Student’s Research Sheds New Light on Infamous Brain Studies

Submitted on Thursday, 2/23/2012, at 10:29 AM

February 15, 2012

The Red Wing studies of 1943 gave scientists great insight into how the human brain functions. But in the years since investigators conducted the series of experiments—which involved schizophrenic patients, prison inmates and youthful offenders—the studies have gained notoriety for their use of questionable test subjects and have even been deemed among the worst in the history of psychiatry.

The research and analysis of Brian Smith ’12, however, could change some people’s thinking. Through some good old-fashioned detective work, Smith uncovered a box of never-before-seen documents that shed new light on the methods and motives of the research team.

“Looking at the studies from today’s viewpoint is a little unfair—they deserve to be analyzed in the context of the time the research was conducted,” he said. “Without knowing all the details of how the experiments were carried out, it’s easy to cringe. But when you have all the information, you realize that the investigators actually went above and beyond the ethical guidelines of the 1940s.”

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Smith recently published a paper in the journal Perspectives in Biology and Medicine explaining this analysis and discussing the original historical research he conducted on the Red Wing studies. The experience of reading and writing about the experiments—which were named for and carried out in Smith’s own hometown of Red Wing, Minn.—was one of the most intellectually challenging and rewarding exercises of his academic career, Smith said.  

“If people read the paper and aren’t okay with how I looked at the studies, that’s understandable,” he said. “I would love to talk to them about it. It’s an ongoing learning process for me, and I don’t want it to stop.”

The studies attempted to pinpoint what was causing World War II pilots to pass out while engaging in high-speed airplane maneuvers, especially while quickly pulling up after dive-bombing. Hypothesizing that impaired cerebral blood flow was to blame, researchers Herman Kabat, a physiology professor at the University of Minnesota; Ralph Rossen, a physician and superintendent of a psychiatric facility; and John P. Anderson, founder of the Anderson Center for Biological Research, developed a set of experiments in which they placed a leather collar they’d invented around the necks of their test subjects. When inflated, this so-called KRA cuff would suddenly cut off the blood supply to the wearers’ brains, enabling researchers to observe how bodies respond to lack of oxygen. The most common symptoms included unconsciousness, dilated pupils, seizure-like movements and loss of bladder and bowel control. The findings laid the groundwork for many significant studies on brain physiology and function. They also led to the development of the human centrifuge, which is used in the training of pilots and astronauts, and the G-Suit, a special garment, worn by high-speed aircraft crews, that can be pressurized to prevent blackout during certain maneuvers.

Results notwithstanding, what made the experiments controversial and prompted a group in the United Kingdom to decry them as one of the “10 worst publications in the history of psychiatry,” said Smith, were the aforementioned test subjects. Specifically, researchers have hotly debated whether these subjects—who volunteered for the testing—could truly have given what today’s scientists call “informed consent.”

“When I first heard about the Red Wing studies, I was shocked. Using the mentally ill and prisoners for experiments seemed grotesque, really,” said Smith. “But when I started looking into them in more detail, I was able to form a new context behind it.”

That “new context” involved the box of documents that Anderson’s son turned over to Smith after Smith tracked down the son and spoke with him about the experiments. The box was full of highly detailed papers belonging to Anderson that revealed, among many other things, two important facts: that, before the cuff was used on the study’s subjects, it was first tested on animals, and that Kabat, Rossen and Anderson tested it on themselves, too.

While acknowledging that the use of animals for such testing can be controversial today, Smith noted that it was part of the regular practice of the time, as was using prisoners for medical research. The scientists’ decision to test the cuff on themselves, however, was an unusual—even extraordinary—measure, according to Smith.

“After using the cuff on animals, they knew what their boundaries were for use on humans,” Smith explained. “Then, by using the device on themselves before trying it on their test subjects, they actually went above and beyond what was required of them. That’s not something many other researchers would have done then—or would do now. It is really intriguing to consider, ethically and medically.”

Anderson’s papers also contained remarkable documentation about the experiments, such as the IQs of the test subjects (the average was 106.2, and all were within what is considered a normal range of 74 to 160) and handwritten letters from many prisoners to the investigators expressing gratitude for enabling them to do their part in the World War II effort. “There was a real sense of patriotism in many of the letters. Of course, whether or not the inmates were forced to be a part of this—which was, again, done quite a bit back then—or coerced into writing the notes, I haven’t been able to discover.”

