Page Comparison - Canyon Creek Schoolhouse Laboratory 100th Anniversary Mission (v.36 vs v.37)

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When researching a disease, scientists and physicians ask some pretty basic questions: Is there a disease? What causes it? How do you get it? Can you test for that specific disease? What does it do to you? Can we treat or cure it? Can we prevent you from getting it?

When the Canyon Creek Schoolhouse laboratory opened in 1921 to investigate Rocky Mountain spotted fever (RMSF), only one of these questions had been answered definitively: Is there a disease? Yes, definitely! Other questions had partial answers that had created more questions. Two big unknowns were how to treat or cure RMSF and how to prevent people from getting it in the first place. The mission of the laboratory was to answer as many of these questions as possible.

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What causes RMSF?

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Collecting Ticks

Although it was known that RMSF was caused when the Rickettsia rickettsii bacteria infected a Dermacentor andersoni tick that then bit a human, more questions remained. Was the bacteria spread by other species of ticks? And exactly how did the ticks get infected? To find out where the ticks were picking up the infection and to answer a number of other questions, ticks had to be collected in the wild.

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Man dressed in white with pants tucked in boots waves large white flag over meadow grass in high mountains.

A staff member of the Canyon Creek Schoolhouse Laboratory—possibly Dr. Ralph Parker, C.M. Salisbury, or George Cowan—dragged a white flannel flag over brush and grass to gather ticks in the Bitterroot Valley, Montana. He wore a white jump suit over his regular clothes, tucking his pant legs into the top of his high, laced boots. When they returned from such outings, the men would check each other closely in case a tick had attached itself to one of them.

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Image: Office of NIH History and Stetten Museum, 1522

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In 1923, a mountain goat (perhaps this mountain goat kid) taken by George Cowan had over 1,000 ticks engorged ticks on it. It was with these ticks that Dr. Roscoe Spencer came up with his idea for an RMSF vaccine.

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Image: Rocky Mountain Laboratories, 264

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Cataloguing Ticks

As the field researchers gathered many species of ticks and ticks in many stages of their life cycle, Dr. Robert Cooley developed a huge collection of them. Cooley was the head entomologist at Canyon Creek Schoolhouse laboratory. This collection would help later researchers solve questions about other tick-borne diseases. In this photo, Cooley shows off his world-class tick collection kept in jars in a huge card file cabinet. The photo was taken in Building One (which opened in 1928), not the Canyon Creek Schoolhouse laboratory, on December 3, 1946. Cooley had been developing this collection since his first days studying RMSF forty years before.

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Image: Wikimedia Commons

How do you get RMSF?

How do you get RMSF?div

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Occurrence

One way of finding out how a disease is spread is by looking at where it occurs. Rocky Mountain spotted fever came to be studied in Montana’s Bitterroot Valley because the bites of the western slope’s ticks caused a particularly deadly infection, meaning that more people died. By mapping and charting where they found ticks or where people got RMSF, the researchers could find the ticks and animals they needed to study. Mapping turned up interesting insights, such as one area may have a heavily infected tick population, but an area across a stream did not. Ticks do not like to swim.

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C.M. Salisbury drew this grid map of an area of land near Mill Creek in 1922. Included were the sites of stumps, trees, and roads. The researchers could use it to keep track of where they collected ticks.

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Image: Rocky Mountain Laboratories, 961b

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Life cycle of ticks

Studying the life cycle of ticks provided important pieces of the RMSF puzzle. Knowing the life cycle meant that scientists could study questions such as: When did the ticks pick up the bacteria causing RMSF—was it when they were newly hatched? When they were adults? And was the infection passed on to a new generation of ticks through the eggs? The answers to these questions could be used in control efforts and in developing a new vaccine.

a new vaccine.

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Tick with eggs bunched together in bundle larger than tick

The life cycle of the tick: a fertilized female lays thousands of eggs on the ground. When they hatch as larvae, they attach to small animals and feed. Then they drop off to digest their meal, and molt (shed their old shell) to become nymphs. The first winter they spend as unfed nymphs.

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Female and Male ticks on white background

In spring, the nymphs once again attach to an animal and feed, drop to the ground, and digest their meals. This time they molt to adults, like these Rocky Mountain wood ticks, Dermacentor andersoni. They spend their second winter as unfed adults.

