At first he thought that this would be a fairly simple task, but as he researched the literature he discovered a situation different from that which he anticipated. He found that it was not feasible to write a comprehensive work on the subject within a ealistic time period, primarily because of the massive amount of literature that would have to be reviewed. In his "Notes from the History of Leprosy" (1) he states that at the time there were some 18,000 references on the subject. He also quoted a remark attributed to Armoire Hansen in 1901 to the effect that "There is already too much literature on leprosy." And after "Do Skinned" undertaking many hundreds more references have been added to the literature, thus compounding the problem in writing about the history of this illness an illness which with some exceptions is referred to as Hansen's disease in the following article. Also, this article in part emphasizes the American and more specifically the Carville historical perspective of HD.

Historical events evoke varying degrees of interest, and indeed fascinate some. To others, history may evoke little or no interest. The history of diseases can also be interesting. In the case of Hansen's disease (HD), it is evident that considerable interest does exist, most of which is a genuine desire to learn about the disease. Certainly, many of us can learn from the past. The history of HD can help us to better understand it, and can even help us to better understand specific aspects, such as its epidemiology. And, there is much to be gained from accounts of past successes, failures, and mistakes.

The past tells us that those afflicted with HD or thought to be, have been inhumanely treated in many parts of the world over many centuries. Even today, the disease is often regarded in a different light than all other ailments. Examples of this include inaccurate and unfair descriptions of the disease in various movies, novels, other publications and statements, and deplorable references to "leprosy" and "lepers" which imply that the disease and those affected by it should be avoided or shunned. Other regrettable and offensive language is often applied in a different context. One example is the use of the term "moral leper." Others include statements made by some persons suffering from the Acquired Immune Deficiency Syndrome (AIDS) to the effect that they were being treated as though they had "leprosy."

History, both past and recent, tells us of such happenings as the burning of all personal effects of patients, and sometimes their houses; the removal of uninfected children from school; expulsion of patients from their families and society, divorce, the loss of friends, and dismissal from work. History tells us about people who suffered terrible wrongs even though the disease was under excellent control and noncommunicable, and that such treatment often was received by persons whose disease was totally arrested decades earlier. History also tells us that once a diagnosis of Hansen's disease, and especially "leprosy" is made, most people carry the diagnosis with them until the day they die. Unfortunately, even after death the stigma can persist.

During the Middle Ages there existed such events as the "Leper Masses" - and subsequent declaration that the afflicted one was officially dead. There was the forced use of bells or warning clappers, the wearing of distinctive garments, and banishment into the countryside. Worst of all, it is most probable that many persons with leprosy" have been executed in various parts of the world, both in the distant past and during relatively recent years.

Other examples of discrimination and mistreatment occurring perhaps this very day will become part of tomorrow's history. Hopefully, it will not be too long before such misguided behavior will indeed be history, not current events.

Hansen's disease is sometimes referred to as the oldest disease known to affect humans. There is no basis for such a statement because it is impossible to determine which disease came first or when or where it emerged. Legionnaire's disease is an example of an illness that historians 1,000 years hence should be able to discuss with some degree of certainty when and where it was first encountered, but even then there could be controversy.

It is known that HD has existed for many centuries, but it is not known where or when it first developed. It is, of course, possible that it may have started in more than one area of the world at roughly the same time. Ancient writings from India, China, and the Middle East suggest that the disease did exist in these regions during those times. This is especially true of India and China. In India, what some experts regard as a description of the disease as we know it today was mentioned as Kushtia in the Vedas, written ca 1400 BC; however, others doubt that this work actually describes it.

The great Indian leprologist Dharmendra (2) and many others are certain that a clear account of the clinical signs and treatment of HD is contained in the Sushrata Samhita written ca. 600 BC. In China a disciple of Confucius was said to have died from it about 500 BC, but the references to this incident contained in the Analects are not convincing. The Nei Chi, presumably written by Huang Ti, describes signs which could well have represented HD. He mentions loss of eyebrows, nodules, ulcerations, and numbness (1). The date of this work is unknown, but is most often mentioned as probably being written ca. 500 BC. An authentic description found in the "Complete Secret Remedies" by Hua To, a Chinese surgeon who was born about 190 AD. He mentions skin with no sensation, white spots, red spots, ulcerations of the feet, loss of eyebrows, blindness, deformed lips, and hoarseness (1).

Turning to Greece and the Middle East, some historians speculate that the soldiers of the Persian conquerors Darius and Xerxes introduced the disease into Greece during the fifth century BC, and that the troops of Alexander the Great may have brought the disease from India to Egypt about a century later. Some scholars believe that works of Aristotle in ca 345 BC and those of Hippocrates, who preceded him, described the disease, but the consensus of HD experts is that probably neither man had knowledge of the disease.

