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Submission to the Senate Community Affairs Legislation Committee Concerning the Research Involving Embryos and Prohibition of Human Cloning Bill 2002 Matthew Downey BSc(Hons) Home: (07) 3391 0775 Work: (07) 3391 0775 37 Salstone Street Kangaroo Point QLD 4169 Introduction Debate surrounding the use of embryonic stem cells for medical research purposes has generated immense public debate. The raft of opinions and emotions raised by this controversial issue is justifiable considering what is at stake. For medical researchers the use of embryonic stem cells represents an area of research which has the potential to quickly advance our understanding of developmental biology, create a safer method for assessing drug toxicity and provide a means for developing cures and/or therapies to treat some of the most debilitating and fatal of human diseases and conditions. Similarly, the people and subsequent families affected by these afflictions also have a vested interest in seeing this potential realised. With the current governments’ emphasis on promoting biotechnology research and the infrastructure and economic environment in which this research can be commercialised, the income derived from patents and other intellectual property rights surrounding the use of embryonic stem cell technology could be considerable. Despite these scientific, humanitarian, and economic considerations, it is the ethical aspect of embryonic stem cell research which is causing the most confusion and consternation among all Australians, the members of the federal House of Representatives and Senate included. Ethical considerations have been raised by almost every religious group and also by those who lack any religious affiliation. Personally and collectively we are being asked to answer questions which challenge our definition of human life and the value we place on our human existence. The reality of the situation is that we are approaching a period in human history in which we will possess the knowledge and technology to manipulate life as we know it at the most basic and fundamental of levels. Our responsibility therefore is to ensure that we use our intellectual and creative abilities to create a world in which future generations exist and flourish like none previous. In order to make a well considered and informed decision, a thorough and objective consideration of the facts must be made separate from the emotion and opinion in which these facts can, either intentionally or unintentionally, be distorted. In this submission I will present a brief review of some of the facts concerning the research into spinal cord regeneration and place this within the context of the current and potential contribution of stem cell research. Spinal Cord Injury (SCI) Approaches to treating SCI Surgeons who treat people with spinal cord injury (SCI) are interested in three things with regards to spinal cord regeneration: what can be done to minimise neurologic injury, what can be done to enhance neurologic function and what can be done for the patient with longstanding paralysis? (Kwon and Tetzlaff, 2001). In terms of preserving nerve cell function and thus minimising neurologic injury, considerable work on the movement of various ions across nerve cell membranes has suggested the local application of substances antagonistic to the movement of these ions may assist in preserving nerve function (Kwon and Tetzlaff, 2001). Failure of SCI patients to regain motor function has been attributed, conceptually at least, to two apparent characteristics of central nervous system (CNS) nerve cells: 1) the injured nerve cells have a limited intrinsic capacity to regenerate, and 2) the nature of the environment in which these cells must regenerate is not permissive of such growth (Kwon and Tetzlaff, 2001). As a consequence, research has focussed on characterising the intrinsic regenerative ability of CNS nerve cells, augmenting the nerve cells’ regenerative ability and characterising the inhibitory nature of the CNS environment (Kwon and Tetzlaff, 2001). Cellular transplantation attempts to overcome this inhibitory environment and promote functional regeneration (Kwon and Tetzlaff, 2001) and it is here that research into stem cells finds its application. Cellular transplantation As stated by Kwon and Tetzlaff (2001), the primary candidates for use in cellular transplantation strategies include neural stem cells, fetal cells, Schwann cells and olfactory ensheathing cells (OECs). Adult Neural Stem Cells Research has revealed that the mouse adult brain and spinal cord contain neural stem cells that can generate many of the cells required for normal neurological function (Clark et al., 2000). Studies utilising developing chick embryos have demonstrated that mouse-derived adult neural stem cells are also able to give rise to various cell types that contribute to the generation of several tissues and organs (Clarke et al., 2000). Similar experiments are yet to be performed using human adult neural stem cells however experiments in which human adult CNS stem cells have been cultured indicate that these cells exhibit the capacity to generate various cells types (Temple, 2001). While it has been noted that there exists no evidence for the ability of adultderived stem cells to make the types of nerve cells observed in the embryo, this observation must be qualified by the fact that with reference to SCI studies, research