Medical Sleuthing

By Caroline J. Hanna

World War II was well under way when three researchers gathered in Red Wing, Minn., to consider a mystery that was confounding the military brass: Why were Air Force pilots passing out midflight—specifically, during high-speed airplane maneuvers and most often while quickly pulling up after dive-bombing?


Brian Smith ’12

The scientists suspected that impaired cerebral blood flow was to blame, and they set out to test that hypothesis. Herman Kabat, Ralph Rossen and John P. Anderson developed a set of experiments that, viewed through a 21st-century lens, are disquieting. The tests involved placing a leather collar around the necks of human test subjects. When inflated it would suddenly cut off the blood supply to the wearer’s brain, enabling researchers to observe how the body responded to lack of oxygen.

The most common symptoms included unconsciousness, dilated pupils, seizure-like movements and loss of bladder and bowel control.

If the experiments themselves are troubling, the choice of test subjects is even more so. The Red Wing Studies of 1943 were conducted on schizophrenic patients and prison inmates, some of whom were in the juvenile court system. Researchers have long debated whether these subjects—who volunteered for the testing, according to records—had the intellectual capacity to truly give what today’s scientists call “informed consent.” In fact, a group in the United Kingdom has gone so far as to decry the paper on the experiments as one of the “10 worst publications in the history of psychiatry,” right up there with articles on the Satanic abuse of children and the invention of the lobotomy.

At the same time, the Red Wing findings advanced scientific knowledge, laying the groundwork for significant studies on brain physiology and function. They 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.

In contrast to the public outrage against the Tuskegee syphilis study—perhaps the most decried clinical experiment in U.S. history—debates about the Red Wing tests have taken place almost exclusively behind the scenes, among medical ethicists and scientists, not in newspapers. If the general public associates anything with Red Wing, Minn., it is likely to be the city’s namesake shoe company or its natural and architectural beauty. The experiments have been mostly forgotten to history.

Red Wing, a city of 16,000 on the Mississippi River, is also the hometown of Brian Smith ’12, who was in high school before he heard anyone mention the experiments. “I was shocked,” he says. “Using the mentally ill and prisoners for research seemed grotesque, really.”

He set out to learn more. Using old-fashioned detective work and an abundance of persistence and initiative, Smith, while still in high school, uncovered a box of never-before-seen documents that shed new light on the methods and motives of the Red Wing researchers—documents that could change some people’s thinking. Last spring, he published a paper about his original historical research in the journal Perspectives in Biology and Medicine. Because of Smith, a more complete story of the Red Wing studies is finally being told.

Smith’s interest in the research began during a conversation with one of his family physicians, David Robertson, a specialist in autonomic nervous system disorders. Years earlier, as a medical resident, Robertson had unsuccessfully attempted to learn more about the Red Wing studies. When Smith asked the doctor for leads on summer research opportunities, Robertson, who is based at Vanderbilt University, suggested he look into the experiments.“In my field, the Red Wing studies were frequently referenced, but never discussed,” Robertson says. “I often wondered about it, so I had Brian see what he could find.”

Initially, Smith faced a series of dead ends. The county and state historical societies and town library he contacted had no information. The research facility associated with the family of John P. Anderson, one of the Red Wing investigators, suggested he speak to Anderson’s sister, Jean Chesley. The Chesleys told him to contact Anderson’s son Hans, who, they believed, had family records on the study. “That whole process took a few months,” Smith says. “I called a number of different Andersons, Hedins and Chesleys in Red Wing, Minneapolis, St. Paul, Hastings and Stillwater. All in all, I probably made somewhere between 30 and 40 phone calls.” Anderson’s daughter shared contact information for her brother in Wisconsin. When Smith called the number in Wisconsin, Hans Anderson invited him to his house and see a cardboard box he’d been storing for years.

The box provided the big break in the case. Inside, Smith found films of the research being conducted, data on the test subjects and letters from the subjects themselves. The papers 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.

“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,” Smith says. “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.”

As Smith discovered, the three researcher—including John P. Anderson, above—acted as their own test subjects.

The use of animals for such testing, while often controversial today, was standard practice in the 1940s, as was using prisoners for medical research. The scientists’ decision to test the cuff on themselves, however, was an unusual—even extraordinary—measure, Smith says.

“After using the cuff on animals, they knew what their boundaries were for use on humans,” he explains. “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 included long-forgotten 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), as well as handwritten notes to the investigators from many prisoners, 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,” Smith says. “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.” (Privacy issues have prevented Smith from learning the full names of the subjects; in any case, few, if any, are likely to be alive today.)

From Anderson’s materials, Smith also learned more about the researchers’ thinking in using schizophrenic patients as test subjects. The scientists saw themselves as helping the patients; they did not view them as human guinea pigs, Smith says. “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. And Rossen, for one, felt that the experiments could really benefit the schizophrenic patients.” What they found, Smith says, is that after releasing the cuff from the test subjects’ necks, the patients exhibited no 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 modern inclination to revisit decades-old experiments and their ethics is hardly unusual. Rebecca Skloot’s 2010 best seller The Immortal Life of Henrietta Lacks examines the myriad ethical issues surrounding the case of a poor, African-American tobacco farmer 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 and led to many significant studies on cancer. 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 1972, an Associated Press story about the Tuskegee study caused a public outcry that led to an immediate end to the research and the payment of reparations to the participants. But until Smith began his work, no one had taken a second look at the Red Wing studies.

After scouring the materials in Anderson’s cardboard box, Smith 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,” says the physician. “Because of his entrepreneurial spirit, we now know a lot more about this benchmark study.”

Impressed, Robertson invited Smith to Vanderbilt the summer following his first year at Amherst. There, the student worked with Robinson and ethicist Ellen Wright Clayton, who is director of Vanderbilt’s Center for Biomedical Ethics and Society. Smith spent three months polishing 17 drafts of the paper that Perspectives in Biology and Medicine would eventually publish. (Stephen George, the Manwell Family Professor of Life Sciences at Amherst, provided guidance about where to submit the work.) Robertson and Clayton are listed as Smith’s coauthors.

“Do I think the Red Wing studies would pass muster in 2012?” asks 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 agrees. “I was very pleased that Mr. Smith was the catalyst for this research being written up,” says Schechter, who works at the National Institutes of Health.

“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 the ethics of medical research. The more we know about how things were done in the past, the better we can make rules for the future.”

Smith says that, at some point, he might want to expand the project into a book. “There are questions that still need to be answered,” says the neuroscience major, who hopes to go to medical school someday. “I’m really interested to hear from the participants, for example, if they’re still around.”

He continues to view his assessment of the Red Wing tests as a work in progress. “If people read the paper and aren’t okay with how I looked at the studies, that’s understandable. I would love to talk to them about it. My position 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.”

Caroline J. Hanna is director of media relations at Amherst.

Top photo by Rob Mattson; bottom photo courtesy of Brian Smith ’12