October 2003 Human stem cell research: a novel technology that will benefit patients Information and Position Paper EuropaBio, the European Association for Bio-industries, has 35 corporate members operating worldwide and 21 national biotechnology associations representing some 1200 small and medium sized enterprises involved in research and development, testing, manufacturing and distribution of biotechnology products. EuropaBio, the voice of European bio-industries, is a promoting force for biotechnology and to present its proposals to industry, politicians, regulators, NGOs, and the public at large. New technologies using stem cells are often described as scientific breakthroughs that could potentially revolutionize medicine. Ultimately, stem cell research may result in important cell-based therapies to treat serious diseases and conditions including heritable diseases, neurodegenerative disorders such as Parkinson s disease, Alzheimer s disease and spinal cord injuries, as well as diabetes, stroke, burns, skin disorders, heart disease and genetic disorders. Stem cells have the potential to become a renewable source of replacement cells and tissues. Although research involving adult stem cells is not controversial, the use of human embryonic stem cells raises important ethical and societal questions. Below is the position of EuropaBio on human stem cell research followed by an overview of what stem cells are, what their significance is for biomedical research and the healthcare biotechnology industry, what EuropaBio believes the ethical issues are and why there is controversy about these issues. 1. EuropaBio Position EuropaBio is committed to progress in biomedicine and believes that appropriately regulated, high quality research in the field of human stem cells is important. The Association supports carefully considered biomedical research on different types of human stem cells as these will be an important tool to further our understanding of fundamental biological processes in human diseases with an aim to more successful treatment, cure or even prevention of some of these diseases. EuropaBio adheres to the ethical principles stated in its Core Ethical Values (www.europabio.org) including opposition to the use of cloning technologies for the sole purpose of reproducing identical human beings. EuropaBio supports research on adult stem cells and its applications and believes that there is no obstacle to the immediate adoption of an appropriate regulatory framework in respect of this research which is not ethically sensitive. Embryonic stem cell research must be allowed in order to advance knowledge in biomedicine and its applications in healthcare. Given the divergent cultural and religious beliefs about research using human embryos, a consensus on human embryonic stem cell research in Europe seems unlikely at this time. For this reason, Member States and their constituencies should remain free to decide about the acceptance and applicability of embryonic stem cell research and to adopt appropriate rules. Av. de l Armée 6 - B 1040 Brussels Tel. : (32.2) 735 03 13 - Fax. : (32.2) 735 49 60 Website : www.europabio.org e-mail : mail@europabio.org
EuropaBio recognizes that stem cells obtained from fetal tissue remaining after a terminated pregnancy have potential for patient therapies in the future. However, the Association opposes the deliberate initiation of pregnancies for the sole purpose of obtaining fetal tissues by terminating such pregnancies. Not enough is known at the present time to ascertain the full potential of embryonic, fetal or adult stem cells, respectively. To advance our basic understanding of biomedicine, research involving all types of human stem cells, namely embryonic, fetal and adult should be allowed under controlled conditions. 2. Embryonic, fetal and adult stem cells: current practices and future prospects Stem cells are unspecialized master cells that differ from other kinds of cells in the human body in that they have a unique capacity to multiply and differentiate into many types of specialized cells and tissues. Stem cells exist at all stages of human development from early embryos to fetuses to adults. In general, there are three types of stem cells: embryonic, fetal and adult. To date, human embryonic stem cells (hesc) are the most versatile stem cells that can be propagated in culture. According to current scientific knowledge, they have the potential for many future medical applications such as therapeutic transplants and may lead to therapies for the replacement or regeneration of damaged or diseased cells or tissues. These cells are considered pluripotent which means that they have the capacity to develop into almost all cell lineages. However, this pluripotency may also limit their application in medical practice if the capacity of hesc to differentiate cannot be controlled appropriately. Today, there are only two ways to obtain hesc: they can be derived from supernumerary early human embryos or blastocysts created during in vitro fertilization (IVF) procedures and donated for research purposes with the informed consent of IVF patients. In this context, early human embryos are also referred to as pre-implantation. Alternatively, hesc can be obtained from an embryo created specifically for the purpose of stem cell research either by in vitro fertilization or somatic cell nuclear transfer also known as therapeutic cloning. The latter technique involves the use of fertilized eggs from which the nucleus has been removed. To date, the feasibility of somatic cell nuclear transfer for humans has not been documented. The use of human pre-implantation embryos as a source of stem cells gives rise to serious ethical concerns because this research requires the use and destruction of early human embryos, whether they are surplus embryos or created specifically for research. Thus, ethical debate