Translations of the Bible from Hebrew to Greek, ca. 300 BC, have resulted in a great deal of confusion and are responsible for much of the stigma attached to leprosy that still exists today. Biblical accounts of leprosy in Leviticus employed the Hebrew word tsaraath, which was translated into Greek as lepra, which word then evolved into leprosy. It is widely conceded, however, that biblical descriptions of leprosy do not resemble the disease as we know it today (3).

The above accounts, as well as many others not mentioned here, do not tell us where Hansen's disease was first described with certainty. Probably this will never be known. A frequently quoted reference relative to ancient times is the description of a clay jar by Yoeli (4), which date to 1411-1314 BC, thought to be the period of the Exodus. The molding of the jar suggests the leonine faces of Hansen's disease. If indeed it was, it is probable that the disease was introduced into Canaan by the Israelites. However, a variety of grotesque moldings were commonly made at that time, and the jar certainly could represent some other condition or someone's imagination. If indeed HD did exist, it would have been regarded as unclean, and such a jar, which would normally have been used for drinking water or for grain, would probably not have, for religious or esthetic reasons, been molded into such a likeness. Thus, there is no clear evidence that Hansen's disease existed in the Middle East in those early days, although there is a good possibility that it did for at least several centuries BC.

Hansen's disease may have been introduced into Italy in 62 BC by Pompey's soldiers, and later the Roman conquests may have spread it widely in Europe, as very possibly did the Crusades. The first accurate descriptions of the disease in Europe were written by Aretaeus the Cappadocian, ca 150 AD. He referred to it as elephantiasis. Aretaeus (5) describes large nodules and ulcers of the cheeks, chin, fingers, and knees, as well as loss or absorption of fingers and toes; and he states that the disease was not fatal. This suggests that HD was introduced into the Mediterranean countries of Europe at an earlier date, perhaps centuries earlier. Galen, at about the same time, also referred to a similar disease, writing primarily about the condition as it existed in what is now Germany.

The disease was apparently quite prevalent in Europe between 1000 and 1400 AD. Lazar houses numbered in the hundreds, probably in the thousands, but these houses did not exist necessarily to enforce isolation. General Sir William MacArthur (6) indicates that rather strict rules of conformity existed that had to be followed for the patient to remain. In essence, one followed the rules of the house or was asked to leave.

No doubt many people placed in these homes did not have Hansen's disease, but skeletal examinations by Do Miller-Christensen in Denmark suggest that at least during the Middle Ages, a high percentage of people in lazar houses actually did have the disease, the major finding being the loss of the anterior nasal spine and absorption of the alveolar process of the maxilla. (7). Otherwise, many persons who had the disease probably never knew it, nor did anyone else, considering the diagnostic problems in those early days.

Of fascination to many persons are the large numbers of paintings and other art work depicting both biblical and contemporary leprosy which emerged, especially from Europe, during the Middle Ages. Although many of the works did not depict obvious anifestations of the disease, enough of them did to convince anyone but the most skeptical that the disease tended to be widespread in Europe during the Middle Ages (8).

Why the disease subsequently faded in Europe is not known, but possibly was in part the result of the great plagues which killed millions of persons, especially the already ill. However, this period was followed by an improvement in the standard of living, and this one factor may be most responsible for its decline.

Hansen's disease in endemic form apparently disappeared from England about the year 1800, but it is still found to a low degree in Spain, Portugal, the Baltic region, European Russia, Turkey, Italy, and Greece. In the mid-1800s Norway reported some 3,000 cases, but later the disease virtually disappeared (9).

The disease is thought to have been brought to the Western Hemisphere by the sailors of Columbus and was further spread during later explorations and by immigrants from Europe and other areas. Slaves from West Africa added to the problem. The situation was similar for both North and South America. Explorers and immigrants also spread the disease to the islands of the Pacific.

Thousands of historical events have been related to Hansen's disease, some more important than others, but it is not possible to rank them all in the true order of their importance or to achieve anything resembling a consensus. However, there are four milestones which most persons knowledgeable about the disease deem of great importance. The first of these was the discovery by Do G Armoire Hansen of Norway in 1873 of the bacillus which causes leprosy (10). This microorganism was later to be classified as Mycobacterium leprae. Next was the initial use in 1941 of sulfone therapy in the form of promin by Do Guy Faget, of Carville, and the report in 1943 of its dramatic beneficial effects (11). It was this study which initiated the "modern era" of the treatment of HD. Then in 1960 Do Charles Shepard of the Centers for Disease Control in Atlanta reported that the mouse foot pad supported the multiplication of M. leprae (12). This was the first successful cultivation of M. leprae in any medium, and it provided a means whereby numerous studies of the bacterium and drugs to treat it could be conducted in the laboratory.

There followed in 1968 the inoculation of armadillos with M. leprae by Do Waldemar Kirchheimer of Carville and Do Eleanor Storrs of the Gulf South Research Institute in New Iberia, Louisiana. They demonstrated, as described in their 1971 report, that the nine-banded armadillo is highly susceptible to developing disseminated leprosy after being inoculated (13). The enormous multiplication of bacilli in these animals made it possible to prepare the amount of vaccines necessary to conduct the large-scale vaccine trials now in progress in various parts of the world.

