Genetic Engineering of Drugs in the Sense of Substitutional Therapy

(This stage has already been reached)

Method: missing proteins are extracted from animals or blood conserves by means of genetic engineering and given as drugs

Examples: diabetes and bleeder's disease

Ethical perspective: as previous development and taking of drugs

Legal situation in Germany: covered by Drug Act AMG

Somatic Genetic Therapy to Treat Genetic Diseases

Method: a defective gene is replaced by an intact one, which is injected into the body cells (not germ cells)

Problem: the transition into the germ cells cannot be excluded, since the means of transport (viruses, fat globules) do not yet allow this

Examples: cystic fibrosis/mucoviscidosis, immune stimulation in cancer patients

Ethical perspective: comparable to surgical interventions, however, with unclear level of intervention, since effects on germ cells cannot be excluded.

Legal situation in Germany: the application is covered by the consent of the patient as well as by law practice. The development of the methods is impeded by prohibiting the necessary in vitro embryo research by means of the Embryo Protection Act (EmbSchG).

Bioethics Convention: permission of genetic therapy (Article 13) as well as permission of in vitro embryo research (Article 18)

Somatic Genetic Therapy to Treat Genetic Diseases of Unborn Children

The Pre-Implantation Diagnosis PID which should lead to Pre-Implantation Therapy PIT

Problem: due to the omnipotence of embryonic cells the germline is also quite probably regularly affected

Ethical perspective: the level of intervention exceeds the parents' right to consent. However, according to the authors of the "Escalation Model": A safe therapy could play a determining role as to the course of decision" (Winnacker et al.: 1997: 34). That means: if the pre-implantation therapy is successful, it will find acceptance.

Legal situation in Germany: not covered, since the development and the application of PID is prohibited by the Embryo Protection Act

Bioethics Convention: permission of predictive genetic testing (Article 12) in combination with permission of PID to select sex related diseases of in-vitro-fertilisation (Article 14) as well as permission of in-vitro embryo research (Article 18)

Germline Therapy to Treat Hereditary Defects Causing Diseases

Method: a defective gene in the germ cells is replaced by an intact gene

Example: BRCA-1-Gene (breast cancer)

Ethical perspective: the level of intervention exceeds the right to consent of the individual of today, since it is the descendants who are affected

Legal situation in Germany: not permitted, however, there is no explicit legal basis for a non-application, whereas the development of the procedure means violation of the Embryo Protection Act

Bioethics Convention: still excludes the application (Article 13), however, does permit preparing research (point 91 of the explanatory report of the Convention). The application could probably be covered by the adaptation in 5-year's stages (Article 32-4) after having developed the technique.

Germline Therapy with Introduction of New Genes to Prevent Diseases

Genetic vaccination

Examples: MxA-Gene from transgenic mice to prevent influenza, HIV-resistance gene of baboons to treat HIV

Ethical perspective: the level of intervention cannot be estimated, the danger for the whole population is unclear, since it is unknown how the insertion of an foreign gene affects the genome, e.g. the existing protective functions; danger of a chain reaction

Legal situation in Germany: see stage 4

Bioethics Convention: see stage 4

Germline Therapy as Prevention Against Risk Factors or Deviation from Norm

Examples: obesity, height

Ethical perspective: see stages 4 & 5; furthermore unclear concept of disease, danger of human beings according to norm

Legal situation in Germany: see stage 4

Bioethics Convention: see stage 4

Germline Therapy to Change the Human Species

Examples: intelligence, aggression

Ethical perspective: see all other stages; and who determines which evolutionary caused development stage can be ignored?

Legal situation in Germany: see stage 4

Bioethics Convention: see stage 4

In my opinion one more stage should be attached to this Escalation Model, stage 0, which is already integrated into our everyday life:

Genetic Registration

Application: selection of germ cells and embryos, selective distribution of resources

Examples: prenatal diagnosis, working place qualification diagnosis, insurance companies' admittance diagnosis

Ethical perspective: is subject to the consent of the parents or the person concerned

Problem: is voluntariness still guaranteed if genetic testing has become a social norm or the prerequisite for the distribution of resources?

Legal situation in Germany: covered by legal situation (e.g. Embryo Protection Act) as well as by legal practice.

The above model makes the danger of escalation of biomedicine clear in quite a few respects. As to the level of intervention it shows the threatening development of individual treatment to a treatment influencing all descendants, and as to the level of medical action it indicates the practice of healing diseases and the prevention of disabilities to the breeding of human beings according to norm. As to the level of concept of disease the model clearly demonstrates the spreading of apparently somatic diseases to disabilities, behavioural deviations and last to individual characteristics, and thus to the threatening biologisation of the social issue by a future genetically fixed medicine.

