Cover by Alisa Zhang

Research and Ethics of HM

By Reva Prabhune

From ancient Egyptians removing the brain through the nostrils and throwing it away when creating mummies to Flemish anatomist Andreas Vesalius being the first to draw highly detailed and accurate maps of the nervous system, there is no denying that our knowledge of the brain has come a long way. However, despite understanding the importance and the structure of the brain for several millennia, we still were not sure of how the brain actually functioned until the last couple hundred years. More so than dissections or molecular research, it is mainly through head injuries and mental disorders that we have discovered the physiology of the brain. In the field of neuroscience, the names that every student, physician, and researcher has embedded into their memories are those of the patients whose mysterious symptoms led to these breakthroughs. While most people see these patients as case studies that have propelled neuroscience and psychology forward, it is important to remember that they were human as well. They had lives before and after their incidents. Early physicians may have been much more concerned with learning all they could about their conditions, but research nowadays allows us to learn from injuries like theirs while also putting the patient first. By analyzing the iconic case of Henry “HM” Molaison as both a patient and as a person, we can see the benefits that come from the intersection of ethical research and humanity.  

Henry Gustav Molaison, commonly nicknamed H.M. in academia for privacy reasons, is probably the most consequential case regarding memory. Molaison was an American man who suffered from epilepsy due to a childhood accident where he was hit by a bicycle. His epilepsy was so bad by the time he was 27 that he suffered ten seizures a day. It had such a drastic impact on all aspects of his life, that his high school principal wouldn’t let him walk across the stage to get his diploma, in fear that he would have a seizure and cause a scene. In 1953, as an experimental treatment to these seizures, neurosurgeon Dr. William Beecher Scoville offered Molaison a bilateral surgery to remove his medial temporal lobes as a sort of less destructive version of a transorbital lobotomy. Dr. Scoville offering him an experimental surgery in the midst of such debilitating epilepsy was the only ray of hope that he had. So H.M. reluctantly said yes. This operation did improve Molaison’s epilepsy, but there was a very unexpected result that Molaison lost the ability to make certain types of new memories and could not remember up to three years before the surgery. In order words, Molaison now suffered severe anterograde amnesia and partial retrograde amnesia, respectively. This was incredibly surprising because until this point, it was commonly believed that memory was distributed throughout the cerebral cortex. Scoville contacted Dr. Wilder Penfield, the pioneer of the surgery performed on Molaison, regarding this case. Penfield consulted with neuropsychologist Brenda Milner who then based her career on studying Molaison. There began Scoville, Penfield, and Milner’s extensive study on Henry Molaison. Scoville and Milner published research that established a strong connection between the memory and the hippocampus, a brain structure deep in the temporal lobe, as they were able to prove that “the degree of memory loss appears to depend on the extent of hippocampal removal.” By studying Molaison and other patients with similar afflictions, they were able to conclude that the removal of the hippocampi bilaterally results in anterograde amnesia, meaning that memory must be localized in the hippocampus.  

It is unfortunate that after Dr. Scoville performed the experimental lobotomy on H.M., H.M. basically lived the rest of his life in 30-second intervals. The only reason that H.M. even agreed to a lobotomy was out of desperation. In fact, the whole field of psychosurgeries came out of desperate times for the mentally ill. In an interview with PBS, Luke Dittrich, the author of the book Patient H.M. : A Story of Memory, Madness, and Family Secrets describes how, “There were no real good, effective treatments for a lot of the things that they suffered from, and the lobotomy rose up as a sort of — a quick fix.” The vast majority of patients who underwent lobotomies were women. This was because the lobotomies would make patients passive and docile, which were seen as desirable and feminine qualities to men at that time. It was a treatment to mental illness, with the intent to change personality. Lobotomies were even performed on children as young as 7 years old, to treat qualities that we would consider normal childish behavior like juvenile delinquency and misbehavior. People were even lobotomized for homosexuality. It was an extreme and irreversible treatment often for conditions that weren’t actually conditions.  