(Other important accomplishments and events are most worthy of note, but with apologies for the omissions the majority cannot be listed herein. They include the works of Mitsuda, Dharmendra, and Fernandez with lepromin, a skin injectable material prepared from M. leprae. Their studies led to a better understanding of some of the immunological aspects of HD, to a means of helping to classify, the disease, and to one of the criteria for identifying M. leprae. Also important was Binford's work with golden hamsters which suggested that these animals might be susceptible to developing leprosy (14); Rees' studies involving thymectomized mice which provided for greater multiplication of M. leprae than did the standard mouse (15); Stanley Browne's work with clofazimine (B663) in Africa (16) which eventually resulted in this dye substance becoming one of the drugs of choice for the treatment of HD; and Sheskin's discovery that thalidomide is a truly effective drug for the treatment of severe erythema nodosum leprosum (ENL) (17) an often serious inflammatory reaction associated with lepromatous HD which can involve skin, peripheral nerve and eyes.

More recently, a variety of studies have been performed with rifampin, which have proved invaluable to modern treatment. However, coupled with the highly beneficial effect of the drug was the ominous report of rifampin resistant HD by Jacobson and Hastings (18); this finding, when added to the serious problem of sulfone resistance magnified the need to continue the search for new drugs. Paul Brand's accomplishments in the field of rehabilitation deserve special mention as do Robert Cochrane's monumental efforts in almost every phase of Hansen's disease. The textbook edited by Chochrane and Davey in 1964 remains a classic covering a wide range of material (19). The recently published (1985) textbook entitled "Leprosy", edited by Robert Hastings is an excellent current source of information.

Accounts of HD in Hawaii, beginning about the middle of the last century, which include the isolation settlements of Molokai and the work of Father Damien and others who followed has proven to be of considerable interest to many readers, as has the history of the beginnings and founding of the "Louisiana Leper Home" at Carville in 1894, and of what is now the Gillis W Long Hansen's Disease Center which also had its orgins at Carville when the US Public Health Service assumed responsibility for the facility in 1921. From then until about 1960 most newly diagnosed HD patients in the continental US were required to be admitted to Carville. Thereafter admissions became voluntary and as the numbers of patients increased primarily as a result of refugee arrivals from Southeast Asia, increasing numbers of these patients were treated in Public Health Service general hospitals and clinics. The closure of the PHS hospitals and clinics, except for Carville, in 1981 led immediately to the creation of the PHS supported Regional HD Program which provides care in the areas of the largest concentrations of HD patients throughout the country.

Except for the latter development, much of the information about HD in the US, especially as it relates to Carville, is contained in the book Alone No Longer by Stanley Stein (20) who was also the founder in 1941 of The Star, the Carville patient-produced magazine, which remains one of the most widely read HD publications in the world. The history of this magazine, and of Stanley Stein and of Louis Boudreaux who succeeded him as editor is a lesson in dedication, accomplishment, and courage.

Historians have already listed the HD work of a number of others as being of great value (21). Examples, looking toward our close neighbor to the south, were the efforts of Do Rafael Lucio (1819-1886) after whom a special type of HD is named, and those of Do Fernando Latapi (1902-1989) who for half a century was considered to be the dean of Mexican leprologists. Regretfully, the accomplishments of so many others, not only in Mexico, but throughout the world cannot be given the mention they deserve in this article, but their place in history is secure (21).

Some recent contributions which, are approaching the status of considerable historical interest and significance, are the discovery of naturally occurring armadillo leprosy by Walsh and his associates (22), which finding has become of increasing interest and importance with the discovery that the disease not only exists in wild armadillos, but may affect a high percentage of such animals in Louisiana and Texas (23); and that the disease may have been transmitted to these animals in at least several instances by a thorn stick, thus suggesting the possibility of M. leprae existing in such places as the soil (24). Transmission of HD from armadillos to humans is now a real and disturbing possibility.

Other significant works involve studies with monkeys and chimpanzees being conducted at the Delta Regional Primate Research Center, Covington, Louisiana in collaboration with the Armed Forces Institute of Pathology (25).

Many future events will most probably be added to the history of HD, and as we enter the last decade of this century, we can now include the apparent early excellent results of multidrug therapy (MDT) as recommended by the World Health Organization, and later this decade the results of ongoing vaccine trials.

This decade probably will also see the development of a reliable and specific early diagnostic test for HD; and hopefully the realization of one of research's most elusive goals -- the cultivation of M. leprae in the laboratory on artificial media.

We can predict that the next century will see the elimination of Hansen's disease - one of the world's major public health problems - and some years later, when serious disability related to sensory loss caused by the disease has also been eliminated, the final chapters on the history of HD can then be written.