September 15

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

patient-hm_luke-dittrichThe patient, H.M. as he has been widely known within the neuropsychological literature for more than five decades was Henry Molaison whose identity was made public only after his death in 2008.

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.

walter-freemanNeurosurgeons used chisels, ice picks to pry open skulls of living humans
In the early era of brain mapping, when little was known about the function of specific brain regions, a doctor who identified the location of a function “could secure lasting glory.” Dittrich speculates that his grandfather become frustrated with the limitations of operating on mentally impaired patients. What could removing a portion of the brain in someone who wasn’t “normal” possibly tell him about the role of that area in someone who was healthy?

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
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 Molaison
Henry Molaison

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
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)

Dr. Suzanne Corkin
Dr. Suzanne Corkin

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?”

Luke Dittrich
Luke Dittrich

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.

  1. 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)

  1. 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.… She 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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