia after chemo- or radiotherapy treatments. These stem cells are found in adult bone marrow and in the umbilical cord blood of the newborn.

But in addition to haematopoietic stem cells, there are epithelial stem cells, such as those found at the bottom of the crypts of the intestinal epithelium, mesenchymal stem cells, which can be found in the bone marrow, and even neural stem cells, circumscribed to the dentate gyrus of the hippocampus and the subventricular zone.

Challenges posed by stem cells

For stem cells to become true auxiliaries in tissue renewal and replacement, two types of methods need to be developed: on the one hand, discovering the products or enzymes that allow stem cell differentiation to be channelled in the direction that is of interest in each case.

On the other hand, discovering the method that achieves stem cell dedifferentiation to convert them into multipotent and even embryonic stem cells would be to artificially achieve what the oocyte cytoplasm does on the adult nucleus that has been transferred. An example may clarify the importance of achieving stem cell differentiation in the lineage of interest in a given case. In Parkinson's disease, implantation of dopamine-secreting cells in the caudate body of the brain produces an improvement B . employee The cells that have been used so far (from the adrenal medulla and the substantia nigra of aborted foetuses) are only temporarily effective, as they eventually become necrotic. The solution would be to implant the individual's own dopaminergic neurons. At the moment, neural stem cells are available, but the method for their differentiation into dopaminergic neurons needs to be developed. Many groups of scientists are working to discover the culture media and the messenger signals that allow the stem cells to multiply and differentiate into the appropriate cell line. This research is not only of scientific and humanitarian interest, but also of financial interest, as the companies patenting these methods will make a substantial profit, as millions of patients could benefit from this subject treatment.