about research on hesc relates to the status of a human embryo: those who oppose the technology affirm that the preimplantation embryo is a human being and therefore, must be afforded the same the rights as human beings; while others affirm that the pre-implantation embryo is not a human being although it has a special moral status and dignity. The core ethical question is whether the end - the prospect of developing future therapies for seriously ill patients - justifies the means - conducting research on human embryos? Or, should the perception of the status of the human embryo dictate whether it may or may not be used for therapeutic purposes? Another source of human stem cells is tissue isolated from miscarried fetuses 1. However, this application also poses an ethical question related to the high number of fetuses i.e. between five and seven needed to obtain sufficient neural tissue to treat a patient. A human adult stem cell is an undifferentiated cell found among differentiated cells in a tissue or organ; can renew itself and differentiate to yield the major specialized cell types of the tissue or organ. 1 European Group on Ethics, Adoption of an Opinion on Ethical Aspects of Human Stem Cell Research and Use (Paris, November 2000) 7. 2
The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found e.g. bone marrow, fat, skin, brain, muscle, blood and cornea. Adult stem cells are multipotent and thus, can only give rise to a limited number of different cell lineages. Blood-forming, hematopoietic stem cells from bone marrow have been used in transplantation procedures for many years 2, particularly in the treatment of leukemia and other cancers. In 1988, however, a new source of human hematopoietic stem cells was found, namely, blood remaining in the human umbilical cord and placenta after birth 3. Umbilical cord blood is rich in stem cells: a single cord may provide sufficient stem cells for transplantation in an adult patient. Diseases, traditionally treated by bone marrow transplants, such as leukemia and Hodgkin s disease, are increasingly being treated with cord blood hematopoietic stem cells 4. Differentiated cells generated from pluri- or multipotent stem cell lines could also serve as a basis for testing the safety of new medicines for established targets as well as testing and developing new classes of drugs that activate dormant stem cells in the patient s body and achieve in-situ regeneration of tissues and organs. Most human adult stem cells, however, only exist in minute numbers in the body. Currently, research is being conducted to evaluate if adult stem cells possess potential comparable to that of embryonic stem cells, in particular, whether they can be used instead of their embryonic counterparts in certain medical applications. Recent reports suggest that some adult stem cells are not only capable of differentiating into the cell types of the specific tissue or organ from which they originate, but also into cell types from other tissues or organs. This feature is known as plasticity. Future research may find ways to grow human adult stem cells from one tissue and reprogram them to generate cell types of other tissues. To realize the promise of novel cell-based therapies for serious diseases and bring these treatments to patients, scientists must be able to work with all stem cell types easily. Although in the future the promise of stem cells from adult tissues might equal or even surpass that of embryonic stem cells, the knowledge gained from research on the latter will be essential to better understand how to exploit the potential of adult stem cells. 3. Cloning human embryos for biomedical research Cloning techniques first came to public attention in 1997 with the cloning of Dolly, the sheep, by the Roslin Institute and again, in December 2002, when the Raelian sect announced that they had cloned the first human baby. This claim, however, remains unconfirmed as yet. The realization that cloning techniques could be used to produce human stem cells which are genetically almost identical to those of the person donating the somatic cell nucleus and which could potentially be used to develop treatments for serious diseases raises many ethical concerns.. The U.S. President s Council on Bioethics defines human cloning as the asexual production of a new human organism that is, at all stages of development, genetically almost identical to a currently or previously existing human being. More specifically, nuclear material of a human somatic cell 5 is introduced into a human oocyte (egg cell) whose own nucleus has been removed, thereby yielding a new entity that has a human genetic constitution almost identical to the donor somatic cell. In Somatic Cell Nuclear Transfer, embryos could be created for research purposes and then dissociated when they total approximately 100 cells to isolate embryonic stem cells that are genetically almost identical to the donor. 2 Puilaetco Bankers, Stem cells transforming medicine (Brussels: 2002) 19. 3 EU Commission, Stem cells: Therapies for the Future Presentation by Professor Eliane Gluckman, Eurocord Project Coordinator, Bone Marrow Unit, Hôpital Saint-Louis, Paris (Brussels: December 2002). 4 Scientific American. For which diseases or conditions is umbilical cord blood stem cell therapy most effective? December 1997 5 A somatic cell is an undifferentiated cell found in tissues or organs of the human body. Somatic cells can renew themselves to yield specialized cell types except for cells belonging to the germ line i.e. egg or sperm cells 3