Against the historic background this predicted development could be described as the development of a "negative eugenics" (genetic examination and selection) to a "positive eugenics" (healing of society, the human species, formerly the 'Volkskörper'). The danger of this kind of ethics as part of the escalation lies in a stepwise transition from a medicine determined by individual ethics towards a medicine determined by collective ethics.

To this fundamental change of view the authors themselves seem to already succumb. By indicating a possible success which would justify a germline therapy they no longer follow the in Europe still broadly prevailing rejective attitude. "It is not the effect on a undefinable number of descendants which speaks against germline therapy", so they say, "but the not existing consensus on the mandate of the medical profession" (Winnacker et al.: 1997: 41). Here, you could add that this consensus could be altered. Only in their final remarks do they mention that science must respect the limits between individual treatment and the treatment of the 'human species' (Winnacker et al.: 1997: 49). However, a fundamental no to influencing the germline is missing. This ambivalence at such a decisive point, however, is in my opinion significant for the threatening future development of medicine and medical ethics even in Germany where positions of fundamentally ethical responsibility are slowly replaced by bioethical oriented moral-cost-benefit-analyses, thus more and more joining the international trend.

Does the Code only have a historic or even a generally definite significance?

Or put differently: Can it be only understood out of the historic context? Does it only aim to judge the practices of the Nazi-physicians? Or does it have a general validity for medical research in a civilised world in the first place?

In the United States these questions were discussed particularly in the 60s and 70s. The background was the disclosure of the cancer experiments in the Jewish Chronic Disease Hospital in Brooklyn in 1963, where 22 chronically ill women with intellectual disabilities were injected with cancer cells, and furthermore the disclosure about the Tuskegee-Syphilis-Study during which 400 blacks remained untreated or only apparently treated over decades just to study the process of the disease. The people concerned did not give their consent but thought they were treated. Against this background the German American historian Jay Katz finds it quite understandable that at that time the general validity of the Nuremberg Code was denied in the United States. It was not binding for a democracy but only for a dictatorship

The historic evidence and a view on the Code undeniable speaks for the claim of a general validity.

Telford Taylor, the chief prosecutor of Nuremberg stated in his introduction that the trial was no mere murder trial, since the defendants were physicians having sworn the Hippocratic oath, and thus having become murderers in the execution of their profession. Logically, the judges created with the Nuremberg Code a basis of judgement of crimes which became possible within the bounds of medicine. The judges described the statements of the Code as basic principles "which must be followed so that human experiments comply with moral, ethical and legal principles"(Mitscherlich, Mielke 1960: 273).

Besides, the famous first phrase of the Code and the following detailed explanations as to voluntariness, the test person and the researcher, to the quality of the information in view of the Auschwitz and Hadamar-medicine, would have been meaningless, even almost absurd, had they not been seen as general rules.

Here, the second question arises: B.Does the Code have a purely legal character to reclaim the human rights' protection of the individual or does it have the character of an ethical code for a humane medicine in the first place?

It is obvious that the informed consent is the core of the Nuremberg Code. "The Principles of Ethics Concerning Experimentation with Human Beings" presented at court in December 1948 by Andrew Ivy were based on the Hippocratic ethics of the responsible Physicians' behaviour. To these principles the judges of Nuremberg deliberately added the irrevocable human rights of the test person: the absolute necessity of the informed consent in point 1 and the right to withdraw from the experiment in point 9. By doing this, however, they did not replace the statements as to the responsible physicians' behaviour, which will be described in point 2-8 as well as in point 10.

The Nuremberg Code of 1947 thus is a really brilliant link between the Hippocratic ethics of physicians' responsibility and human rights. The answer to the question can only be 'yes': the Code is characterised by human rights and lawfulness, and it is an ethical code for a humane medical research.

In this sense the German Section of International Physicians for the Prevention of Nuclear War presented on the 20th August 1997, the 50th anniversary of the pronouncement of the judgement in the Nuremberg Physicians' Trial, the Nuremberg Code of 1997. It is based on the historic experiences and the basic ideas of the old Code of 1947 in order to answer current questions of medicine to the application of bio-sciences to human beings. Ten topics such as medical experiments, reproductive medicine, genetic diagnostics and therapy, transplantation, euthanasia, and distribution of resources are dealt with. The Nuremberg Code thus follows the widespread practice of considering the informed consent to be the principal idea in all fields of Public Health.

In Germany a rather different but important objection against the informed consent is raised: In view of the threatening genetic screening and manipulation of human beings by bio-medicine it is foolish to still rely on the free consent as instrument of correction. Neither are individuals free, they who are supposed to make decisions, nor are they able to really understand the things they should decide on. Rather is there the "legitimisation by procedure" in the sense of Theordor Adorno, that is the approval of an unstoppable inhumane technique by the informed consent developed into its pure form^[3].

I don't share this criticism. It is obvious that the principle of informed consent must fail if celebrated as the only moral-ethical authority. Inhumane practices, such as the active euthanasia or interventions in the germline, affecting the lives of future individuals, cannot not be justified by the informed consent of individuals of today (3).