Well, you may be asking, why women, children, homosexuals, or even patients like H.M. consent to lobotomies? In the 1940’s informed consent was not really a thing that existed the way that it does now. In fact, Walter Freeman, a famous lobotomist of the time, argued that the more a patient fought against being lobotomized, the more that indicated that that patient should be lobotomized. Dittrich said, “It's hard to argue that it was a good outcome for [Molaison]. But it's one of those sort of murky cases that you find in the history of medicine, in the history of science, where his tragedy — it was a boon to science. We're still learning from him now." This highlights the lack of patient protection in those times, where patients were not put first. Dittrich describes those times as “an era [of lobotomies] when the lines between medical practice and medical research were fairly blurry, and, you know, people crossed some lines that they most likely shouldn't have crossed.”  

Taking a closer look at how H.M. was studied after his surgery raises a question that is still applicable today - how should a physician straddle the need for scientific breakthrough but also acknowledge that these patients are people? Dr. Stephen D. Meriney, Professor and Chair of Neuroscience at the University of Pittsburgh and the Co-Director of the Center for Neuroscience, said,  “The scientific community today reveres and respects these patients and people, while at the same time recognizing the unique opportunity their illness, surgery, or accident presented in the context of what was known at the time…Today, I think there are many fewer problems along these lines [of seeing patients as people]. I think we now put patient care first, and research second.” Because of the research done on H.M., the progress that we have made scientifically is undeniable, but the progress we have made in the ethics of how research is conducted has transformed how millions of patients are treated and studied every day. 

Even with all the progress that has been made in the field of neuroscience, it is still, in essence, the study of one of the most mysterious aspects of life. Our tremendous progress in understanding the physiology of the brain can partly be credited to the tireless research by the physicians of patients who presented confusing and unexpected symptoms. The detailed clinical case reports on these patients and well-preserved brain slices have often been revisited with newer technologies and research methods, leading to even more discoveries. Reflecting on the way that patients were studied and treated has also helped further the scientific community and change how we approach studying patients as a whole. Dr. Meriney explains, “I think scientists and physicians treat patients as people first, but are open to noticing interesting clinical and scientific data from these patients that impact our theories about the underlying pathophysiology and function of the nervous system. However, when a patient is recognized as presenting a unique opportunity to learn important information, then these patients are approached and asked to give permission to participate in further research. Most patients agree because they want to contribute to helping others - even if the research will not help them. I have seen this first-hand in Lambert-Eaton myasthenic syndrome patients - they all sign up to donate blood with the satisfaction that they might help the next generation of patients.” We can appreciate and thank such patient volunteers for their contribution to science. 

And so whether you are just being introduced to the marvels of the brain or have been studying neuroscience for years, the names and cases of landmark patients like Henry Molaison will forever be appreciated for their multiple contributions. H.M.’s case came during the era of lobotomies where the line between medical practice and medical research was blurry. However, considering how the scientific field has evolved to more sophisticated models for research, it is also important how research ethics have evolved since the times of these patients. By the nature of clinical research, scientists test treatments and drugs by putting some patient volunteers at risk for the good of the greater population. So like it has in the past, clinical research has the potential to exploit these patients. The NIH even explicitly acknowledges that the ethical guidelines in place today are primarily a response to past abuses. For this reason, we now have influential codes of ethics such as the Nuremberg Code and the Declaration of Helinski that guide ethical research. The Nuremberg Code outlines that “The voluntary consent of the human subject is absolutely essential.” By developing this concept of informed, voluntary consent we can avoid leaving desperate patients like H.M. with severe memory loss. And we can avoid giving people treatments against their will the way that women, children, and homosexuals were forced into getting lobotomies. The Declaration of Helinski acknowledges the question raised by H.M.’s case - how should we straddle the need for scientific breakthrough but also acknowledge that these patients are people. The Declaration of Helinski states that “This goal can never take precedence over the rights and interests of individual research subjects.” Thus, this progress in ethical research is proof that we should appreciate iconic cases like H.M.’s for leading to both groundbreaking discoveries as well as teaching us about how patient research should be conducted.