hm case study ethical considerations

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Patient H.M. & Neurology Research: Ethical or Not?

Although tremendous advances in research and medical ethics have been made since the mid-20th century, questions continue.

The author of a recently published book questions ethics of research involving one of the best-known neurology patients, evoking a passionate response from both the public and the research community.

The positive impact of medical research on the quality of life today is undoubted. Along with the victories, medical research had its failures, such as devastating consequences of early-day psychosurgery, but lessons from these early failures contributed to success of modern research just as much. The case of Henry Molaison, formerly known as Patient H. M., is one of such therapeutic failures that taught us so much. Breakthroughs in understanding of memory aside, an important lesson learned from this and similar cases was that of ethics. Although tremendous advances in research and medical ethics have been made since the mid-20th century, it continues to be questioned. Most recently, the issue came up in Patient H.M.: A Story of Memory, Madness, and Family Secrets , a book by Luke Dittrich. 1

Briefly, in a fragment of his book published in The New York Times Magazine , Dittrich suggests that Suzanne Corkin, PhD, a researcher who dedicated her life to studying Patient H. M., destroyed research data, opposed publication that could question the validity of her work, and violated research ethics principles. 2 The fragment and, shortly after, the book evoked a range of responses from the public, research community, and the Massachusetts Institute of Technology, where Corkin conducted her research.

The public found Corkin’s actions, as described by Dittrich, disturbing, judging by the comments on The New York Times website such as “Dr. Corkin comes across as evil!” Many were convinced by Dittrich’s story, which he, as a journalist, so skillfully tells. (I was unable to confirm whether Dittrich has any medical or research background.) In a follow-up interview to The New York Times , Dittrich shares his reasons for telling the story: “I believe Henry’s story is important … because of what his case can teach us about our sometimes ruthless pursuit of knowledge.” 3

Even if we assume for a second that Corkin indeed pursued her research interests ruthlessly, this lesson has been learned many times over, and multiple measures are now in place to minimize the risk to research participants. Thus, Dittrich’s motives for telling his version of this story are unclear to me, as is its educational value. In fact, his mention of “researchers who’d built their careers on [Henry] and who had an interest in presenting his story in a particular way” made me wonder about Dittrich’s interest in telling the story in the way he does.

Unlike the public, I was not disturbed by Corkin’s actions because I am familiar with research practices. I found her actions not only acceptable but perhaps even appropriate, and my opinion echoed that of the research community’s. 4 As I am not currently involved in research and do not represent interests of any research institution, my opinion lacks bias the public might suspect in opinions of researchers.

What I did find disturbing was the fact that the book was published shortly after Corkin’s death, when she could no longer defend her work and remediate the damage the book did to the public perception of research. I was very pleased to see the research community take on this role by sending an open letter to The New York Times . 5 As long as journalists with little knowledge of research practices feel the need to tell their stories, researchers must continue to tell theirs to help the public to form an educated, unbiased opinion. 

References:

1. Dittrich L. Patient H.M.: a Story of Memory, Madness, and Family Secrets. New York: Random House; 2016.

2. Dittrich L. A brain that could not remember. The New York Times Web site. http://www.nytimes.com/2016/08/07/magazine/the-brain-that-couldnt-remember.html?_r=1 Accessed October 16, 2016.

3. Carey B. A Brain Surgeon’s Legacy Through a Grandson’s Eyes. The New York Times Web site. http://www.nytimes.com/2016/08/09/health/brain-patient-hm-book-dittrich.html Accessed October 16, 2016.

4. Hurley D. New allegations in book about patient HM kick up controversy on medical, scientific ethics . Neurology Today. 2016;16(19):48-50.

5. International Community of Scientists. Letter to the Editor of the New York Times Magazine. The MIT Department of Brain and Cognitive Sciences Web site. https://bcs.mit.edu/news-events/news/letter-editor-new-york-times-magazine Accessed October 16, 2016.

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Henry Gustav Molaison: The Curious Case of Patient H.M. 

Erin Heaning

Clinical Safety Strategist at Bristol Myers Squibb

Psychology Graduate, Princeton University

Erin Heaning, a holder of a BA (Hons) in Psychology from Princeton University, has experienced as a research assistant at the Princeton Baby Lab.

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Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

On This Page:

Henry Gustav Molaison, known as Patient H.M., is a landmark case study in psychology. After a surgery to alleviate severe epilepsy, which removed large portions of his hippocampus , he was left with anterograde amnesia , unable to form new explicit memories , thus offering crucial insights into the role of the hippocampus in memory formation.

• Henry Gustav Molaison (often referred to as H.M.) is a famous case of anterograde and retrograde amnesia in psychology.
• H. M. underwent brain surgery to remove his hippocampus and amygdala to control his seizures. As a result of his surgery, H.M.’s seizures decreased, but he could no longer form new memories or remember the prior 11 years of his life.
• He lost his ability to form many types of new memories (anterograde amnesia), such as new facts or faces, and the surgery also caused retrograde amnesia as he was able to recall childhood events but lost the ability to recall experiences a few years before his surgery.
• The case of H.M. and his life-long participation in studies gave researchers valuable insight into how memory functions and is organized in the brain. He is considered one of the most studied medical and psychological history cases.

Who is H.M.?

Henry Gustav Molaison, or “H.M” as he is commonly referred to by psychology and neuroscience textbooks, lost his memory on an operating table in 1953.

For years before his neurosurgery, H.M. suffered from epileptic seizures believed to be caused by a bicycle accident that occurred in his childhood. The seizures started out as minor at age ten, but they developed in severity when H.M. was a teenager.

Continuing to worsen in severity throughout his young adulthood, H.M. was eventually too disabled to work. Throughout this period, treatments continued to turn out unsuccessful, and epilepsy proved a major handicap and strain on H.M.’s quality of life.

And so, at age 27, H.M. agreed to undergo a radical surgery that would involve removing a part of his brain called the hippocampus — the region believed to be the source of his epileptic seizures (Squire, 2009).

For epilepsy patients, brain resection surgery refers to removing small portions of brain tissue responsible for causing seizures. Although resection is still a surgical procedure used today to treat epilepsy, the use of lasers and detailed brain scans help ensure valuable brain regions are not impacted.

In 1953, H.M.’s neurosurgeon did not have these tools, nor was he or the rest of the scientific or medical community fully aware of the true function of the hippocampus and its specific role in memory. In one regard, the surgery was successful, as H.M. did, in fact, experience fewer seizures.

However, family and doctors soon noticed he also suffered from severe amnesia, which persisted well past when he should have recovered. In addition to struggling to remember the years leading up to his surgery, H.M. also had gaps in his memory of the 11 years prior.

Furthermore, he lacked the ability to form new memories — causing him to perpetually live an existence of moment-to-moment forgetfulness for decades to come.

In one famous quote, he famously and somberly described his state as “like waking from a dream…. every day is alone in itself” (Squire et al., 2009).

H.M. soon became a major case study of interest for psychologists and neuroscientists who studied his memory deficits and cognitive abilities to better understand the hippocampus and its function.

When H.M. died on December 2, 2008, at the age of 82, he left behind a lifelong legacy of scientific contribution.

Surgical Procedure

Neurosurgeon William Beecher Scoville performed H.M.’s surgery in Hartford, Connecticut, in August 1953 when H.M. was 27 years old.

During the procedure, Scoville removed parts of H.M.’s temporal lobe which refers to the portion of the brain that sits behind both ears and is associated with auditory and memory processing.

More specifically, the surgery involved what was called a “partial medial temporal lobe resection” (Scoville & Milner, 1957). In this resection, Scoville removed 8 cm of brain tissue from the hippocampus — a seahorse-shaped structure located deep in the temporal lobe .

Bilateral resection of the anterior temporal lobe in patient HM.

Further research conducted after this removal showed Scoville also probably destroyed the brain structures known as the “uncus” (theorized to play a role in the sense of smell and forming new memories) and the “amygdala” (theorized to play a crucial role in controlling our emotional responses such as fear and sadness).

As previously mentioned, the removal surgery partially reduced H.M.’s seizures; however, he also lost the ability to form new memories.

At the time, Scoville’s experimental procedure had previously only been performed on patients with psychosis, so H.M. was the first epileptic patient and showed no sign of mental illness. In the original case study of H.M., which is discussed in further detail below, nine of Scoville’s patients from this experimental surgery were described.

However, because these patients had disorders such as schizophrenia, their symptoms were not removed after surgery. In this regard, H.M. was the only patient with “clean” amnesia along with no other apparent mental problems.

H.M’s Amnesia

H.M.’s apparent amnesia after waking from surgery presented in multiple forms. For starters, H.M. suffered from retrograde amnesia for the 11-year period prior to his surgery.

Retrograde describes amnesia, where you can’t recall memories that were formed before the event that caused the amnesia. Important to note, current research theorizes that H.M.’s retrograde amnesia was not actually caused by the loss of his hippocampus, but rather from a combination of antiepileptic drugs and frequent seizures prior to his surgery (Shrader 2012).

In contrast, H.M.’s inability to form new memories after his operation, known as anterograde amnesia, was the result of the loss of the hippocampus.

This meant that H.M. could not learn new words, facts, or faces after his surgery, and he would even forget who he was talking to the moment he walked away.

However, H.M. could perform tasks, and he could even perform those tasks easier after practice. This important finding represented a major scientific discovery when it comes to memory and the hippocampus. The memory that H.M. was missing in his life included the recall of facts, life events, and other experiences.

This type of long-term memory is referred to as “explicit” or “ declarative ” memories and they require conscious thinking.

In contrast, H.M.’s ability to improve in tasks after practice (even if he didn’t recall that practice) showed his “implicit” or “ procedural ” memory remained intact (Scoville & Milner, 1957). This type of long-term memory is unconscious, and examples include riding a bike, brushing your teeth, or typing on a keyboard.

Most importantly, after removing his hippocampus, H.M. lost his explicit memory but not his implicit memory — establishing that implicit memory must be controlled by some other area of the brain and not the hippocampus.

After the severity of the side effects of H.M.’s operation became clear, H.M. was referred to neurosurgeon Dr. Wilder Penfield and neuropsychologist Dr. Brenda Milner of Montreal Neurological Institute (MNI) for further testing.

As discussed, H.M. was not the only patient who underwent this experimental surgery, but he was the only non-psychotic patient with such a degree of memory impairment. As a result, he became a major study and interest for Milner and the rest of the scientific community.

Since Penfield and Milner had already been conducting memory experiments on other patients at the time, they quickly realized H.M.’s “dense amnesia, intact intelligence, and precise neurosurgical lesions made him a perfect experimental subject” (Shrader 2012).

Milner continued to conduct cognitive testing on H.M. for the next fifty years, primarily at the Massachusetts Institute of Technology (MIT). Her longitudinal case study of H.M.’s amnesia quickly became a sensation and is still one of the most widely-cited psychology studies.

In publishing her work, she protected Henry’s identity by first referring to him as the patient H.M. (Shrader 2012).

In the famous “star tracing task,” Milner tested if H.M.’s procedural memory was affected by the removal of the hippocampus during surgery.

In this task, H.M. had to trace an outline of a star, but he could only trace the star based on the mirrored reflection. H.M. then repeated this task once a day over a period of multiple days.

Over the course of these multiple days, Milner observed that H.M. performed the test faster and with fewer errors after continued practice. Although each time he performed the task, he had no memory of having participated in the task before, his performance improved immensely (Shrader 2012).

As this task showed, H.M. had lost his declarative/explicit memory, but his unconscious procedural/implicit memory remained intact. Given the damage to his hippocampus in surgery, researchers concluded from tasks such as these that the hippocampus must play a role in declarative but not procedural memory.

Therefore, procedural memory must be localized somewhere else in the brain and not in the hippocampus.

H.M’s Legacy

Milner’s and hundreds of other researchers’ work with H.M. established fundamental principles about how memory functions and is organized in the brain.

Without the contribution of H.M. in volunteering the study of his mind to science, our knowledge today regarding the separation of memory function in the brain would certainly not be as strong.

Until H.M.’s watershed surgery, it was not known that the hippocampus was essential for making memories and that if we lost this valuable part of our brain, we would be forced to live only in the moment-to-moment constraints of our short-term memory .

Once this was realized, the findings regarding H.M. were widely publicized so that this operation to remove the hippocampus would never be done again (Shrader 2012).

H.M.’s case study represents a historical time period for neuroscience in which most brain research and findings were the result of brain dissections, lesioning certain sections, and seeing how different experimental procedures impacted different patients.

Therefore, it is paramount we recognize the contribution of patients like H.M., who underwent these dangerous operations in the mid-twentieth century and then went on to allow researchers to study them for the rest of their lives.

Even after his death, H.M. donated his brain to science. Researchers then took his unique brain, froze it, and then in a 53-hour procedure, sliced it into 2,401 slices which were then individually photographed and digitized as a three-dimensional map.

Through this map, H.M.’s brain could be preserved for posterity (Wb et al., 2014). As neuroscience researcher Suzanne Corkin once said it best, “H.M. was a pleasant, engaging, docile man with a keen sense of humor, who knew he had a poor memory but accepted his fate.

There was a man behind the data. Henry often told me that he hoped that research into his condition would help others live better lives. He would have been proud to know how much his tragedy has benefitted science and medicine” (Corkin, 2014).

Corkin, S. (2014). Permanent present tense: The man with no memory and what he taught the world. Penguin Books.

Hardt, O., Einarsson, E. Ö., & Nader, K. (2010). A bridge over troubled water: Reconsolidation as a link between cognitive and neuroscientific memory research traditions. Annual Review of Psychology, 61, 141–167.

Scoville, W. B., & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions . Journal of neurology, neurosurgery, and psychiatry, 20 (1), 11.

Shrader, J. (2012, January). HM, the man with no memory | Psychology Today. Retrieved from, https://www.psychologytoday.com/us/blog/trouble-in-mind/201201/hm-the-man-no-memory

Squire, L. R. (2009). The legacy of patient H. M. for neuroscience . Neuron, 61 , 6–9.