The principle of informed consent does not mean what is practicable should be practiced, only if a person agrees to it. The principle of informed consent is an absolutely necessary prerequisite, but no sufficient predicament for a humane medicine. Thus, the presented Nuremberg Code 1997 contains apart from the personal consent of the test person, naturally further prerequisites, such as the expected benefit for the health of concrete persons or groups, the prevention of unnecessary experiments by applying already existing knowledge and the avoidance of unnecessary pressure of the test person, the publication of the results, the observing of the ethics-commission's decisions and many more.

However, it is alarming that almost all following revisions of the Nuremberg Code did not further describe the additional prerequisites of a socially responsible medicine, but relativise and degrade the principle of informed consent.

The first revision was the Declaration of Helsinki of the World Medical Association of 1964. Here, the scientific progress is the most important thing, whereas the rights of the individual are only seen in relation to it. For the clinical research in the sense of an individual healing attempt the consent should be given by a legal representative in case of incapacity of the person concerned. The explanations as to the non-therapeutic clinical research are ambiguous. On the one hand it is said that it "cannot be undertaken without his free consent". On the other hand it is said: "if he is legally incompetent the consent of the legal representative should be procured" (Annas/Grodin: 1992: 333).

Thus the 'spare' consent of the legal representative is not completely licensed, nor is it excluded. The fundamental statement of the Nuremberg Code is replaced by unclearness and the statements of the World Medical Association of Tokyo (1975), Venice (1983) and Hong Kong (1989) with the tendency to dissolve the principle of informed consent by the regulations of systematic research.

The current revision attempt consists of the suggestion to amend the Declaration of Helsinki, which will be presented by the American Medical Association in 1999. Afterwards no difference should be made between healing attempts and experiments for the benefit of others. In both cases the personal consent will no longer be necessary and can be always replaced by the consent of a legal representative (German Medical Magazine 1998, B-2403).

In this context Jay Katz referred to the draft versions of Helsinki of 1962 according to which the following groups are excluded from any experiments: prisoners of war, civilians, detained as a result of military occupation, prisoners and "persons incapable of giving consent because of age, mental incapacity, or being in a position in which they are incapable of exercising the power of free choice" (Katz 1992:233)

Since Helsinki 1964 this statement corresponding precisely the Nuremberg Code of 1947 was step by step undermined due the discrepancy to the practice of research in the United States and more and more obscured by new wordings. The Bioethics Convention would finally put an end to this long and vehement battle for the benefit of unhindered research by means to an International Law Declaration, as would the World Medical Association by means of a declaration of commitment according to their medical profession. The historic norm of the Nuremberg Code characterised by endless suffering, would definitely be broken.

Against this background the arguments of those aiming at legitimating research on people unable to consent must be measured:

The referring of the adherents of the Convention at 'minimal risks' and 'minimal burden' for the people concerned has no quietening effect whatsoever. Even the taking of blood, which they always mention, is experienced by persons with intellectual disabilities as rather threatening since they are able to only grasp certain situations intuitively^[4]. Particularly the concept of 'minimal risk' is in not at all satisfactorily explained and could become a gateway to various research methods. The Explanatory Report already mentions further examples such as procedures replacing x-ray treatments or experiments with vegetative state patients to improve intensive medicine.

Nor does the fact that the legal representative must give his consent thus protecting the rights of the people concerned improve the whole situation. For good reasons neither the parental right nor the German Guardianship Act include such kind of regulation. If the Convention was introduced to German law and the Guardianship Act was changed accordingly, the current understanding of parental custody as well as the legal guardianship would be turned upside down.

Against the background of history references to the well-being of the same patient groups or age groups as well as to the necessary solidarity of people with disabilities, who should "make sacrifices for the benefit of others" (German Department of Justice 1998: 21), are completely obsolete. Solidarity requires voluntariness and agreement. If this is renounced people with intellectual disabilities and everybody who is unable to give his consent will again become a victim to a very dubious progress. For good reasons this kind of sacrifice of the above group is not required.

In this context references to 'higher interests' and the 'well-being of future generations' or the 'human species' follow a dangerous historical continuity. They stand for the dangerous undermining of the individual ethical commitment of medicine in favour of collective ethical commitment.

The concept of informed consent has still another meaning: that is the dialogue between two individuals. On the one hand the researcher has to explain each step of the experiment so that the test person is able to understand it. On the other hand the test person asking questions, tiring but necessary ones, can withdraw from the experiment any time. The concept of informed consent does in any case include the rights to full treatment information, confidentiality, dignity and respect, mentioned in the US-debate on the Bill of Patients' Rights (Annas 1998: 69ff). I believe the informed consent aims at control and the guarantee of the necessity to prove the usefulness of research more than any present ethics commission. If research on people unable to consent was allowed it would mean a further step towards a research without dialogue.