Written by Judit Sándor, Professor at the Central European University, Budapest, Director of the Center for Ethics and Law in Biomedicine
When a social scientist reads professional articles written by biomedical researchers on stem cells, she always encounters acronyms (such as ES/iPS, PGCs, hES, VSELs, PGCs) by which the various sources of stem cells are distinguished and the different technologies of processing them are indicated. The wide range of abbreviations should not discourage the social scientist, as behind each dry letter combination there are exciting stories and lively debates about the discoveries of how stem cells work and what they can do for you. Stem cells are cells that have an unlimited capacity to divide and multiply, and thus they are able to produce new cells and regenerate or repair themselves. Depending on the degree of development potential of the stem cells they can be totipotent, pluripotent, multipotent, or unipotent. Totipotent stem cells can transform into any type of cell, while multipotent stem cells may develop into specialized cell types. Totipotent and pluripotent stem cells can be found only in embryos, but multipotent stem cells are abundant in different tissues of the adult organism.
Discovering the different types of stem cells has a long history and it was not without controversies and setbacks: the competition for developing stem cell therapies resulted in numerous scandals. A Jewish Polish-German embryologist, Robert Remak, was the first to assert in 1855 that new cells are generated by the division of existing ones. Ernst Haeckel, the German biologist, was the first to use the term ‘stem cell’ in 1868 to describe the ancestor cell from which all other cells develop. In 1908 the Russian anatomist, Alexander Alexandrowitsch Maximow proposed a theory that all blood cells come from the same ancestor cell and that blood stem cells are multipotent: they are able to differentiate into several types of cells. However, it was only in 1963 that the Canadian scientists Ernest McCulloch and James Till found evidence that blood stem cells indeed exist, when they extracted hematopoietic stem cells from umbilical cord blood.
Stem cells raise not only biological and medical questions, but also philosophical ones. What is the origin of their unlimited capacity to multiply and differentiate? What makes them different from regular somatic or blood cells? There are a number of excellent theories that try to answer these questions, and one of my favorite books in this vein is Lucie Laplane’s Cancer Stem Cells Philosophy and Therapies, which is not only a remarkable philosophical treatise but also a significant contribution to the stem cell therapies of tumorous diseases.
As we gradually learned how stem cells differentiate, we started to understand that somatic cells can be reverse programmed as well: in other words, it is possible to create pluripotent stem cells from already differentiated stem cells. At first researchers thought that programming stem cells is possible only towards differentiation, but now they are starting to discover the ways of reversing the process. In 2006 two Japanese scientists, Kazutoshi Takahashi and Shinya Yamanaka, published the results of their research in the journal Cell and claimed that they had been able to produce pluripotent stem cells from fibroblasts. A year later, the two researchers demonstrated that somatic cells may be transformed into cells that behave like embryonic stem cells—and these cells are now called induced pluripotent stem cells (iPS). These type of cells are excellent resources for repairing damaged tissues and they can be used for the artificial regeneration of different types of tissue cells in the kidney, pancreas, or other organs.
Developments in the methods of reprogramming adult tissue cells have recently reached the previously unthinkable: germ cells can be now produced from tissue cells. This is indeed a new breakthrough as germ cells have a special feature: unlike other cell types, they do not have all of our genes. Another special characteristic of germ cells is that they have to be able to go through the process of meiosis, when chromosomes are halved, as this is necessary for a successful reproduction. Applying iPS technology in extracting germ cells has so far been impossible as somatic cells contain epigenetic memory, which makes transforming them into germ cells even more difficult.
Research on primordial germ cells (PGCs) has shown, however, that these can be also transformed into germ cell lines that have similar developmental potential to embryonic germ cell lines. PGC cell lines have a differentiation potential that matches the capacity of embryonic stem cells, thus these can be also used for a wide variety of purposes.
Producing germ cells from adult somatic cells has transgressed a boundary that had been seen as impermeable. Although this breakthrough has been observed so far only in research on animals, philosophers, bioethicists and lawyers have started to ponder the consequences of the previously unthinkable possibility of human reproduction independent of sexuality, designed and programmed from somatic cells. This would be a new epoch in the history of human reproduction, and indeed in the history of mankind. In September 2018, the Japanese researcher Mitinori Saitou announced the creation of oogonia cells – from which oocytes can be produced. Thus, we can state that there are now promising experimental researches on artificially creating egg cells in animals. The same Japanese research team announced in 2011 that they could produce mice sperm artificially from the skin cells of mice.
If it indeed becomes possible to create germ cells from skin cells, then this completely changes what we have so far known about infertility and childlessness, and indeed about human reproduction in general. Reprogramming stem cells extracted from somatic cells could be a solution for practically any form of infertility. Reproductive technologies intending to cure or mitigate infertility have produced innovative solutions every ten years or so, giving the possibility of having a child for different groups of individuals of previously involuntarily childless people. At first we had artificial insemination, then in vitro fertilization, then it became possible to inseminate the mother’s egg with only one sperm of the father. Preimplantation genetic testing of in vitro embryos has also become possible; new storing, freezing and vitrifying technologies have extended the life span of germ cells and eggs. All these technologies have contributed to the birth of more, and healthier children.
So what are the possible consequences of having a greater abundance of embryos produced more conveniently than ever before? What happens when germ cells can be easily replaced? Quite possibly, would-be parents may become more choosy, and instead of pondering about having a child, they are going to think about having specific types of children. In other words, when human reproduction is not limited by a shortage of good quality germ cells, then elderly or young couples, infertile or same-sex couples, single women and men will be capable of having their own children. But then, with such a great abundance of reproductive material, would it not devalue the regular, common germ cell reproduction? Would common sexual reproduction be overshadowed by premeditated, designed, scientific planning of children? Would this technology separate sexuality and reproduction even more radically than in vitro fertilization?
Thomas Greely, the bioethicist and law professor at Stanford University, claims that in forty to fifty years this is going to be the way to reproduce – in other words, sexuality and reproduction will depart from each other considerably. Single people, same-sex couples, elderly or infertile people could overcome any possible biological obstacle to having children. As sexual intercourse loses its significance in reproduction, it is quite possible that ethically more neutral and less problematic cells, such as skin cells, can pave the way to designing and programming reproduction. There are much weaker emotional attachments to skin cells than to sexual intercourse, and the moral, cultural dimensions of sexuality are going to be replaced by the scientific planning or engineering of children. In a way, one could only welcome this overcoming of biological limitations, but the question remains: what role would emotions would play in this form of reproduction? Could skin cell reproduction convey emotions? Or will love reside in the desire for the perfect child?
It seems that the phrase ‘planning children’ is going to become truly meaningful. If stem cell research develops at such a rapid pace, in about forty years many children are going to be “manufactured” under the microscope. Nevertheless, it will take many skin reproduction experiments with our four-legged animal friends before we can see that the children of our grandchildren evolve from the skin cells of our grandchildren.
Please note that blog posts are not peer-reviewed and do not necessarily reflect the views of RHM as an organisation.