Questionable LSD experiments lurk in bioethics icon’s background

A scathing indictment of the ethics of medical research, published 50 years ago today, sparked a firestorm of controversy in the medical community and led to an overhaul of the rules of research involving humans. The fact that it was written by a physician who led some iffy experiments with LSD makes the message more nuanced, but no less compelling.

The report, “Ethics and Clinical Research” — sometimes called Beecher’s bombshell — appeared in the New England Journal of Medicine on June 16, 1966. Its author, Dr. Henry Knowles Beecher, an acclaimed professor of anaesthesia at Harvard Medical School and department chair at Massachusetts General Hospital, accused scientists at some of the nation’s top medical schools, hospitals, and other research institutions of unethical research that could have, and sometimes did, harm research subjects, many of whom had no knowledge they were even part of a study.

Although he didn’t name names, Beecher described 22 ethically corrupt experiments. In one study, researchers withheld penicillin from more than 500 men with strep throat infections in order to test a less-effective treatment. About 5 percent of them developed strep-related rheumatic fever, which can cause severe heart damage. In another of Beecher’s examples, living cancer cells were injected into 22 participants in a study of cancer immunity. In neither case were the participants informed about the specifics of the study.

I am fascinated by this paper for two reasons: One is that Beecher himself had played loose with the ethics of informed consent in his top-secret search for a “truth serum” for the US Army. The other is that the upshot of the report — greater oversight of clinical trials by outsiders — is the antithesis of what Beecher would have wanted.

I learned about Beecher and heard whispers about his work with LSD when I joined Mass General as an anesthesiologist in 2006. When I was appointed the first Henry Knowles Beecher Professor of Anesthesia in 2013, I decided to take a closer look at this enigmatic man. I spent hundreds of hours poring over the Beecher collection in Harvard Medical School’s Countway Library of Medicine and reading all I could find that others had written about him. He was something of a pack rat, having kept thousands of letters, reports, and even the medical notes he made on the battlefield at Anzio during World War II, which led to safer ways to treat wounded soldiers.

I learned that Beecher kept many secrets. One was that he wasn’t the Boston Brahmin he pretended to be, with kinship to Harriet Beecher Stowe and Henry Ward Beecher. Instead, he was the son of Mary Julia and Henry Eugene Unangst, a night watchman for the Coleman Lantern Company in Wichita, Kan. He changed his name to Beecher just weeks before entering Harvard Medical School in 1928.

A more troubling secret is Beecher’s potentially unethical work to help the Army find drugs for “narcoanalysis,” better known as truth serum, that could be used to interrogate prisoners. As part of that work in the 1950s, he tested benzedrine, morphine, scopolamine, “extract of cannabis indica” (a form of marijuana), and even LSD in college students. How carefully he informed his subjects of the purpose of these tests is an open question, since his papers offer little information this topic. A colleague who worked with Beecher and published the LSD results with him in 1956 later remarked that they never discussed ethics or informed consent at all in those years. I spoke with two former Harvard students who took part in experiments with LSD, whom a colleague and I tracked down by placing a notice in the Harvard alumni magazine. Neither remembered having been told much about the drug or the test.

That’s not to say that Beecher ignored or was unaware of the ethics of the situation. When the Army asked him to explore LSD as a truth serum, he wrote his Army handler long before the first experiment, “There is, as I know you will realize as well as I, a considerable problem here in the use of healthy young volunteers.” I think he was puzzling through the ethics problem at the same time he was doing what he always did — recruiting volunteers and doing experiments.

Beecher’s thinking about the ethics of clinical research coalesced into a talk he gave in 1965 to science writers at a symposium sponsored by the pharmaceutical company Upjohn and his publication of an expanded version a year later in the New England Journal of Medicine. His purpose for spreading this information was his belief that “unethical or questionably ethical procedures are not uncommon” and should be reined in.

The solution to more ethical research, Beecher argued, “is the presence of a truly responsible investigator.” The NIH had other ideas. It created new rules for research that it funded. The rules explicitly required researchers to document that they had obtained informed consent from people taking part in clinical research. The rules also created panels for outside review of research protocols by boards that include lay people, ethicists, clergy, other clinicians — the institutional review boards (IRBs) that are today a mainstay of clinical research. Beecher would have despised this bureaucratic approach to improving research ethics.

Beecher’s secret work with the Army represents an interesting side note. But it should in no way detract from his major contributions to American medicine. In addition to his work in bioethics, Beecher pioneered work on the placebo effect in the early 1950s. He also played a lead role in defining ways to determine brain death, an important step for moving forward the nascent field of organ transplantation.

Few other American physicians can boast such a legacy.

James P. Rathmell, MD, is chair of the Department of Anesthesiology, Perioperative, and Pain Medicine at Brigham and Women’s Health Care and professor of anaesthesia at Harvard Medical School. His monograph on Henry Knowles Beecher, “The Moralist,” cowritten with John Lancaster, has been published on The Big Roundtable.