Rocky Mountain Laboratories
by Charles Richter and John S. Emrich
July 2022
From a humble beginning in an old schoolhouse in Montana, the Rocky Mountain Laboratories (RML) have become a premier research hub and an integral part of the National Institutes of Health (NIH). Many significant scientists in the U.S. Public Health Service (PHS) and AAI came through the lab or made it their long-term research home.
Rocky Mountain Spotted Fever
As European settlers moved west into the northern Rocky Mountains and began to colonize the area that would become Montana, they began to experience outbreaks of a new deadly disease of unknown origins.
This malady was named for the telltale, distinctive dark measles-like rash all over the body and dangerously high—and sometimes weeks-long—fever. It could also produce a variety of additional symptoms, including neck stiffness, body aches, vomiting, diarrhea, inflammation of major organs, gangrene of the toes and fingers, and neurological issues such as severe headaches and confusion. Prior to the creation of effective treatments, those who were infected faced long-term complications like liver damage, hearing oss, neurological deficits, and partial paralysis. Once the rash presented, the disease was fatal in up to 80% of cases.
Originally referred to as “black measles,” it became commonly referred to as Rocky Mountain spotted fever (RMSF), especially after the 1890s, when frequent outbreaks occurred in the Bitterroot Valley of southwest Montana.
By the turn of the century, RMSF was a significant enough problem that the newly formed Montana State Board of Health (MSBH) made it one of its first priorities. In February of 1902, MSBH agreed to investigate cases as soon as they appeared that spring. When those first cases emerged, a Great Falls physician named Earle Strain noticed a tick on one of the victims. Strain, who had been to Europe to study bacteriology, was aware of recent discoveries of arthropod vectors for disease and advised the Board of the tick’s potential role in transmission.
The First Labs
Working out of temporary laboratory quarters in a local hospital, MSBH researchers, with the help of the PHS, began a two-pronged approach: physicians gathered epidemiological data on all cases, while pathologists examined the tissues of spotted fever sufferers. By the summer of 1902, an unknown parasite was regularly seen in the red blood cells. This evidence, coupled with the timing of the disease to correspond with the annual emergence of ticks, seemed to confirm Strain’s suspicions.
At the beginning of the 1903 tick season, bacteriologist and future director of the PHS Hygienic Laboratory John F. Anderson (AAI 1918) arrived in Montana. He examined the collected epidemiological data and decided that it all supported a tick vector: cases correlated with activities that involved likely exposure to ticks. Nearly all patients had a history of tick bites a week before the onset of spotted fever. Comparing the blood-borne parasites with those of malaria and Texas cattle fever, he found similarities that further supported a bacterial agent transmitted by a tick. He was so sure of this finding that he suggested renaming the disease “tick fever.”
To prove the tick hypothesis, MSBH staff went tick hunting. They dragged large white cloths across the Montana scrublands to collect countless ticks and other possible vectors for study. One of the likely suspects found during these collections, the Rocky Mountain wood tick, was named Dermacentor andersoni, after Anderson, in 1908.
Identifying the Agent
In 1906, Howard T. Ricketts, then a University of Chicago pathologist, came to Montana to perform research on tissue samples from spotted fever patients. His laboratory was no more than a tent on the grounds of the Northern Pacific Hospital in Montana. By using guinea pig models, he was able to study the disease year-round, not only during tick season.
The breakthrough came when Ricketts inoculated several guinea pigs with either washed cells, serum, or filtered serum, from one nine-year-old patient. When only the guinea pigs injected with filtered serum avoided infection, he knew the agent had to be a blood-borne bacterium and not what was then known as a filterable virus. Ricketts had identified a new class of vector-borne obligately intracellular bacteria that became known as Rickettsiae. The bacterium responsible for RMSF was described as Rickettsia ricketsii.
Ricketts also conducted an experiment on transmission somewhat similar to the one by Theobald Smith (AAI 1920) in Texas that first established ticks as a disease vector. He took ticks from infected guinea pigs and transferred them to healthy ones, which then showed signs of spotted fever. This confirmed the tick transmission theory once and for all.
Public Health Measures
Armed with this new knowledge, research into prevention and cure for RMSF could begin. After 1910, the Montana State Board of Entomology began a cattle-dipping program to kill ticks on livestock with a quick bath in an arsenic solution. Public health officials educated locals about the tick menace and how to protect themselves from exposure.
