Editor’s note: The Bulletin occasionally publishes articles based on winning entries in the History of Surgery Poster Competition, which occurs in conjunction with Clinical Congress. The following article is based on the 2021 first-place entry. An article based on the third-place entry appeared in the March issue.*
Do you obtain a patient-signed informed consent for every procedure that you perform? How can you be certain that your patient understands the information you provided? Who wrote the informed consent form that you use? Is anything missing from the document?
For most surgeons, informed consent is a routine component of clinical practice. In the realm of clinical research, initiating a project is nearly synonymous with filing for institutional review board (IRB) approval. Yet, mandatory informed consent for research participants and the IRBs that enforce it are relatively new requirements. While informed consent in research has its origins in the late 19th century, proponents of this practice struggled against the widely held belief that individual American researchers already conducted ethical studies without the need for bureaucratic oversight.1-3
In 1966, Henry K. Beecher, MD, disproved this assumption with the publication of his bombshell report outlining dozens of severe ethical violations in prominent American research studies. Dr. Beecher’s work reinvigorated calls for mandatory consent in research and serves as an example of ethical vigilance that is as important today as it was then.4
A Vow to Protect Patients
Consideration of ethical guidelines for the medical profession dates back to the Hippocratic Oath in 400 BCE, which called upon providers of care to protect patient privacy and practice within the limits of their ability.2,3 British physician Thomas Percival, MD, built upon these principles in Medical Ethics, the first formal text on medical ethics in western medicine. This text emphasized compassionate care of patients and declared “veracity…a jewel of inestimable value.” The treatise formed the philosophical foundation for the American Medical Association’s (AMA) 1847 Code of Ethics.2,3 Other medical and specialty groups adopted similar guidelines, although enforcement remained haphazard. Moreover, regulations focused on clinical practice, not research, which was a relatively rare activity for physicians until the mid-20th century.
Dr. Beecher’s work reinvigorated calls for mandatory consent in research and serves as an example of ethical vigilance that is as important today as it was then.
In 1916, the AMA proposed a move to expand its ethical guidelines for clinical practice by considering a mandate for informed consent in clinical research.2,3 AMA members dismissed this resolution, leaving the responsibility for ethical conduct of research to individual investigators.
Calls for mandatory informed consent for research participants reentered the conversation following the discovery of the atrocities that Nazi scientists inflicted upon their research subjects, which were revealed during the Nuremberg trials in 1947.1-3 The Nuremberg Code insisted on prior animal experimentation and demanded the voluntary consent of any human subject but was not enforced. Most Americans viewed the Nuremberg Code as appropriate for Nazi war criminals but not relevant to American researchers.
In 1953, the National Institutes of Health established a policy that required researchers to receive informed consent from healthy volunteers. However, these regulations were viewed as largely unnecessary and were ignored.1-3 American researchers vocally opposed mandated informed consent in US Senate deliberations on research ethics as legislators debated the Kefauver-Harris amendments to the Federal Food, Drug, and Cosmetic Act in 1962, and again during the World Medical Association’s 1964 convention in Helsinki.1-3 In each case, researchers decried restrictive legislation that hampered drug development to protect the public from what they believed were rare instances of criminal activity.
Outside of the political arena, the topic of informed consent caught fire among a small group of scientists who had gathered at Brook Lodge near Kalamazoo, MI, for a conference hosted by Upjohn, a pharmaceutical company. The event took place in March 1965 and was intended to be an opportunity for scientists to explain the process and challenges of drug development to science journalists while fostering congenial relations between the press and the pharmaceutical industry.1,3,5 Speakers were well-known academics from across the country, and topics ranged from experimental design to the placebo effect to safety issues. Attendees represented all wire services, major daily newspapers including the Los Angeles Times and New York Post, as well as periodicals such as Time and Newsweek.5
At the time, Dr. Beecher was a respected professor of anesthesiology at Harvard University, Boston, MA; a pioneer of battlefield trauma care during World War II; and a published researcher on the placebo effect and the effects of lysergic acid diethylamide (LSD) on human volunteers. At some point, Upjohn tapped him to discuss the medical ethics of experimentation.5-7 Dr. Beecher expended significant effort on his speech, describing it as “a bombshell” in a letter to the Upjohn company, pleading for additional time at the podium.5 In his 40-minute talk, he discussed the abrogation of ethical responsibility among American researchers, citing 18 of the most egregious examples in the published literature.5 He elected to preserve the anonymity of these investigators.
