Aiming at supererogation

Study medical sciences and you will quickly learn of the extent to which man is able to commit atrocities on his fellow man in the name of progress and understanding. For example, as an undergraduate of physiology I was required to study the Dachau Hypothermia Experiments. The immersion-hypothermia project was conducted at the Dachau concentration camp between August 1942 and May 1943. Its purpose was to establish the most effective treatment for victims suffering with immersion hypothermia, with a view to helping German aircrew shot down into the cold waters of the North Sea. 

In the 1980s, when I was studying for my degree, there was some debate over whether or not it was ethical consider such data. Positions ranged from a total ban on using the material as it represented "such a gross violation of human standards that they are not to be trusted" [1] to its adoption in recognition of the sacrifices made by the wretched victims and potential of honouring their sacrifice in saving future lives. As an undergraduate I was somewhat remote from the debate but fully aware of the predicament. In the end, I hope that learning about this dark chapter of science's history gave me an insight into writing with humility and empathy when writing about the diseases that afflict us.

Although we think we live in more enlightened times, even within my own lifetime we have noted examples of our unforgivable treatment of research subjects. For example, the Tuskegee Study funded by the US Public Health Service that only ended in 1972. The study looked at untreated syphilis in nearly 400 impoverished African-American males. They were told that the study was only going to last 6 months, but it actually lasted 40 years. Although they were given free medical care, meals and free burial insurance, researchers withheld the treatment of subjects with penicillin 30 years after it had been found to be an effective cure.

Beyond recognition of our own ability to behave inhumanely, the Tuskegee Study is important because it was the revelations about the treatment of its participants that were instrumental in establishing the ethical research framework that we follow today. And that is a milestone that it is worth taking a moment out of our busy day to reflect on.This year is the 40thanniversary of the Belmont Report.

The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was formed in 1974 by the National Research Act. From the outset the Commission adopted a broader and more sensitive approach to developing a framework for the future consideration of research. Four years of discussions culminated with a 4-day meeting at the Smithsonian’s Belmont Conference Center that was eventually translated into the Belmont Report [2]. The emerging directive needed to navigate not only the communities that had been betrayed by unethical experimentation but also policymakers, researchers and the public, ensuring that ethical guidelines for evaluating research would prevent future abuses and engender trust. Today, through its emphasis on informed consent and special protections for vulnerable individuals, the report’s reach and influence extends around the globe.

Formerly entitled Ethical Principles and Guidelines for the Protection of Human Subjects of Research, the Belmont Report was released in in 1978 but was only published in the US Federal Register in April, 1979. Among other issues, the Commission was charged with identifying the basic ethical principles that should underlie the conduct of biomedical and behavioural research involving human subjects, placing emphasis on:

• the boundaries between biomedical and behavioural research and the accepted and routine practice of medicine;
• the role of assessment of risk-benefit criteria in the determination of the appropriateness of research involving human subjects;
• appropriate guidelines for the selection of human subjects for participation in such research;
• the nature and definition of informed consent in various research settings. 

In an elegant framework, Belmont identified the three basic ethical principles of respect for persons, beneficence, and justice that must underlie the conduct of all biomedical and behavioural research in human subjects. Unlike most other reports issued by commissions, the Belmont Report did not make specific recommendations for administrative action, rather it requested that its instructions be adopted in their entirety, as a statement of policy.

Fast-forward to the present day and it is difficult not to marvel at the impact that a single document continues to have after 40 years of research, scholarship, and regulation. The enduring nature of the Belmont Report speaks to the care and deliberation with which it was created, the necessity for its framework and value of the principles woven into the rules we now follow. Though many may not know the full history behind the rules for ethical conduct, researchers from lowly scientist to principal investigator understand that those involved in clinical research must:

• Ensure the study is approved by an independent ethical review committee;
• Obtain informed consent from study subjects;
• Ensure that subjects understand the full extent of the experiment;
• Guarantee that participation isn't coerced by means of threatening or bullying;
• Warrant that all episodes during a clinical trial are reported;
• Respect the privacy of a participant’s identity and their motivation to join or refuse the experiment;
• Ensure that all subjects get (at least) the minimal care needed for any condition.

Two further understandings to emerge from the initiative are that researchers must share the findings of their procedures regardless of them being considered ‘good’ or ‘bad’ results. Also in the case someone who does not want to participate in research but would like treatment should not be turned away and must be treated with the same standard care.

Today we find that important questions are being asked about whether the report’s principles are adequate to address the challenges of modern-day research. Notably, the Belmont Report does not specify how its three ethical principles should be weighted or prioritized. Ethics committees must weigh up these principles and decide if any one should be considered more or less important depending upon the particular circumstances of the research in question. Equally, is it possible to show respect for a person’s privacy in the context of collection of vast quantities of online data and biospecimens? How can we manage safely the de-identification of data?

It may well be time for ‘Belmont 2.0’. For now however, we might want to spare a moment of thought for a job well done.

1. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Department of Health, Education and Welfare (DHEW) (30 September 1978) Published April 1979.
2. Moe K. Should the Nazi research data be cited? Hastings Cent Rep 1984; 14(6):5–7.

Tim Hardman is Managing Director of Niche Science & Technology Ltd., a bespoke services CRO based in the UK. He is also Chairman of the Association of Human Pharmacology in the Pharmaceutical Industry and an occasional commentator on science, business and the process of drug development.