THREE FRONTAL LOBE GUYS John F. Rice, MD, FACR January 9, 2007 My topic this evening dates back to the Twentieth Century. I will discuss the professional and personal lives of three amazing individuals, all trained in the fields of Neurology and Psychiatry, and their quests to understand and treat diseases which, in large part, involve the frontal lobes of the brain. I will not be recounting the contrived lunacy of The Three Stooges; nor will I contribute to the pseudointellectual adoration of Iglesias, Domingo and Pavarotti, The Three Tenors. Much as I admire and emulate The Three Pickers-Earl Scruggs, Doc Watson and Ricky Skaggs, they have little to interest a medical history audience. Rather, my Three Guys are veritable Giants: Egas Moniz, Walter J. Freeman and Spafford Ackerly. In their professional careers these three physicians faced the misery and despair of patients locked away in the great Asylums of America and Europe in the first half of the Twentieth Century. Psychiatry was at that time emerging as a clinical discipline, but it offered only a limited treatment algorithm, resulting in ever expanding State Institutions that, in the worst cases, more closely resembled a veterinary facility than a hospital. In the late Nineteenth and early Twentieth Century, European and American scientists had made important observations about the function of the brain in psychiatric disease. The German Friedrich Golz in 1890 showed a calming effect in dogs that had undergone temporal lobe cortical ablation. In 1892 Gottlieb Burckhardt, in Switzerland, performed craniotomies on six patients with schizophrenia, removing areas of brain that he thought related to the patients’ varied symptoms; some behavior alteration was observed, particularly in the two patients who died. Burckhardt was universally criticized for this in vivo experimentation. Experimental work on chimpanzees by Fulton and Jacobsen at Yale in the 1930s demonstrated that aggressive animals could be made manageable, yet still retain memory and other higher functions, after frontal lobe interruptions. Based in part on this early experience, Dr. Antonio Egas Moniz of Lisbon developed an interest in a surgical procedure to alter the behavior of patients with intractable, unmanageable psychoneurotic symptoms. Moniz is a fascinating character, diplomat, bon vivant, and esteemed as a founder of my field of medicine, Neuroradiology. He was born Antonio Caetano de Abreu Freire, in 1874. As a young man he adopted the name “Egas Moniz”, to commemorate a 12th Century Portuguese patriot, sort of a Portuguese “El Cid”. Apart from his subsequent productive medical career Moniz was also an involved public citizen-member of the National Parliament in Portugal, Minister to Spain, Minister of Foreign Affairs, and signatory of the Treaty of Versailles for Portugal in 1919. Trained as a neurologist, Moniz studied brain injuries from World War I, and also wrote a text on the Neurology of Human Sexuality. In 1927 he reported his work with Dr. Almeida Lima, a neurosurgeon, on the x-ray technique to visualize the cerebrovascular circulation. For this signal work he received a nomination for the Nobel Prize in 1928. Moniz was appointed Dean of the Lisbon medical faculty, and he began to focus on psychiatric disease. In 1935 he and Lima began working on “leucotomy”, a procedure to interrupt white matter tracts in the prefrontal region. Moniz referred to these procedures as “psychosurgery”, introducing that word to the neurosurgery vocabulary. Prior to his first leucotomy efforts Moniz had attended the Second International Neurological Congress in London, in 1935. At that important meeting, also attended by the American Dr. Walter Freeman, a breakout session on frontal lobe disorders was held. There was much discussion of the Fulton/Jacobsen monkey work, as well as speculation about the famous traumatic frontal lobe amputation of poor Phineas Gage, reported in 1847. Additional presentations of the recent resections of massive frontal lobe meningiomas by Wilder Penfield (his sister!) and Walter Dandy (Joe A-patient of Dr. Richard Brickner at the Neurological Institute of New York) were made. In that same year Dr. Ackerly reported at the American Psychiatric Association meeting in Washington, D.C. of his patient (operated on by Innominate Founder Dr. Glen Spurling) who had lost three-fourths of her prefrontal lobe tissue after removal of a large olfactory groove meningioma. The clinical resolutions of these subjects were somewhat similar postoperatively: loss of self-restraint and ability for complex thought, impulsiveness, poor judgment, distractibility, and a notable decrease in aggression and temper tantrums in the famous monkeys. Although Moniz did not cite the Congress as significant in his decision to pursue prefrontal leucotomy, it is a fact that later that same year, November 1935, Moniz and Lima performed their first frontal leucotomy, utilizing an intracerebral injection of ethanol, on an inmate of the Bombarda Asylum suffering from agitated depression. Moniz pronounced her cured; however, she never left the