Laying Ethical Foundations for Clinical Research
Harkness, Jon, Lederer, Susan E., Wikler, Daniel, Bulletin of the World Health Organization
Progress in international health will require further research involving human subjects, and this may often take place in developing countries. In recent years, human experimentation has been dogged by controversy. Scientists from industrialized countries, where strict ethical standards protect participants in research and help to win public trust, have been accused of using double standards in carrying out research in poorer countries that they would not be permitted to perform at home.
Even as these debates continue in scientific journals and in the popular press, it is worth while to recall that participants in research in the wealthiest countries have not always been afforded such protection. In his essay "Ethics and clinical research" in 1966 (1), Henry K. Beecher identified ethical lapses in research carried out by physician--scientists in renowned universities and published in the world's leading journals. In this paper, which has rightly been deemed the most influential single paper ever written about experimentation involving human subjects (2), Beecher demonstrated that poor treatment of human subjects was not confined to the barbaric practices of Nazi doctors that had been documented by the Nuremberg war crimes tribunal after the Second World War. Beecher's paper prompted a reconsideration of research practices that laid the groundwork for today's ethical codes and review committees.
In 1936 at the age of 32, four years after graduating from Harvard Medical School, Beecher became anaesthetist-in-chief at Massachusetts General Hospital and joined the medical faculty; in 1941 Harvard installed him in the world's first endowed professorship in anaesthesiology. During his career, he trained over 300 anaesthesiologists, 50 of whom became professors at other medical schools around the world. When Beecher published this paper he had been the world's foremost figure in anaesthesiology for almost three decades. Beecher made many original scientific contributions in his chosen field, but his research also had broader implications for medical science: he developed a number of techniques for the quantitative measurement of clinical responses that researchers had previously viewed as largely subjective, including pain, thirst, nausea, and even mood. He was also a pioneer in recognizing the placebo effect in medical practice, and was among the most influential early advocates of the need for double-blind controlled studies to account for this phenomenon in clinical research.
It was towards the end of the 1950s that Beecher became increasingly concerned with the ethical aspects of human experimentation. Historian David Rothman has emphasized that Beecher's specialty played a role in this orientation, as well as his commitment to high quality research and the fear that unethical research would bring discredit to the scientific enterprise (3). Beecher's deep Christian faith (he is said to have read a chapter of the Bible every day) may also have encouraged his excursion into research ethics (4). It also seems possible that he harboured some guilt over experiments that had taken place under his supervision; in a 1965 public lecture, he found himself "obliged to say that, in years gone by, work in my laboratory could have been criticized" on ethical grounds (5).
Beecher's first major publication on research ethics appeared in the Journal of the American Medical Association in 1959 (6), but this extensive scholarly consideration of research ethics did not create much of a professional or public stir. Beecher's agitation over the widespread moral laxity he perceived among his peers grew to a point where he was no longer satisfied with academic discourse, and he exercised his capacity for drama in the spring of 1965, when he chose to explore the problems and complexities of clinical research before a group of journalists convened by the Upjohn Pharmaceutical Company at the Brook Lodge Conference Center in rural Michigan (5). …