The Australian policy debate about human embryonic stem cell research.

• Author: Hall, Wayne

1. Introduction

   Australia is a pluralistic liberal democracy in which no ethical theory commands universal assent, so contentious ethical issues must be resolved by the political process. The usual outcome is a policy that is the most acceptable, or the least objectionable, to the most citizens. (1)

   The major competing ethical theories in the Australian stem cell debate have been utilitarianism and deontological theories. Utilitarianism is a consequentialist theory in which individual acts or moral rules are assessed by their net effect for good and ill on all who are affected by them. (2) Deontological or duty-based theories derive obligatory rules for moral conduct from general ethical principles, such as, the rule that it is wrong to take innocent human life. (3) These ethical theories do not exhaust the possibilities (4) but they have dominated the Australian debate about human embryonic stem (hES) cells.

2. Embryonic Stem Cells

   Embryonic stem cells are self-renewing, undifferentiated cells that are extracted from the inner cell mass of a 5-6 day old embryo or blastocyst. (5) The embryo is destroyed in the process of extracting the stem cells. (6) Embryonic stem cells are pluripotent, that is, they can differentiate into many different cell types but they cannot give rise to an embryo. Adult stem cells which are found in small numbers in bone marrow, brain and lining of the gut are multipotent, that is, they can give rise to a limited number of cell types.

   A number of potential uses can be made of hES cells. The first use has been undervalued in public debate: this is the contribution they may make to improve our understanding of the processes of cell differentiation and development in human beings. (7) The second potential use is to expedite drug development by testing the efficacy and toxicity of new drugs in target human tissues in the test tube. (8) A third potential use of stem cells is to provide a vehicle for somatic gene therapy in genetic disorders, such as, cystic fibrosis, haemophilia, haemochromatosis etc. (9) The fourth possible use has dominated the public debate because of the potential benefits it may provide for people with serious illnesses and disabilities. This is their use in "cellular" or "regenerative medicine" to generate replacement tissues and organs that could be transplanted into persons with genetic, congenital or acquired diseases and disabilities. (10)

3. Somatic Cell Nuclear Transfer and Therapeutic Cloning

   A major technical problem in using hES cells for regenerative medicine is that they are unlikely to be immunologically compatible with the recipient and so will provoke an immune reaction that will lead (in the absence of immunosuppressant drugs) to their rejection. (11)

   One solution to this problem would be to create a hES cell tissue bank, that is, a large number of different hES cell types that would allow matching between donor and recipient. (12) A major disadvantage with the hES cell tissue bank is that this would require a huge number of hES cell lines (the number required being a matter of debate). Such a hES cell bank would be technically difficult and expensive to generate and the number of human embryos that would be required to produce such a stem cell bank would test public support for hES cell research.

   A second solution is "therapeutic cloning" which involves generating hES cells from the recipient of the transplant by means of Somatic Cell Nuclear Transfer (SCNT) or "nuclear transfer". (13) SCNT creates and embryonic clone of the patient by inserting a nucleus from one of the patient's cells into an oocyte or egg from which the nucleus has been removed (i.e. an enucleated oocyte). The new composite cell is then induced to develop into an embryo. (14) After 5-6 days hES cells are "harvested" from the inner cell mass of the blastocyst. These cells are used to generate new tissue that is immunologically identical to the patient and hence can be transplanted without tissue rejection.

   The hope is that SCNT could produce: pancreatic islet cells for diabetes; dopaminergic neurones for Parkinson's disease; cardiomyocytes for heart disease; and neurones for spinal cord injuries. (15) These hopes are inspired by studies, which demonstrate that SCNT is feasible in mice. (16) SCNT technology has not yet been used in humans, with no human embryos having reached the blastocyst stage.

   There are a number of other technical challenges. First, hES cells need to be grown on human tissues rather than on the mouse feeder cells to avoid xenotransplantation. Second, researchers also need to better control cell differentiation so that they can direct hES cells to develop into the required type of cell. Third, they also need to purify the regenerated tissue of hES cells in order to eliminate the risk of producing teratomas. This occurs in mice when undifferentiated ES cells are implanted into normal tissue.

4. Adult Stem Cells

   Adult stem (AS) cells in the bone marrow (haematopoietic cells) have been shown to be multipotent, that is, capable of differentiating into a number of different cell types, e.g. different types of blood cells, muscle and neurones. (17) So far they have not been shown to be pluripotent like hES cells. AS cells potentially provide a direct way to generate immunocompatible tissue and organs (18) that does not require the creation of new embryos via SCNT or the destruction of surplus IVF embryos.

   There are also a number of technical obstacles to the use of AS cells for regenerative medicine. AS cells are found in very small numbers in adult tissue (though they are much more plentiful in umbilical cord blood). They have so far proven difficult to identify, isolate and culture, and so cannot yet be used to produce therapeutically useful numbers of cells for tissue replacement, with the exception of bone marrow transplants which are used to treat cancers of the lymphatic system. As with hES cells, these may not...