OPINION: Scientists are beginning to find ways of achieving results in specialised cells previously only thought possible in embryo-harvested cells, writes PATRICK CUNNINGHAM
STEM-CELL research is not in itself controversial. Bone marrow stem cells have been used for decades in the treatment of leukaemia. However, research in recent years has opened up wider possibilities with cells derived from embryos and very recently with reprogrammed cells from adult tissue. It is the use of cells derived from human embryos which has brought great challenges on both the legal and ethical fronts.
There is great variation in the legal position of embryos and embryonic stem cells between countries, and even between states within countries such as the USA. In Ireland this area is the responsibility of the Department of Health and Children. At present there is no legislation here governing assisted human reproduction or stem-cell research. Medical practice, however, is governed by guidelines issued by the Medical Council.
The Commission on Assisted Human Reproduction, established in March 2000, published its report in May 2005. The main recommendation was for the establishment of a regulatory body for assisted reproduction purposes. It also recommended, by majority, that embryo research should, under stringent conditions, be permitted on surplus embryos donated specifically for research. The report was referred to the Joint Oireachtas Committee on Health and Children. Following a public consultation, the Irish Council for Bioethics published an opinion on stem-cell research in April 2008. Its recommendations are similar to those of the Commission on Assisted Human Reproduction.
Article 40.3.3 of the Constitution acknowledges the right to life of the unborn, with due regard to the equal right to life of the mother. In a judgment given on December 15th, 2006, the High Court (in R v R, a frozen embryo case) decided that the three frozen embryos concerned were not “unborn” as defined under the Constitution. The case has been appealed to the Supreme Court, whose judgment is expected soon.
Under the EU research programmes (FP7) funding will not be provided for research activities intended to destroy human embryos, including for the procurement of stem cells. However, the rules do allow for research on pre-existing stem cell lines derived from excess embryos from in vitro fertilisation.
The central issue in the present context is whether it is ethical to harvest stem cells from human embryos, in a process which leads to the death of the embryo. If one starts from the premise that human life begins at conception, and that it is unethical to terminate a human life, then the harvesting of stem cells would be considered unethical. This is the official view of the Catholic Church and of many other groups and individuals. However, in this country, the hierarchy advised voting in favour of the 2002 referendum on abortion in which, as the former attorney general John Rogers has pointed out, the protection of the Constitution was effectively defined as beginning at implantation, not at conception. The referendum was narrowly defeated.
Other groups and individuals (and even countries) take the view that human life can be defined as beginning at some point of development after conception, usually implantation, and that it is therefore not unethical to harvest stem cells from embryos before that point. Others permit destruction of an embryo through abortion at varying stages post implantation, arguing that if there are ethical issues in causing the death of the foetus they are counterbalanced by other arguments in favour of abortion.
Clearly, science alone cannot resolve the differences between individuals, between groups within society, and between societies across this wide range of views on the ethics of interference with the earliest stages of life.
Every cell in the body contains the full set of genetic instructions for the growth and functioning of a complete human being. As development proceeds from the initial fusion of sperm and egg to form a single cell, and then multiple cells, leading on to multiple differentiated tissues, these genetic instructions are progressively activated to produce different component tissues. As specialised organs develop, genes that the organ does not require for its growth and functioning are silenced. As each tissue or organ develops to maturity, the process of programmed maintenance and replacement of cells in that tissue is called into action.
Science is at a very early stage of understanding how this immensely complex process of development is managed from the genetic coding contained in each cell to the complexity of a functioning individual.
Stem cells offer the prospect of therapies for a range of debilitating diseases. Most current research is focused on the cultivation of particular tissue types in the laboratory for detailed investigation of the mechanisms underpinning these diseases at the cellular level. The goal in the first instance is to develop new pharmaceutical therapies. The popular expectation that stem cells can be used directly to regenerate tissue in patients to treat neurodegenerative diseases or spinal cord injuries is premature. Such direct therapies are only likely to emerge over the next 10 or more years.
However, the science is accelerating. Until two years ago, it had proved impossible to take a cell from a differentiated tissue and reactivate the full set of genetic information it contained. On the other hand, cells harvested from very early embryos still retained the capacity to develop into a range of different tissue types. These embryonic stem cells (ES) are referred to as “pluripotent”.
In 2006, Takahashi and Yamanaka (Cell, Vol 126, 663-676) demonstrated for the first time that cells from differentiated tissues could be reprogrammed to become pluripotent. These are known as iPS cells or induced pluripotent stem cells. This discovery, and the work which followed it, has raised the prospect of being able to achieve with iPS cells everything that was thought possible with ES cells harvested from embryos.
For those who regard harvesting of embryonic stem cells as ethically unacceptable, this prospect strongly reinforces the case for legally prohibiting research on embryonic material. However, at this early stage of research on iPS cells, it is far from clear whether these reprogrammed cells can be fully pluripotent. The problems concern difficulties in controlling the sequenced switching on and switching off of specific genes necessary for an iPS cell line to produce tissue of a specific type. Researchers working on stem cells therefore are generally in favour of continuing work on embryonic stem cells until the reprogrammed iPS cells can be shown to be as effective.
No one can say with any confidence if or when these iPS cells will be able to do everything that can be done by cells harvested from embryos but the science is evolving rapidly. If the optimists are right, this development may defuse one of the most divisive ethical and legal issues concerning the practice of science and medicine.
Prof Patrick Cunningham is chief scientific adviser to the Government. He is taking part in a three-day conference starting today in Dublin. Organised by Dr Stephen Sullivan of the Roslin Institute in Edinburgh, Science Foundation Ireland and Abcam, a Cambridge-based group of scientists dedicated to building a catalogue of the best antibodies, it will discuss the potential applications of human pluripotent stem cells