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Article Contents

Influential case studies, psychosurgery and asylums, temporal lobectomy, controversy, author notes.

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Remembering H.M.: Review of “PATIENT H.M.: A Story of Memory, Madness, and Family Secrets”

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David W. Loring, Bruce Hermann, Remembering H.M.: Review of “PATIENT H.M.: A Story of Memory, Madness, and Family Secrets”, Archives of Clinical Neuropsychology , Volume 32, Issue 4, June 2017, Pages 501–505, https://doi.org/10.1093/arclin/acx041

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Although many influential case reports in neuropsychology exist ( Code, Wallesch, Joanette, & Lecours, 1996 ), there are certain patients who stand out because, based upon the historical zeitgeist in which their brain injuries occurred and the attention that those cases received, their neurobehavioral deficits and circumstances of their injury greatly altered our knowledge of brain-behavior relationships.

Among the most famous of these cases is Phineas Gage, the railroad foreman whose personality dramatically changed following frontal lobe injury in 1848 from an accidental explosion that thrust his tamping iron through his skull. Gage's survival after such a serious injury was a surprise, but Gage's contribution to clinical neuroscience was his significant personality change, aptly described by his physicians with the pithy observation, “Gage was no longer Gage” ( Macmillan, 2000 ). Although his personality changes were well documented soon after the accident, much of Gage's long-term outcome may have been exaggerated for entertainment value ( Macmillan & Lena, 2010 ). Thus, the lasting neurobehavioral effects of Gage's frontal lobe injury and how the deficits may have evolved over time remain clouded in the historical record due to the absence independent scientific characterization.

The second patient is Louis Victor Leborgne, whose expressive language disturbance from a left frontal lobe lesion was described in 1861 by the famous French neurologist Pierre Paul Broca. Monsieur Tan, as he was informally called because “tan tan” was his typical verbal output, retained his capacity to understand commands. The deficits of Monsieur Tan, supported by subsequent cases, demonstrated that language could be fractionated into different components associated with distinct brain regions, and that language was predominately a function of the left brain. Monsieur Tan's contribution, however, was in no small part due to Broca's distinguished reputation as a physician and scientist since localized language effects had been previously described by Jean-Baptiste Bouillard ( Sondhaus & Finger, 1988 ).

The third and most studied of these three cases is patient Henry Molaison (H.M.). H.M. suffered a dense and persistent anterograde amnesia following bilateral medial temporal lobectomy in 1953 to treat intractable epilepsy ( Scoville & Milner, 1957 ). His scientific fame derives from the dramatic demonstration of the critical role that the mesial temporal lobe structures play in learning and memory. Unlike Gage and Monsieur Tan, H.M.’s brain injury was iatrogenic, being an unanticipated adverse event associated with the surgical treatment of his epilepsy. Another important difference is that H.M.’s surgery injury occurred in what can broadly be considered to be the beginning of the modern era of neuroscience ( Shepherd, 2010 ). Thus, his cognitive abilities were subjected to formal characterization with extensive neuropsychological testing over five decades, providing a much richer characterization of his clinical semiology compared to Gage or Monsieur Tan.

H.M.’s amnesia framed how the neuroscience community would eventually conceptualize basic memory mechanisms, beginning with Brenda Milner's early demonstration that multiple memory systems exist such that declarative and procedural memory are readily dissociable ( Milner, 1965 ). Clinically, H.M.’s amnesia meaningfully influenced pre-operative epilepsy surgery protocols across the world. After several additional cases of post-surgical amnesia developed following unilateral temporal lobectomy, it was hypothesized that the functional reserve of the contralateral temporal lobe was insufficient to support the encoding of new memories following resection of the epileptogenic temporal lobe and mesial structures, and multiple methods for characterizing functional hippocampus status were developed ( Milner, 1975 ). What remains poorly reported in standard textbooks, however, is the historical context in which the decision to undergo epilepsy surgery was made, the blurring between experimental clinical techniques and informed consent, and the profound effects on H.M.’s quality of life.

To provide this broad historical context of H.M., Luke Dittrich has published PATIENT H.M.: A Story of Memory, Madness, and Family Secrets ( Dittrich, 2016a ). This is far from a narrative review of H.M.’s contributions to understanding memory, and it is also not a typical biography. However, as the grandson of William Beecher Scoville, MD, the neurosurgeon who performed H.M.’s operation and a prolific practitioner of psychosurgery, Dittrich provides a unique “insider” perspective and captivating description of that era's medical zeitgeist that could not be easily achieved without such a personal relationship. In fact, much of the book does not directly involve H.M.’s life story, but rather, the management of significant psychiatric disease prior to the development of neuroleptics.

Scoville's neurosurgical practice primarily involved surgery for psychiatric indications rather than epilepsy surgery. The early development of psychosurgery's goals is exemplified with a quote from the 19th century physician Dr. Gottleib Burckhardt, who resected undifferentiated brain areas, that illustrates the depersonalization of patients with psychiatric disease: “Mrs. B. has changed from a dangerous and excited demented person to a quiet demented one” (p. 79). It was in late 1935, after listening to the report of operations on two chimpanzees, that Egas Moniz oversaw the first in his series of approximately 20 frontal leucotomies/lobotomies. This series significantly influenced Walter Freeman (neurologist) and James Watts (neurosurgeon) who initially worked together performing prefrontal lobotomies. The distinct approaches to frontal lobotomy developed by Scoville and Freeman also provide a striking contrast in how to best decrease the institutional burden of psychiatric disease. Although Scoville is described as an adventurer who liked expensive sports cars, he was a meticulous neurosurgeon with painstaking preparation before and during all surgical cases. Freeman's enthusiastic efforts to expand the use of frontal lobotomy was reflected by his technique in which an ice pick, inserted through the orbital sockets to a depth of approximately 3 inches, was moved back and forth for frontal disconnection before repeating the procedure on the opposite side. As practiced by Freeman, frontal lobotomy required approximately 15 min to complete, could be performed without a surgeon or an operating room, and multiple procedures could be easily performed in a single day. “Any reasonably competent psychiatrist (could be trained) to perform the ice-pick lobotomy in an afternoon” (p. 151). One can go elsewhere for the complete story of Freeman, his activities and their aftermath, which has been covered by others including the exquisite text by Elliot Valenstein (1986) .

Dittrich's concerns regarding psychiatric therapies during this era are not limited to psychosurgery. His grandmother, Scoville's wife, experienced a breakdown sometime after their marriage, suffered a brittle psychiatric course, and was institutionalized at the Hartford Institute of Living while her husband was director of neurosurgery there and was performing lobotomies at both the Institute of Living and Hartford Hospital. A variety of harsh non-surgical but unproven psychiatric treatments were used that included: (1) Continuous hydrotherapy in which patients were submerged in a tub with only their heads protruding through a small aperture. (2) Pyrotherapy in which patients were placed in a small copper coffin appearing device that, over a repeated treatment period of days, would elevate core temperatures to 105–106 °C. (3) Electric Shock Therapy. In response to patients’ fears about these therapies, treatment names were changed. “Since these treatments produce states of unconsciousness akin to normal slumber … we are adopting the names that are more truly descriptive of these treatments—INSULIN, METRAZOL, and ELECTRIC SLEEP” (p. 73). Karl Pribram, who was head of research at the Institute of Living at that time, claimed that Scoville had performed a frontal leucotomy on his wife, although Dittrich could not independently substantiate that assertion.

A recurring theme throughout PATIENT HM is the concept embodied by the Hippocratic Oath of “ primum non nocer ” (first, do no harm) as it contrasts with “ melius anceps remedium quam nullum” (it is better to do something than nothing). The tension between these approaches lies at the foundation of modern informed consent in which risks and benefits are carefully weighed as part of the decision-making processes prior to treatment initiation or when deciding to participate in clinical research. Informed consent discussion is not restricted to psychosurgery, shock therapies, or H.M. The rationale for informed consent includes the development of surgical treatment for vesicovaginal fistula by J. Marion Sims during the mid-19th century that was conducted on his slaves prior to application to white women, to the U.S. Public Health Service Tuskegee Syphilis Experiment in the 1930s, and the history of the Doctors Trial at Nuremberg after World War II resulting in the Nuremberg Code.

Scoville was a practitioner of psychosurgery rather than epilepsy surgery, and prior to H.M.’s surgery, Scoville had performed multiple bilateral temporal lobectomies for psychiatric indications. Although he describes H.M.’s surgery as an “experimental operation,” he also states that the procedure was considered due to H.M.’s seizure frequency and severity despite adequate medical therapy, and that surgery was “carried out with the understanding and approval of the patient and his family” ( Scoville & Milner, 1957 ).

By the time of H.M.’s surgery in 1953, the first reported series of temporal lobectomies for epilepsy had been published from the Montreal Neurological Institute (MNI) ( Penfield & Flanigin, 1950 ). Dittrich describes the important contributions of Wilder Penfield in epilepsy surgery development that ranged from identification of motor and sensory homunculi to how Penfield established a multidisciplinary and state of the art institute by including neurology, electrophysiology, and neuropsychology colleagues. It was in this context that Penfield hired Brenda Milner. A brief biography of Milner's early life is presented in which she designed psychological aptitude tests at Cambridge University during World War II before moving to Montreal and enrolling at McGill University as a graduate student of Donald Hebb.

Although H.M.’s surgery was not performed at the MNI, Milner's neuropsychological testing of epilepsy surgery patients at the MNI made her arguably the most appropriate individual to characterize H.M.’s memory impairment. The first formal scientific presentation of H.M.’s amnesia was published in 1957 by Scoville and Milner although his “very grave, recent memory loss” was described in 1953 at a meeting of the Harvey Cushing Society ( Scoville, 1954 ). However, the 1957 report also contains formal testing on additional temporal lobectomies performed on “seriously ill schizophrenic patients who had failed to respond to other forms of treatment” (p. 11), two of whom also developed significant amnesia following bitemporal resection. Orbital undercutting was extended to include the medial temporal lobes in the “hope that still greater psychiatric benefit might be obtained” (p. 11). The significant psychiatric disease of these patients decreased clinical awareness of memory change without Milner's formal testing given that “the psychotic patients were for the most part too disturbed before operation for finer testing of higher mental functions to be carried out” (p. 12). Thus, the extent of the memory impairment was unknown due to the significant overlaying psychiatric disease in the non-epilepsy patients on whom Dr. Scoville had performed bitemporal resection prior to H.M.

Scoville was sufficiently enthusiastic about the procedure to travel to teach other surgeons the technique. Interesting is mention of Scoville's trip to Manteno State Hospital, an extremely large psychiatric facility located south of Chicago in Manteno, Illinois. Here faculty from the University of Illinois were performing anterior temporal lobectomies that included hippocampal resection, something not undertaken by Percival Bailey in his series in Chicago. Dittrich mentions another severely amnestic case (D.C.) as an outcome of Scoville's surgery at Mantero, a physician from Chicago with a premorbid IQ of 122. He was evaluated postoperatively with the resulting amnesia, comparable to H.M., confirmed by Brenda Milner. This case was apparently very unsettling to Scoville.

It is impossible to review PATIENT HM without consideration of outside events that occurred after its publication. The New York Times Magazine published a book excerpt on August 3, 2016, beginning with interviews with H.M. illustrating the magnitude and severity of his memory impairment, briefly discussing post-mortem brain ownership disagreements between the University of California at San Diego and Massachusetts Institute of Technology, presenting background material on the tension between research groups surrounding manuscript preparation describing an previously unknown lesion in H.M.’s frontal lobe that was detected at autopsy, and discussing how H.M.’s court-appointed guardian was identified. The excerpt concludes with interview quotations from Dr. Suzanne Corkin, who was the principal investigator of H.M.’s amnesia since 1977 following the death of Hans-Lukas Teuber. Again, in an interesting personal twist, Corkin lived across the street from the Scovilles, and was one of Dittrich's mother's best friends during their childhood and adolescence.

After The Times’ excerpt appeared, MIT and other organizations quickly issued statements disputing Dittrich's assertions and conclusions ( Eichenbaum & Kensinger, 2016 ; MIT News Office, 2016 ). The main points of contention included: (1) allegation that research records were or would be destroyed or shredded, (2) allegation that the finding of an additional lesion in left orbitofrontal cortex was suppressed, and (3) allegation that there was something inappropriate in the selection of (the conservator) as Mr. Molaison's guardian. In addition, a letter signed by over 200 scientists supporting Corkin dated August 5, 2017 was sent to The Times ( DiCarlo et al., 2016 ) asserting that Dittrich's claims were untrue.

Part of the interest in the quick response by the scientific community presumably was that Corkin died on May 24, 2016 prior to the book's publication and was unable to respond to these concerns. While Dittrich (2016b) has directly addressed each of the MIT concerns, their response has nevertheless led many of our colleagues and students to assume that Dittrich's book was incendiary, and whose entire story should not be believed.

While the interested reader will examine both sides of the argument (see Vyse, 2016 ), there is no evidence to suggest that any of Dittrich's factual allegations are wrong. Thus, there are two important points to consider when deciding if this controversy should make otherwise interested individuals pass on reading the book. First, in response to the assertion that research records were shredded, some have suggested Corkin's use of “shredding” was either colloquial or referred to material no longer considered relevant. Corkin is explicit in her description of data shredding in the audio clip of her interview that Dittrich posted ( Dittrich, 2016b ). Certainly, the presence of many files in a storage room says nothing about whether any files had been shredded, particularly since there has never apparently been a comprehensive catalog of the material established. Non-published information can still inform our understanding of H.M.’s clinical course as demonstrated by Dittrich's observation that H.M. had a significant memory impairment prior to surgery, a fact that had not been formally published. Similarly, non-significant findings or “failed experiments” also demonstrate a broader representation of functions either affected or unchanged following surgery. As Dittrich notes, Corkin was a “meticulous investigator, keeping careful notes” (p. 270), and these notes have both scientific and historical value.

