History of Johne's Disease

• Before 1910
• 1910-1930
• 1930-1950
• 1950-1970
• 1970-1990
• 1990-Present

Before 1910

Pre-Johne's disease

As early as 1826, a chronic debilitating intestinal disease of cattle was recognized which did not have the characteristics or etiology of any currently known disorder. However, it was not until 1894 that it was recognized as an infectious disease with a unique etiology (cause).

The discovery by Johne and Frothingham

October 23, 1894, in the Oldenburg region of Germany, a farmer purchased a cow that failed to produce milk or gain weight satisfactorily. A local veterinarian by the name of Herr Frederick Harmes examined the cow and, noting the diarrhea and weight loss (Guernsey with clinical signs, 276.9K), suspected intestinal tuberculosis, however, the cow tested negative by the tuberculin skin test. The cow died the following spring, and Dr. Harmes sent its intestines, stomach, and omentum for examination to the Veterinary Pathology Unit in Dresden. There the tissues were examined by Dr. H.A. Johne (photograph, 276.9K) and Dr. L. Frothingham, a visiting scientist from the Pathology Unit in Boston, Massachusetts. They noted the thickened intestinal mucosa (Gross pathology, thickened intestine, 219.7K) and mesenteric lymph nodes, and on histologic examination, found an intestinal wall heavily infiltrated with leukocytes and epithelioid cells and occasional giant cells. Using an acid-fast stain, abundant acid-fast (red staining) bacteria were seen throughout the inflamed tissues. Although the organisms resembled those that caused tuberculosis, they failed to cause disease after being injected into guinea pigs. Johne and Frothingham concluded that the disease observed in the cow was caused by the bacterium that causes tuberculosis in birds (Mycobacterium avium) and, in recognition of the pathological similarity to intestinal tuberculosis (normally caused by the bacterium that causes tuberculosis in cattle, Mycobacterium bovis), proposed the name pseudotuberculous enteritis for the disease.

1900-1910

By the early 1900's, pseudotuberculous enteritis was well recognized as a new disease and one that was widespread. Scientists proposed a variety of alternative names for the disease, such as paratuberculosis and hypertrophic enteritis. In the Annual Report for 1906 of the Principal of the Royal Veterinary College, J. McFadyean coined the term "Johne's disease". Most publications since then have used either Johne's disease or paratuberculosis to name the disease.

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1910 - 1930

The 1910's witnessed many discoveries about Johne's disease. In Denmark, O. Bang discovered that animals with Johne's disease responded weakly or not at all to intradermal injection of antigens prepared from the tubercle bacillus (Mycobacterium bovis), but responded well to avian tuberculin (antigens prepared from Mycobacterium avium). On the basis of this observation, Bang suggested that avian tuberculin could be used for diagnostic testing of animals. This was confirmed a year later in England by G.P. Male. Thus, even before the bacterium that caused Johne's disease was isolated by laboratory culture of the organism, it was recognized to be related to the bacterium that caused tuberculosis in birds. The difference was that the cause of avian tuberculosis could be grown on laboratory culture media while the bacterium causing Johne's disease could not.

In 1911, during attempts to culture the bacterium that caused Johne's disease, a serendipitous observation by the British scientist F.W. Twort led to the isolation of the etiologic agent. Twort's failure to keep pace with cleaning of laboratory glassware and a perceptive eye resulted in the observation of small bacterial colonies growing like satellites around larger colonies in old cultures he was preparing to discard. The larger colonies were contaminants of the common hay bacillus, Mycobacterium phlei. Suspecting that the M. phlei bacteria were providing some essential nutrient, Twort incorporated a heat- killed preparation of the organism into his culture medium. This new culture medium, he discovered, could grow a new acid-fast bacterium which he named Mycobacterium enteriditis chronicae pseudotuberculosae bovis Johne. In 1912, H. Holth also reported successful isolation of the cause of Johne's disease. Holth recognized the disease descriptions of Bang and simply called the organism he isolated the paratuberculosis bacillus and failed to receive much recognition for his discovery. (electron micrograph, 73.4K)

After the etiologic agent could be cultivated in the laboratory, antigens were obtained for use in skin testing (as is done for tuberculosis), and for assays to detect antibodies in serum samples using complement fixation and agglutination techniques. The man who first referred to the disease as Johne's disease coined the term "johnin" for the skin test antigen since the equivalent preparation for skin testing for tuberculosis is called tuberculin. The next several decades were devoted to evaluation of these and other diagnostic tests and to improvements in the methods for laboratory cultivation of the organism.