Dr. Beecher’s talk was met with instant and withering criticism. Thomas Chalmers, MD, and David Rutstein, MD, the latter a Harvard colleague, held a press conference the following day refuting Dr. Beecher’s findings and accusing him of “gross and irresponsible exaggeration.”1,5,8 Beecher was aghast at his peers’ reaction. Blaming the venue, he wrote a heated letter to Upjohn denouncing the “kangaroo court” he felt had unfairly judged him at the conference.5
The presentation and ensuing controversy generated national publicity, which, along with his indignation, prompted Dr. Beecher to transform that talk into an article.
Publication of the “Bombshell”
The New England Journal of Medicine (NEJM) published Dr. Beecher’s article, “Ethics and Clinical Research” in June 1966 after the Journal of the American Medical Association rejected it for being too long and controversial.1,4,8 NEJM editor-in-chief Joseph Garland, MD, had overruled six of seven peer reviewers who opposed the article for being one-sided, too lengthy, and overly polemic. Dr. Garland worked with Dr. Beecher to shorten, sharpen, and improve the writing.1 Recognizing its potential impact, Dr. Beecher alerted major press outlets prior to publication, which led to a series of searing newspaper articles that echoed his critiques of informed consent.8
Dr. Beecher described 22 examples selected arbitrarily from contemporary scientific literature. He purposefully did not “name names” or include the citation in order to protect the identity of the investigators, although many were well-known and recognizable studies.1,3,4 They appeared in—and had passed through the editorial boards of—the most prestigious medical journals in the country. Many had received federal funding for their research.1,3,4 Rather than being exceptional, Dr. Beecher said, these unethical studies provided “evidence that unethical…procedures are not uncommon,” citing hundreds of other examples in his text and references.4
He described cases in which researchers withheld penicillin from soldiers with rheumatic fever, conducted unindicated thymectomies to study its immunologic effect, transplanted a melanoma tumor from one patient to another, and intentionally infected disabled children with hepatitis to determine the period of infectivity, among other egregious examples.4 Of the 22 studies, three were explicitly surgical and another eight required surgical techniques such as cannulating arteries and performing liver biopsies, placing 50% of Dr. Beecher’s examples in the surgical realm.4 What most galled Dr. Beecher was the lack of any real informed consent and the willingness to cause harm to subjects without the possibility of benefiting these individuals for “the sake of science.”4,9
Absent from the report were any of Dr. Beecher’s own studies. For instance, his 1956 article published in the Journal of Clinical and Experimental Psychopathology examined the effect of LSD on different personality types, using student volunteers. He described “a tense student” who, after a mildly probing interview, exhibited a “vasomotor disturbance with pallor, cold clammy skin, nonpalpable pulse, slight convulsive movement of the face, and stiffening of the body.” Dr. Beecher made no mention of informed consent despite what appears to be significant physiologic aberrations.10
Response to Dr. Beecher’s Findings
Prior to the publication of Dr. Beecher’s report, mounting support for enforceable informed consent regulation met significant resistance from researchers on the grounds that ethical violations were the exception, rather than the rule. Dr. Beecher’s presentation and subsequent publication armed proponents of regulation with concrete evidence of widespread impropriety. New voices were incorporated as discussions of informed consent and bioethics were broadcast to a wider audience. Nonacademic clinicians generally supported Dr. Beecher, aghast at the horrors committed in their own country and within their own profession.1,8 The public, both shocked and infuriated by the cited studies, was scathingly critical of clinical research and developed mounting distrust of the medical profession.3,8 Researchers fought this negative publicity by challenging the generalizability and truth of Dr. Beecher’s claims.1,8
In response to growing discontent, the US Surgeon General requested formal institutional review for proposed human subjects research.1 Yet, despite increasing public distrust, no new federal regulations were enacted until after the revelations of the Tuskegee syphilis study in 1972. At that time, the National Research Act established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.3,11 This commission would go on to release the Belmont Report in 1979, which established the principles guiding federal oversight of clinical research. These principles became law with the passage of the Common Rule in 1981, formally requiring IRB approval for research involving human subjects.11
A Complicated Legacy
As for Dr. Beecher, he conducted landmark research on the placebo effect, physiology, and anesthetic safety while helping to formulate the definition of brain death.6,7 His pioneering work in the area of informed consent makes him most remembered as the father of modern bioethics.