H.M.’s legal guardianship merits greater discussion compared to disagreements about scientific ownership and publication disputes, however, which unfortunately are sufficiently common that university committees exist to address such conflicts. Conservatorship, however, is central to this story because it affects the informed consent for H.M.’s research participation, as well as influencing the final disposition of H.M.’s brain after autopsy. Similar to research study reporting standards, the nature of informed consent has evolved over the course of H.M.’s research participation. Consequently, the absence of any conservator or formal consent process early in H.M.’s research participation reflected generally accepted standards at that time. In 1992, an independent conservator was sought for H.M. to mitigate against unintended conflict of interest by H.M.’s investigators, reflecting greater overall awareness of the importance of informed consent.

The eventual conservator was a son of a former landlady of H.M. Dittrich provides evidence that, in contrast to formal court filings, the conservator was not a relative, and that one of H.M.’s relatives was a first cousin sharing H.M.’s last name (Frank Molaison). We will never fully know how the various points are intertwined or even if H.M.’s relatives had been contacted and were not interested in assuming the role of conservator, and part of this controversy is that Corkin's perspective on Dittrich's claims cannot be obtained. Nevertheless, Dittrich's reporting these issues are neither irrelevant nor inappropriate. Careful consideration of H.M.‘s ability to provide informed consent, and how conservatorship is established in circumstances in which research subjects cannot fully consent, will increase awareness of ambiguities that will allow future researchers to confidently ensure full and appropriate consent is obtained prior to research participation.

Most of the book presents a non-controversial narrative, however, and that was not adequately captured by The Times’ excerpt. What we found to be particularly enjoyable in this book is that it provides new details on the contours of H.M.’s life. Prior to H.M.’s death, there were few personal details known to the scientific community, so it should not be surprising that much of this book's appeal is due to its biographical content reporting a variety of details about H.M.’s past. Upon hearing of H.M.’s death, the initial knowledge of his full name was both exciting but then also associated with some sense of guilt and dismay as if suddenly becoming privy to secret information that had been inadvertently revealed. We enjoyed reading about H.M.’s confusion of The Beatles with The Rolling Stones when examining a photograph, but then accurately spelling B-E-A-T-L-E-S rather than beetles, but there are many others throughout the book such as H.M.’s thick New England accent. When asked “Who, or what, is Sue Corkin,” H.M. replied “She was a … well, a senator.” The book also describes frequent angry outbursts including physical harm to himself, which contrasts with the typical H.M. description of his being agreeable and passive, and it is interesting to speculate whether this behavior might have been related to the orbitofrontal damage identified during autopsy. These pieces of personal information help humanize H.M. rather than simply being either a research subject or clinical syndrome. A particularly poignant comment by H.M. was his statement that “every day is alone in itself. Whatever enjoyment I've had, and whatever sorrow I've had” (p. 375).

Despite the controversies that arose after publication of The Times’ excerpt, or perhaps because of them, this book provides a unique glimpse into the blurring of experimental therapy and research during the mid-20th century, motivations for finding treatments for psychiatrically intractable patients prior to the development of neuroleptics, as well as professional interactions and conflicts that may arise in collaborative research settings. Unlike Gage and Monsieur Tan, the depth of clinical research and the modern era in which he lived not only makes H.M. one of the most influential case studies in clinical neuroscience, but also provides one of the most compelling individual stories about how unanticipated surgical effects robbed H.M. of the capacity to form meaningful and lasting relationships with others due to the inability to form new memories. Though clearly not a textbook, and undeniably chatty at times, this is a volume that neuropsychologists at all levels of training and experience, and particularly those with interests in the history of medicine, will enjoy reading and remembering for a long time.

PATIENT H.M: A Story of Memory, Madness, and Family Secrets received the 2017 The PEN/E. O. Wilson Literary Science Writing Award. We thank Kimford J. Meador for his helpful comments on an earlier draft of this review.

Code , C. , Wallesch , C. W. , Joanette , Y. , & Lecours , A. R. ( 1996 ). Classic cases in neuropsychology . New York : Psychology Press .

Google Scholar

Google Preview

DiCarlo , J. J. , Kanwisher , N. , Gabrieli , J. D. E. , Adcock , R. A. , Addis , D. R. , Aggleton , J. P. , et al.  . ( 2016 ). Letter to the Editor of the New York Times Magazine. Retrieved from https://bcs.mit.edu/news-events/news/letter-editor-new-york-times-magazine .

Dittrich , L. ( 2016 b). Questions & Answers about “Patient H.M.” Retrieved frrom https://medium.com/@lukedittrich/questions-answers-about-patient-h-m-ae4ddd33ed9c#.apelhqx85.

Dittrich , L. ( 2016 a). PATIENT H.M.: A story of memory, madness, and family secrets . New York : Random House .

Eichenbaum , H. , & Kensinger , E. ( 2016 ). In defense of Suzanne Corkin. Retrieved from https://www.psychologicalscience.org/observer/in-defense-of-suzanne-corkin#.WKIOVE3rvL8 .

Macmillan , M. ( 2000 ). Restoring Phineas Gage: A 150th retrospective . Journal of the History of Neurosciences , 9 (1), 46 – 66 .

Macmillan , M. , & Lena , M. L. ( 2010 ). Rehabilitating Phineas Gage . Neuropsychological Rehabilitation , 20 (5), 641 – 658 .

Milner , B. ( 1965 ). Visually guided maze learning in man: Effects of bilateral hippocampal, bilateral frontal, and unilateral cerebral lesions . Neuropsychologia , 3 , 317 – 338 .

Milner , B. ( 1975 ). Psychological aspects of focal epilepsy and its neurosurgical management . Advances in Neurology , 8 , 299 – 321 .

MIT News Office ( 2016 ). Faculty at MIT and beyond respond forcefully to an article critical of Suzanne Corkin. Retrieved from http://news.mit.edu/2016/faculty-defend-suzanne-corkin-0809 .

Penfield , W. , & Flanigin , H. ( 1950 ). Surgical therapy of temporal lobe seizures . AMA Archives of Neurology & Psychiatry , 64 (4), 491 – 500 .

Scoville , W. B. ( 1954 ). The limbic lobe in man . Journal of Neurosurgery , 11 , 64 – 66 .

Scoville , W. B. , & Milner , B. ( 1957 ). Loss of recent memory after bilateral hippocampal lesions . Journal of Neurology, Neurosurgery & Psychiatry , 20 , 11 – 21 .

Shepherd , G. M. ( 2010 ). Creating modern neuroscience: The revolutionary 1950s . New York : Oxford University Press .

Sondhaus , E. , & Finger , S. ( 1988 ). Aphasia and the CNS from Imhotep to Broca . Neuropsychology , 2 (2), 87 – 119 .

Valenstein , E. ( 1986 ). Great and desperate cures: The rise and decline of psychosurgery and other radical treatments for mental Illness . New York : Basic Books .

Vyse , S. ( 2016 ). Consensus: Could two hundred scientists be wrong? Retrieved from http://www.csicop.org/specialarticles/show/consensus_could_two_hundred_scientists_be_wrong .

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September 15

Patient H.M. Dark Roots and Dubious Ethics: Neuroscience Research Methods

Medical Research Ethics

Luke Dittrich is an award winning journalist whose recently published book, Patient H.M. A Story of Memory, Madness and Family Secrets (August 2016), critically examines a dark arena of medical ethics that the scientific literature is mostly silent about. Even journalists dare not probe too critically, fearing that a serious challenge to neuroscientists’ research methods will end a journalist’s career.

The book opens with a quote from the world renowned neurosurgeon, Dr. Paul Bucy, who became President of the American Neurological Association:

“man is certainly no poorer as an experimental animal merely because he can talk.”

With that mindset, American neurosurgeons began to perform all sorts of experimental psychosurgical brain-cutting procedures on human patients. Procedures that had once been limited to chimpanzees became a paradigm of experimental neuropsychiatry. Neurosurgeons performed exploratory surgical procedures, in which they removed brain tissue from different parts of patients’ brains to study brain functions. (Read the scientific perspective in Understanding the Human Brain : A Lifetime of Dedicated Pursuit. Interview with Dr. Brenda Milner, McGill Journal of Medicine, 2006; read the devastation from the human subject’s perspective: AHRP compilation of Mind Control Experiments )

The popularity of lobotomy grew by leaps and bounds disregarding the evidence that surgeons were destroying brain tissues. They had no regard for the consequences to patients’ lives. By 1948, the Connecticut State Hospital reported optimistically in its Annual Report that “more inmates received lobotomies that year than had received dentures.” (Cited in  Book Review : ‘Patient HM’ by Luke Dittrich, Chicago Tribune, Aug, 2016)

Doctors blurred the boundary between medical treatment and research Whenever the boundary between medical treatment and research has been blurred, the results, most often have been catastrophic for the patients who have been misled into believing that research offers an opportunity to benefit from an advanced improved therapy. When, in fact, research involves risk and the odds of benefiting are much like gambling.

Henry M. was one among numerous casualties of a medical culture that blurred the line between medical treatment and medical research. At the age of 27 Henry was subjected to an experimental bilateral lobotomy as a “treatment” for epileptic seizures. The experimental surgery was performed by Dr. William Beecher Scoville, a prominent neurosurgeon, a professor at Yale University, who, Dittrich reveals, was his grandfather. He was “one of the most prolific lobotomists in history” second only to Walter Freeman, who continually experimented (mostly) on psychiatric patients. In one experiment, mentally ill patients were lobotomized in the hope of easing overcrowding in Connecticut’s asylums. Scoville continued to perform lobotomies on thousands of patients at Hartford Hospital until 1970.

Most shocking is that his grandson suspects that his grandfather even lobotomized his own schizophrenic wife who was institutionalized and subjected to the horrific treatment modalities that were used on the mentally ill. At one point, she was submerged in a tub of cold water for hours at a time; at another, she was locked in a “copper coffin and cooked” until her temperature reached 105 degrees.

“ Lacking a specific target in a specific hemisphere of Henry’s medial temporal lobes, my grandfather had decided to destroy both…The risks to Henry were as inarguable as they were unimaginable. The risks to my grandfather, on the other hand, were not. At that moment, the riskiest possible option for his patient was the one with the most potential rewards for him.”

Henry was a victim of dubious medical research that robbed him of the ability to form new memories. Scoville performed a “limbic lobotomy” removing two slivers of tissue from Henry’s temporal lobes on each side of his brain, including the hippocampi. As a result, Henry suffered profound anterograde amnesia . After the surgery, he was unable to retain anything beyond 30 seconds; nor was he able to connect new experience to memory. His memory was forever frozen at 1953.

“ The holes that Scoville cut to expose Henry’s brain to his instruments stand as a grisly metaphor for the science that underpinned the operation: small patches of illumination surrounded by an uncharted expanse of darkness .” London Review of Books , 2013

Dr. Scoville referred him to Dr. Wilder Penfield and Dr. Milner at the Montreal Neurological Institute.

“they quickly realized that Henry’s dense amnesia, his intact intelligence , and the precise neurosurgical lesions made him the perfect experimental subject. For 55 years Henry participated in numerous experiments, primarily at Massachusetts Institute of Technology (MIT) where Professor Suzanne Corkin and her team of neuropsychologists assessed him. Access to Henry was carefully restricted to less than 100 researchers.”       ( Psychology Today , 2012)

“ That outcome ,” Dittrich writes, “though   devastating to Henry, was a boon to science “:

Slide of HM’s damaged brain The Scientist “By 1986, Patient H.M. — as he was called in countless journal articles and textbooks — had become arguably the most important human research subject of all time, revolutionizing our understanding of how memory works.  Of course, Henry didn’t know that…” “I followed Henry’s trail down all sorts of unexpected paths, and what I uncovered was alternately fascinating and disturbing, starting even before the day my grandfather drilled two holes in Henry’s head, levered up his frontal lobes and suctioned out some of the deepest and most mysterious structures in his brain. The questionable ethics that were the backdrop to Henry’s operation — a catastrophic blurring of the lines between medical research and medical practice — became clear early on, but my reporting also eventually raised serious questions about Henry’s treatment after he left the operating room, during the decades he spent as a human research subject, as well as in the eight years that have passed since his death.”

Much to the consternation of the neuro-scientific establishment, Dittrich judges the actions of his grandfather on a continuum with the Nazi doctors who used inhumane medical experimental methods on human beings to test the limits of human endurance. (Dr. Scoville’s obituary is posted on the website of the Society of Neurological Surgeons . There is no mention whatsoever about either Dr. Scoville’s career as a lobotomist or his responsibility for having performed an extremely dangerous surgical method that rendered Henry Molaison profoundly incapacitated for the rest of his life.)

Henry then spent his life – until the age of 82 – as a human subject of hundreds of experiments at the Massachusetts Institute of Technology (MIT) – including invasive painful experiments such as: being fed multiple meals in a row to test whether he remembered having just eaten; being burned to test his pain threshold . Dittrich corrects the misperception that the surgery cured his epilepsy –it did not.

Dittrich holds both past and current research practices up for critical examination : noting the cultural divide between the class of prominent researchers at elite institutions and the human subjects of their experiments. He recognizes that researchers objectify human subjects, viewing them as the means for obtaining information; data for publication, and the means for advancing their academic careers.

He credits Dr. Brenda Milner , the Canadian neuroscientist at McGill University who collaborated during the first five years of research on Henry, as the scientist whose monumental achievements overturned the prevailing theory of memory which had held that memory was stored throughout the brain, rather than localized in a single area. Two of her publications, he concluded, provided the seminal foundation of current memory science research.

