User:Rvdizon/Derek Denny-Brown (neurologist)

Derek Denny-Brown (neurologist)

Pre-America Years
Denny-Brown was born in Christchurch, New Zealand in 1901. He earned his M.B. (Bachelor of Medicine) and Ch.B. (Bachelor of Surgery) degrees from the University of Otago in Dunedin, New Zealand in 1924. He then applied for and received a Beit Fellowship to study in the laboratory of the world-renowned physiologist, Sir Charles Sherrington, at Oxford.

While at Oxford, Denny-Brown observed and defined the distinctive properties of red and white muscles, validated Sherrington's theoretical concept of the motor unit, and developed the technique of antidromic stimulation for the analysis of motoneuron responses. By the time he completed his tenure at Oxford, Denny-Brown had established himself as a major contributor to physiology. His experience with Sherrington was enhanced by the presence of other students who would later also become world-renowned scientists: S. Cooper, E.G.T. Liddell, R.S. Creed, J.C. Eccles and R. Granit.

Upon completing his fellowship, Denny-Brown returned to clinical medicine, and for the rest of his life applied his skills as a scientist to determine the mechanisms underlying diverse types of neurological diseases. In 1928 he became resident medical officer at the National Hospital, Queen Square, London, which at that time was the leading center for the developing medical specialty of neurology. In 1931 Denny-Brown Sylvia Summerhayes and they were married in 1937, having four sons together. Denny-Brown served as Lecturer at the National Hospital from 1931 to 1939 and as a Registrar at Queen Square and Guy's Hospital from 1931 to 1935. From 1935 to 1941 he held the positions of Assistant Physician, National Hospital, and Neurologist, St. Bartholomew's Hospital, London. Despite his time-consuming clinical responsibilities during this period, Denny-Brown began to apply his research training to neurologic problems. He conducted what he referred to as one of his most "intimate" collaborations with his colleague, Graeme Robertson, studying the reflexes involved in micturition using themselves as subjects. Denny-Brown also introduced the electromyograph as a clinical tool and initiated the procedure of muscle biopsy as a means of seeking a direct tissue diagnosis of neuromuscular diseases. In 1936 Denny-Brown received a Rockefeller Fellowship to study with John Fulton at Yale University. He chose to work with Fulton on the basis of their acquaintance at Oxford. Denny-Brown worked with Fulton and a neurosurgeon, Harry Botterell, studying the effects of ablating portions of the precentral cerebral cortex in primates.

When Denny-Brown returned to England in 1937, he resumed his clinical practice and teaching at the National Hospital, Queen Square. In 1939 he published an edited compilation of many of Sherrington's papers, which contained in particular those that had become unavailable. In 1939 Denny-Brown received an offer that would eventually foster the development in the United States of the British approach to clinical neurology. The offer was for the position of Professor of Neurology at Harvard Medical School and Director of Harvard's Neurological Unit at the Boston City Hospital (BCH). The Denny-Browns sailed to Boston to consider the position, and after meeting with Harvard's president, James Conant, accepted it. Before Denny-Brown could assume this position, Britain declared war on Germany and he was called to active status in the Royal Army Medical Corps. Denny-Brown informed Conant that he could not accept the position, and Conant replied that he would hold the position open for a limited period. Between 1939 and 1941, Denny-Brown pursued a productive line of research on concussion at a newly formed head-injury hospital at Oxford. In 1941, Conant met with Sir Winston Churchill and requested that Denny-Brown be released from active military duty to assume his responsibilities in Boston. Churchill granted the request, and Denny-Brown along with his wife and two young sons moved to Boston. In 1945, owing to the shortage of physicians in the Royal Army Medical Corps, Denny-Brown was recalled to service, and was assigned to organize the neurological services in India and Burma. In 1946 he returned to Boston to stay, receiving the appointment of the James Jackson Putnam Professor of Neurology, a position that he held until his retirement in 1967.

