Abstract
In a series of four articles published between 1916 and 1919 in The Journal of Medical Research, precursor to The American Journal of Pathology, the investigative pathologist S. Burt Wolbach unambiguously showed that Rocky Mountain spotted fever has a tick-borne mode of transmission, the causative agent replicates intracellularly, and the disease is fundamentally a vasculitis. Although underappreciated, Wolbach's tour-de-force work epitomized investigative pathology. These four articles should be mandatory reading for young investigators and are recommended also to seasoned investigators who seek reinvigoration in the beauty in their craft.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 291-293 |
| Number of pages | 3 |
| Journal | American Journal of Pathology |
| Volume | 182 |
| Issue number | 2 |
| DOIs |
|
| State | Published - Feb 2013 |
ASJC Scopus subject areas
- Pathology and Forensic Medicine
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In: American Journal of Pathology, Vol. 182, No. 2, 02.2013, p. 291-293.
Research output: Contribution to journal › Comment/debate › peer-review
}
TY - JOUR
T1 - S. Burt wolbach, rocky mountain spotted fever, and blood-sucking arthropods
T2 - Triumph of an early investigative pathologist
AU - Musser, James M.
N1 - Funding Information: One need only skim the titles of articles published in The Journal of Medical Research in the early 20th century to realize how closely connected infection biology and investigative pathology were at that time. Indeed, the inextricable linkage of pathology, microbiology, and infectious disease research was underscored by the existence of many Departments of Pathology and Biology. (Of note, this tradition continues at the University of Nebraska College of Medicine, which has a Department of Pathology and Microbiology.) Wolbach’s findings were reported in a tightly clustered series of four single-author articles 3–6 published between 1916 and 1919 in The Journal of Medical Research , precursor to The American Journal of Pathology . Collectively, this work is striking in scope and scholarship, and should be mandatory reading for all young investigators. The articles shed light on the workings of an inquisitive and organized mind, with strong interests and roots in natural history, as it sought answers to complicated biomedical riddles. In these four articles, Wolbach elucidated the pathogenesis of the disease now known as Rocky Mountain spotted fever. Using guinea pigs and monkeys, Wolbach demonstrated that the disease is transmitted by ticks and that it is caused by an unusual pathogen that replicates intracellularly in endothelial cells; furthermore, he showed that the resulting disease is essentially a vasculitis. To describe the morbid anatomy associated with Rocky Mountain spotted fever, Wolbach examined tissue obtained from individuals who died of the disease, examination that confirmed the presence of intracellular organisms and critical vascular lesions. In his final report, Wolbach concluded, “The lesions of the blood vessels are due to the presence of the parasite and constitute the distinctive pathology of the disease, and warrant the definition [as] ‘an acute specific infectious endangiitis, chiefly of the peripheral blood vessels....’” (page 181 in 6 ). The pathogenesis he described was novel at the time. Wolbach did everything our field of investigative pathology strives to accomplish but few are fortunate enough to achieve so regularly: identify the problem, proceed straight to the gist of the matter by experimental means and clear thinking, and delineate the pathological mechanism. His efforts set the standard for much subsequent work on other arthropod-transmitted agents, including the example of Borrelia burgdorferi , the causative agent of Lyme disease. 7 One cannot read these and other articles written by Wolbach without concluding that first and foremost he was a biologist and naturalist who strived to understand pathological processes and mechanisms using a broad array of the tools available at the time: superb intellect, keen powers of observation, the microscope and related modest laboratory paraphernalia, experimental animals, necropsies and autopsies, and histopathological analyses. His investigative approach is a tour de force from an early systems biologist who excelled in interdisciplinary research. The present commentary will not address Wolbach’s substantial contributions to our understanding of other infectious agents (including trypanosomes, influenza viruses, and streptococci, as well as other rickettsial diseases), nor discuss his extraordinary body of work in the field of vitamin deficiency states. Woodward et al 8 exquisitely summarized many aspects of Wolbach’s career, and readers interested in the rich history of research on Rocky Mountain spotted fever are referred to Harden’s definitive work on this subject. 