ETHICS OF HUMAN TESTING: BACKGROUND 217 However, based on the Christian doctrine of "do no ill to thy neighbor," Claud Bernard, a French physiologist and ethicist, in 1927 developed a code (5) forbidding experimen­ tation on man which "might be harmful to him to any extent, even though the result might be highly advantageous to science, i.e. to the health of others." He concluded, "among the experiments that might be tried on man, those that it can only do harm are forbidden. Those that are innocent are permissible and those that may do good are obligatory." This effectively ruled out all non-therapeutic human studies. To establish the possibility of immunizing against syphilis by inoculation with serum from syphilitic patients, Albert Neisser in 1892 used, without their full knowledge and consent, three adolescent prostitutes as the test group and four healthy children as the control group. The prostitutes developed syphilis. This otherwise renowned scientist was fined and ordered to pay significant costs and his reputation was tarnished. The well­ publicized study led in 1900 to the first governmental position on research using human subjects (6). It states (I) ... medical interventions for purposes other than diagnosis, therapy and immunization are absolutely prohibited, even if all other legal and ethical requirements ... are fulfilled if: The person in question is a minor or is not fully competent on other grounds The person concerned has not declared unequivocally that he consents to the intervention The declaration has not been made on the basis of a proper explanation of the adverse conse­ quences that may result form the intervention (II) In addition ... Interventions of this nature may only be performed by the director of the institution himself or with his special authorization In every intervention of this nature an entry must be made in the medical case-record book, certifying that the requirements laid down in Items 1-3 of section 1 have been fulfilled, speci­ fying details of the case. (III) This directive shall not apply to medical interventions intended for the purpose of diagnosis, therapy and immunization. This Prussian directive provides for informed consent, delineates non-therapeutic and therapeutic research, and offers protection for the most vulnerable groups against use in non-therapeutic experiments. It reinforces the ethos of the competency of the investi­ gator and of peer review by restricting the work to the unit director or his nominee. One of the weakest elements is the absence of risk-benefit considerations since there is no requirement for the investigator to weigh the risks to the subject in relation to any benefits to society. The nearest assessment is that conducted by the volunteers them­ selves, who decided whether or not to consent after being informed of the hazards. The rapid expansion of the pharmaceutical industry in Germany during the 20th century brought about a shift from ad hoc, small-scale, individual physician-controlled investi­ gations to widespread industry-controlled research. Despite the existence of the com­ prehensive German directive, research trials were frequently criticized in the German press, and following the death of 7 5 children in a program of studies on tuberculosis vaccines, the Reich Minister of the Interior published guidelines (3 b, 7) in 1931, key elements of which include • All staff entering into employment must sign the guideline • An explanation provides for the need for therapeutic and non-therapeutic research • Confirmation that responsibility for the "life and health" of the subject rests with the physician

218 JOURNAL OF COSMETIC SCIENCE • A requirement for risk-benefit considerations with adequate animal experimentation to underpin the human studies • A need for informed consent from the subject or legal guardian • Provision of special consideration for vulnerable groups such as children and those with social hardship • Creation of special cases when using live micro-organisms • The responsibility of the unit director should be highlighted • A requirement for the work to be written up in a report and documentation of the consideration given to ethical justification of the study • The need for work to be published while maintaining the dignity of the subject (the first allusion to the confidentiality of the subject) • Additional constraints for non-therapeutic research: (a) Prohibition where consent was not obtained (b) Primacy and preference for laboratory and animal studies to generate data to either negate the need for human experiments or to ensure the validity of the human study (c) Prohibition of studies on minors if there is any risk to the child (d) Prohibition of tests on the dying • Provision of an ethical imperative to carry out research where current known methods are likely to fail • Academic training for physicians carrying out research, in the ethical and scientific aspects of their studies and in their publication Fewer cases of unethical experiments on humans have aroused so much widespread public condemnation than the Nazi atrocities during the Second World War (36). Twenty-three physicians stood trial for war crimes and crimes against humanity. Ex­ periments had ranged from determining for military purposes the survival period at sub-zero temperatures or low atmospheric pressure, to the assessment of the efficacy of antibiotics and immunization therapies. Malaria experiments resulted in 30 deaths from malaria and a further 300-400 from complications. Female prisoners were given simu­ lated battle wounds and deliberately infected with gangrene to determine the efficacy of sulphanilamide many died and others were left permanently disabled. Vast collections of human skeletons and organs were amassed to perform anthropological measurements and to study racial specificity. Programs included forced sterilization of Jews, Gypsies, and Poles of child-bearing age using drugs and concealed X-ray units. Less macabre experiments had been conducted elsewhere, including 15,000 criminals and mentally-ill subjects forcibly rendered sterile in the USA (36). Indeed, the French Nobel Laureate Alexis Carrel suggested (36) that criminals and the mentally ill should be "humanely and economically disposed of in small euthanasia institutions supplied with the proper gases." Studies to determine the effect of withdrawing various quantities of blood from subjects were conducted in the US (8) and Germany. In the UK, experi­ ments into the spread and treatment of scabies were performed on volunteers drawn from conscientious objectors to the war (9). Despite the availability of guidance material, unethical studies were still being conducted, e.g., Children with learning disabilities at Willowbrook School were deliberately infected with hepatitis in order to follow its natural history. It was claimed that the parents of the children consented. However, the information provided to them was deliberately deceptive as it made the inoculations appear to be part of a vaccination programme (10).