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Close up of ticks on grass stalks in meadow

The next spring they climb grass and bushes to attach to animals.

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Engorged tick swollen many times its normal size

But as adults, ticks mate as well as feed. This is when the ticks can get the Rickettsia rickettsii bacteria from the animals they feed on. Even though the bacteria don’t hurt the ticks, it infects all of their cells, and is passed on through the egg. The next generation of ticks will be infected.

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Images: Office of NIH History and Stetten Museum, 1554-58

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Constant collecting

As RMSF gave up its mysteries, researchers still had other tick-borne diseases to study. They constantly collected ticks where outbreaks of Rickettsial diseases occurred.

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Men pose on top of a mountain ridge, wearing work clothes and carrying tick collecting equipment

In 1929, LeRoy Jones, Harley G. Sargent, Harry L. Sargent, and James Kerlee posed at the top of Blodgett Canyon in the Bitterroot Range. Each holds several white cloth bundles tied to a stick for specimen collection. James Kerlee’s brother, Arthur LeRoy Kerlee, had died the year before of RMSF that he had acquired in the laboratory.

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Image: Office of NIH History and Stetten Museum, 1449

How do you know you have RMSF?

How do you know you have RMSF?

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Diagnostic test

In a world filled with ticks and the diseases they carry—and diseases that have similar symptoms—being able to diagnose a disease quickly might be beneficial for treatment or for clues to how to control it. The classic feature of RMSF, the rash, appears days after the initial infection. The other symptoms can be confused with diseases such as typhus.

In 1916, the Weil-Felix reaction was developed to diagnose epidemic typhus. In 1928, LeRoy Kerlee and Dr. Roscoe Spencer did their own tests on guinea pigs, rabbits, and people at the Canyon Creek Schoolhouse laboratory. They reported that the Weil-Felix reaction could diagnose RMSF. The test became widely used to diagnose many Rickettsial diseases; although it has been replaced by newer diagnostic techniques such as indirect immunofluorescence, it can be useful in parts of the world without access to such technology.

Kerlee and Spencer’s results were published shortly after Kerlee died of Rocky Mountain spotted fever in 1928. Learn more about Kerlee [link to his bio].

“Rocky Mountain Spotted Fever: A Preliminary Report on the Weil-Felix Reaction,” A. L. Kerlee and R. R. Spencer, Public Health Reports (1896-1970), Vol. 44, No. 4 (Jan. 25, 1929), pp. 179-182

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The Bitterroot Valley stretching into the distance as seen from the top of a mountain

Overlooking Hamilton, Montana, where the Canyon Creek Schoolhouse laboratory was located. How many ticks were on those hills?

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Image: Office of NIH History and Stetten Museum, 1562-3

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Can you prevent getting ill?

The best way to deal with a deadly disease is to not get sick with it. But avoiding a disease can depend on how it’s spread, where you live or what you do for a living, and the possibility for a protective vaccine.

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Control efforts

Because it was known that ticks carried RMSF, one way to eradicate the disease was to keep people from getting bitten by infected ticks. That could mean changing the way that ranchers, shepherds, woodsmen, and others did their jobs.

There was another approach to tick control: eradicating the rodents and other small animals in an area where RMSF outbreaks occurred, often by using poison. The attempt to eradicate small animals in areas infested with RMSF failed; it wasn’t clear which animal or animals gave the infections to ticks, and new animals kept moving in.

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Cattle swim through a concrete trough directly toward viewer

To protect the workers most in contact with animals that could harbor ticks, Dr. Robert Cooley, the Montana State Entomologist and head Entomologist at the Canyon Creek Schoolhouse laboratory, recommended dipping livestock in disinfectants to kill the ticks, as was being done in this photo.

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Image: Office of NIH History and Stetten Museum, 15201520

Developing a Vaccine

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Developing a Vaccine

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One of the surest ways to stop the spread of a disease is to develop a vaccine against it. At the Canyon Creek Schoolhouse laboratory, bacteriologists (Dr. Roscoe Spencer) and entomologists (Dr. Ralph Parker) worked together to that end. Despite the limited technology and understanding of bacteriology of the 1920s, once Spencer and Parker began to work together in 1921, a vaccine was developed in less than three years.

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Two men wear white coats working together at wood table with guinea pig cages behind them. They are handling the animals.

