Can it be unethical to heal the sick?

August 17, 2001

Stem-cell research is too important to be banned, argue Ian Wilmut and Lesley Ann Paterson. The effects of conditions such as Parkinson's, diabetes, spinal-cord injury and organ disease are hard to imagine. In each case there is a limited amount of treatment available and no cure. Moreover, drugs given to Parkinson's patients can induce severe and debilitating side-effects; diabetes patients remain susceptible to other complications such as limb amputation, blindness and organ disease or failure that may lead to premature death; and spinal-cord injury patients are forced to live with partial or complete paralysis.

Stem-cell therapy has the potential to treat not only these life-shattering conditions, but many more. However, research is being held up by ethical debates over the use of human embryos. Embryo stem cells can be harvested from a cluster of cells known as the "inner cell mass". This cluster is formed once the embryo mushrooms into a hollow ball of cells and begins to prepare for implantation in the womb after fertilisation and multiple cell division. ES cells are "pluripotent" and therefore have the potential to form any type of cell in the human body. By harvesting these cells and growing them in the laboratory they have the potential to be "coaxed" - for example by adding certain hormones - into forming different cell types including dopamine-producing nerve cells for the treatment of Parkinson's, heart-muscle cells for treating heart disease and insulin-producing Islet cells for treating diabetes.

Injection of new nerve cells into a damaged spinal cord or heart-muscle cells into a diseased heart could significantly improve patients' conditions. In the case of Parkinson's disease, the specialist nerve cells could be injected into a patient's brain. The brain has a limited immune response and therefore has great potential for this treatment. But in other organs and tissues, injection of cells would cause an immediate immune response and the tissue would be destroyed by the body's defence mechanism.

To prevent this occurring, patients would have to take a cocktail of immunosuppressive drugs. Alternatively, stem-cell research could be combined with nuclear transfer (cloning), as used to create Dolly the sheep. In this case, the genetic material would be removed from a donated human egg and then replaced by the genetic material from a patient. The egg would be activated to start developing to form an embryo. After a number of divisions, ES cells could be taken from the embryo and would have the exact genetic make-up of the patient. Once these cells have developed into the required cell type and been injected into the diseased organ or tissue, they are unlikely to be rejected by the body.

But culturing cells useful for only one patient is likely to be expensive. A more viable option might be to create and maintain a wide range of genetically different ES cell types that would be matched as closely as possible with the patient's genetic make-up to prevent or reduce a rejection response.

The ethical problem occurs because a human embryo is required to obtain ES cells. This can be achieved from a frozen human embryo, surplus to an in vitro fertilisation procedure (subject to the appropriate ethical consent). Alternatively, for nuclear transfer procedures, an embryo would have to be made from a donor cell nucleus and a donated egg. The cells could be removed from the embryo at six days. At this stage, the embryo is a minute bundle of non-specific cells with absolutely no consciousness or feeling. The ES cells could then be taken, cultured and grown in the laboratory for therapeutic purposes. Adult stem cells do exist, but can form only a very limited range of body cell types.

ES cells show the greatest promise for therapeutic cloning. They are also excellent for laboratory research because, compared with adult stem cells, they multiply much more readily when cultured. Hence it is from ES cells that we can learn the most.

As more is learnt about how these cells form into different types, it is hoped we can reprogramme adult stem cells and so remove the need to use embryos. Adult stem-cell research should continue, but not at the expense of ES cells - the potential of these malleable young cells is too great to ignore.

On paper, stem-cell therapy appears relatively simple - but there is a long way to go. Extensive laboratory research is required to establish good techniques for harvesting the ES cells, growing the ES cells, performing the nuclear transfers, and manipulating the ES cells to form other cell types. In addition, we have the logistical problems of trying to obtain enough donated human eggs and/or embryos. We also have to ensure that once new cell types are created, they are safe to use and will not cause deleterious effects to patients who receive them.

We must not allow the debate on human cloning to cloud our judgement over therapeutic stem-cell research. As many countries struggle with the ethical dilemma of whether to allow this work, time is slipping away.

Ian Wilmut is joint head of the department of gene expression and development of the Roslin Institute. Lesley Ann Paterson is his scientific secretary. Wilmut will be speaking in a THES -supported debate on the future of genetic science at the Edinburgh International Book Festival on August 21.

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