Each year, Harvard Medical School awards the Annual Henry K. Beecher Prize in Medical Ethics to a student performing exceptional work in medical ethics.6,7 However, following his death in 1976, reports surfaced of his involvement with the Central Intelligence Agency and former Third Reich researchers who were brought to the US during the Cold War through Operation Paperclip, complicating his legacy.
Dr. Beecher reframed the need for informed consent and dutiful maintenance of research ethics as a priority for all researchers, including himself, rather than a punishment for a minority of malicious individuals.
Nonetheless, Dr. Beecher’s report was pivotal in the development of bioethics and the regulation of research. Though discussions of informed consent gained traction following World War II, Dr. Beecher reframed the need for informed consent and dutiful maintenance of research ethics as a priority for all researchers, including himself, rather than a punishment for a minority of malicious individuals. He asserted that the best defense against unethical research was honest, compassionate, and competent researchers, yet his work eventually combined with growing public distrust of medical professionals at the time to promote the advent of IRBs for third-party oversight.
Today, IRB review is the primary means of assuring the ethical validity of human subjects research. These activities require informed consent, though the ways in which hospitals, universities, and laboratories achieve informed consent is determined by each institution. Some include language consenting to research studies as part of surgical consent forms. As such, cells and tissues removed from a patient’s body become property of the hospital and may be used for research without the patient knowing exactly to which projects they have consented. This situation raises questions about whether this type of “blank check” consent obtained before surgery can be considered truly informed and freely given.
The modern era features forms of research in which cells can be cultured and immortalized from surgically biopsied tissue, genomes can be sequenced, charts are preserved in electronic health records, and full surgical procedures are recorded and stored on devices for case reports and device development. It is challenging to imagine how even the most thoughtful investigators can rightly inform research participants about research methods and potential uses of their personal data not yet invented.
Although the types of studies and techniques used today are markedly different from those decried by Dr. Beecher in the 1960s, questions of how best to obtain informed consent for research from patients without sacrificing innovation remain at the forefront. An environment of ever-changing technology also highlights the limitations of informed consent as the standard for ethical conduct of research. Following Dr. Beecher’s example, we must maintain a critical eye to ensure that ethical practices are maintained in all labs and studies.
*Fallon EA, Harman AL, Harrington DT. Sir Arthur Conan Doyle, MD: Ophthalmologist, Author, and Defender of Justice. Bull Am Coll Surg. 2022;106(3):33-40. Available at: https://bulletin.facs.org/2022/03/sir-arthur-conan-doyle-md-ophthalmologist-author-and-defender-of-justice/.
- Jones DS, Grady C, Lederer SE. “Ethics and clinical research”—the 50th anniversary of Beecher’s bombshell. N Engl J Med. 2016;374(24):2393-2398.
- Lederer SE. Subjected To Science: Human Experimentation in America Before the Second World War. Henry E Sigerist Series In The History of Medicine. Baltimore, MD; Johns Hopkins University Press; 1995.
- Rothman DJ. Strangers at the Bedside: A History of How Law and Bioethics Transformed Medical Decision Making. New York, NY; BasicBooks; 1991.
- Beecher HK. Ethics and clinical research. N Engl J Med. 1966;274(24):1354-1360.
- Beecher HK. Henry K. Beecher papers, 1848–1976. Harvard Medical Library, Boston, MA.
- Fowle F. Henry K. Beecher, doctor in Boston. The New York Times. July 26, 1976. Available at: https://www.nytimes.com/1976/07/26/archives/henry-k-beecher-doctor-in-boston-won-world-fame-for-work-in.html. Accessed February 16, 2022.
- Welch CE. Henry K. Beecher, MD. N Engl J Med. 1976;295(13):730.
- Freidenfelds L. Recruiting allies for reform: Henry Knowles Beecher’s “Ethics and clinical research.” Int Anesthesiol Clin. 2007;45(4):79-103.
- Beecher HK. Consent in clinical experimentation: Myth and reality. JAMA. 1966;195(1):34-35.
- von Felsinger JM, Beecher LL, Beecher HK. The response of normal men to lysergic acid derivatives (di- and mono-ethyl amides). J Clin Exp Psychopathol. 1956;17(4):414-428.
- Fischer BA. A summary of important documents in the field of research ethics. Schizophr Bull. 2006;32(1):69-80.