asylum. Following the ethanol experience Lima and Moniz began direct physical interruption of frontal lobe white matter with a surgical instrument, the “leucotome”, sometimes making several approaches per side through burr-hole craniotomies. The lesions generated were significant. Moniz reported his initial results in Paris in 1936, and the encouraging findings stimulated international interest in the procedure. In 1937, Moniz reported on his further experience in the American Journal of Psychiatry. His summary is a monument to scientific arrogance and naivete: Following this exposition I do not wish to make any comment since the facts speak for themselves. These were hospital patients who were well studied and well followed. The recoveries have been maintained. I cannot believe that the recoveries can be explained upon simple coincidence. Prefrontal leucotomy is a simple operation, always safe, which may prove to be an effective surgical treatment in certain cases of mental disorder. In 1939 Moniz was attacked by a former patient, and this injury, in addition to his advanced gout, caused him to curtail his medical practice and lobotomy work. He now had, however, an evangelical advocate in the person of American neurologist Walter J. Freeman, of George Washington University. The two men corresponded for many years, until Moniz’ death in 1955. Moniz was awarded the Nobel Prize in 1949 for his work on “Prefrontal Leucotomy”. His more notable and earlier work in cerebral angiography was passed on by the Nobel committee. Walter Jackson Freeman,Jr., born in 1895, was the son and grandson of physicians. Maternal grandfather William Williams Keen was an eminent Philadelphia surgeon. He was involved in the clandestine surgical procedures performed on then sitting President Grover Cleveland, who suffered from an oral malignancy. Keen, who was also interested in what later became known as neurosurgery, had reported on his technique for tapping the cerebral ventricles to reduce elevated intracranial pressure at the same Berlin meeting in which Gottlieb Burckhardt had described his brief, and reviled, experience with cranial surgery for schizophrenia. Keen’s son in law, Walter Jackson Freeman Sr., was an otolaryngologist with his office in the home. A humorless, distant father, he discouraged his children from a career in medicine. As a young boy Walter Jr. developed generalized lymphadenopathy, and grandfather Dr. Keen operated to remove the larger cervical nodes, producing damage to the left spinal accessory nerve, and giving the youngster a head tilt and shoulder depression seen in this photograph. Nevertheless, Walter Jr. was very fond of his distinguished grandfather, and imprinted strongly on him. Young Walter attended Yale as an undergraduate, and did his medical schooling at Penn, where he developed an interest in neuropathology under the influence of Charles Frazier. Following his neurology residency he traveled in Europe as a sort of visiting fellow in Paris and Rome, quite an experience for a young man in the years between world wars. Upon Walter’s return, his influential grandfather had found an opening for the young neuroscientist at St. Elizabeth’s Hospital, in Washington, D.C. A federal institution for the insane, St. Elizabeth’s is now the home of failed presidential assassin John Hinckley. Freeman was to be senior medical officer in charge of laboratories, and he assumed that post in July 1924. At St. Elizabeth’s Freeman was primarily a neuropathologist, and he performed a large number of autopsies in futile search for brain abnormalities in the insane patient population. He also functioned as a psychiatrist clinically, although the 4,300 bed facility was largely a domiciliary. Like others at the hospital, Freeman began a private practice. In addition he became affiliated with local hospitals and medical schools, such as the U. S. Naval Medical School, and Georgetown University, primarily as an autopsy demonstrator. At nearby George Washington University his eccentric and theatrical teaching abilities were much appreciated by the students, and in 1926 he was appointed Professor and Chairman of the Department of Neurology at GWU. The dynamic GWU professor maintained his association with Georgetown as a graduate student, earning a Ph.D. in 1931 for studies of biometrics in psychiatry. At this same time he was working on his first book: Neuropathology:The Anatomic Foundation of Nervous Diseases, which was published in 1933. Freeman eventually left St. Elizabeth’s and devoted himself to GWU, where he remained until 1954. The energetic academic neurologist was becoming an influential figure locally and nationally. In 1934 he was part of the group which established certification by the American Board of Psychiatry and Neurology. He also worked to enhance the teaching environment at GWU. One of his priorities was to obtain a neurosurgeon, preferably a Harvey Cushing trainee who would devote himself to neurological surgery. The persistent, flamboyant and eccentric W. J. Freeman found his mark in James Winston Watts, and Watts joined the GWU faculty in 1935.