For several years in the mid-20th century, West Virginia was at the forefront of efforts to popularize a now discredited form of brain surgery.

In 1935, Portuguese neurologist Egas Moniz pioneered the leucotomy, a radical form of brain surgery designed to quell anxiety and mood disturbance in otherwise untreatable patients. The following year, American neurologist Walter Freeman, working with surgeon James Watts, adopted the practice for use in the United States. Over the next decade, the pair performed hundreds of the procedures, now renamed lobotomy by Freeman, who quickly became a fervent proponent of the operation. In 1946, Freeman adapted a variation of the surgery called the transorbital lobotomy. The transorbital technique involved entering the brain from the front by inserting an orbitoclast (colloquially known as an ice pick, which it resembled) under the upper eye lid, rapping it sharply with a mallet to break through the skull into the brain cavity, and moving it back and forth to sever the connections between the thinking and emotional areas of the brain.

Simplifying the procedure was a major advantage, given Freeman's intention of reducing the overcrowding of mental health hospitals and the corresponding financial burden that many states faced. Transorbital lobotomies could be completed quickly and did not, in Freeman's mind, require surgical training or an operating room. By teaching the transorbital protocols to doctors and psychiatrists, Freeman hoped to advance his ultimate goal of ridding the world of mental illness.

The first lobotomy in West Virginia was performed in January 1948. Until 1952, the state was average in the number of surgeries performed. In the summer of that year, however, the West Virginia Lobotomy Project was launched by Freeman, with the consent of the State Board of Control, which oversaw mental health protocols at that time. The project's purpose was to examine the effectiveness of lobotomy by comparing lobotomized patients with matched individuals who had not been lobotomized. Why West Virginians were targeted is not clear, but it was likely a combination of an available patient population, a sympathetic and financially burdened state government, proximity to Freeman's home base in Washington, D.C., and prohibitions by other states limiting the operation's scope.

Between 1952 and 1955, 787 West Virginians were lobotomized at the four state mental hospitals of the era: Huntington, Spencer, Lakin, and Weston. Freeman travelled back and forth from Washington to do most or perhaps all of them. More than 100 persons had had the surgery before 1952, meaning approximately 900 state residents in total endured the procedure, the largest number per capita of any U.S. state. Many of the patients never consented to the surgery. The procedure's effectiveness was doubtful, despite Freeman's claims to the contrary. Lobotomy was palliative, sometimes making otherwise uncontrollable patients docile to the point that they could be released from the hospital but with corresponding blunting of volition, abstraction and personality. The introduction of psychotropic medications in the mid 1950's, plus longitudinal studies disputing the claims of the operation's success, led to the end of the West Virginia Lobotomy Project in 1955.