The Training Program
The development of a neurological unit at BCH had been endowed by the Rockefeller Foundation in 1925 for the purpose of advancing academic clinical neurology in the United States based on both clinical and laboratory investigation. Denny-Brown was ideally suited to this goal of reviving the influence of neurology in this country, which had declined due to the rapid advancement of neurosurgery and psychiatry during the 1930s. Once in Boston, Denny-Brown began accepting house officers in neurology selected principally from internal medicine programs, and developed a neuropathology program. A weekly "brain-cutting" conference was instituted that became an essential component of neurological training at BCH, and rapidly at other centers of training in neurology. In seeking to bring medical neurology more closely into an alliance with internal medicine, where Denny-Brown believed it belonged, in 1947 his service began accepting rotating house officers from each of the three university medical services at the hospital: Harvard, Tufts, and Boston Universities. Denny-Brown trained these physicians in addition to the three to five neurology house officers he recruited annually. Denny-Brown also eliminated the tradition of house officers rotating through neurosurgery. In 1946 he first published a small manual intended to instruct his trainees, Handbook of Neurological Examination and Case Recording. This handbook became a classic that generations of medical students and house officers in neurology and neurosurgery found extremely valuable, and which is still used. Denny-Brown's reputation as a teacher, clinician and investigator grew rapidly, and soon the neurological unit became a mecca for students, house officers, fellows, and well-established neurological clinicians and neuroscience investigators. In 1952 he presented the Shattuck Lecture of the Massachusetts Medical Society. This lecture, "The changing pattern of neurologic medicine," and its subsequent publication in the New England Journal of Medicine, had enormous influence. He reiterated the independence of neurology in training and research, convincing many formerly dissenting professors of psychiatry, medicine and neurosurgery to recognize the new programs in neurologic medicine and the practitioners of this branch of medicine. Denny-Brown's influence grew during the 1950s so that by the early 1960s, of 41 Departments of Neurology in the United States, 19 had chairmen who had received a major part of their training under his direction at the Neurological Unit. Denny-Brown was a dedicated member of the American Neurological Association (ANA), which is the oldest neurological society in the world and the senior society for academic neurologists. He was president in 1959-60, received the prestigious Jacoby award in 1968, and served as the Bennett lecturer in 1975. He also was elected president of the American Association of Neuropathologists despite his disapproval of the separation of that body from the ANA.

Denny-Brown or one of his close colleagues usually presented research findings from his laboratory at the annual meetings of the ANA. Denny-Brown also frequently discussed other presentations at these meetings, and had a formidable presence. He was usually highly critical and incisive, and at times devastatingly frank. Similarly, he did not tolerate sloppy or faulty work when he made clinical rounds at BCH, and many house officers, particularly rotating medical residents, were terrified to present patients to him. Nevertheless, after thoroughly scolding a house officer for incompetent, careless, or incomplete work, he might later show unexpected kindness towards the chastised officer. Despite their initial fear, Denny-Brown's trainees quickly learned to appreciate and respect this great teacher. Five of his former trainees wrote laudatory obituaries of him, which appeared in Annals of Neurology, Neurology, Archives of Neurology, Journal of the Neurological Sciences, and the Canadian Journal of Neurological Sciences. Denny-Brown taught his students more than neurology. He was a compulsively self-sufficient man, and his students also received training in plumbing, carpentry, photography and electronics. Rather than purchasing equipment, he would build his own, e.g., he built an electromyograph. Presumably, this self-reliance developed from his tenure in Sherrington's spartan laboratory and his extensive experience prior to federal funding of research. Denny-Brown was also blind to race and money. All patients were treated equally and Denny-Brown's lack of interest in achieving wealth was well-known.

Denny-Brown was masterful in teaching his students how to approach a problem, whether it be clinical or scientific. His approach was to define the problem, observe the phenomenon without measuring devices if possible, then decide how best to record and measure the phenomenon. If necessary, he constructed a new piece of equipment for the measurements. He considered meticulously detailed records essential for either clinical or experimental work. Upon arrival, all new neurology residents who entered the BCH program received from the other residents a document, "Pointers for Assistant Residents," that had been written by some of the senior residents. The document provided guidelines concerning proper behavior during the residency program and concluded, "You are privileged to be working in the only portion of medieval England ever transported to this side of the Atlantic. Should you ever neglect to follow one of the pieces of advice and come to grief thereby, after you have finished licking your wounds, stop and ask yourself, 'Who is the reason why I am here?' and it may seem worthwhile after all. It does to us."

