Playing God? Benefits and challenges abound in human embryo research

Published: April 6, 2005  |  Source: pharmaceutical-business-review.com
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While most people believe that reproductive human cloning equates to unethical practice, advocates of therapeutic cloning and stem cell therapy have been left dismayed at the lack of distinction between the two areas in the recent UN declaration on the subject. Datamonitor’s Victoria Williams assesses the possible future application of cloning and stem cell techniques.

In March 2005 the UN passed a contentious declaration urging the governments of member states to ban all human cloning. While the declaration was not legally binding, it infuriated member states that had voted against the move, such as the UK. The point at issue is the declaration’s failure to differentiate between reproductive and therapeutic cloning, thus indicating that both types ought to be prohibited and therefore also embryonic stem cell research, which utilizes cloning technology and methods.

While both types of human cloning are fraught with ethical controversies, reproductive cloning – the creation of a sentient, genetically identical copy of an individual – is widely considered to be unethical and reprehensible by most in the scientific, political and religious communities. It is the implications for therapeutic cloning – the creation of embryonic stem cells that are genetically identical to a patient to generate perfectly matched tissues for the treatment of disease – that most concern those who oppose the UN plan.

Uncharted waters

Human cloning occupies an uncertain territory, somewhere between genetic engineering and assisted reproductive techniques, such as IVF, which both influence the ethical concerns over the practice, for example the potential for the genetic modification of offspring. One can argue here that it is the genome manipulation that is the more morally contentious issue. However, therapeutic cloning, in itself, is less about altering the genome than copying it.

The key potential benefit of therapeutic cloning is the possibility of creating transplant tissue perfectly matched to the patient, thus avoiding problems of rejection and reliance on immunosuppressive drugs, and allowing the replacement or Regeneration of damaged and non-Functional organs or tissue. Human therapeutic cloning involves the combination of human cell nuclear transfer, stem cell culture and stem cell therapy. It holds huge potential in the treatment of genetic and degenerative diseases as well as serious injuries. Therapeutic cloning is also one of the most important sources of embryonic stem cells for research, utilizing the technique of stem cell nuclear transfer (SCNT) in order to create cloned embryos from which stem cells matching the patient are created and specific tissues can be grown.

Alternative sources of human embryonic cells (hES) currently used include aborted and miscarried fetuses, and surplus blastocysts left over from IVF. A disadvantage of non-cloned embryos in clinical practice is that the stem cells generated would not be genetically identical to the patient, and would face the problems inherent in standard organ transplantation. In addition, there is simply not a large enough supply of embryos from these alternative sources to keep up with research needs. So, if research investigating the full therapeutic potential of stem cells is to continue to produce viable products, human cloning is a necessary process. Embryonic stem cell therapy could hold the cure, or at least the key to better treatment, for a number of diseases that affect millions of people worldwide, such as heart failure, diabetes, Parkinson’s, Alzheimer’s and also spinal cord injury.

Three stem cell varieties

While animal cloning has been in existence for many years, it was only in 1998 that researchers at the University of Wisconsin succeeded in isolating pluripotent stem cells from human embryos. Stem cells, by definition, are unspecialized immortal cells, with the capacity to develop into two or more tissue types. There are three kinds of stem cell, determined by their potential to differentiate: totipotent, pluripotent and multipotent. Totipotent stem cells are only found in the early blastocyst and have the potential to develop into a whole organism or to become any of the over 200 types of cell in the body. Pluripotent stem cells, also only found in the early embryo, can become many different types of cell but cannot develop into a whole organism. Multipotent stem cells can only differentiate into a limited number of tissue types, they are found in both the embryo and in adults, in bone marrow cells for example.

Objections to the use of embryonic stem cells turn on the premise that the practice involves the destruction of human life, or more precisely perhaps, the destruction of the potential for human life. As with the arguments surrounding abortion, anti-hES cell research proponents, religious and pro-life groups and some bioethicists argue that life begins at conception and therefore equate the fertilized egg and embryo as equivalent to an individual with the fundamental right to life. In this argument, using embryos, even cloned ones that will ultimately be destroyed, could then be considered tantamount to murder and hence morally unacceptable.

However, counter arguments propose that cloned embryos or those created using SCNT are never intended for to be implanted in utero, thus it is inappropriate to compare them to a fetus, baby or child. Furthermore, the strongest argument against those opposing hES research is that the potential for human life is not the same as actual human life. When it comes to human cloning, should a week-old ball of cells be valued above the life of an existing person or child who is suffering from an otherwise untreatable disease or injury?

Manifold challenges

Furthermore, one of the problems faced by hES cell research at present is developing ‘clean’ embryonic stem cell lines, i.e. those that stand no risk of contamination from animal product based culture systems. Almost all embryonic stem cell lines to date have been grown in the presence of either mouse or other human cells, which could pose a threat of contamination with viruses or other pathogens, potentially making the cells unsuitable for transplants.

Adult stem cells, or multipotent cells, might overcome the ethical objections and scientific obstacles to using embryonic stem cells, however, researchers are yet to prove that adult cells are as flexible as those from embryos. Work that suggests that adult stem cells do have significant flexibility is ongoing, although the probable disadvantages of this approach are that if adult cells are harvested from older patients, one of the key groups in need of this kind of therapy, the cells are likely to have suffered some of the defects of aging.

On the other hand, one of the advantages of MAPC cells (or multipotent adult progenitor cells) is that they do not form tumors; one of the known risks with ES cells. This has been shown in early experiments using a rat model of Parkinson’s disease, which involved the transplant of mouse ES cells into the part of the rat brain associated with dopaminergic cell loss. Although the experiment demonstrated some success, with the ES cells shown to have differentiated into dopaminergic cells and some improvement in Motor function in some rats, 20% of the animals developed a brain tumor, or teratoma. At present there is no way to control the growth or kill off transplanted stem cells upon the occurrence of abnormal development, such as tumor formation. This kind of safety mechanism might be necessary before human ES transplants can be considered a real therapeutic strategy.

There is another theory that suggests adult cells could become pluripotent (more like hES cells) if we can make them dedifferentiate to more primitive stem cell types which can then be made to specialize into specific cells e.g. neurons. A number of research teams have already shown that patients suffering from heart failure experienced an improvement in blood flow in and out of the heart, and in some cases no longer needed a transplant, after being treated with their own stem cells, derived from bone marrow, which were injected into heart tissue. However, it is not known by what process the stem cells were able to exert these effects, be it by dedifferentiating into a less specialized stem cell type before differentiating again into heart tissue or by some other process. Much more research with adult stem cell dedifferentiation is needed and at present the technology lags far behind that with hES cells.

Source: Datamonitor Expert View