Kingston, Rhode Island, United States
|Howard T. Ricketts in Mexico City laboratory. National Library of Medicine|
“Black measles” was a common name for spotted fever, which regularly killed people in the western United States. Symptoms included a spotty rash on the extremities, fever, chills, headache, and photophobia. No one knew what caused it. The first recorded case in Montana’s Bitterroot Valley was in 1873.1 Twenty-three similar cases were reported in 1899. In 1901, Montana had seventeen fatal cases. Three years later, the Public Health Service (PHS) sent a research team to Montana to investigate the local spotted fever.
A Chicago pathologist named Howard Ricketts joined the research effort in 1906 and discovered that the vector of disease was the Rocky Mountain wood tick (Dermacentor andersoni). Ricketts scribbled in his notebook, “Ticks are around the house, on trees, on ground, everywhere. Everybody bitten innumerable times. . . .”2 Examining the blood of a young patient, he found a “bacillus-like body,” and later an “astonishing number” of the bacilli in tick eggs. He wrote “the salivary glands, alimentary sac and ovaries of infected [tick] females are literally swarming with exactly similar microorganisms.” The tick-borne bacterium Ricketts identified in 1909 is now called Rickettsia rickettsii. It is the etiological agent for Rocky Mountain Spotted Fever (RMSF).
Other researchers came to Montana to study RMSF and its tick vector. Some of them were less willing to use the tents, sheds, and abandoned farmhouses that Ricketts and other pioneer-scientists relied on for laboratory space. One such researcher, Ralph Parker, persuaded the PHS to rent an abandoned schoolhouse on the west side of the Bitterroot River. This became known as the Schoolhouse Lab.1 (Interestingly, Parker knew something about hard living and inadequate facilities. His physician father spent fourteen years on tiny Penikese Island caring for the residents of a Massachusetts leper colony.)3
|The Schoolhouse Lab, 1921. PHS Publication No. 688, 1960.|
Since there was no effective treatment for RMSF and the infection was often fatal, a vaccine seemed to be the only approach to prevent new infections and deaths. In 1919, for example, the state bacteriologist Arthur McCray died of laboratory-acquired RMSF while working to develop a “curative serum” for the infection.4
Unfortunately, the rickettsia bacteria could not be cultivated in vitro. Parker and Roscoe Spencer, a PHS officer, hit on the idea of using rickettsia-infected ticks as a source of antigen for a vaccine. In 1924, working from the Schoolhouse Lab, they produced a spotted fever vaccine using phenol-inactivated rickettsia from emulsified tick tissue.4 Spencer became the first human recipient of the vaccine.5 Between 1927 and 1940, half a million people in the region received the Spencer-Parker vaccine.
The demand for the vaccine challenged the mortar-and-pestle manufacturing methods of Parker and Spencer and their Schoolhouse colleagues. Montana’s Board of Entomology—which had been involved in tick eradication programs since Ricketts discovered the vector—asked the legislature for a new research building. In 1927, the state government approved funds for a building to house the state’s entomology programs and provide rental space for the PHS to continue vaccine research.4
Not everyone was happy about a new tick lab. It would be in the town of Hamilton on the east side of the Bitterroot Valley. Local belief held that ticks and spotted fever were found only on the west side. The river was assumed to be a barrier to tick migration. The local concerns may have been the first “not in our backyard” protest involving an infectious disease lab. According to Armstrong, “The new lab would bring ticks over the river, violating the geographic barrier that culturally defined the risk of the disease.”6
|1931, Line for RMSF vaccine at Montana clinic. Rocky Mountain Laboratory, NIAID Source.|
A lawsuit was filed. Janitors and other staff were hauled into court to describe lab accidents, loose animals, and wandering ticks at the old Schoolhouse Lab. The scientists blamed the old building’s facilities for any accidents, loose ticks, or stray animals.6 In the end, the east-side Hamilton lab was built in 1928. But it had a moat of water around it to keep the ticks from crawling into town.