Dr. Brenda Milner “She demonstrated, with elegance and rigor, that Henry’s amnesia was profound — possibly the most catastrophic she had ever seen — and declared that it must have been a result only of the relatively small and specific bilateral lesions to his hippocampus and other medial temporal structures left by the operation. This was an astonishing revelation. Five years after Milner’s first paper about Henry, she published a second that was almost as revelatory. That paper documented Henry’s gradual improvement over a three-day period on a difficult hand-eye coordination task. His improvement came despite his inability to ever remember his previous attempts at the task, indicating that there are at least two different memory systems in the brain — one responsible for our conscious, episodic memories, the second responsible for task-or-skill related “procedural” memories — and that these two systems seem to rely on entirely distinct parts of the brain. This was another fundamental step forward in our understanding of how memory works. Together, Milner’s two Henry-­related revelations can be viewed as the cornerstones of modern memory science.” (Patient HM)

During the following decades, the research about Henry was led by Dr. Suzanne Corkin and a team of MIT neuroscientists.  While Corkin acknowledged in later years that the abuses of psychosurgery were becoming conspicuous by the early 1950s, she hastens to caution against condemning neurosurgeons. In her book, she defends Scoville who, she suggests “ arguably saved Henry’s life, even if he took his memory. ”

Before turning to the specific serious questions that Dittrich raises about the ethical integrity of Dr. Corkin, who was a prominent neuroscientist who died earlier this year, we make note of the culture within which neuroscientists are trained. That culture is characterized by a chilling detachment from the patients on whom they experiment. That culture of detachment is pervasive in the neuroscience specialties — neurology, neuropsychology, psychiatry, psychopharmacology, and psychosurgery.

The dark side of neurscience: The neuroscience literature is entirely silent about the nefarious mind destroying experiments that neuroscientists performed on behalf of the CIA at prestigious universities; in particular, McGill University in Montreal, and Harvard, Yale, Columbia, and many others in the U.S. For that facet of their career, one must turn to critics outside of the neuroscience specialty. Thus, one learns from the eminent historian, Alfred McCoy that Dr. Donald Hebb’s experiments in sensory deprivation at McGill University provided the CIA with the torture paradigm used to this day. (Read: Alfred McCoy, “ Science in Dachau’s Shadow : Hebb, Beecher, and the development of CIA Psychological Torture and Modern Medical Ethics,”  Journal of the History of the Behavioral Sciences , 2007; read also, How McGill Pioneered psychological Torture , McGill Daily , 2012; and read  AHRP’s compilation of  Mind Control experiments )

Both Dr. Milner and Dr. Corkin were trained at McGill; their careers were advanced by the research they conducted on H.M. who became the most famous patient in the history of neuroscience, the subject of 12,000 journal articles; though Henry Molaison didn’t know it. Dr. Corkin was a strict gatekeeper to every facet of HM’s life and even afterlife.  After his parents died he should have had a conservator to represent his interests; none had been delegated. From 1981 -1992, he was essentially under the control of the principle researcher, Dr. Corkin, and during those years signed consent for all the non-ending experiments he underwent.

Dittrich cites Dr. Corkin’s own recollection about her response upon seeing Henry’s brain after it was extracted during autopsy:

“ The men carefully pulled out Henry’s brain, and Corkin gazed at it through the glass, marveling at this object she had spent her career considering at one step removed. Later, reflecting on that moment, Corkin could think of only one word to describe her feelings. She was, she wrote, “ecstatic.”

Her response after having interacted with this human being for 50 years encapsulates the chilling detachment that neuroscientists exhibit toward their human patient/ subjects. Indeed, Carl Zimmer, a columnist in The New York Times and author of 13 books including a history of neurology, critiqued Dr. Corkin in his review of her book, Permanent Present Tense (2013) in The Wall Street Journal :

  “too often Ms. Corkin slips into a clinical, unemotional voice. This is a tone that as a science writer I hear all the time, and I understand why scientists strive for it. They want to be objective and unassuming. But Molaison’s story is drenched in emotion—happiness, grief, fear, fascination. And Ms. Corkin’s own life became intertwined with Molaison’s. She spent much of her life observing his life at close quarters, yet she doesn’t delve much into how that experience affected her.”

And the final sentence of a review in the London Review of Books (May 2013), quotes her own words: “My interest in Henry…had always been primarily intellectual; how else would I explain why I had stood on a chair in the basement of Mass. General, ecstatic to see his brain removed expertly from his skull?”

The ethical violations Dittrich raises are often replicated at elite medical institutions:

• Conflicts of interest – both personal and institutional— ensure that the researchers’ interest and the institution’s interest are served; whereas the human subject’s interest takes a back seat as servants of science.
• Dubious consent to experimental research was obtained – 1981-1992 – from a person who was profoundly amnesiac; whose mental incapacity precluded his understanding what he was consenting to.
• Dubious appointment of a conservator selected by Dr. Corkin in 1992, who misrepresented himself as next of kin to the probate court judge. He gave blanket consent to experiments on HM and donated his brain.
• Laying claim to proprietary ownership of the data . Dr. Corkin laid claim to total proprietary ownership of all the research data, and the research narrative by denying access to other scientists for independent scientific interpretation, and even claimed ownership of his brain after death. She argued that published articles had undergone “peer review” the gold standard of validation. This is a most disingenuous claim in light of the high volume of retractions when an increasing number of “peer reviewed” journal articles have been found to be flawed or outright fraudulent. (See, Retraction Watch ) Dittrich writes:

“When I first explored the possibility of writing about Henry, he was still alive, but I abandoned that effort after Corkin presented me with a confidentiality agreement stating that M.I.T. would allow me access to the ‘research project entitled ‘The Amnesic Patient H.M.’  only if the university had editorial control over anything I intended to publish.”

MIT’s confidentiality agreement mirrors pharmaceutical company confidentiality agreements which demand “editorial control” over the published reports. This has led to the proliferation of toxic, harm producing drugs and medical devices whose adverse effects have been covered up.

5. Disputes about who owns human tissue are not uncommon in hospitals and research institutes.After Henry’s death, a secret war was waged by four major academic institutions about the custody of Henry’s brain. The institutions were: M.I.T.; Mass General Hospital; the University of California, Davis; against the University of California, San Diego.

Henry’s brain was on loan to neuroanatomist, Dr. Jacopo Annese, at the University of California, San Diego, where he painstakingly partitioned Henry’s brain after death into 2,401 thin slices and then mounted the slices onto slides. His analysis of the tissue revealed a previously unreported lesion in Henry’s frontal lobe—a significant finding which undercut much of the neuropsychological literature about H.M.

6.Selective publication of data: For decades Dr. Corkin had relied on the erroneous assumption that his lesions were restricted to the medial temporal lobes, and that his frontal function was intact. However, Dr. Jacopo Annese who conducted a post mortem analysis of Henry’s brain tissue raised two significant matters of contention about selective publication and manipulation of data:

a) Failure to mention in published articles a psychological assessment of Henry prior to the botched surgery, which showed evidence that his memory was already severely impaired even before the failed experimental operation that transformed Henry Molaison into the amnesiac Patient H.M.,

b) Failure to publish evidence of a lesion in Henry’s frontal lobe.

Both of these undisclosed significant facts about H.M.’s brain deficits and injuries likely undercut much of the interpretations in neuropsychological literature about H.M. When Dr. Annese pointed out his discovery of the lesion in the frontal lobe, she attempted to prevent him from publishing his findings. Ultimately, Postmortem Examination of Patient HM’s Brain was published in Nature Communications (October 2013) and Dr. Suzanne Corkin is listed as one of the authors.

• Destruction of data : according to Dr. Corkin’s recorded statements, she destroyed original data and claimed ownership of the Henry’s brain. The recording is posted here

“You didn’t need to be a scientist to grasp what this destruction meant. My grandfather had cut a hole into Henry’s memory, and now one of the many people who profited from that act was cutting another irreparable hole, this one into our memory of Henry.” “The causes and significance of Henry’s preoperative memory deficits can be debated, but their existence only underscores the importance of preserving the complete record of the most important research subject in the history of memory science. I wondered what other surprises might be found in a full accounting of Henry’s data, at least the data that hadn’t already made its way to Corkin’s shredder.” (Patient HM)

• Published reports by Dr. Corkin painted inaccurate description of Henry Molaison’s emotional status, reporting “no evidence of anxiety, major depression or psychosis.” However Dittrich found Henry’s written responses to the questionnaire suggesting that, contrary to Corkin’s written description, he was an extremely sad and lonely man with no hope for the future: he circled: “I feel that the future is hopeless and that things cannot improve” and “I feel that I am a complete failure as a person…”

This disclosure, as MIT Professor Seth Mnookin points out (in his book review in The New York Times, Sept. 4, 2016) raises questions about what else is contained in the unpublished data that might reveal new insights into the mental anguish of Henry Molaison.

An extensive excerpt of the final chapters of the book was published in The New York Times Magazine (August 3, 2016).

“A great deal of what we know about how our brains work has come about through intensively scrutinizing individuals whose brains don’t work… In that pantheon of illuminatingly broken men and women, Henry stands apart. It is difficult to exaggerate the impact he has had on our understanding of ourselves. “Prior to the research conducted on Henry, the prevailing theory of memory held that its functions could not be localized to a single cortical area; learning was thought to be distributed across the brain as a whole. That theory was built upon the experimental lesioning of the brains of rats. The battery of experiments conducted on Henry Molaison upended this view.” “As the experiments piled up and the data accumulated, Henry became a boon not just to science but also to Corkin’s career. She started her own lab at M.I.T., and although she and her colleagues conducted research in a number of areas, the papers that generated the most attention were always the ones about Henry. When they first met, Corkin was a young graduate student in her 20s. She grew older. She became a renowned professor of neuroscience at one of the world’s greatest universities.” “After Henry died [in 2008] and I decided to take another run at telling his story, Corkin turned down repeated interview requests, telling me that she was working on her own book about Henry and that her literary agent had advised her not to speak with me.”

The Times excerpt of the book prompted letters disputing the portrayal of Dr. Corkin. Dr. James DiCarlo, head of Brain and Cognitive Science department and two other brain scientists to send a letter to the editor disputing three allegations, to which Dittrich posted a response rebutting their arguments.

Another letter, signed by 200 academics in cognitive psychology, psychiatry and neuroscience stated that they are “disturbed” by a book excerpt:

“ which describes Professor Suzanne Corkin’s research in what we believe are biased and misleading ways.   A number of complex issues that occur in research with humans, from differing interpretations of data among collaborators to the proper disposition of confidential data, are presented in a way so as to call into question Professor Suzanne Corkin’s integrity. These assertions are contrary to everything we have known about her as a scientist, colleague, and friend . … S he was a highly accomplished scientist, an inspiring teacher, a beloved mentor to students and faculty, and a champion of women in science.”

In interviews with PBS, The New York Times , Luke Dittrich explained:

“ For most of his life, though, Henry was just a pair of initials floating in front of a constellation of clinical and experimental data. His story was tightly controlled by the researchers who’d built their careers on him and who had an interest in presenting his story in a particular way. I believe Henry’s story is important not only because of what he contributed to our understanding of memory, but also because of what his case can teach us about our sometimes ruthless pursuit of knowledge. … any time we tinker with the human brain — either pharmacologically, electrically, or physically — we obviously need to be careful. You’re messing with our primal material, what makes us, us.” ( A Brain Surgeon’s Legacy Through a Grandson’s Eyes , The New York Times; Bringing New Life to ‘Patient H.M.’ PBS , August 2016)

The book has been lauded by reviewers as an outstanding achievement in the realm of medical ethics narratives:

A review in Discover Magazine , July 7, 2016; an extensive interview in  Discover Magazine, August 12, 2016 Jenni Odgen, PhD. A Tale of Science, Ethics, Intrigue, and Human Flaws, Psychology Today,   August 8, 2016 Carla Johnson, of Associated Press compares its significance with Rebecca Skloot’s “ The Immortal Life of Henrietta Lacks . Book Review: ‘Patient HM’ by Luke Dittrich, by Jeni Laidman, Chicago Tribune (Aug, 2016) Most recently a review in The New York Times Book Review by Professor Seth Mnookin, Director of MIT’s graduate program in science writing.  (Sept.4, 2016)

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In Defense of Suzanne Corkin

• Cognitive Psychology
• Long-Term Memory
• Neuroanatomy
• Short-Term Memory

In “The Brain That Couldn’t Remember,” published in The New York Times Magazine * on August 7, 2016, journalist Luke Dittrich raises what he suggests are ethical issues surrounding the testing of Henry Molaison, the well-known amnesic patient referred to as H. M. in the scientific literature. Proper scientific procedures and the responsible use of humans as research participants are critically important topics, and a scholarly analysis of the history of developments in these areas could be applied usefully to the case of H. M. Instead, Dittrich crafts a portrayal of Massachusetts Institute of Technology (MIT) neuroscientist Suzanne Corkin’s work with H. M. that utilizes personal opinion and innuendo. Dittrich’s sensational accusations run counter to all we witnessed first-hand during Corkin’s life and all that we have known about her as a scientist, mentor, and colleague.

Sadly, she passed away on May 24, 2016, so we will not be able to hear from her directly. However, in response to the article, we have heard from more than 200 scientific colleagues who signed a letter to The New York Times supporting Corkin (posted here ; Flaherty, 2016), and we have heard separately from the MIT department and Corkin’s colleagues at the Massachusetts General Hospital, who rebutted several of Dittrich’s claims (DiCarlo, 2016; van der Kouwe et al., 2016). Here, as Corkin’s former research collaborators, we expand on these rebuttals and present an alternate and documented perspective for some of Dittrich’s claims.

Identity Protection

One of the issues Dittrich raised was about the intensity with which H. M.’s identity was guarded. Dittrich states: “It was an odd sort of fame: The scientists kept even his first name a closely guarded secret from the outside world and didn’t reveal it until after his death, when it was unveiled in a front-page obituary in this newspaper.” It is standard practice in psychological research to refer to participants only by initials, and it is required by most human ethics committees to keep the identity of individual participants confidential. (In this article, we refer to Molaison as H. M. out of respect for the scientific contributions he enabled by his participation in research.) Probably every researcher who met H. M. was approached by people — ranging from undergraduate students to journalists — who were curious about the personal life of the man referred to in text books as H. M. It is unclear to us why Dittrich would think that publicly revealing H. M.’s identity during his lifetime would have augmented his quality of life or would have prioritized his interests. The fact that his identity was protected for decades is a testament to Corkin’s deep respect for H. M. as a person and her fidelity to research ethics.