In the 1920s, paratuberculosis was described in animals on the African and Asian continents. Valle and Rinjard, recognizing the subcutaneous injection of M. paratuberculosis did not cause disease, evaluated vaccination as a means to control spread of the Johne's disease. In 1923, the first edition of Bergey's Manual of Determinative Bacteriology was published and officially named the causative agent of Johne's disease Mycobacterium paratuberculosis. [Bergey's Manual is a book that catalogues all bacteria and their characteristics: "the bible" of bacterial identification.] The 1920s was a period of vigorous searching for a small laboratory animal model of Johne's disease. Although some investigators will debate this conclusion, the goal of finding a small laboratory animal that develops pathology and disease typical of Johne's disease after experimental challenge with M. paratuberculosis remains elusive.

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1930 - 1950

Paratuberculosis was described in South America and on the Indian continent during the 1930s, thereby completing evidence of the worldwide distribution of the disease. That decade brought about realization that paratuberculosis was a menace to the cattle industry and warnings regarding its continued spread. A major achievement of the 1930s was the observation of age-dependent resistance of animals to infection by M. paratuberculosis.

In the 1940s, paratuberculosis was recognized to be a problem not only in domesticated livestock, but in wildlife as well. Paratuberculosis was observed to have many similarities with human leprosy. Continued evaluation of diagnostic tests led to the discovery of cross-reactivity, resulting in false-positive tests, with bacteria in the genus Corynebacterium and other antigenically-related bacteria.

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1950 - 1970

Vaccination as a means to control paratuberculosis was the subject of many studies in the 1950s. In addition, various strains of M. paratuberculosis were recognized during that decade including pigmented variants and strains that failed to grow on artificial culture media.

The young scientific discipline of immunology brought its techniques to bear on the study of paratuberculosis in the 1960s. More diagnostic tests, such as the leukocyte migration and fluorescent antibody tests, were devised and evaluated. The 1960s saw renewed efforts to find an acceptable laboratory animal model of Johne's disease. Important epidemiological observations were made in the 60s: 1) clinically normal but infected animals (carriers) actively excreted M. paratuberculosis in their feces, and 2) M. paratuberculosis could be found in the semen of infected bulls and the uterus of infected cows indicating the possibility of intra- or trans-uterine infection of fetuses.

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1970 - 1990

As the pace of veterinary research and discovery accelerated in the 1970s and 1980s, knowledge and understanding about many facets of M. paratuberculosis and Johne's disease became more complete. It is impossible to single out any individual or scientific achievement that was critically important. It was a global research effort that advanced the field of paratuberculosis research. Some of the many individuals who made substantial contributions to this effort were: Finn Saxegaard (Norway), J.B. Jorgensen (Denmark), Tony Lepper (Australia), Marie Thorel (France), N.J.L. Gilmour (Scotland), Ramon Juste (Spain), Des Collins and Geoff de Lisle (New Zealand), J. Goudswaard and Gert Benedictus (The Netherlands), B. Kormendy (Hungary), Y. Yokomizo (Japan), and Claus Buergelt, Diana Whipple, A.B. Larsen, Dick Merkal, Rod Chiodini, and Mike Collins (USA). Seeing a need to foster closer collaboration and international communication, Dick Merkal, working at the National Animal Disease Center, Ames, Iowa, USA, organized the First International Colloquium on Paratuberculosis. It was held in Ames in the summer of 1983. A second International Colloquium was organized by Dick Merkal and Marie Thorel and held at the Veterinary School in Maisons-Alfort, France. At that meeting, Rod Chiodini and Dick decided to organize the formation of the International Association for Paratuberculosis and other Intestinal Mycobacterioses. This group was officially born and published the first Paratuberculosis Newsletter on January 1, 1989 (See sources of print information). Two more international colloquiums followed: the third, organized by Claus Buergeldt and Rod Chiodini was held in Orlando, Florida in 1991, and the fourth, organized by John Hermon-Taylor and Mike Collins, was held in Cambridge, England in 1994. The Fifth International Colloquium on Paratuberculosis will be held in Madison, Wisconsin, September 29- October 4, 1996.

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1990 - present

The new age of paratuberculosis research was ushered in with the discovery of a genetic element unique to M. paratuberculosis. This nucleotide sequence in the chromosomal DNA of the organism was simultaneously and independently discovered by Des Collins in New Zealand and the research team led by J.J. McFadden in England in 1989. The sequence was found to be an insertion element and was designated IS900. It was the first insertion element ever reported in mycobacteria. The importance of this discovery was that it made possible development of genetic tools for detection of M. paratuberculosis without having to cultivate the bacterium on artificial laboratory media, a process typically requiring 12 to 16 weeks.

Today, IS900-based "gene probes" are providing new and intriguing information on the ecology and host range of this intestinal pathogen. Most provocative are reports that M. paratuberculosis is found in the tissues of over half of humans Crohn's disease. This chronic, untreatable intestinal disease bears marked clinical and pathological similarity to Johne's disease. To date, the cause of Crohn's disease is unknown. Determination of the role that M. paratuberculosis plays, if any, in the pathogenesis of Crohn's disease will almost certainly occupy much of the research effort of paratuberculosis investigators in the 1990s.

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