The federal government took control of the building—the Rocky Mountain Laboratory—in 1932. Five years later, RML became part of the National Institute of Health. Today, RML is part of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Tick-borne diseases (e.g., Lyme disease, tularemia, relapsing fever) remain of interest to RML researchers. The RML moat is long gone, replaced now with BSL-3 and -4 labs.
Howard Ricketts did not live to see the steady evolution of Montana’s frontier science and woodshed laboratories. Budget cuts in 1910 led him away from Montana to Mexico City to help investigate a dangerous outbreak of epidemic typhus. His Chicago friend and mentor, Ludwig Hektoen, telegraphed him: “McCampbell’s assistant dead. Typhus. No insect bite. Be careful.”2 As he had done back in Montana, Ricketts slept in a tent on the hospital grounds. He could not avoid the typhus ward, however, where he likely picked up lice and then contracted the infection. He died in May 1910 at age thirty-nine.7 The bacterium that killed him is known today as Rickettsia Prowazekii.
In the 1930s, investigators learned how to cultivate rickettsia in egg yolk sacs. By 1940, the original Spencer-Parker vaccine was replaced with a formaldehyde-inactivated rickettsia preparation from yolk sacs.8 After World War II, the widespread availability of antibiotics put an end to the use of a rickettsia vaccine that was often painful to receive and of questionable efficacy. “The most conclusive evidence concerning the efficacy of available RMSF vaccines was supplied by Du Pont, et al. with volunteers. Neither the current yolk sac vaccine nor the original tick vaccine . . . conferred protection in humans.”9 In 1984, another researcher wrote, “A vaccine . . . would be useful in some medical practices in the southeastern United States because of the life-threatening nature of the disease, including the possibility of a fulminant course and the frequent difficulty in diagnosis. Further studies should be pursued toward the goal of developing an effective vaccine against Rocky Mountain spotted fever.”10 Today, however, the only research on RMSF vaccines is directed at protecting dogs.11
- McConnaha M. “The ‘schoolhouse lab’ is a Bitterroot Valley icon.” Ravalli Republic. August 20, 2014. Available online: https://bit.ly/3f4XeVS. Accessed: April 29, 2020.
- Margulis L and Eldridge BP. “What a Revelation Any Science Is!” ASM News. 2005;71 (2):65-70.
- Silvia J. “The tragic story of Massachusetts’ leper colony and the ‘lights of Penikese Island,’ Dr. Frank Parker and wife Marion.” 2019. Available at: https://bit.ly/3d2XYt4. Accessed May 1, 2020.
- Harden VA. Rocky Mountain Spotted Fever: History of a Twentieth-Century Disease. Johns Hopkins University Press, Baltimore, Maryland. 1990.
- Altman LK. Who Goes First?: The Story of Self-Experimentation in Medicine. University of California Press. 1998.
- Armstrong M. Germ Wars: The Politics of Microbes and America’s Landscape of Fear. University of California Press. 2017.
- Hektoen L. “Memorial Address at University of Chicago (15 May 1910).” Available at: https://bit.ly/2KGV0y2. Accessed: April 29, 2020.
- Cox HR and Bell EJ. Epidemic and Endemic Typhus: Protective Value for Guinea Pigs of Vaccines Prepared from Infected Tissues of the Developing Chick Embryo. Public Health Reports. 1940;55(3):110-115. DOI: 10.2307/4583153
- Kenyon RH and Pedersen CE. Preparation of Rocky Mountain Spotted Fever Vaccine Suitable for Human Immunization. J. Clin. Micro. 1975;1(6):500-503.
- Walker DH. Rocky Mountain spotted fever vaccine: a regional need. South Med J. 1984;77(4): 447-449.
- Alhassan A., et al. Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host. Infect. Immun. 2019;87(2):e00628-18. DOI: 10.1128/IAI.00628-18.
EDWARD MCSWEEGAN, Ph.D., is a microbiologist in Rhode Island. He worked at the National Institute of Allergy and Infectious Diseases, and later at the Global Virus Network in Baltimore. He writes about infectious diseases and history.