Stories from psychiatry’s past: dissecting the brain

An example of a freezing microtome. Invented in 1881, this type of microtome used ice and salt to freeze specimens.
(Credit: Science Museum, London. Wellcome Images.)

The study of the brain is today more often associated with scanners than with scalpels. But dissecting the brain remains an important part of neurological research, and contemporary methods have more in common with nineteenth century practice than you might think. Jen Wallis writes a history of slicing and splicing. 

In December 2009, technicians at the Brain Observatory at the University of California, San Diego mechanically sliced a frozen brain into 2,401 paper thin sections over a 53-hour session. This undertaking was part of ‘Project HM’, which is examining the brain of a single patient, Henry Gustav Molaison.

Henry Molaison had brain surgery in the 1950s in an attempt to stop his epileptic seizures, which had become increasingly debilitating. After the surgery, however, he developed amnesia, forgetting that he had eaten lunch an hour earlier, or reading a book repeatedly without recognising its contents. Throughout his life he was studied extensively for what his case revealed about memory loss and memory modification, and – via Project HM – he continues to inform our knowledge of the brain.

A video of the 2009 sectioning depicts a strange fusion of the mechanical and the artistic. Henry’s brain, embedded in a large block of frozen gelatin, passes slowly underneath a large blade, before a waiting technician delicately removes the resulting section with a damp brush. It is at once a repetitive and fascinating process, and one that would have captivated doctors and pathologists of the 19^th century. Whilst the techniques of Project HM are distinctly modern, the motivations behind it mirror those of early neurological research.

By the late 1800s, the specialist journal Brain had been founded, Paul Broca had linked frontal lobe lesions to language disorder, and the National Hospital for Diseases of the Nervous System (Queen Square) had been established. The fabric of the brain seemed to hold the key to solving the mystery of mental illness, and medical literature of the period is replete with references to examination methods. Brain sections were preserved for teaching purposes, with larger asylums maintaining ‘pathological museums’ of specimens, and sections were often photographed to illustrate articles in which structural anomalies were linked to the patient’s symptoms during life.

Dissecting the brain effectively, so as to make it more easily readable, was a central concern for the asylum investigator. It was also a task that involved significant labour. ‘Defibering’, for example, entailed scraping away the brain tissue with a fine needle. Similarly, freehand sectioning with a knife or razorblade was a task that required both skill and patience. In ‘The brain under the knife’, Heini Hakosalo emphasised the importance of serial sectioning techniques in changing our view of the brain. Advancements such as the development of cytoarchitectonics – examining the cellular structure of tissue – for instance, would have been impossible without the serial sectioning of tissue.

Hakosalo argues that the microtome was pivotal to these developments. The machine in the Project HM video is a large-scale example of a modern microtome, a device used to cut thin sections of tissue (not just the brain) for examination. Early hand microtomes, however, were, writes Hakosalo, ‘little more than a metal tube that [held] the embedded specimen and whose edges support[ed] the knife or the razor’; they struggled to deal with large pieces of tissue such as a whole brain.

Throughout the 19^th century, there were a number of attempts to modify and improve upon this model and microtomes became increasingly complex. Amongst the various models were several that used freezing as a means of hardening tissue for sectioning. These ‘freezing microtomes’ typically used either ice and salt or ether to freeze tissue specimens, and greatly reduced the time it took to produce sections. William Bevan Lewis, of the West Riding Asylum, claimed that his model allowed frozen sections to be cut within 20 to 30 seconds. In contrast, brains hardened using chemical methods might take weeks to prepare. Edwin Goodall, in The Microscopical Examination of the Human Brain, wrote that hardening a whole brain with Müller’s fluid (a potassium-based solution) took ‘some 3 months’ and that ‘12 months and more [was] not detrimental’!

For men like Bevan Lewis and Goodall, the sectioning of the whole brain represented a pinnacle of achievement. It was a goal many aspired to, to the extent that, as Brian Bracegirdle notes in his History of Microtechnique, the drive to complete the dissection of an entire organ sometimes compromised the quality of the resulting sections.

One can only imagine the awe these men would have felt at a microtome on the scale of that used at the Brain Observatory. In principle, though, the instrument has changed little since the 19^th century. The brain was then, as it remains now, an object that exerted remarkable influence on the world around it, its substance determining methods of examination and directing the development of medical technologies.

You can read more about Patient HM, in this historical case study which accompanies the latest edition of Big Picture magazine: ‘Inside the Brain’.