Chances are that if you have spent any time performing clinical research you have encountered the Institutional Review Board, or IRB. The IRB is the gateway to clinical research, and determines if the project upholds the rights of participants, the kind of protections that need to be in place for subjects, and, ultimately, if the project is acceptable research [1]. Chances are also that if you have submitted a research proposal to an IRB you have had it returned with corrections. Despite the burden this places on researchers, the IRB serves a critical role in clinical research as a safeguard of patients’ rights.
There are countless incidents in the history of medicine of questionable research practices that would today be considered unethical. Even Edward Jenner—whose work with a smallpox vaccine is said to have saved more lives than any other person in history—conducted research that would make medical ethicists today uncomfortable [2-3]. However, the IRB is not a creation of the distant past or of modern Europe, but arose in response to a pattern of unethical post-war research in the United States.
In 1965, Dr. Henry K. Beecher gave a presentation to a group of journalists at the Brook Lodge Conference Center during which he warned, “What seem to be breaches of ethical conduct in experimentation are by no means rare, but are almost, one fears, universal” [4]. He presented a review of eighteen examples of clinical research that he believed to be unethical, and warned that these ethical problems were not restricted to remote corners of academia but were found in the nation’s elite medical schools, health centers, and military hospitals [4-5]. While some of his colleagues countered that these were rare cases, he followed up with a publication in The New England Journal of Medicine outlining an additional 22 contemporary examples of unethical experimentation [4]. It was originally intended to be 50 examples, but he cut it down to save space [5].
At the time of his presentation, Dr. Beecher was a professor of anesthesiology at Harvard Medical School and one of the foremost experts on anesthesiology in the world [4]. Furthermore, during his presentation he declined to provide the names of investigators or the journals in which their research could be found to prevent any repercussions against them [4-5]. As a respected member of the academic elite with relatively little to gain from upsetting the academic status quo, his warnings garnered significant attention in the United States [5]. A reporter who attended his presentation at the Brook Lodge Conference Center wrote a front-page article in the Boston Globe that headlined “Are humans used as guinea pigs not told?” [4].
Among the studies he reviewed were methods such as injecting cancer cells into hospitalized patients, injecting mentally delayed children with viral hepatitis, a double-blind study to test the dose of chloramphenicol needed for toxic bone marrow suppression, and multiple vesicourethrography performed on babies less than forty-eight hours old to test the ureteral reflux of normal bladders [6]. In a particularly horrific case, a mother volunteered to have her daughter’s melanoma grafted onto herself “in the hope of gaining a little better understanding of cancer immunity and in the hope that the production of tumor antibodies might be helpful in the treatment of [her daughter]”[6]. Doubtless, the researchers knew that nothing could be gained that would save the daughter as they had already classified the cancer as terminal, and the daughter died later that same day [6]. Twenty-four days later the graft was removed from the mother, and she “died from metastatic melanoma on the four hundred and fifty-first day after transplantation. The evidence that this patient died of diffuse melanoma that metastasized from a small piece of transplanted tumor was considered conclusive” [6]. If performed today, any one of the 22 examples Dr. Beecher listed would certainly lead to a revocation of the investigator’s medical license and, most likely, lead to criminal proceedings.
Dr. Beecher’s exposé—in addition to the infamous Tuskegee Syphilis Study, the human radiation experiments by the United States government and leading medical institutions, and the human experiments of the CIA and other intelligence agencies—made it clear that the United States was not dealing with isolated incidents but a pandemic of unethical research. In response to the mounting controversy, Richard Nixon signed The National Research Act of 1974 which authorized federal agencies to create rules and regulations to monitor human research in medicine and required IRB boards to oversee and regulate their institutions [7].
Although 1974 may feel like distant history and our collective memory has since forgotten the era of these experiments, we cannot easily overlook the medical community’s role in them. Ultimately, these studies were generally instigated and pursued by physicians as the principal investigators. Even Dr. Beecher himself has been accused of testing hallucinogens as a means of interrogation on Cold War prisoners based on CIA documents declassified in the 1990s [8-9]. The next time you submit a research proposal to the IRB and wait three months to hear back that they didn’t like the wording of a sentence and require a resubmission, just remember the potentially thousands saved from unethical research between 1974 and 2020. And who’s to say that you would not have been one of that number?
[1] IRB-FAQs. Food and Drug Administration website. Updated April 18th, 2019. Accessed September 1st, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/institutional-review-boards-frequently-asked-questions.
[2] Meet the Man Credited with Saving More Lives than Any Other. Atlantic Health Partners website. Updated July 7th, 2015. Accessed September 1st, 2020. https://www.atlantichealthpartners.com/immunization-insights-1/2015/7/9/meet-the-man-credited-with-saving-more-lives-than-any-other.
[3] Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005;18(1):21-25.
[4] Beecher HK. Ethics and clinical research. 1966. Bull World Health Organ. 2001;79(4):367-372.
[5] Kopp VJ. Henry Knowles Beecher and the development of informed consent in anesthesia research. Anesthesiology. 1999;90(6):1756-1765.
[6] Beecher HK. Ethics and clinical research. N Engl J Med. 1966;274(24):1354-1360.
[7] Grady C. Institutional Review Boards: Purpose and Challenges. Chest. 2015;148(5):1148-1155.
[8] Mashour GA. Altered states: LSD and the Anesthesia Laboratory of Henry Knowles Beecher. Bull Anesth Hist. 2005;23(3):11-14
[9] Moreno, J. D. (2016). Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century. Perspectives in Biology and Medicine, 59(1), 107- 121.
Ian Singleton is a member of The University of Arizona College of Medicine – Phoenix, Class of 2021. He graduated from University of California, Santa Barbara with a Bachelor of Science in Microbiology. He enjoys working out and surfing.