The Research Program
Once he had assumed the directorship at BCH, Denny-Brown immediately began investigating problems he had encountered during World War II. He published a series of papers on the effects of closed head injuries, peripheral nerve disorders, and vestibular disturbances. One of his major early accomplishments while at BCH was his work in Wilson's disease with L.L. Uzman. In 1948 they described the occurrence of amino aciduria in Wilson's disease. Subsequently, with Huntington Porter, Denny-Brown demonstrated that treatment with the chelating agent BAL (British anti-lewisite) can significantly improve the neurologic disorders of patients with Wilson's disease. For an interval of several years before the introduction of penicillamine, therapy with BAL provided symptomatic relief for many patients with Wilson's disease and became a standard treatment. On the 10th floor of the medical building of BCH were the basic research laboratories and an animal facility that housed experimental animals, primarily monkeys and cats. For his investigations, Denny-Brown stocked this facility with macaque monkeys and conducted a total of 12 distinctive series of experiments on about 450 monkeys during his tenure at BCH and his later years at the New England Regional Primate Center. In these experiments he used primates as models of many of the disorders he observed in patients. Although he did publish some lengthy articles detailing the results of these studies, Denny-Brown mainly assimilated the results of these experiments into two classic books, The Basal Ganglia and Their Relation to Disorders of Movement, and The Cerebral Control of Movement. A summary of his work was published in 1974 in a book by Orthello R. Langworthy entitled, The Sensory Control of Posture and Movement. In addition to his experimental work, Denny-Brown published numerous articles based on his clinical work. He published original papers on cerebrovascular disease, subacute necrotizing encephalopathy, myoclonus, head injury, seizure disorders, multiple sclerosis, muscular dystrophy, nervous system changes associated with porphyria, myokymia, motion sickness, electromyography, spasticity, poliomyelitis, hereditary sensory radicular neuropathy, muscle atrophy, meningitis, apraxia, thiamine deficiency, parkinsonism, cachexia and pain. His seminal contributions to so many fields of neurology when considered together constitute a remarkable achievement. To a large extent, this was his goal, as he considered himself a pathfinder, not one who works out minute details.

Retirement
In 1967 Denny-Brown retired from BCH and became the James Jackson Putnam Professor Emeritus at Harvard Medical School. With his retirement from active practice, management of a neurology service and clinical teaching, he had more time available and initiated yet another productive period of research at the New England Regional Primate Research Center. During this period he and his collaborators investigated the size of the receptive fields supplied by dorsal roots and demonstrated that the dermatomal distribution is not fixed, but can be greatly influenced by presynaptic inhibition. He also investigated the functions of the descending trigeminal tract in the mechanisms of intersegmental sensory facilitation, the role of the tract of Lissauer in sensory transmission, and studied postural and movement disorders that result from lesions of the cerebral cortex and basal ganglia in the infant primate. Throughout his career, Denny-Brown traveled extensively in the United States and abroad presenting lectures and grand rounds, most notably the highly prestigious Croonian and Sherrington lectures in England. In 1957 he returned to New Zealand and was the stimulus for the formation of the Neurological Association of New Zealand. He was made an honorary fellow in that organization and received an honorary doctorate from his alma mater, the University of Otago, during its centennial celebrations in 1969. Denny-Brown "retired" again from his position at the New England Regional Primate Center in 1972 to become a Fogarty Scholar in Residence at the National Institutes of Health in Bethesda, Maryland. The Denny-Browns enjoyed their year at the NIH in the company of elder scholars from other disciplines. All the scholars lived in the same house, and shared meals and intellectual discourse. During the period from 1972 until his death owing to multiple myeloma on April 20, 1981, Denny-Brown continued to analyze data he had accumulated for years and to publish the findings. Despite the intense physical pain he felt from this disease he also continued to attend meetings, presenting a paper on the tegmental mechanism for conjugate eye movement at the 1980 ANA meeting and one on the pioneers of Boston neurology at the one-hundredth anniversary of the Boston Society of Psychiatry and Neurology that same year.

Legacy
Denny-Brown made an enormous contribution to American neurology. He was instrumental in guiding neurology into becoming an independent and highly respected field of medicine. He trained over 300 neurologists, many of whom continued into careers in academic medicine. His research contributed greatly to understanding many neurological problems and continues to influence contemporary scientists. The citation that accompanied the honorary degree of Doctor of Laws awarded to him by Wayne State University read, "an inspiring and effective director of research projects, he has trained many of the world's leading scientists in modern neurological techniques; by his penetrating insights and brilliant deductions, he has broadened the concepts and pioneered in exploring new techniques in neurologicial research. This work has laid the foundation for an advancement of knowledge rarely matched in the career of any scientist in modern medicine."