Treatment of H. M.

Throughout the article, Dittrich paints an unsettling portrait of Corkin’s treatment of H. M. as a research participant, at multiple points exaggerating the truth in service of this portraiture. For example, Dittrich states: “Corkin and her colleagues learned that if you placed a pain-inflicting device called a dolorimeter to Henry’s chest, he wouldn’t complain even as his skin began to turn red and burn.” Although Dittrich provides no citation for this statement, based on the details he provides it is reasonable to assume that he is referring to the published report of Hebben et al. (1985). If so, his statement represents a fundamental mischaracterization of how this experiment was conducted; the publication describes these experiments in detail. The heat was never raised to the level of skin burning and, importantly, each participant held the dolorimeter to their own skin and were free to withdraw the device at any time (labels including “withdrawal” were placed in front of participants to ensure they knew their options). In addition, H. M. was among six participants with global amnesia and 15 normal control participants who underwent this standard thermal-pain-perception test.

At another point, Dittrich characterizes researchers as questioning H. M. “relentlessly.” The reality was far more benign. H. M. visited the Clinical Research Center at MIT, which was staffed with nurses and provided around-the-clock care. (Corkin gives detailed descriptions of this center in her 2013 book, Permanent Present Tense: The Unforgettable Life of the Amnesic Patient .) It was evident to those of us who worked with H. M. that he received affectionate attention from the staff and researchers in the center, and his demeanor during these visits suggested that he enjoyed himself. During his visits, he was tested for only a few hours each day. He was given leisurely breaks between testing sessions, during which he would return to his private room or spend time in a lounge talking with the nursing staff or with other research participants. Much of the time, the testing simply consisted of conversations between H. M. and researchers. For example, he might be asked what he remembered about his past or what he knew about particular events, people, or words. In later years, he also played computerized games designed to assess different aspects of cognitive function. Research staff were trained to give H. M. frequent breaks because he would not be able to determine how much time had passed, and to ask him at regular intervals if he would like to stop. Tremendous thought — by Corkin in consultation with MIT’s Committee on the Use of Humans as Experimental Subjects — went into ensuring that H. M.’s assent was meaningful.

Even more pernicious than these exaggerations is Dittrich’s use of the phrase “chief inquisitor” to describe Corkin’s relationship with H. M. While this stylism certainly draws attention, we believe that, in the context of a discussion of how H. M. was treated, allusion to an era when human beings were physically and mentally tortured for the sake of dogma is inappropriate.

Dittrich alleged that there was something improper in the selection of H. M.’s legal guardian. In her book, Corkin described the events and process in detail. From the time of his surgery until 1974, H.M. was cared for by his mother, who accompanied him on visits to Corkin’s laboratory at MIT, as well as to Brenda Milner’s laboratory in Montreal, Canada. When his mother’s health was failing, H. M. moved in with Lillian Herrick, whose first husband was related to H. M.’s mother. In 1980, when Herrick’s health also failed, H. M. was admitted to a nursing home founded by her brother. In 1991, the Probate Court in Windsor Locks, Connecticut, appointed Herrick’s son, Tom Mooney, as H. M.’s conservator after a valid legal process, which included providing notice of a hearing and appointment of counsel. No evidence has come to light about anything untoward or inappropriate about the course of H. M.’s guardianship.

Disposition of H. M.’s Brain

Dittrich also tells the story of a so-called “secret custody war” between Corkin and neuroanatomist Jacopo Annese over the ownership of H. M.’s brain after his death. (She earlier had arranged to have Annese perform anatomical studies on H. M.’s brain.) Indeed, the scientists’ relationship did become contentious, but the dispute regarding the custody of H. M.’s brain was resolved amicably between the institutional parties. They agreed to transfer the brain to David Amaral, a well-known expert on medial temporal lobe anatomy at the University of California, Davis, who will pursue the histological findings in maximum detail (DiCarlo, 2016).

The Shredding Conversation

Dittrich also reports a verbatim exchange in which he asks Corkin about the shredding of some data. The specifics are hard to understand and Dittrich concludes by stating: “Elements of her story seemed to be shifting and flexing in real time. Whatever the details, though — whatever Corkin had or hadn’t yet shredded — the whole idea of willfully shredding any of Henry’s data struck me as deeply troubling.” Adding to the ambiguity, the tape-recorded interview that Dittrich himself posted online , ended with Corkin saying, “We kept the H. M. stuff.”

Given that Corkin made herself available for his interview despite ill health and ongoing chemotherapy, and given the puzzling and seemingly contradictory remarks she made, it is unfortunate that Dittrich did not clarify her statements using other sources. MIT has confirmed that it still has a room full of files (see also Connally, 2016) and indicates that Corkin clearly instructed her assistant to preserve all materials related to H. M. (Begley, 2016). Corkin’s preservation of these data would be consistent with the meticulous way she had organized and stored them over many decades.

Damage to Prefrontal Cortex

The article additionally implies that Corkin had a rigid storyline for H. M.’s abilities, and that she was willing to go to great lengths to ensure that this storyline was not broken. In particular, Dittrich suggests that Corkin attempted to suppress recent evidence of a small lesion in the left orbital prefrontal cortex for fear that it would threaten her long-held conclusions. Dittrich states: “…for the previous six decades, neuropsychologists like Corkin had interpreted their experimental results with Henry under the working assumption that his lesions were restricted to the medial temporal lobes. The discovery of this new lesion might call some of their conclusions about the functions of the medial temporal lobes into question and require a reexamination of all that old data.” This statement may reflect Dittrich’s perception, but in fact, Corkin and her colleagues never worked under the assumption that H. M.’s lesions were restricted to the medial temporal lobes. In published articles, Corkin and her colleagues reported that H. M.’s lesions involved multiple portions of the medial temporal-lobe area that serve distinct functions, including extensive damage to hippocampal areas thought to be the basis of the memory deficit, plus removal of the amygdala and temporal polar neocortex, and his cerebellum also was extensively atrophied (Corkin et al., 1997).

The notion that Corkin would have suppressed evidence of an orbitofrontal lesion is incompatible with the fact that she and her colleagues had forecast the presence of such a lesion in an earlier study (Eichenbaum et al., 1983). The results of this study revealed a deficit in odor discrimination and identification that was similar to that observed in patients with orbitofrontal lesions in other reports. Based on this evidence, Corkin and her coauthors suspected H. M.’s olfactory abnormality was due to orbitofrontal damage during the surgical approach — a hypothesis that will or will not be verified by continuing progress in the histological examination of his brain. Therefore, Corkin had indeed already considered the implications of a potential orbital prefrontal lesion, just as she also pursued the consequences of H. M.’s lesion in the amygdala (Hebben et al., 1985).

Corkin’s Role in Scientific Discovery

More broadly, Dittrich’s statements seem to reflect a fundamental misunderstanding about the nature of the science of human memory and Corkin’s contributions in this scientific progress. H. M. provided a core foundation on which the cognitive neuroscientific study of memory was built, and Corkin’s work with H. M. was key in advancing these foundational discoveries. Dittrich implies that Corkin championed these discoveries, then resisted evidence contrary to early conclusions. In truth, Corkin’s later studies on H. M. led her to extend and revise those conclusions (e.g., O’Kane et al., 2004). By no means was she one to maintain dogma and resist contrary evidence with regard to either the anatomical or psychological aspects of H. M.’s case. Corkin studied H. M. as a landmark case of amnesia, but at the same time understood that he was not the best case for anatomical localization of the memory deficit. The scientific understanding of memory has progressed through decades of research on humans with brain damage limited to the medial temporal lobes and areas within the medial temporal lobes, as well as with animal model studies that can pinpoint specific medial temporal areas. These studies have refined and extended the observations on H. M. Corkin elegantly discusses these advances in research on the medial temporal lobes and memory in her recently published book (Corkin, 2013).

Suzanne Corkin’s research with H. M. was only one facet of her research; by her own account, her research with H. M. resulted in only 22% of all of the output from her laboratory (Corkin, 2013). She made important contributions to the understanding of human memory through her research with many patient populations, including those with Alzheimer’s disease and Parkinson’s disease, and by utilizing neuroimaging methods. She was respected by her colleagues for her exacting standards and her meticulous attention to detail. Dittrich’s portrayal of her in The New York Times Magazine may have served as a promotional advertisement for his new book on H. M., but in so doing it sacrificed facts.

Dittrich’s article does not discuss extensive relevant literatures on the ethics and approved procedures for use of humans as research participants, including the protection of their identities, and he does not report any discussions with the ethics committees that reviewed Corkin’s submitted research protocols. Similarly, he does not discuss a large literature on the proper maintenance of raw data from experiments nor consider reasons why ethical guidelines may require the responsible disposal (i.e., shredding) of some confidential files. Dittrich provides no citations to the scientific literature referred to him by Corkin. He could have contacted any of the 200 scientists who signed the letter to The New York Times about the potential scientific relevance of H. M.’s orbital prefrontal lesion. The absence of these straightforward additional steps leaves the impression that Dittrich’s article capitalized on innuendo to create a narrative that implied malfeasance.

For more informed and comprehensive treatments of Corkin’s contributions, please see a recent summary of her career (Postle & Kensinger, 2016) and the obituary for Corkin, also published in The New York Times (Carey, 2016).

*Among those signing the Letter to the Editor to The New York Times Magazine were a number of prominent APS leaders, including President-Elect Suparna Rajaram ; Past Presidents Henry L. Roediger, III , and Elizabeth A. Phelps ; and Past Board Members Lisa Feldman Barrett , Morris Moscovitch , and Sharon L. Thompson-Schill . Another noteworthy signatory is APS William James Fellow Brenda Milner , who was Corkin’s graduate school advisor at McGill University and who conducted the foundational research on H. M. Also signing the letter were APS William James Fellows James. L. McClelland , Marcia K. Johnson , and Daniel L. Schacter . The full list of signatories is available here .

Begley, S. (2016, August 9). MIT challenges New York Times over book on famous brain patient. STAT News . Retrieved from https://www.statnews.com/2016/08/09/mit-brain-sciencefuror/?s_campaign=stat:rss&trendmd_shared=0

Carey, B. (2016, May 28). Suzanne Corkin, who helped pinpoint nature of memory, dies at 79. The New York Times . Retrieved from http://www.nytimes.com/2016/05/28/ science/suzanne-corkin-who-helped-pinpoint-nature-ofmemory-dies-at-79.html?_r=2

Connally, E. (2016, Aug 24). Speaking for Sue. Don’t Mind the Unicorn . Retrieved from http://tinyurl.com/hlb5uxn

Corkin, S. (2013). Permanent present tense: The unforgettable life of the amnesic patient, H. M. New York, NY: Basic Books.

Corkin, S., Amaral, D. G., González, R. G., Johnson K. A., & Hyman, B. T. (1997). H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging. Journal of Neuroscience, 17 , 3964–3979.

DiCarlo, J. J. (2016, August 20). Additional information as of August 20, 2016, further rebutting Luke Dittrich’s allegations against Professor Corkin . Retrieved from http://bcs.mit.edu/newsevents/news/additional-information-august-20-2016-furtherrebutting-luke-dittrich%E2%80%99s-allegations

DiCarlo, J. J., Kanwisher, N., Gabrieli, J. D. E., Adcock, R. A., Addis, D. R., Aggleton, J. P., … Ziegler, D. A. (2016, August 5). Letter to the Editor of The New York Times Magazine by International Community of Scientists . Retrieved from https://bcs.mit.edu/ news-events/news/letter-editor-new-york-times-magazine

Eichenbaum, H., Morton, T., Potter, H., & Corkin, S. (1983). Selective olfactory deficits in case H. M. Brain, 106 , 459–472.

Flaherty, C. (2016, August 11). Defending a late colleague. Inside Higher Ed . Retrieved from https://www.insidehighered.com/ news/2016/08/11/new-book-criticizing-well-known-professorneuroscience-who-died-year-sparks-ire-her

Hebben, N., Corkin, S., Eichenbaum, H., & Shedlack, K. (1985). Diminished ability to interpret and report internal states after medial temporal resection: Case H. M. Behavioral Neuroscience, 99 , 1031–1039.

O’Kane, G., Kensinger E. A., & Corkin, S. (2004). Evidence for semantic learning in profound amnesia: An investigation with patient H. M. Hippocampus, 14 , 417–425.

Postle, B. R., & Kensinger, E. (2016). The unforgettable career of Suzanne Corkin. Hippocampus . Advance online publication. doi:10.1002/hipo.22618

van der Kouwe, A., Augustinack, J., Salat, D., Stevens, A., Frosch, M., Fischl, B., & Rosen, B. (2016, August 22). Martinos Center investigators respond to article critical of Suzanne Corkin . Retrieved from https://www.nmr.mgh.harvard.edu/ news/20160822/martinos-center-investigators-respond-articlecritical-suzanne-corkin

With all due respect, if we really want a scientific and critical evaluation of Dittrich’s claims, shouldn’t a special investigatory panel be set up instead of relying on anecdotal and hearsay evidence? Again, with all due respect, but when did testimonials become data/evidence?

As an example of a point that needs further examination, Eichenbaum and Kensinger in the section “Identify Protection”, they say: “It is standard practice in psychological research to refer to participants only by initials, and it is required by most human ethics committees to keep the identity of individual participants confidential.”

Phlip Hilts, in his 1995 book on “Mr. M” titled “Memory’s Ghost”, wrote: ” From those notebooks, I see we recorded a lecture by Suzanne Corkin on the brain and memory. ‘H.M. is a gold mine, the most famous neurological patient in the world.’ After one lecture, a student asked her ‘Is Henry still living in that nursing house in Connecticut?’ ‘Sssh!’ said Dr. Corkin as she glanced down the table at me. ‘There’s a reporter present! We have to be careful.” Thus I learned his first name is Henry.” (page 107)

Apparently Dr. Corkin referred to H.M. by his first name in lectures as well as provided additional personal information, such as where he was located. I don’t know if Eichenbaum and Kensinger are unfamiliar with Hilt’s book or whether they consider Corkin release of such information — long before H.M.’s death — is consistent with the ethical standards for confidentiality they present. But perhaps an objective third party should decide whether confidentiality was breached (which a strict reading of Eichenbaum and Kensinger’s position would seem to suggest).

