DR. GEORGE HUNTINGTON
(1850-1916)

Huntington was born in the U.S. and was trained here in medicine. His interest in hereditary chorea began in 1871 and he wrote and presented his paper on this in 1872. He always acknowledges that his grandfather and father had kindled his interest in chorea. He spent a lifetime in this specific medical infirmity but still worked as a general practitioner in medicine. He was never on a medical faculty nor did he do any other research but he will be remembered as making the most lucid and accurate description of this illness.

On what must have been a chilly winter day, February 15, 1872, Dr. Huntington, a young family practitioner of the small Ohio River city of Pomeroy, Ohio, traveled over the bleak countryside five miles to the larger town of Middleport, Ohio to address the local medical society, composed of physicians of sparsely populated Meigs and Mason Counties. His brief, uniformly anecdotal and entirely unreferrenced address, not suffering publication delay, was put eight weeks later in the Medical and Surgical Reporter of Philadelphia (v 26, no. 15, April 13, 1872). This has become one of the classical descriptions of neurological disease. George Huntington dealt with hereditary chorea as a reminiscence of his childhood spent on the eastern extremity of Long Island (New York), where, as the son and grandson of physicians, he recalled patients from his father's practice. The hereditary chorea, as he called it, was a rare but terrible disease. Its essential features, tersely noted by Dr. Huntington in three short paragraphs, included a "hereditary nature," a "tendency toward insanity" and "its manifestation as a grave disease in adult life." He also commented on the grotesque nature of associated abnormal movements and the lack of knowledge of both the cause and cure of the disorder.

George Huntington published his paper while only one year out of medical school (Columbia University, 1871) but his written observations of patients with "that disease" probably went back to his boyhood. In his original manuscript of the 1872 paper, his father penciled notes and suggestions which were incorporated into the finished version. Of this writing, William Osler stated that "In the history of medicine, there are few instances in which a disease has been more accurately, more graphically or more briefly described." Yet Dr. George Huntington was no academician; he never even held a demi-professorship. He was no researcher; he never sought after a grant or performed an experiment. His authorship was limited only to a couple of papers, the first medical classic and the second thirty years later, an invited honor of his first work by the New York Neurological Society.

Dr. Huntington did not much care for Ohio and "the West." He returned to Duchess County, New York, in 1874 and practiced there, taking care of the sick, enjoying his wife, family, music and hunting and his patients until his death at the age of 66 years. He was an exceptionally handsome man, and was described as one of good manners, patience, and charm. Dr. Russell DeJong of the University of Michigan is to be thanked for his life-long avocation of culling and publishing information about the life and times of Dr. Huntington the man.

George Huntington's paper, however, gave rise to a great interest in the origins of the disease now bearing his name. Its clear hereditary nature, and the established fact that the condition is rarely if ever sporadic led quickly to searches for the original Huntington disease person or community. The most famous, interesting and quite possibly misleading of these efforts was led by Vessie, who in 1932 suggested that the disorder may have originated in Bures, a small Suffolk village in England. Choreics from this locale were sent from England, probably with the aid of paid witch hunters, to the Massachusetts Colony where their disease and social discord arising from it are adequately recorded in a continuous variety of historic records. Fanning out through New England and later Connecticut, females in family lines became victims of the New England Witch Hunts, led by two then recent graduates of the Harvard School of Divinity, the Reverends Cotton Mather and Samuel Paris. These men and their followers believed that the genetically-afflicted likes of the Mercy Disbrough, the famous Groton witch, were possessed by the devil and in their involuntary throes, doing a parody of Christ upon the Cross, an act rewarded with the dismal pageantry of public immolation.

Huntington chorea is unlikely to be of origin in a single clone. While Nichols, Wilkes (or Wilkie) and Jeffers, the shipmates of the Winthrop fleet, may be responsible for many American cases, the disease has been confirmed in all races, and from widely flung places about the globe. In all places the diseases must be reviewed outside its medical context and seen in terms of its social and individually human effects. A touching work in this regard has been provided by Joe Klein in Woody Guthrie: A Life (Knopf, 1980).

The genetic nature and generally adult onset of this terrible disease led to more than a century of attempts to identify those persons at risk to develop, and hence to pass on the dominant disorder. Provocative studies, such as the easy precipitation of choreoathetosis by the administration of moderate amounts of L-dopa have now largely been given up.

In 1983 Gusella, Wexler, Coneally and their colleagues reported the discovery of a polymorphic DNA marker on the fourth human chromosome predictably linked to Huntington disease. A decade later a precise, novel gene was identified at the 4p16.3 gene site which contained a trinucleotide repeat (CAG repeat) of variable but abnormal length. The CAG repetition at this site is specifically related to Huntington disease and to the protein "huntingdin" whose role, still not entirely clear, is fundamental to the cellular-metabolic basis of the neurologic disorder.

The 4p16.3 gene locus is amenable to laboratory analysis and has led to the availability of highly reliable, diagnostic, predictive and exclusionary test for Huntington: The presence of an abnormal length CAG repeat at that site means Huntington disease, presently symptomatic or not. DNA analysis of this gene site has also been used in prenatal diagnosis.

These tests represent tremendous advances in understanding Huntington disease and predicting it and diagnosing it. However these tests are not without their moral, ethical, and legal dilemmas. Huntington disease has still not yielded up the secrets as to its precise cause. Unhappily there is still no existing capacity to treat a person whose Huntington disease is unmasked by premature discovery. Hopefully newer methods of biochemical investigation, immunogenetic discovery and derivative therapy will counter these remaining difficulties.