The Schoolhouse Laboratory
The earliest labs that would become the RML were temporary structures or borrowed woodsheds. Only in 1921 did Ralph Parker, an entomologist assigned by the PHS, secure an abandoned schoolhouse on the Bitterroot River as a more stable home for research. At the “Schoolhouse Lab,” the research teams kept countless live ticks, all collected from the countryside and painstakingly catalogued by species, source, and life cycle stage. Parker and Roscoe Spencer managed to produce the first effective vaccine against RMSF in 1924 by emulsifying tick tissue and killing the bacillus with phenol.
Green Light
The struggle to defeat RMSF at RML was dramatized in the 1937 film Green Light, starring Errol Flynn as a wrongly disgraced surgeon who goes to Montana to research spotted fever. There, he falls victim to the disease and receives an experimental dose of the vaccine. Based on a best-selling novel by Lloyd C. Douglas and inspired by the actual scientific endeavor, Green Light was well received by critics and at the box office, showing that a scientific drama could captivate audiences.
Expansion of the Laboratories
In 1928, Montana finally approved funds for a new permanent facility in the town of Hamilton. Through the 1930s, the RML grew from a single building and 26 employees to a federally owned and operated campus of seven buildings and more than 100 staff, including virologists, bacteriologists, and parasitologists. In 1937, RML became part of the NIH.
Wartime Vaccine Production
The Second World War transformed RML from a regional research center into an essential vaccine production facility. Using seed virus from the Rockefeller Institute and serum donated by students at Montana State University in Missoula, RML began producing the yellow fever vaccine in February 1941. When the United States was drawn into war in the Pacific after the attack on Pearl Harbor later that year, vaccines against yellow fever and other tropical diseases became an essential part of military readiness, administered to every member of the armed forces.
Two researchers at RML, Mason Hargett and Harry Burruss, developed their own novel yellow fever vaccine in 1941 that did not rely on human serum. After several lots of the Rockefeller vaccine were found to be contaminated with hepatitis B, the Hargett-Burruss vaccine, produced with chick embryo protein in an aqueous base, became the standard vaccine for the U.S. Army by May 1942. Throughout the war, RML was also a vital production site for vaccines against RMSF and typhus.
Vaccine Innovations
After the war, RML remained an important research site. John J. “Jack” Muñoz (AAI 1951) and his team were instrumental in the development of acellular vaccines that use only a part of the bacterial agent to induce immunity. Working with B. pertussis in the 1970s and 80s, this group of researchers isolated the piece of DNA that contained the genes for pertussis toxin, eventually making possible the pertussis vaccine that is included in today’s DTaP vaccine.
RMSF and RML Today
Today RMSF is found in the United States, Mexico, Canada, and Central and South America. In the United States, 60% of the cases are from five states—North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri—though it can still be found in the area where it was first discovered. When treated early with antibiotics (typically doxycycline) and palliative care, symptoms diminish within a few days and patients make a full recovery. In the United States, in addition to the Rocky Mountain wood tick, the American dog tick and the brown dog tick have been discovered to serve as vectors for RMSF.
The RML continue to produce important and innovative basic research into a wide array of human and livestock diseases, including mad cow disease, Lyme disease, Q fever, and SARS-CoV-2. The facility, now comprising 30 buildings on 36 acres, features BSL-4 laboratory space equipped to handle the most dangerous infectious organisms—a far cry from the tent laboratories where the earliest discoveries were made.
References
- Anderson, John F. “Spotted Fever (Tick Fever) of the Rocky Mountains.” Hygienic Laboratory Bulletin 14.
- Cobb, J. O. “The So-called “Spotted Fever” of the Rocky Mountains—A New Disease in Bitter Root Valley, Mont.” Public Health Reports 17, no. 33.
- Emrich, John S. and Charles Richter. “A Brief History of Bovine Immunology in Texas.” AAI Newsletter, March/April 2018: 62–5.
- Harden, Victoria A. Rocky Mountain Spotted Fever: History of a Twentieth-Century Disease. Baltimore: Johns Hopkins University Press, 1990.
- Hettrick, Gary R. “Vaccine Production in the Bitterroot Valley during World War II: How Rocky Mountain Laboratory Protected American Forces from Yellow Fever.” Montana: The Magazine of Western History 62, no. 4.
- Ricketts, Howard T. “Observations on the Virus and Means of Transmission of Rocky Mountain Spotted Fever.” Journal of Infectious Diseases 4, no. 1.
- Walker, David H. “Ricketts Creates Rickettsiology, the Study of Vector-Borne Obligately Intracellular Bacteria.” Journal of Infectious Diseases 189, no. 5.
- Wilson, Louis B. and Willam M. Chowning. “Studies in Pyroplasmosis Hominis (‘Spotted Fever’ or ‘Tick Fever’ of the Rocky Mountains).” Journal of Infectious Diseases 1, no. 1.