English Summary "Biomedical Interventions in Humans A Model for the Gradual Ethical Assessment of Gene and Cell Therapy"

Biomedical research and its application have rapidly been evolving in the last years. Elucidation of the complete genome sequences of several different organisms - including humans - has given substantial new insights into the differentiation of human cells. New therapeutic methods as well as innovative approaches for drug design demonstrate successful bench to bedside translation of basic research into new medical therapies. Accordingly, many effective therapies in medicine have been achieved by the application of the scientific advances of gene and cell biology.

One prerequisite for this successful development has been the discovery of DNA as the mediator of hereditary in the midst of the last century. Following discovery, new methods of restriction and synthesis of DNA have founded gene technology as a new discipline. For some years now, gene technology has been complemented with a new area of research – stem cell biology.

The recent dynamics in scientific research have been mainly triggered by the successful preparation of embryonal stem cells. Embryonal stem cell research led to the detection of tissue-specific stem cells in many different organs, to in vitro cultivation of stem cells, and to the establishment of stem cell lines. Moreover, it also revealed pluripotency of embryonal stem cells, i.e. the capacity of embryonal stem cells to differentiate into every single cell type of the organism. The first successful experiments to reprogram adult cells might set off another revolution in stem cell biology.

Since the discovery of DNA, gene technology has raised hopes and high-flying expectations in biological research but was at the same time confronted by fundamental opposition and major scepticism. Modern genetic research has caused and still causes committed debates not only within the scientific community but most of all in the public.

The main issue of these debates lies repeatedly in the ethical assessment of gene technology and its medical applications to humans. This question affects the relationship between science and public. On the one hand, general public needs to be properly informed about scientific research results; on the other hand science is dependent on a sustainable public consensus for its discoveries of new frontiers.

In 1997, the institute Technik-Theologie-Naturwissenschaft (TTN) of the Ludwig-Maximilians-Universität München contributed to the aforementioned debate with a study that develops a model for the ethical assessment of gene technology.* The current study is a complete revision that takes into account the advances in biomedical research, its medical applications, and its public debate.

In the course of the increasing medical application of gene technology and stem cell biology it has become apparent that the early expectations and aims were overshooting and the fears too general. Advanced research resulted in a differentiation of aims and projects, thereby contributing to a sobered public debate. Scientific concepts have been translated into the practice of clinical trials.

The debate about science-fiction-like scientific developments has been displaced by concrete results in the field of cell biology and by a serious discussion of their therapeutic application and tolerance. Our new study takes into account this more substantiated debate on biomedical research and its therapeutic application.

However, the ethical discussion of the scientific advances in gene technology and stem cell biology has not been focussed towards the actual or the most probable medical applications. For gene therapy, the debate was dominated by those interventions into the human genome that would alter human nature. For stem cell research, much attention has been paid to the ethical issues of stem cell derivation from human embryos. These issues are prone to polarize between general rejection and unreserved approval.

Such polarisation harbours the danger to affect the whole field of gene technology and stem cell biology. It not only fails to detect the complexity and diversity of the scientific problems but also counteracts a liable ethical debate. Between the poles of general rejection and unreserved approval lies the field of concrete assessment and solid decisions. Here, public education and problem-oriented clarification are a prerequisite for any broader application of the new scientific technologies.

The already realized and the prospective applications of gene and stem cell technology raise the issues whether such applications can be legitimized in humans and by which criteria further advancement of these technologies can be encouraged. Our model of gradual ethical assessment is supposed to overcome the aforementioned polarisation of the ethical debate.

Differentiated analysis and assessment of the already realized and the prospective applications of gene and stem cell research will help to reflect on the ethically relevant differences within gene and stem cell medicine. Our model and the governing criteria which have been prepared as several theses, will contribute exemplarily to the discussion of these bioethical issues. In this context, exemplarily means that the theses and their case by case explanation will be explicitly restricted to gene and stem cell interventions in humans which have already been successfully applied or which can be regarded as well feasible.

Ethical judgement formation on therapeutic applications of biomedical research results must carefully consider those convictions which are fundamental to a broad public, cultural, and normative consensus. Elsewise, the ethical assessment will not have the necessary power to convince.
Gene and stem cell medical interventions - as discussed here – can only be carried out by physicians. This means that ethical considerations have a clearly defined starting point: the physician who is the executing and fully responsible subject. As such, the medical profession is the reference point for the relationship of scientific research and its therapeutic application.

For that reason, the here presented ethical assessment will be based upon the professional ethics of the physician. The physicians’ ethos forms the framework for biomedical interventions in humans. The professional ethics of the medical scientist as a physician implies that all actions of the physician are aimed at the healing of the disease of individuals. This comprises the following fundamental elements: autonomy (as part of human dignity), adequate risk-benefit ratio, therapeutic indication, and research that is open to the public. When these general fundamental ethical elements are related to the medical application of gene and cell technology, the following more specific criteria are obtained: risk of interventions, reversibility of interventions, proliferation of altered cells, and emerging legal and ethical conflicts, which will serve as an indicator for public approval of such interventions.

On basis of these criteria, we grade the medical applications of gene and stem cell technology into four levels. Briefly, they escalate from “ethically unproblematic” (level 1) to “ethically not justifiable” (level 4). Our model of gradual assessment starts with the “unproblematic” cases and successively moves on to the more complicated cases.