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Human embryonic stem cells (hES cells), are currently discussed, not only by the biologists by whom they were discovered, but also by the medical profession, media, ethicists, governments and politicians. There are several reasons for this. On the one hand, these 'super cells' have a major clinical potential in tissue repair, with their proponents believing that they represent the future relief or cure of a wide range of common disabilities; replacement of defective cells in a patient by transplantation of hES cell‐derived equivalents would restore normal function. On the other hand, the use of hES cells is highly controversial because they are derived from human pre‐implantation embryos. To date, most embryos used for the establishment of hES cell lines have been spare embryos from IVF, but the creation of embryos specifically for deriving hES cells is also under discussion. The most controversial variant of this is the transfer of a somatic cell‐nucleus from a patient to an enucleated oocyte (unfertilized egg) in order to produce hES cells genetically identical to that patient for 'autologous' transplantation (so‐called 'therapeutic' cloning); this may prevent tissue rejection.

The question 'Can these cells be isolated and used and, if so, under what conditions and restrictions' is presently high on the political and ethical agenda, with policies and legislation being formulated in many countries to regulate their derivation. The UK has been the first to pass a law governing the use of human embryos for stem cell research. The European Science Foundation has established a committee to make an inventory of the positions taken by governments of countries within Europe on this issue (European Science Foundation, 2001).

In order to discuss the moral aspects of the isolation and use of hES cells, which is the aim of the present article, it is first essential to understand exactly what these cells are, where they come from, their intended applications and to define the ethical questions to be addressed.

What are (embryonic) stem cells?

'Stem cells' are primitive cells with the capacity to divide and give rise to more identical stem cells or to specialize and form specific cells of

somatic tissues. For example, in mammals, somatic cells make up all the internal organs, skin, bones, blood and connective tissue, while mammalian germ cells give rise to spermatozoa and ova which fuse during fertilization to produce a cell called a zygote, which divides and differentiates into the cells of an embryo.

Broadly speaking, two types of stem cell can be distinguished: embryonic stem (ES) cells which can only be derived from pre‐implantation embryos and have a proven ability to form cells of all tissues of the adult organism (termed 'pluripotent'), and 'adult' stem cells, which are found in a variety of tissues in the fetus and after birth and are, under normal conditions, more specialized ('multipotent') with an important function in tissue replacement and repair.

What is the difference between cell types?Totipotent cells can form all the cell types in a body, plus the extraembryonic, or placental, cells. Embryonic cells within the first couple of cell divisions after fertilization are the only cells that are totipotent. Pluripotent cells can give rise to all of the cell types that make up the body; embryonic stem cells are considered pluripotent. Multipotent cells can develop into more than one cell type, but are more limited than pluripotent cells; adult stem cells and cord blood stem cells are considered multipotent.



hES cells are derived from the so‐called 'inner cell mass' of blastocyst stage embryos that develop in culture within 5 days of fertilization of the oocyte (Thomson et al., 1998; Reubinoff et al., 2000). Although hES cells can form all somatic tissues, they cannot form all of the other 'extraembryonic' tissues necessary for complete development, such as the placenta and membranes, so that they cannot give rise to a complete new individual. They are therefore distinct from the 'totipotent' fertilized oocyte and blastomere cells deriving from the first cleavage divisions. hES cells are also immortal, expressing high levels of a gene called telomerase, the protein product of which ensures that the telomere ends of the chromosomes are retained at each cell division and the cells do not undergo senescence. The only other cells with proven pluripotency similar to that of ES cells are embryonic germ (EG) cells, which as their name implies, have been derived from 'primordial germ cells' that would ultimately form the gametes if the fetus had not been aborted. In humans, hEG cells were first established in culture in 1998, shortly after the first hES cells, from tissue derived from an aborted fetus (Shamblott et al., 1998). Biologically, hEG cells have many properties in common with hES cells (Shamblott et al., 2001).

In the adult individual, a variety of tissues have also been found to harbour stem cell populations. Examples include the brain, skeletal muscle, bone marrow and umbilical cord blood, although the heart, by contrast, contains no stem cells after birth (reviewed in McKay 1997; Fuchs and Segre, 2000; Watt and Hogan, 2000; Weissman et al., 2000; Blau et al., 2001; Spradling et al., 2001). These adult stem cells have generally been regarded as having the capacity to form only the cell types of the organ in which they are found, but recently they have been shown to exhibit an unexpected versatility (Ferrari et al., 1998; Bjornson et al., 1999; Petersen et al., 1999; Pittenger et al., 1999; Brazelton et al., 2000; Clarke et al., 2000; Galli et al., 2000; Lagasse et al., 2000; Mezey et al., 2000; Sanchez‐Ramos et al., 2000; Anderson et al., 2001; Jackson et al., 2001; Orlic et al., 2001). Evidence is strongest in animal experiments, but is increasing in humans, that adult stem cells originating in one germ layer can form a variety of other derivatives of the same germ layer (e.g. bone marrow‐to‐muscle within the mesodermal lineage), as well as transdifferentiate to derivatives of other germ layers (e.g. bone marrow‐to‐brain between the mesodermal and ectodermal lineages). To what extent transdifferentiated cells are immortal or acquire appropriate function in host tissue remains largely to be established but advances in this area are rapid, particularly for multipotent adult progenitor cells (MAPCs) of bone marrow (Reyes and Verfaillie, 2001). Answers to these questions with respect to MAPCs, in particular whether they represent biological equivalents to hES and can likewise be expanded indefinitely whilst retaining their differentiation potential, are currently being addressed (Jiang et al. 2002; Schwartz et al., 2002; Verfaillie, 2002; Zhao et al., 2002). For other adult stem cell types, such as those from brain, skin or intestine (Fuchs and Segre, 2000), this may remain unclear for the immediate future. Although the discussion here concerns hES cells and the use of embryos, the scientific state‐of‐the‐art on other types of stem cell is important in the context of the 'subsidiarity principle'

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