(Note: almost refers to the fact that while the nuclear DNA is identical to the donor somatic cell, the mitochondrial DNA, representing about 0.1% of all genes, is derived from the egg donor and is identical to the egg donor.) The vast majority of scientists who support the use of embryos for research purposes accept that another key objective of such research is to reduce or if possible eliminate the need to create new embryos. Two major areas of research are emerging that address this challenge: 1) The use of genetic engineering to enhance the immuno-compatibility of a limited number of universal donor hesc lines that could be used to generate tissues for the majority of the population without the need for immunosuppression 2) Novel strategies to tolerize the immune systems of transplant patients in advance of treatment to accept cells and tissues derived from a limited range of master hesc lines without rejection or immunosuppression. Cloning for therapeutic purposes raises profound ethical issues about the deliberate production of human embryos and the possibility that such embryos may also be used in attempts to reproduce genetically almost identical human beings. However, a distinction should be made between therapeutic cloning with the aim of helping a patient if no equivalent treatment exists, and reproductive cloning which is intended to reproduce an entire human being. As stated above, EuropaBio and its members oppose the use of cloning technologies to reproduce human beings. 4. Other challenges There are other concerns which also need to be addressed if human stem cell research is to be translated into clinical applications for the benefit of patients, namely: 1. Scientific: isolating and culturing stem cells to obtain sufficient yields, preventing tumor formation in stem cell grafts. 2. Regulatory: accrediting and licensing stem cell banks to standardize the collection, analysis and storage of stem cell cultures, establishing registries to track sources, distribution and uses of these cultures and to follow the health of any patient treated with such stem cells. 3. Societal: access to human stem cell therapies for patients when these therapies become available. 4. Technical: researchers are encountering delays in the supply and distribution of stem cells due to the long lead times required to characterize and refine hesc. 5. Intellectual property: ensuring that researchers have the widest possible access to human stem cells while also providing academic institutions, non-academic entities and industry with appropriate incentives to justify the costs of developing stem cell cultures and products. 5. Conclusions There are many ways in which human stem cells can be used in basic and clinical research. There are also many hurdles ethical and technical that lie between the promise that stem cell technology holds and its realization. These hurdles will only be overcome by intensive research and continued dialogue among all stakeholders. Some of the most serious medical conditions, including cancer and birth defects are due to abnormal cell division and differentiation. A better understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. Regulating the use of embryonic stem cells in a transparent and flexible way is key to building public trust in stem cell research. Such regulation should be sufficiently broad as to allow scientific and medical research to accommodate the developments that are likely to occur over the next few years whilst also respecting the rights of individuals and society. EuropaBio believes that a continued and open dialogue among all stakeholders on issues in biotechnology including human stem cell research is essential. This is to ensure that effective, credible and responsible policies are delivered that generate the trust, confidence and support of EU citizens. 4
According to the recommendations issued by the EU Commission in its communication of 23 January 2002, Life Sciences and Biotechnology A Strategy for Europe, Life sciences and biotechnology should continue to be accompanied and guided by societal dialogue. Bibliography and references ***************************** 1. EuropaBio website: www.europabio.org 2. European Commission, DG Research/Life Sciences Directorates, Stem Cells: Therapies for the Future. Conference held in Brussels, December 2001. 3. European Commission, Communication from the Commission to the Council, the European Parliament, the Economic and Social Committee and the Committee of the Regions Life Sciences and biotechnology A Strategy for Europe (Brussels: 23 January, 2002) 12. 4. European Federation of Biotechnology (Task Force on Public Perceptions of Biotechnology) & the Genetic Interest Group (GIG), The Report of an Advanced Workshop on Embryo Research Club de la Fondation Universitaire (Brussels: September 2001). 5. The European Group on Ethics in Science and New Technologies to the European Commission, Opinion on the Ethical Aspects of Patenting Inventions involving Human Stem Cells Opinion No 16 (Brussels: May 2002). 6. National Institutes of Health, Backgrounder on Stem Cells (October 2002) and Primer on Stem Cells (updated September 2002). 7. National Institutes of Health, Stem Cells: Scientific Progress and Future Research Directions (Bethesda, MD: June 2001). 8. The President s Council on Bioethics, Human Cloning and Human Dignity: An Ethical Inquiry, Pre- Publication Version, (Washington D.C.: July 2002). 9. Puilaetco Bankers, Sector Report on European Stem Cell Companies: Stem Cells transforming Medicine (Luxembourg: February 2002). 10. Scientific American, For which diseases or conditions is umbilical cord blood stem cell therapy most effective? (July 2002). 11. Jiang Y., et al., Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002, published online 20 June 2002. Vol: 10.1038/Nature00870. 12. LaBarge M.A., Blau H.M. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury, Cell. 111 (2002): 589-601. 13. Theise N.D., Krause D.S. Toward a new paradigm of cell plasticity Leukemia 16 (2002): 542-548. 14. Suzuki A., Zheng Yw Y.W., Kaneko S., Onodera M., Fukao K., Nakauchi H., Taniguchi H. Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver J Cell Biol. 156 (2002): 173-184. 5