It is one thing to come to the defense of a friend and colleague. It is another to get as close as possible to the truth.

Where is my comment from Sunday (10/02/2016) morning? And please operationalize “a short delay” — clearly it is an ambiguous term.

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About the Authors

APS Fellow Howard Eichenbaum , Director of the Center for Memory and Brain at Boston University, collaborated with Corkin in research on H. M. in the 1980s.

APS Fellow Elizabeth Kensinger is Director of the Cognitive and Affective Neuroscience Laboratory at Boston College and was Corkin’s student, receiving her PhD in 2003.

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IB BioPsychology

Helpful Biology & Psychology notes for IB students

Ethical Considerations in the biological approach

In this essay, I’ll describe the ethical considerations in the biological approach studies. Research of the biological level of analysis poses various different ethical considerations, including concerns regarding the protection of harm, informed and conscious consent. I’ll describe two studies that rise different ethical questions regarding the studies: the Newcommer (1999) experiment and the HM Milner (1966) case study. 

The Newcommer (1999) study’s aim was to examine the role of stress on the verbal declarative memory: VBM. The participants were all students of the same university. Prior to the experiment they were assessed by a physician, and excluded from the sample if they had suffered a head injury, had a history of mental illness, suffered a head trauma or were pregnant. 

They were then divided into three groups. Each of the participants was to take a pill containing a set dosage of cortisol, a substance often called a ‘stress hormone’. It’s responsible for controlling thirst, hunger, need for sleep, as well as controlling the glucose levels in the bloodstream. 

The first group of participants was given pills containing 160mg of cortisol, an amount similar to these experienced when under a highly stressful life event. The second group was given pills with 40mg cortisol, which corresponds to a concentration similar to a mildly stressful event. Third group served as a control, and was given placebo pills with no cortisol. 

The participants were to listen and recall a prose paragraph. Each day of the experiment, there were given a different fragment. The paragraphs were counterbalanced to ensure the difficulty of the paragraphs wasn’t a confounding variable. The study first started with a baseline study to make sure there were no differences in memorizing capacities between participants. It should be noted down the experiment was double-blind, neither the participant, nor the researcher knew who received what treatment. 

The participant’s ability to memorize the prose paragraphs was then measured the first and fourth day of the pill treatment. 

On the first day of the experiment, the differences between groups were statistically insignificant, however on the fourth day participants who received the 160mg pills had a significantly worse VBM performance recorded, as compared to the placebo. On the other hand, cortisol given to the participants of the 40mg group might’ve assisted their memory formation.

It’s been concluded that prolonged exposure to severe stress impairs memory. The results are reasonable as there are cortisol receptors at the hippocampus- part of the brain responsible for the transfer of short-term memory to long-term memory. 

One ethical consideration that is concerning in this study is the protection from harm. It’s hard to evaluate to what extent were the participants able to comprehend the effects of receiving cortisol pills. Furthermore, participants were not under surveillance of the researcher at all times during the experiment, which poses a potential risk in their daily life activities. The additional stress the participants underwent might’ve negatively affected their mood, relationships or affect their judgement. On the other hand, after six days after finishing the procedure, participants memory was assessed again to make sure there were no long-terrm effects on the health of participants. Furthermore, the participants were properly informed about the procedure before giving a consent. Their health has also been assessed prior to the experiment, which further aligns the study with the ethical standards.

Other study that concerns the ethical issues is the case study of HM. As a 7-year-old boy, HM suffered a head trauma, as he was hit by a bicycle. He started to experience epileptic seizures when he was 10. At the age of 27 the seizures disabled his ordinary functioning, and therefore he decided to have a surgery procedure. William Scoville, a renowned neurosurgeon, removed both sides of his hippocampus as well as the medial temporal lobe. The surgery ceased HM’s seizures. His IQ slightly improved, and his personality was largely intact. However, soon after surgery it became evident HM suffered from a retrograde and anterograde amnesia. HM couldn’t remember past 12 years before the surgery, and wasn’t able to acquire new semantic and episodic knowledge. Brenda Milner, a researcher that was examining his case, found out that his procedural memory was left functioning- he still remembered how to mow a lawn, and could learn to draw a star while looking in a reflection in the mirror. The retrograde amnesia retreated with time- by 1966 HM was missing about 1 year of events before the surgery. The anterograde amnesia persisted. His memory was being assessed over the course of 50 years. Milner used method triangulation- psychometric and cognitive tests, as well as interviews with family members, HM and the observation of his behaviour. While taking a test, he could remember numbers if he would constantly repeat them to himself, but few minutes after the test, he wouldn’t even remember he’d taken one.

The Milner’s research significantly contributed to understanding of the brain functions, and helped to develop understanding about the localization of a function of the brain, as well as its compartmentalization. The hippocampus was found to be responsible for the transfer of short-term memory to long-term memory. Without it, HM was unable to create new ones. Furthermore, the medial temporal lobe as well as hippocampus are responsible for recall and organization of already created long-term memories, which explains HM’s reversable retrograde amnesia. 

Milner’s case study of HM meets high ethical standards of consent, confidentiality and protection from harm. The study was longitudinal, taking over 50 years. During that time, HM’s real name wasn’t known to the public until his death. Milner acquired consents for HM’s study from him, as well as his family. Concerning factor, however, is whether HM was really able to give a conscious consent, given his condition. Understanding the true extent and length of the research done by Milner might’ve been impossible to HM, as he wasn’t able to remember any of the studies, after they’d taken place. His brain was extensively studied for the majority of his life, which raises some concerns about the reduction of harm. Spending such an extensive time under expertise could’ve hindered HM’s abilities of focusing on personal goals. Furthermore, not all of his memory was shut. He was able to create new, procedural memories. He retrieved his amygdala, which leads to believe his emotional memory might’ve also been partially functioning. Therefore, it’s uncertain whether procedures performed on HM made him more self-conscious than he’d be normally be.  This, however, is significantly overweighted by the previously mentioned advantages of Milner’s research.

To conclude, ethical concerns in biological approach are not always objectively measurable. Although a study might meet ethical standards, it does not guarantee that all of the side effects were considered. It’s impossible for researchers to completely eliminate the risks, however it’s highly important participants are well informed and aware of the procedure of the experiment, are protected from both psychological and physical harm, their data is appropriately debriefed, and that they are not deceived. Newcommer and HM studies both make sure the consent of the participants is given, however HM study might be concerning in regards to the participant’s ability to grant it. Studies rise concerns about the protection from harm. Newcommer participants health could’ve been negatively affected as a result of a mood change and memory impairment, while HM could’ve experienced some psychological stress as a result of being aware of his situation. Newcommer study participants were also debriefed after taking the experiment. The anonymity of participants of the both of the studies was appropriately kept anonymous.

Popov, Alexey, et al.  IB Diploma Programme: Psychology Course Companion . 2nd ed., Oxford University Press, 2017. 

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HM and his Hippocampus

Travis Dixon October 22, 2016 Uncategorized

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Here’s an example SAQ that explains HM’s Case Study .

You can find more information here…

Here’s a wonderfully melo-dramatic re-creation video that tells the story of HM from before his operation to the conclusions of the case study on HM:

[youtube=http://www.youtube.com/watch?v=7mvx-mAUJL8&w=560&h=315]

Here is a link to a website that you might find interesting. It is to do with the role of the hypothalamus, which we looked at with Herethington and Ranson’s study on rats (this is useful information in the course companion to cover when discussing ethical considerations related to studies at the biological level of analysis).

http://blog.seattlepi.com/hormonallychallenged/2012/10/11/your-hypothalamus%E2%80%94the-boss-of-your-body/

Here’s a fascinating video with stories about neuroplasticity and the power of your brain.

Here’s a video about Brenda Milner, the neuropsychologist who studied HM for years.

Travis Dixon is an IB Psychology teacher, author, workshop leader, examiner and IA moderator.

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Milner carried out a classic case study of the role of the hippocampus on memory formation. You can use this study for the following content in the biological approach:Research methods used in the cognitive approach.Techniques used to study the brain.Localization of function.In addition, for the cognitive approach, you can use this study to address models of memory - particularly, the evaluation of the Multi-Store Model.

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Psychology Sorted

Psychology for all, ethics in psychological research.

A very common question that is asked is to ‘Discuss ethical considerations with research into….’ A very common, but incorrect, way to answer this is to think of the most unethical study you can, and blast away at it! Instead, re-read the question, which is asking about ethical consideration s, in other words ‘What do researchers need to consider when planning to research this topic?

Organisations such as the British Psychological Society and the American Psychological Association issue ethical guidelines as a set of principles designed to help researchers be confident that their research has been conducted with integrity, and with the protection and dignity of their participants at the forefront of their research design. Such guidelines include:

Informed consent

Confidentiality of data/information

Anonymity of participants

Causing no psychological or physical harm to participants

Allowing withdrawal of self and data at any time in the process

Supplying a full debriefing after the procedure

Let us take the example of HM: many people like to think of this as a prime example of research that had an issue with informed consent . Surely poor HM, with his severely damaged memory was incapable of consenting to psychological research, be it the cognitive interviews of Brenda Milner (the surgeon’s graduate student); the MRI scans of Suzanne Corkin (Milner’s graduate student); or even the post-mortem freezing and slicing of his brain by  Jacopo Annese, director of the Brain Observatory in San Diego?

While it is true that HM could not give informed consent, his mother gave consent for him, until in 1974 his mother and he moved in with Lillian Herrick, whose first husband was related to HM’s mother. Mrs. Herrick is described as caring for HM until 1980, when she was diagnosed with advanced cancer, and HM was admitted to a nursing home founded by her brother.

In 1991, the Probate Court in Windsor Locks, Connecticut, appointed Mrs. Herrick’s son, Tom Mooney, as HM’s conservator (person able to give consent). This family took an active interest in helping HM and his mother, and was able to help place him in the nursing home that took care of him. It looks as if for 11-12 years, there was no proper informed consent, and in the book written by the surgeon’s grandson recently, there are some controversial points made about this.

So, any discussion of informed consent has to be nuanced: guardians do have the right to give consent, and guardians, when they are not parents or close relatives, are appointed by the courts.

His anonymity was preserved throughout his life, with his name only revealed in the New York Times obituary after his death in 2008 at the age of 82. The writings of Milner and Corkin give us a picture of a man who was treated with respect and whose intelligence remained intact after his anterograde memory was destroyed.

It is impossible to know if any psychological harm was caused to HM during the extensive interviews and scanning, as he wouldn’t have been able to remember them a few moments after they had occurred. Though as he was cared for by people who seemed to have liked and respected him, it is to be hoped that he suffered no harm.

This is the sort of approach that needs to be taken. It is also relevant for the brain scanning and interviewing of people suffering from Alzheimer’s disease or those who are too young to give consent for themselves.

When answering a question on ethical considerations, choose two and discuss them in detail, with reference to a relevant study – and it can be an ethical study, as all you need to do is discuss how the researchers planned the study and conducted it, right up to publishing findings, in order to preserve the integrity and anonymity of the participants.

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Key ethical issues encountered during COVID-19 research: a thematic analysis of perspectives from South African research ethics committees

Theresa burgess.

1 Centre for Medical Ethics and Law, WHO Collaborating Centre for Bioethics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

2 Division of Physiotherapy, Department of Health and Rehabilitation Sciences, Faculty of Health Sciences, University of Cape Town, F45 Old Main Building, Groote Schuur Hospital, Anzio Road, Observatory, Cape Town, 7725 South Africa

Stuart Rennie

3 Department of Social Medicine, UNC Bioethics Center, University of North Carolina, Chapel Hill, USA

Keymanthri Moodley

Associated data.

The datasets generated and analysed during the current study are not publicly available due to consent not being obtained for public sharing. However, data may be available from the corresponding author on reasonable request and with permission of the Stellenbosch University Health Research Ethics Committee and the University of Cape Town, Faculty of Health Sciences Human Research Ethics Committee.

The COVID-19 pandemic presents significant challenges to research ethics committees (RECs) in balancing urgency of review of COVID-19 research with careful consideration of risks and benefits. In the African context, RECs are further challenged by historical mistrust of research and potential impacts on COVID-19 related research participation, as well as the need to facilitate equitable access to effective treatments or vaccines for COVID-19. In South Africa, an absent National Health Research Ethics Council (NHREC) also left RECs without national guidance for a significant duration of the COVID-19 pandemic. We conducted a qualitative descriptive study that explored the perspectives and experiences of RECs regarding the ethical challenges of COVID-19 research in South Africa.

We conducted in-depth interviews with 21 REC chairpersons or members from seven RECs at large academic health institutions across South Africa that were actively involved in the review of COVID-19 related research from January to April 2021. In-depth interviews were conducted remotely via Zoom. Interviews (60–125 min) were conducted in English using an in-depth interview guide, until data saturation was achieved. Audio-recordings were transcribed verbatim and field notes were converted into data documents. Line-by-line coding of transcripts was performed, and data were organised into themes and sub-themes. An inductive approach to thematic analysis was used to analyse data.

Five main themes were identified, namely: rapidly evolving research ethics landscape, extreme vulnerability of research participants, unique challenges to informed consent, challenges to community engagement during COVID-19, and overlapping research ethics and public health equity issues. Sub-themes were identified for each main theme.

Conclusions

Numerous, significant ethical complexities and challenges were identified by South African REC members in the review of COVID-19 related research. While RECs are resilient and adaptable, reviewer and REC member fatigue were major concerns. The numerous ethical issues identified also highlight the need for research ethics teaching and training, especially in informed consent, as well as the urgent requirement for the development of national guidelines for research ethics during public health emergencies. Further, comparative analysis between different countries is needed to develop the discourse around African RECs and COVID-19 research ethics issues.

