The blight of the Bitterroot, the mysterious Rocky Mountain spotted fever, and the significant role of Wilson and Chowning—a commentary

In 1902, Louis B. Wilson, who subsequently went on to become director of the Mayo Clinic, and his pathologist assistant, William M. Chowning, both from the University of Minnesota, began a significant study of the little-known, but widely feared, Rocky Mountain spotted fever. Property values in the Bitterroot Valley in Ravalli County, a few miles east of the Idaho border in Montana, were dropping rapidly as resident farmers and lumbermen were taken sick by the mysterious malady, “a blight on the Bitterroot”. Before 1875, the Salish or Flathead Indians lived there, eating the bitter roots of a pink spring flower as a medicine. They ground the roots in a mortar and pestle and made a medicinal porridge or tea, and named the river and the valley after the plant. The Salish showed no evidence of the illness that affected subsequent occupants of the valley. The Indians did know about it, however. Michie and Parsons reported in 1916 that an elderly Indian told them that in the spring evil spirits occupied the canyons west of the Bitterroot Valley (Lo Lo Canyon, a notorious site of infection). A primary contribution of Wilson and Chowning is the recognition of tick bites as the probable mode of transmission and of the role of local groundsquirrels as the likely reservoir of human infection. It is interesting to speculate that Indians native to the area avoided the tick-infested sites or meticulously removed the ticks, whereas other Indians traversing the valley and unaware of the local conditions may have acquired the ticks and the resulting disease.

When the full epidemiology of the disease was elucidated many years later and the ecological impact of the white settlers and lumbermen was evaluated, their interaction with the heavy springtime tick infestations became clear, as did the importance of groundsquirrels (Citellus columbianius) and other rodents. The study of Rocky Mountain spotted fever proved to be a seminal lesson in the integral interdependence of natural history with the activities of humans, vector, etiological agent, and zoonotic carriers of the infection. It also set off a decades-long series of studies that made the Bitterroot Valley a center of pioneering epidemiologic investigations. A happy by-product of these efforts was the impetus it provided for the establishment of what rapidly became a world-famed epidemiologic research center in the nearby town of Hamilton. This was the Rocky Mountain Laboratory, now under the umbrella of the National Institute of Allergy and Infectious Disease of the National Institutes of Health.

The spark of insight that suggested the possibility that wood ticks (genus Dermacentor) were responsible for transmitting the infection is reported to have been given to Albert Longeway, the secretary of the Montana Board of Health, by his medical colleague, Earle Strain. He found a tick in the genitals of one of the fever victims and recalled a lecture on mosquitoes as the vector of yellow fever—a serendipitous association. Wilson and Chowning, however, made the crucial association: the agent of Texas Fever of cattle or Redwater Fever (Babesia bigemina) was discovered by Smith and Kilbourne in 1893 to be carried by the cattle tick Boophilus annulatus. This pioneering study was the first demonstration of arthropod biological (as opposed to mechanical) transmission of any disease. It was one of the most brilliant discoveries of the century, quite on par with the great findings of Robert Koch. Though Wilson and Chowning mentioned the implication of ticks in Texas cattle fever, they do not refer to the publication or mention the authors, presumably because their publication was “A Preliminary Report to the Montana State Board of Health.” However, even the early white settlers in the Bitterroot Valley learned to associate the local disease with ticks, calling it “tick fever,” as well as “spotted fever.”

The two University of Minnesota pathologists were sent on the recommendation of the secretary of the Minnesota State Board of Health when Longeway appealed to the secretary for immediate help in investigating this highly fatal disease that was terrifying the Bitterroot Valley residents. Knowing that the disease strikes only in the spring, Wilson and Chowning promptly went to work after their arrival in May, setting up a laboratory in Missoula in a room in the Northern Pacific Railroad Hospital. They worked with great efficiency, collecting data from nearly all of the local physicians on past cases, their precise distribution, case histories, fatality rates, and other information. Within the first 10 days, they conducted 3 autopsies; subsequently, they conducted 5 more. Their description of the symptoms they observed is a fine example of careful observation, without the myriad of laboratory tests that now so often substitute for critical direct examination. Their anatomic evaluations were similarly precise and careful. Many of their histologic studies had not been completed at the time of this preliminary report, but the critical findings were clearly described. These included the presence of parasites in red blood cells, the presence of numerous petechial hemorrhages in the kidneys and ventricle, and distended capillaries filled with parasitized red cells in the skin, resulting in microhemorrhages that caused the characteristic spots. Their more definitive study, published in 1904, covered the 2 seasons of their work, during which they studied records of 126 cases of Rocky Mountain spotted fever, with a case fatality rate of 87%. Their return for the 1904 season was prevented by lack of funds from the Montana State Board of Health, a not unfamiliar scenario.