As Smith notes, testing on schizophrenic patients in the 1940s was not standard practice. Still, the researchers’ decision to conduct experiments on them was viewed as a way to help them, he learned from Anderson’s materials; they were never viewed as human guinea pigs. “This was during an era when people were becoming more interested in psychiatric research on human patients—lobotomies, for example, were a relatively common practice at this time,” Smith said. “And Rossen, for one, felt that the experiments could really benefit the schizophrenic patients. What they found, actually, is that after they stopped the blood cutoff, the patients didn’t exhibit any schizophrenic symptoms for a half hour afterwards. It’s an intriguing and promising result, but one that will have to remain mysterious, because it will probably never be replicated.”

The seed of Smith’s interest in the studies was first planted by a doctor based at Vanderbilt University, David Robertson, a specialist in autonomic nervous system disorders and one of Smith’s family physicians, when Smith was a high school student. Years earlier, as a resident, Robertson himself had unsuccessfully attempted to find more information about the Red Wing studies. When Smith casually asked the doctor for leads on possible research opportunities, Robertson suggested looking into the experiments.

“In my field, the Red Wing studies were frequently referenced, but never discussed,” Robertson explained. “I often wondered about it, so I had Brian see what he could find.”

The modern inclination to revisit decades-old experiments and the ethics of them is, of course, not unusual. The best-selling The Immortal Life of Henrietta Lacks, for example, examines the myriad ethical issues surrounding the case of a woman whose cancer cells have been the basis for a vast amount of research. Cells belonging to the book’s namesake were taken without her consent, but they led to many significant studies on cancer. Similarly, the notorious Tuskegee Syphilis Study recorded the natural, untreated progression of the sexually transmitted disease in 600 black men, also without the patients’ informed consent. (In July 1972, an Associated Press story about the study caused a public outcry that led to an immediate end to the research and the payment of reparations to the participants.) But no one had taken a second look at the Red Wing studies, said Smith.

After talking with Robertson about the experiments, Smith dove headlong into the research. He began by reading everything he could on the studies—which was surprisingly little, he said—and then doing some sleuthing. He called every person named Anderson in the Minnesota phone directory until he found John P. Anderson’s son, who gave him the all-important lost box of documents.

Smith then compiled his findings in a report that he sent to Robertson. “He found John Anderson’s son by himself, and then convinced him to turn over these materials to him, which I think is just extraordinary for a young man who hadn’t yet graduated from high school,” said Robertson. “Because of his entrepreneurial spirit, we now know a lot more about this benchmark study.”

Robertson was so impressed, in fact, that he invited Smith to return to Vanderbilt the summer following his first year at Amherst and work with Robertson and ethicist Ellen Wright Clayton, the director of Vanderbilt’s Center for Biomedical Ethics and Society. Smith spent three months there polishing 17 drafts of the paper that would eventually be published in Perspectives in Biology and Medicine.

The final product was something of which both Robertson and Clayton, who are listed as Smith’s co-authors, are proud. “Do I think the Red Wing studies would pass muster in 2012?” asked Clayton. “Of course not, but the norms that were applied at that time are different from today’s norms. Regardless, the story of the studies was one that had to be told, and I think Brian’s work represents true excellence in undergraduate research. It’s a real contribution.”

Perspectives in Biology and Medicine editor Alan N. Schechter, chief of the Molecular Medicine Branch of the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, agrees. “I was very pleased that Mr. Smith was the catalyst for this research being written up,” he said. “What he and his colleagues did was highlight another one of a half a dozen studies from the 1940s that informed the medical community on the need to continuously reexamine of the ethics of medical research.” As recently as this past July, he said, the federal government’s Office of Human Research Protections asked for the public’s input on the ethics, safety and oversight of human research; the office might issue new guidelines as a result. “The more we know about how things were done in the past, the better we can make rules for the future,” Schechter said.

Smith is happy for the compliments on his assessment of the Red Wing studies but still views it as a work in progress. “I do feel comfortable about my analysis of the research, but I definitely am not ruling out the fact that I might one day change my opinion about these experiments,” he said, noting that Amherst biology professor Stephen George provided valuable guidance about where to submit the work. “My position on them is not something I feel like I can be 100 percent definitive on, because, looking at the ethics from the time the research was conducted and the ethics of today, it just goes to show how quickly social thought can change.”