The SARS-CoV-2 pandemic has resulted in millions of infections and deaths across the world. South Africa has the highest infection rate in Africa [ 1 ]. However, the number of COVID-19 deaths may be underestimated, based on excess death numbers recorded by the South African Medical Research Council [ 2 ]. The initial absence of effective treatments or vaccines resulted in drastic public health measures, including national lockdowns, social distancing and contact tracing, to reduce transmission [ 3 ]. These measures caused significant socio-economic disruption, particularly on the African continent [ 4 ]. The COVID-19 pandemic also disproportionately affected a broad range of vulnerable populations and compounded existing health inequities [ 5 ]. In South Africa, the COVID-19 pandemic was also associated with increases in mental health issues, gender-based violence, and substance abuse [ 2 ]. There was also limited access to health care, particularly for antenatal and postnatal services, HIV and TB testing and treatment, and non-communicable diseases such as cancer [ 6 ].

Research is a critical aspect of the response to public health emergencies. Research groups globally have focussed research efforts on COVID-19 disease pathogenesis and management strategies, including therapeutics and vaccines, and numerous clinical trials have been conducted [ 7 ]. While clinical research trials during COVID-19 have predominantly focussed on vaccine trials and drug development or repurposing, such as Chloroquine and Ivermectin, the African Academy of Sciences recommended that research to inform preventative and primary healthcare measures should form an essential component of Africa’s COVID-19 research agenda [ 8 ].

In the early phases of the pandemic, it was proposed that the urgency to produce effective COVID-19 therapeutics and vaccines warranted the consideration of potential modifications to the current elements of the research process. Some suggested modifications included omitting animal studies before Phase I trials in humans, or omitting Phase II trials [ 9 , 10 ]. Previous disease outbreaks and public health emergencies [ 11 – 14 ] have also highlighted the challenges of balancing the need to uphold research ethics principles and standards with the need to produce valuable knowledge quickly [ 15 ]. Several international guidelines have also emphasised the importance of maintaining ethics standards for ethical research during public health emergencies and disease outbreaks [ 16 – 20 ] and the requirement for rapid, robust research ethics review during public health emergencies [ 21 – 23 ].

However, despite the availability of international guidelines to facilitate ethical review and oversight of research during the COVID-19 pandemic [ 24 , 25 ], there is limited understanding of the structural, social, and contextual factors that may have impacted on the preparedness of research ethics committees (RECs) in Africa to operationalise or implement these guidelines, especially during the height of the pandemic. In addition, RECs in South Africa also needed to consider issues such as historical mistrust of research seen in social media, with hashtags such as #AfricansAreNotGuineaPigs, and to ensure equitable access to effective treatments or vaccines for COVID-19 [ 4 ].

In South Africa, the National Health Act 61 of 2003 (NHA) provides statutory authority for governance of health research and the necessary research ethics regulatory infrastructure [ 26 , 27 ]. The National Health Research Ethics Council (NHREC) was established in 2006 in terms of Section 72 of the NHA [ 27 ]. The main functions of the NHREC include setting norms and standards for health research and clinical trials in South Africa, to determine guidelines to facilitate best practice for RECs, and to provide oversight for RECs in South Africa [ 26 ]. Section 73 of the NHA requires every institution, health agency, and health establishment at which health research is conducted, to establish or have access to a REC that is registered with the NHREC. Only NHREC-registered RECs may review and approve health research in South Africa (NHA s 71(1)(a) read with s 73(2)) [ 26 , 27 ]. In South Africa, there are currently 46 RECs that review health research involving human participants registered with the NHREC [ 28 ].

The composition of RECs is outlined in Section 4.4 of the National Department of Health’s Ethics in Research Guidelines (2015), which emphasise that RECs should be independent, multi-disciplinary, multi-sectoral, and pluralistic. Research ethics committees are required to comprise a minimum of nine members, with representation from as many disciplines, sectors, and professions as possible, appropriate to the remit of the particular REC. The composition of RECs must include ethnically and culturally diverse members; an appropriate mix of males and females; lay persons, preferably from communities in which research is conducted; researchers who do not do human participant research; and members from other disciplines [ 26 ]. REC members are also required to undergo research ethics training at least once every three years [ 26 ].

The South African research ethics landscape was complicated by the absence of the NHREC for a significant duration of the COVID-19 pandemic. The NHREC was not re-constituted, without explanation, from November 2019 to December 2020 [ 29 , 30 ]. Therefore, South African RECs needed to independently navigate their way through the first and second waves of the COVID-19 pandemic without national research ethics guidance and oversight. It is also unclear how research ethics oversight was adapted to different emergency contexts across the country or how RECs might have differently interpreted or implemented the National Department of Health’s Ethics in Research (2015) guidelines for research during public health emergencies [ 26 ] or international guidelines for research during the COVID-19 pandemic [ 24 , 25 ]. Our research aimed to explore the perspectives and experiences of South African RECs regarding the ethical challenges of COVID-19 research in South Africa.

The study was designed as a qualitative exploration of pertinent ethical issues that arose during REC deliberations of COVID-19 related research. We conducted in-depth interviews with REC chairs and members from large health science institutions across South Africa.

We used a purposive sampling technique to identify REC chairs or members from health science institutions across South Africa. Potential participants were also identified through snowball sampling. Research ethics committee chairs and members of RECs registered with the NHREC from universities who formally train students in health science professions and conduct health research were eligible for inclusion in this study. Participants were required to have been actively involved in rapid review of COVID-19 research, including all levels of research risk, to be included in the study. We purposively identified REC chairs and members who were involved in the review of COVID-19 clinical trials, including preventative research, therapeutic trials, and vaccine studies. Participants were also required to have regularly attended REC meetings within the six-month period prior to study commencement. Potential participants were sent invitations to take part in the study via email. Diversity of representation of REC chairs and members from different health institutions across South Africa was attempted.

We contacted 31 REC chairs and members and 21 (67.7% acceptance rate) accepted an interview. The participants were based at seven universities across South Africa and all participants served as Chair or member of their institutional REC. In addition, two participants also served on two different national governmental organisation RECs, and a further two participants were also members of the REC for a national charitable foundation. Therefore, 10 RECs were represented in this study, which comprised 21.7% of all RECs (n = 46) registered with the NHREC. It is also estimated that the RECs represented in this study were responsible for over 75% of all moderate- to high-risk COVID-19 research, including candidate therapeutics research and candidate vaccine research conducted in South Africa during the study period (NHREC, personal communication, 29 November 2021).

We did not collect personal identifying information from participants to help protect confidentiality and to avoid identifying research ethics committees and institutions. Eleven participants had formal postgraduate training in bioethics, applied ethics, and research ethics. All participants had completed basic research ethics training within the three years prior to study participation. Research ethics committee chairs and members health-related qualifications and training included social science (n = 2), laboratory and medical science (n = 4), clinical specialists (n = 5), health professionals (n = 6), and members trained in professional care (for example, social work) (n = 2). The descriptive characteristics of participants are shown in Table ​ Table1 1 .

Summary of descriptive characteristics of participants (n = 21)

a denotes formal ethics qualification. All participants had undergone research ethics training in the last three years

Data collection

A clinical health professional trained in bioethics and qualitative research methods (TB) conducted the in-depth interviews with REC chairs and members. Her previous experience as a chair and deputy chair of two RECs in South Africa provided a unique opportunity to identify highly experienced REC chairs or members, many of whom have national or international profiles in research ethics and collect meaningful data.

Interviews were conducted remotely and online to maintain social distancing and reduce any potential infection risks during the COVID-19 pandemic. Interviews took place from January 2021 to March 2021 and lasted between 60 and 125 min each. Participants were asked to choose a private, convenient location for the interviews that protected the confidentiality of information shared during their interview. Interviews were conducted using Zoom, which routinely records both video and audio data. Therefore, video-recordings were deleted immediately after the interview to avoid storage of video material that could identify participants. Participants were also verbally reminded of these recording and storage arrangements prior to the commencement of the interviews. No other personal identifying information was captured. Interviews were conducted in English using an in-depth interview guide. The interview guide included questions regarding REC meetings, standard operating procedures and review processes during COVID-19, reciprocal review and harmonisation of South African REC reviews, and ethical issues associated with COVID-19 research. Interviews were conducted until data saturation was achieved. Field notes were taken during the interviews. Transcripts were password-protected and coded and were stored in the study OneDrive folder. Audio-recordings and transcripts will be stored for up to five years and will be destroyed once all study findings are published.

Recordings of the in-depth interviews were transcribed verbatim and field notes were converted into data documents. One researcher (TB) reviewed the transcripts for accuracy and completeness by comparing the audio recordings with the transcripts. Two researchers (TB and a research assistant) developed the codebook by independently coding four transcribed interviews. Line-by-line coding of transcripts was performed, and data were organised into themes and sub-themes. To improve inter-coder reliability, the coding of these interview transcripts and emerging themes were collectively discussed with the full study team (TB, SR, KM).

The coding was refined until an acceptable level of consensus and inter-coder reliability was achieved. Thereafter, two researchers coded all transcripts (TB and a research assistant). As interviews were coded, the codebook was expanded as required to ensure that novel responses were captured for analysis. Previously coded transcripts were checked to code any novel responses that had not been previously captured. An inductive approach to thematic analysis was used to analyse data. Atlas.ti (Version 6.2.28 Windows, ATLAS.ti Scientific Software Development GmbH, Berlin, Germany) was used to facilitate data analysis. During analysis, the full study team (TB, SR, KM) consulted regularly to review interpretations and discuss results.

This study was approved by the Health Research Ethics Committee at Stellenbosch University (N20/10/062_COVID-19) and the Faculty of Health Sciences Human Research Ethics Committee at the University of Cape Town (HREC REF 045/2021) and was guided by the Declaration of Helsinki’s ethical principle [ 31 ]. In addition, permissions from respective institutional gatekeepers were obtained to access potential participants from different institutions as required. All participants signed a consent form stating that they understood the nature and purpose of the research and that they agreed to their interview being recorded. All personal and institutional identifying data were removed from the interview transcripts before coding and analysis.

Our qualitative analysis revealed five main themes related to key ethical issues that arose during REC deliberations of COVID-19 related research. The themes and sub-themes are outlined in Table ​ Table2 2 .

Five main themes and related sub-themes identified during qualitative analysis

Rapidly evolving research ethics landscape

We asked participants to discuss common ethical issues identified in their REC’s discussions of COVID-19 related research. A central theme throughout the interviews was that the research ethics landscape is rapidly evolving during COVID-19 (see Table ​ Table3). 3 ). Research ethics committee chairs and members were highly cognisant of the speed at which COVID-19 evidence is emerging and the associated impact on REC decisions. The transition from ‘is there equipoise’ and the REC’s approval of research to ‘evidence of harm’ and the REC’s need to withdraw approval or place approved studies on hold was seen as a reflection of the challenges to RECs and was reported consistently by REC chairs and members across different institutions. Risk to benefit analysis was seen as a moving target, with changes in excess death rates, pandemic waves, rapidly emerging evidence, and national vaccine rollout plans all intersecting and making deliberations complex.

Quotations for the theme of ‘Rapidly evolving research ethics landscape’

In addition, the RECs ability to evaluate the robustness of evidence and how to incorporate non-peer reviewed publications and preprint manuscripts in deliberations of risk to benefit ratio and equipoise was a specific ethical concern. Many participants also identified ethical issues associated with the review of complex adaptive trial designs, standard of care, placebo use in vaccine studies, post-trial access, and benefit sharing. Potential social value and harms of COVID-19 related research were also a common ethical concern. Research ethics committee chairs and members were cognisant of a paradigm shift towards an increased focus on public health ethics in REC deliberations. Ethical issues associated with implementation trials during the COVID-19 pandemic were also highlighted.

Extreme vulnerability of research participants

The majority of participants highlighted the extreme vulnerability of individuals and communities during the pandemic broadly, and during COVID-19 related research more specifically (see Table ​ Table4). 4 ). Stigmatisation and prejudice were commonly identified social harms. The significant potential for therapeutic misconception associated with research was highlighted. Many participants commented that the fear of severe illness or death from COVID-19, particularly before effective vaccines were identified, increased the risk of therapeutic misconception. They also questioned the adequacy of informed consent processes to mitigate therapeutic misconception. Some participants were of the view that the urgency at the height of the pandemic rendered traditional considerations of therapeutic misconception irrelevant. This was countered by other participants who felt that a more rigorous approach was needed to mitigate therapeutic misconception due to significant fear, anxiety, and desperation that could unduly influence decisions to take part in research during the COVID-19 pandemic.

Quotations for the theme of ‘Extreme vulnerability of research participants’

Unique challenges to informed consent

Informed consent was identified as a key ethical challenge in the review of COVID-19 related research. Issues included procedural and pragmatic aspects of obtaining socially distanced informed consent as outlined in Table ​ Table5. 5 . Research ethics committee chairs and members highlighted the importance of understanding the reality of the clinical environment during a pandemic and what was feasibly possible in terms of socially distanced consent processes. Participants highlighted the potential effects of fear associated with COVID-19 infection, desperation for an effective vaccination or cure, and isolation from partners or family members on the validity of informed consent. Research ethics committee chairs and members also cited complexities associated with delayed consent processes and consent waivers for COVID-19 research. Participants also had divergent views on when consent waivers or delayed consent were permissible.

Quotations for the theme of ‘Unique challenges to informed consent’

Complexities of the ‘who, when, and how’ of stakeholder engagement

Interestingly, participants identified two sub-themes related to stakeholder engagement presented in Table ​ Table6 6 below. The first sub-theme was the RECs own role in stakeholder engagement. Many participants equated this to the requirement for community or lay representation in the composition of RECs, as outlined in the South African Department of Health’s Ethics in Research Guidelines (2015). The contribution of lay members to REC deliberations was generally viewed as limited or unsatisfactory. Several recommendations for improved community representation and participation in REC deliberations were made.