involving stem cells and other multipotent cells is still in the preliminary stages (Temple, 2001). Embryonic Neural Stem Cells Transplantation studies involving the grafting of fetal human brain-derived stem cells to rat or mouse brains has demonstrated widespread incorporation in the brain of these cells and the production of various primary nerve cells (Temple, 2001). While both adult and embryonic stem cells offer hope with regards to developing therapeutic treatments for SCI, extensive and comprehensive research into the basic biology of these cells needs to be done before we can even begin to contemplate developing applications for human spinal cord regeneration. In contrast the results obtained from the use of olfactory ensheathing cells (OCEs) are far more promising and have been identified as the best option in terms of “bridging” descending and ascending neural pathways in the damaged spinal cord (Lu and Ashwell, 2002). Olfactory ensheathing cells (OECs) Despite residing in the CNS, OECs are derived from the olfactory placode which is found in the nasal cavity (Lu and Ashwell, 2002). OECs exhibit a number of functional attributes including: 1. the ability to migrate over long distances in the adult brain, 2. the ability to provide a matrix amenable to the growth of nerve cells and 3. the secretion of chemicals which promote nerve cell growth (Lu et al., 2002). All of these functions combine to make OECs, and related olfactory ensheathing glia (OEGs), prime candidates for applications in spinal cord regeneration. OEGs derived from the primary olfactory bulb of rats have been shown to promote nerve cell regeneration in the transected rat spinal cord (Ramon-Cueto, 1998). Similarly, human-derived OECs have been demonstrated to exhibit properties similar to their rat counterpart including extremely high viability in tissue culture and the ability to regenerate damaged nerve cells (Barnett, 2000). The most important discovery to date however has been the report that transplanted OEGs collected from adult rats have lead to functional and structural recovery following complete spinal cord transection (Ramon-Cueto, 2000). Conclusion In summary it can be said that research into both embryonic and adult derived stem cells has yielded important information regarding the nature of these cells with respect to developing therapies for the recovery of patients from SCI. The priority of research into stem cells at present is to characterise basic stem cell biology in terms of their role in developmental biology. This fundamental research will aid more progressive research which aims to understand aspects of stem cell biology which impact, in this instance, on treating people with SCI. While research using animal models has revealed similarities/differences and perceived advantages/disadvantages between adult and embryonic-derived neural stem cells I believe that one overriding consideration needs to be kept in mind. The ability to treat a person with tissues derived from their own body will circumvent the considerable problems associated with transplanted tissue rejection. In my opinion this fact alone is reason enough to concentrate our efforts on understanding and developing technologies associated with adult-derived neural stem cells in the treatment of SCI. Despite stem cells displaying such potential for the development of clinical therapies for SCI, the reality is that this potential is already being realised using OECs and OEGs. Research is also rapidly progressing into the chemical factors associated with promoting nerve cell regeneration in the hostile environment of the severed spinal cord. To set stem cell research within an appropriate context, it is envisaged that future therapies will incorporate all these areas of research and their effectiveness will be enhanced by the synergy of these combined fields. This wholistic approach emphasises the fact that advances in stem cell research can only be exploited if concomitant advances occur in related fields. Regardless of the potential exhibited by the use of stem cells in concert with other regenerative strategies, it is suffice to say that the initial advances in treating patients with SCI may in fact lie in developing neuroprotective methods which preserve and promote native nerve cell function by maintaining existing nerve cell function and preventing cell death (Kwon and Tetzlaff, 2001). References Barnett S C, Alexander C L, Iwashita Y, Gilson J M, Crowther J, Clark L, Dunn L T, Papanastassiou V, Kennedy P G E, Franklin R J M. Identification of a human olfactory ensheathing cell that can effect transplant-mediated remyelination of demyelinated CNS axons. Brain 123; 1581-1588. Clarke D L, Johansson C B, Wilbertz J, Veress B, Nilsson E, Karlstrom U L, Frisen J. Generalized potential of adult neural stem cells. Science 288; 16601663. Kwon B K and Tetzlaff W. Spinal cord regeneration from gene to transplants. Spine 2001;26(24S); S13-S22. Lu J, Ashwell K. Olfactory ensheathing cells their use for repairing the injured spinal cord. Spine 8: 887 –892. Ramon-Cueto A, Cordero M I, Santos-Benito F F, Avila S. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron 25; 425-435. Ramon-Cueto A, Plant G W, Avila J, Bunge M B. Long-distance axonal regeneration in the transected adult rat spinal cord is promoted by olfactory ensheathing glia transplants. The Journal of Neuroscience 18(10); 3803-3815. Temple S. The development of neural stem cells. Nature 414; 112-117.