Science's memory man

The man who revolutionised the way we understand the brain continues to provide insights in the workings of human memory two years after his death, says Mo Costandi
Henry Gustav Molaison
Henry Gustav Molaison, whose brain operation led to a new field in neuroscience. Photograph: Suzanne Corkin

In late August, 1953, a 27-year-old man was admitted to Hartford Hospital in Hartford, Connecticut for an operation that not only dramatically changed his life, but also revolutionised the study of the human brain and led to the emergence of the field we now call cognitive neuropsychology.

The patient had been suffering from epileptic seizures for more than 15 years. The seizures occurred so frequently, and were so severe, that he was unable lead a normal life.

The cause of his epilepsy was unknown. It may have been the accident that occurred in his childhood. At the age of 9, he was knocked down by a cyclist, banging his head and losing consciousness briefly. But he also had a family history of epilepsy – three cousins on his father's side of the family also suffered from it.

Regardless of its cause, his epilepsy had become so debilitating that he was ready to try just about anything to have it treated. He had been prescribed the maximum dosage of the strongest available anti-convulsant, but it wasn't working. So when William Beecher Scoville, a neurosurgeon at the Hartford Hospital, suggested a radical experimental procedure, he agreed.

The operation was performed on 1 September 1953, as a last ditch effort to rid him of his debilitating seizures. It involved the surgical removal of two small structures, called the hippocampus and amygdala, from both hemispheres of his brain.

Little did either the surgeon or his patient know how profound the effects of the operation would be. Although it stopped his seizures almost entirely, he was left with severe anterograde amnesia, or an inability to form any new memories. He had not become a different person after the operation, so much as lost certain aspects of his sense of self-identity altogether.

Soon after the operation, Brenda Milner administered to him a comprehensive battery of memory and intelligence tests. The first paper describing the results, published with Scoville in 1957, introduced the patient to the medical community by his initials, HM, and eventually revolutionised memory research.

At the time, investigators knew little about the neural substrates of memory. Decades earlier, in a series of now-famous experiments, Karl Lashley taught rats to find their way through a maze then tried to erase what he called "the memory trace" by lesioning different parts of the cerebral cortex. No matter what part of their cortex had been damaged, his rats could still find their way through the maze, and Lashley concluded that memory was distributed throughout the brain rather than localised in any specific location.

Milner's early work with HM showed without a doubt that the hippocampus is essential for memory. Her tests also showed that he could retain small amounts of information for short periods of time. This suggested that memory consisted of at least two distinct components, and led Richard Atkinson and Richard Schiffrin to propose their influential Dual Memory Model, according to which memory consists of separate short-term and long-term stores.

Milner, working with her PhD student Suzanne Corkin, further showed that HM retained the ability to learn and remember simple motor skills, revealing yet another distinct form of memory. Corkin – who is now a professor of behavioural neuroscience at MIT – subsequently found that HM could draw a relatively detailed map of his house, and suggested this was because the regions surrounding the hippocampus were left intact.

HM died on 2 December 2008, aged 82, and his full name was revealed to be Henry Gustav Molaison. In the 55 years between his operation and his death, Molaison became the best known case study in the history of neuroscience and psychology. His case is to be found in every textbook, and is known to every student of these disciplines.

Scoville and Milner's 1957 paper describing his amnesia has been cited over than 1,700 times since its publication. To say that he has contributed more to memory research than any other individual would be no exaggeration. "Sadly, however," Corkin wrote in a 2002 article, "he will remain unaware of his fame and of the impact that his participation in research has had on scientific and medical communities internationally".

Furthermore, the hippocampus is now the most intensively studied region of the brain. In thousands of labs around the world, researchers dissect slices of hippocampal tissue from the brains of rats and mice, and impale the neurons with microelectrodes in order to elucidate the cellular mechanisms of memory.

Current thinking holds that memory is dependent upon a process called long-term potentiation, whereby the connections between hippocampal neurons are strengthened. This mechanism was first postulated in the late 1940s by Donald Hebb, Milner's PhD supervisor. (Hebb studied for own his PhD under Wilder Penfield, the pioneering neurosurgeon who developed the technique Scoville used to identify the damaged tissue in HM's brain.

Even after his death, HM will continue to provide further insights into memory. Immediately after he died, his brain was removed and carefully transported to the Brain Observatory at the University of California, San Diego, where director Jacopo Annese supervised the sectioning of the organ into thousands of hair-thin slices.

And this is but the first phase of an on-going project. Now that HM's brain has been sectioned, it will be stained in various ways to reveal the cellular architecture. The data will be put online, and made freely available for memory researchers to use.

Molaison will be remembered by non-scientists, too, as the inspiration for the lead character in Christopher Nolan's 2000 film Memento, which remains as one of the few accurate cinematic portrayals of amnesia.

Further reading:

Scoville, WB & Milner, B (1957). Loss of Recent Memory After Bilateral Hippocampal Lesions. Journal of Neurology, Neurosurgery and Psychiatry 20: 11-21. (Click here for pdf format)