Quotations for the theme of ‘Complexities of the ‘who, when and how’ of stakeholder engagement’

The second sub-theme related to community or stakeholder engagement in research trial processes. Participants expressed that the urgency around research ethics review and approval of COVID-19 related research limited the potential for rigorous or authentic community/stakeholder engagement. The challenges associated with being able to delineate who represented a community and how effective community engagement could occur during COVID-19 were recognised.

Overlapping research ethics and public health equity issues

Research ethics committee chairs and members identified that, during the COVID-19 pandemic, there seemed to be a significant overlap between research ethics and public health equity issues (see Table ​ Table7). 7 ). A consistent example that was shared was the prioritisation of COVID-19 related research during the national lockdown and the halting of non-COVID related research, including therapeutic clinical trials, HIV and TB research, except for essential research visits that directly benefitted participants.

Quotations for the theme of ‘Overlapping research ethics and health equity issues’

Similarly, the prioritisation of clinical research that held therapeutic benefit during the recommencement of research during the COVID-19 pandemic also raised equity concerns. Critical social sciences and educational research was not prioritised, and many participants expressed awareness that this may have contributed to increased health-related inequities and structural social harms.

Implementation trials also raised health equity concerns among participants. Research ethics committee chairs and members were specifically challenged by emerging ethical issues related to vaccine access through participation in implementation research and the blurring of lines between research and vaccine prioritisation.

Public health emergencies such as the COVID-19 pandemic pose numerous challenges to health-related research [ 32 ]. The morbidity and mortality rates associated with COVID-19 infection and the social and economic burdens of government measures to limit infection spread contribute to widespread disruptions, distress, and uncertainties associated with the pandemic [ 33 ]. In the African context, research also often takes place in the context of historical inequities and ongoing power imbalances. People who are most disadvantaged or vulnerable, through poverty, marginalisation, or lack of access to healthcare are often disproportionately affected [ 4 , 32 , 34 ].

Emmanuel et al. [ 35 ] identified principles and benchmarks that are necessary for ethical conduct of research. These principles and benchmarks were developed to provide uniform and consistent ethical guidance and to minimise the possibilities of exploitation during multinational research. The ethical principles include collaborative partnership, social value, scientific validity, fair selection of study population, favourable risk to benefit ratio, independent review, informed consent, and respect of recruited study participants and the study population [ 35 ]. In our study, RECs consistently applied these principles in their deliberations of ethical issues in COVID-19 research. These ethical principles and benchmarks have also been identified in other studies investigating ethical challenges in pandemic or public health emergency research [ 36 – 44 ].

However, in our study, RECs were tested in their deliberations around the intersections of research ethics, public health ethics, and global health ethics that were presented by the COVID-19 pandemic and conducting research in emergency settings with national lockdowns. For example, the halting of non-COVID related research by government order raised significant public health equity issues. The stopping of non-COVID related research included therapeutic clinical trials, HIV and TB research, except for essential research visits that directly benefitted participants. South African RECs were mandated to facilitate a responsible and ethical approach to research involving human participants in the context of COVID-19. Limiting infections, preventing transmission, and protecting research participants, their communities, and research staff during the pandemic and national lockdowns were the primary considerations. Research ethics committees were also challenged to adapt quickly to changes in roll-out of the different stages of the South African Government’s COVID-19 Risk Adjustment Strategy. This was also compounded by the absence of the NHREC from November 2019 to December 2020 and resulted in RECs being left without formal national-level guidance and support from the NHREC during the critical first and second waves of the COVID-19 pandemic [ 29 , 30 ]. In addition, when non-COVID related research was permitted to resume, social sciences and educational research was not prioritised, and many participants expressed awareness that this may have contributed to increased health-related inequities and structural social harms.

It has also been recognised that the initial response that was focussed on reducing the COVID-19 death toll and limiting COVID-19 infections had a devastating collateral effect on health and research equity [ 5 ]. Social isolation and movement restriction negatively impacted on health, but also limited access to basic health needs [ 45 , 46 ]. This was compounded in the South African context, where halting of research restricted access to important ancillary health services for participants enrolled in clinical trials. In addition, with limited health and research resources, the diversion of funds and human resources to the fight against COVID-19 has resulted in disproportionate neglect of other infectious diseases such as HIV and TB [ 47 , 48 ]. These inequities point to the need for a careful and balanced approach that considers human rights protection, public health concerns, research ethics, and social measures to avoid discrimination against vulnerable populations during public health emergencies [ 5 ]. Further, RECs struggled with balancing the evaluation of risk to benefit ratios for individual participants with the urgency associated with public health emergency research, and within the broader context of global inequities in vaccine access. Rid et al. [ 49 ] emphasised that while traditional ethical principles that guide clinical research should be retained as a reference point for ethical conduct of pandemic research, accelerating the process of delivering safe and effective treatments and vaccines against COVID-19 is a moral imperative [ 49 ]. However, ethical considerations should not be confined to one-off processes of review and REC deliberations should not occur in a vacuum [ 32 ]. Wright [ 32 ] explained how research ethics issues arise through the lifecycle of research and develop from initial setting of research priorities and funding to the translation of findings into clinical practice or public health implementation. Research ethics issues are also the responsibility of multiple stakeholders in the research process and are highly dependent on context [ 32 ]. It may therefore be appropriate to consider COVID-19 pandemic research partly through a public health lens.

Willison et al. [ 50 ] developed a framework and process to guide ethical reflection on public health projects through their lifecycle, from initial planning to knowledge exchange. These include relational autonomy (individual within community), social justice, reciprocity, respect for recruited participants and communities, and concern for welfare (favourable risk to benefit ratio). This framework retains core research ethics principles of respect for persons, concern for welfare, and justice but is augmented with concepts of relational autonomy and respect for communities, the inter-relationship of individual and community welfare, solidarity, and the common good. In particular, the positive obligation to promote social justice and the importance of reciprocity in public health emergency research, when individual participants carry risk or substantial burden for the benefit of others, are emphasised in this framework [ 50 ].

Further, the Nuffield Council on Bioethics have proposed an ‘ethical compass’ of three core values, namely equal respect, fairness, and helping reduce suffering to support ethical reflection for global health research at the level of policy, as well as on the ground. They also suggest that research funders, institutions, governments, and research journals have a duty to ensure that the research they fund, support, or publish is compatible with these three core values [ 32 ]. This also broadens the responsibility and accountability for the ethical conduct of research during the COVID-19 pandemic.

However, despite the availability of international guidelines for research during public health emergencies [ 18 , 51 – 54 ], in the South African context, there was a lack of clear national guidance to operationalise important ethical considerations for research during COVID-19. For example, the absence of clear guidance to operationalise mutual recognition of ethics review resulted in RECs being underprepared to reduce duplication of effort in urgent research and in conducting rapid reviews of COVID-19 research. In addition, differences in interpretation of national guidelines regarding appropriate limitations of public health emergency research and informed consent processes by individual RECs resulted in disparate ethical reviews and differences in informed consent practices across study sites [ 29 , 55 ]. This was also compounded by the absence of the NHREC during the height of the COVID-19 pandemic, which prevented clear national ethical leadership and updated national guidelines to facilitate ethical review of COVID-19 research.

In South Africa, the absence of the NHREC also resulted in the development of a collaborative network of research ethicists during the first wave of the COVID-19 pandemic. This network was called Research Ethics Support in COVID-19 Pandemic (RESCOP) and served to provide a repository of ethics resources for public health emergencies and COVID-19, to facilitate collaboration between individual RECs in the absence of the NHREC and to develop guidance to operationalise ethics review of COVID-19 research. The RESCOP network also developed guidelines for rapid full committee review of COVID-19 treatment and prevention trials [ 29 ]. These guidelines were developed to align with, and supplement, the National Department of Health’s Ethics in Research Guidelines (2015) [ 26 ] and were compliant with the subsequent WHO guidance for rapid review of COVID-19 research [ 54 ]. The RESCOP rapid review guidelines emphasised the high vulnerability of research participants during the COVID-19 pandemic but cautioned RECs against being overly restrictive and advised that ethical approval processes should occur very rapidly but without compromising the rigour of ethics review. However, while rapid review processes for individual RECs were implemented effectively, efforts to harmonise research ethics review and implement reciprocal review did not work well. This highlighted the need for clear national research ethics guidance to facilitate effective reciprocal review processes, and to ensure the preparedness of RECs for future public health emergencies [ 29 ].

In our study, concerns regarding informed consent processes were one of the main ethical considerations identified by RECs in their evaluation of COVID-19 research. Consent issues included procedural and pragmatic aspects of obtaining socially distanced informed consent, the realities of obtaining informed consent on the ground in challenging and often fraught clinical environments, and what was feasibly possible in terms of socially distanced consent processes. Factors impacting on the voluntariness and validity of informed consent processes, including fear associated with COVID-19 infection, desperation for an effective vaccination or cure, and isolation from partners or family members were consistently identified. Research ethics committees also cited complexities associated with delayed consent processes and consent waivers for COVID-19 research. These informed consent issues identified in our study resonate with other literature regarding issues with consent processed during the COVID-19 pandemic [ 27 , 55 – 61 ]. Largent et al. [ 59 ] highlight how the COVID-19 pandemic has influenced practicability determinations of informed consent. They suggest that, as the pandemic continues, further guidance from bioethicists and regulators is needed to find the best way forward for informed consent approaches during COVID-19 [ 59 ].

Community engagement was another important ethical issue identified by South African RECs. In accordance with national research ethics guidelines, health researchers in South Africa are encouraged to engage stakeholders in their research [ 62 ]. However, community engagement has been complicated in the context of the COVID-19 pandemic, where decisions regarding lockdowns and physical distancing were made rapidly, with little or no time to engage local communities, especially around research. Saxena et al. [ 63 ] recommend increased community engagement in pre-pandemic or inter-pandemic times and consider that this approach might increase public trust [ 63 ]. Research ethics committees have a role to play in shaping researchers’ practices and involving local communities [ 62 ], and this is of particular importance in research during public health emergencies.

The COVID-19 pandemic has highlighted how uncertainty and risk of misinformation can influence community perceptions of research and vaccine hesitancy [ 64 ]. Community engagement is essential to build trust in research and show respect to communities [ 25 , 34 , 65 ]. This approach should also include good information management. However, models to practically implement authentic community engagement regarding COVID-19 research in the context of the pandemic are lacking. Further research is needed to explore RECs own role in community engagement and how to practically execute effective and appropriate community engagement during the COVID-19 pandemic.

Issues of equity and access were some of the critical ethical issues identified by RECs. As stated above, these debates extended beyond traditional standard of care debates within the South African context, and that RECs identified both public health and global health ethics issues that impacted on the conduct of COVID-19 vaccine trials in South Africa. A key issue was the use of placebo groups in vaccine trials in low- and middle-income countries (LMICs) that have limited or no vaccine access. A World Health Organisation expert group identified conditions for the ethical acceptability of a placebo group at the onset of a vaccine [ 66 ]. Some researchers have controversially suggested that there is an opportunity to continue to conduct randomised vaccine trials with a placebo group in LMICs where COVID-19 vaccine access is limited due to cost or a lack of infrastructure to store and distribute vaccines, as research trials will increase the overall number of vaccinated individuals [ 67 , 68 ], although the percentage of national populations involved in research trials is likely to be very low. Beneficence and local stakeholder engagement are considered as important ethical principles for the ongoing use of placebo groups in LMICs [ 69 ]. However, considering the strong results for efficacy of several approved vaccines and participants’ contributions to research, the ongoing justification for placebo groups, even in LMICs, is limited [ 49 ].

Strengths and limitations

While we were able to interview many of the research ethics leaders from seven of the large academic institutions across South Africa, the sample represents a small subset of REC members in South Africa. In addition, we only interviewed each participant once. Given the rapidly evolving nature of COVID-19 research ethics landscape, longitudinal data collection would have allowed us to explore emerging issues in more depth, and to understand changes in REC’s perceptions and experiences over time. However, despite these limitations to generalisability, our findings provide a strong base for future empirical research to further understand ethical challenges in COVID-19 research and their impact on REC deliberations. These findings can also be translated to inform and support the development of ethical policy and guidance for public health emergency research in the African context.

Our findings provide unique insights into the perspectives and experiences of RECs regarding the ethical challenges of COVID-19 research in South Africa. Further comparative analysis between different countries is needed to develop the discourse around African RECs and COVID-19 research ethics issues. The numerous ethical issues identified also highlight the need for research ethics teaching and training, especially in informed consent, as well as the urgent requirement for the development of national guidelines for research ethics during public health emergencies.

Acknowledgements

The authors would like to thank the study participants for their time and generosity in sharing their knowledge, insights, and experiences. We also would like to thank Ms Grethe Geldenhuys and Ms Siti Kabanda for their assistance in transcribing and coding interviews. We thank Prof Marc Blockman for his mentorship, input, and support.

Abbreviations

Author contributions.

TB conceived of the study, conducted and analysed the interviews and wrote the manuscript. KM conceived of the study, assisted with analysis of interviews and provided supervision of the study. SR assisted with analysis of interviews and provided supervision of the study. All authors read and approved the final manuscript.

We gratefully acknowledge funding support from an NIH Fogarty Grant: D43 TW01511-01- Advancing Research Ethics Training in Southern Africa (ARESA): Leadership Program and National Human Genome Research Institute of National Institutes of Health Award number UO1HG008222 and the World Health Organisation, Ethics Support in COVID-19.

Availability of data and materials

Declarations.

This study was approved by the Health Research Ethics Committee at Stellenbosch University (N20/10/062_COVID-19) and the Faculty of Health Sciences Human Research Ethics Committee at the University of Cape Town (HREC REF 045/2021) and was guided by the Declaration of Helsinki’s ethical principles. All participants provided written informed consent prior to taking part in this study.

Not applicable.

The authors declare that they have no competing interests.

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Contributor Information

Theresa Burgess, Email: [email protected] .

Stuart Rennie, Email: ude.cnu.dem@einner_trauts .

Keymanthri Moodley, Email: az.ca.nus@mk .