It was with the etiology of the malady that controversy soon developed. Ticks were thought only to carry protozoan parasites (viruses being unknown). Therefore, the agents of spotted fever, if tick-borne, were necessarily protozoa. This followed Smith and Kilbourne's findings of the malaria-like hematozoon, Babesia (then called Prosoma, later Piroplasma), in their Texas Fever study. Wilson and Chowning considered the etiologic agent of spotted fever to be “a very close relative of the germ causing spotted fever.” Their description of an amoeboid organism of highly variable size and staining characteristics was, in their view, clearly a hematozoon.

This proved to be the chief point of contention for important works to follow. In 1904, the eminent zoologist, Charles Wardell Stiles, director of the Division of Zoology at the Hygienic Laboratory of the US Public Health and Marine Hospital Service, intensively studied the blood and tissues of spotted fever patients. After prolonged study, he found no protozoan parasites and, therefore, could neither duplicate nor accept the findings of Wilson and Chowning. He concluded that because no protozoan was found, ticks could not be involved. In the same year, the equally eminent parasitologist, Charles F. Craig, also failed to find any intracorpuscular parasites and considered that Wilson and Chowning “…have mistaken areas devoid of hemoglobin in the red cell…for protozoan parasites”—a harsh, but probably correct, judgment.

In the confusion and disillusionment that followed Stiles’ and Craig's publications of these negative findings, the American Medical Association and other groups called for further investigation of this increasingly mysterious malady. This led to the definitive studies of Howard T. Ricketts, who, in a brilliant series of investigations that remain classics of epidemiology, proved that a nonfilterable “virus,” and not a protozoan, was the etiologic agent. He further established that ticks were indeed responsible for transmission, which he demonstrated by infected ticks being allowed to bite noninfected guinea pigs that subsequently developed the infection.^,  The wood tick, Dermacentor andersoni, proved to be the vector. Ricketts also established that the organism, now recognized as a rickettsia and not a virus, can be passed by the female tick to its eggs and then through the successive molts of the next generation (transstadial transmission), just as with the tick vector of Texas fever. The tick was misnamed at the time as the eastern wood tick (D occidentalis or D variabilis), which was subsequently shown to be the vector of the eastern strain of the disease (far more common than the Rocky Mountain strain). D andersoni, in fact, is still commonly called the Rocky Mountain spotted fever tick. The infective agent was shown to be an obligate intracellular, nonculturable bacterium, later named Rickettsia rickettsii, in honor of this talented researcher. Ricketts’ great career was tragically struck down by epidemic typhus in 1910. While studying that disease in Mexico City (owing to lack of money to continue his studies in Montana), Ricketts became infected by the louse-borne related agent, Rickettsia prowazekii, and succumbed, becoming one of the great martyrs of medical research.

Wilson and Chowning's breakthrough study of 1902, followed by their more detailed paper of 1904, are the first scientific investigations of a disease that terrified the region. Although they misconstrued the sludged and damaged red cells as containing protozoa, and could not find the far smaller rickettsia with the pathologic techniques they employed, their meticulous observations of the damaged tissues and their epidemiological acuity and thoroughness were remarkable. They defined the disease and established the basic pathology in a series of autopsies. They suggested the correct vector and reservoir of infection, brilliantly corroborated by Ricketts. Their work was the first of a significant series of studies that solved a great medical mystery and helped establish epidemiology as an essential component of medical research.