As illustrated by this photo of two RMSF researchers, the development of a RMSF vaccine was only possible because of cooperation between state and federal agencies, scientific disciplines, and the research staff.

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Image: Office of NIH History and Stetten Museum, 1114

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This bottle of Rocky Mountain spotted fever vaccine from the early 1940s represents much scientific work and practical experimentation. There were no strict research protocols for vaccine development and testing in the early 19^th century. There was no oversight or approvals from the Food and Drug Administration. The Hygienic Laboratory (NIH’s precursor) had regulatory authority, testing commercial vaccines for safety and effectiveness. Spencer worked at the Hygienic Laboratory and was certainly familiar with the tests required to prove that a vaccine worked safely and at what dose it should be given, as well as the standards for producing a safe vaccine. He knew proving that his RMSF vaccine worked would take more than inoculating himself with it.

After experimenting with different combinations of fed vs. unfed ticks and ticks in different stages of their life cycle to get the highest concentration of RMSF in the vaccine, Spencer and Parker were ready for the next step. In February 1925, they conducted an experiment in 18 monkeys to see if the vaccine was effective and safe. None of the vaccinated monkeys died; all of the unvaccinated monkeys did.

Next was to test the vaccine on people, and the Canyon Creek Schoolhouse laboratory staff became the participants in this early clinical trial. Thirty-four laboratory and field workers were vaccinated, and none had a severe reaction.

There were questions about the vaccine: what was the optimum dose? How long did immunity last? And how long did it take to gain immunity after being vaccinated? That last question was answered in April 1925, when a cattle-dipper for the Montana State Board of Entomology was vaccinated. He came down with RMSF a few days later but recovered. Four other people in the Bitterroot Valley who also got RMSF at the same time, but had not been vaccinated yet, all died. From this unplanned experience, Spencer and Parker learned the time required to gain immunity after vaccination: 10 days.

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Glass bottle with yellowed label

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Image: Courtesy of Dr. Marshall Bloom

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Vaccine Production Steps

In 1925, Drs. Roscoe Spencer and Ralph Parker described their method for creating RMSF vaccine. The method would become more streamlined and automated after they moved into the Building One laboratory in 1928 and got better space and equipment than the Canyon Creek Schoolhouse laboratory could provide. These photos include some taken at Building One after the laboratory moved from the schoolhouse.

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The recipe for RMSF vaccine:

Because you use adult ticks, you have to start when the ticks are young the spring before to create a vaccine for the next spring.

1. Lab-reared adult ticks without RMSF are used. Feed female ticks to engorgement on rabbits and mate them.

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A rabbit is being wrapped in white clothe on table

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Image: Office of NIH History and Stetten Museum, 1478

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In this photo, vials of the Spencer-Parker RMSF vaccine sit on the letter or telegram requesting the vaccine from places all over the United States. The Canyon Creek Schoolhouse laboratory was producing as much of the vaccine as possible, but demand for the vaccine exceeded the supply, making the construction of a new building designed specifically for scientific research and vaccine production necessary—Building One of the present Rocky Mountain Laboratories campus in Hamilton, Montana.

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Vaccine bottles to be sent to other places stand on the letters or telegrams requesting them.

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Image: Office of NIH History and Stetten Museum, 1560

Can we treat or cure RMSF?

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A Vaccine Made Unnecessary

One question not answered at the Canyon Creek Schoolhouse laboratory was if there was an effective treatment for Rocky Mountain spotted fever. But in the late 1940s, antibiotics were found to cure the disease; this discovery made the Spencer-Parker vaccine obsolete. This current infographic from the CDC reminds us that RMSF is still a threat to people’s health. Visit their website for more information https://www.cdc.gov/rmsf/index.html

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Image: CDC, https://www.cdc.gov/rmsf/index.html

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Versions Compared

Old Version 36

New Version 37

Key

What causes RMSF?

...

Collecting Ticks

Cataloguing Ticks

How do you get RMSF?

Occurrence

Life cycle of ticks

Constant collecting

How do you know you have RMSF?

Diagnostic test

Can you prevent getting ill?

Control efforts

Developing a Vaccine

Developing a Vaccine

Vaccine Production Steps

Can we treat or cure RMSF?

Office of NIH History and Stetten Museum