9 S. Burt Wolbach was born in Grand Island, Nebraska, on July 3, 1880, a relatively short time after the Nebraska Territory was granted statehood in 1867. This was a time in US history when the western prairie seemed to have no end, stretching to almost unlimited horizons. In 1880, Grand Island, located in south-central Nebraska and in the center of the country, had a population of less than 3000. Wolbach’s childhood was marked by a strong interest in outdoor activities common to rural areas at the time and still today, including hunting, fishing, horseback riding, and others for which observation powers were a tremendous asset. Wolbach graduated from high school in Grand Island in 1897. He decamped for Lawrence Scientific School at Harvard College and then Harvard Medical School, from which he graduated in 1903. He was interested very early on in infection biology, as demonstrated by his publication as a medical student in 1903 with Harold C. Ernst on the tubercle bacillus. 10 This work revealed an affinity for combining his powers of morphological observation, detailed and precise description of natural history, and analysis of pathological material from humans and infected animals. Wolbach was also an innovative investigator, at heart a solver of practical problems. This characteristic was illustrated by his solution to the problem of how to transport live rickettsia-free lice to Poland, which he required for execution of planned studies on epidemic typhus. To ensure that the lice arrived well nourished and ready for experimental action, he and colleagues John L. Todd and Frank W. Palfrey simply strapped louse boxes to their legs, thereby permitting the lice to feed during the slow Atlantic transit. 11 This process resulted in the “T” (Todd) and “W” (Wolbach) strains of lice. Wolbach’s work on Rocky Mountain spotted fever undoubtedly provided him the crucial expertise to subsequently discover the cause of epidemic typhus ( Rickettsia prowazekii ) in Poland and demonstrate its louse-borne mode of transmission. 12 For this work, Wolbach received the Polish award of Commander of the Order of Polonia Restituta. This writer could not determine the precise confluence of events that stimulated Wolbach to travel to western Montana of his own volition and investigate the cause of the disease that was killing settlers in the Bitterroot, a problem that also had substantial detrimental economic impact in the valley. 9 Perhaps it was the call of the northern Rocky Mountains to a man of the Plains then living on the flat East Coast? Perhaps it was simply the desire to apply his distinct investigative pathology skill set to a vexing medical problem? Some have suggested that scientific data and resulting discoveries are the by-product of the clash of human egos and scientific competition. Perhaps he felt that other investigators’ studies and conclusions were simply not up to snuff? In this regard, I cite his statement that “while Ricketts may have encountered the true parasite of the disease in ticks, he was led hopelessly astray by the occurrence of bacteria in his infected as well as non-infected ticks.” 6 Regardless, we as investigative pathologists are fortunate that he chose to focus his attention and considerable talents on this disease. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2013/2
Y1 - 2013/2
N2 - In a series of four articles published between 1916 and 1919 in The Journal of Medical Research, precursor to The American Journal of Pathology, the investigative pathologist S. Burt Wolbach unambiguously showed that Rocky Mountain spotted fever has a tick-borne mode of transmission, the causative agent replicates intracellularly, and the disease is fundamentally a vasculitis. Although underappreciated, Wolbach's tour-de-force work epitomized investigative pathology. These four articles should be mandatory reading for young investigators and are recommended also to seasoned investigators who seek reinvigoration in the beauty in their craft.
AB - In a series of four articles published between 1916 and 1919 in The Journal of Medical Research, precursor to The American Journal of Pathology, the investigative pathologist S. Burt Wolbach unambiguously showed that Rocky Mountain spotted fever has a tick-borne mode of transmission, the causative agent replicates intracellularly, and the disease is fundamentally a vasculitis. Although underappreciated, Wolbach's tour-de-force work epitomized investigative pathology. These four articles should be mandatory reading for young investigators and are recommended also to seasoned investigators who seek reinvigoration in the beauty in their craft.
UR - http://www.scopus.com/inward/record.url?scp=84872735424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872735424&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2012.11.011
DO - 10.1016/j.ajpath.2012.11.011
M3 - Comment/debate
C2 - 23256917
AN - SCOPUS:84872735424
SN - 0002-9440
VL - 182
SP - 291
EP - 293
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -