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The Yellowstone Microbe That Changed the World
A Nobel Prize, big business and scientific breakthroughs including Covid-19 tests and vaccines were decades in the future when microbiologist Thomas D. Brock began taking samples from Yellowstone Park’s hot springs in the summer of 1964. Brock took an extended working trip to Yellowstone the following summer, enlisting the aid of his wife, Louise, also a microbiologist.
They returned in 1965 and, in 1966, Brock added Patricia Holleman to his group, and also honors undergraduate student Hudson Freeze, who had just completed his sophomore year. Over time, graduate students and other assistants joined his work. Brock was then professor of microbiology at Indiana University in Bloomington, Ind.
Decades later, Brock would note that prior to 1964, he had “[no] desire to go to Yellowstone because of its reputation as a heavily visited ‘amusement’ park, rather than a natural area. My first visit to Yellowstone … was a revelation. I had not expected such enormous developments of microorganisms as were present in the runoff channels of the Yellowstone hot springs.”
Brock wrote that before he discovered these life forms, all research on heat-tolerant (thermophilic) bacteria had been done in the laboratory. The upper temperature limit on these bacteria cultures was about 140 degrees Fahrenheit. Because researchers relied on lab techniques, rather than studying microbes in their natural habitat, Brock added, they missed the types of microorganisms he found at Yellowstone.
Discovering Thermus aquaticus
In June 1966, funded by the National Science Foundation, Brock and his assistants “began serious work in Yellowstone.” Late in the summer, they took a sample from a mat of yellow algae from a runoff channel of Mushroom Spring in Yellowstone’s Lower Geyser Basin, its temperature approximately 156 degrees Fahrenheit. That fall, in the lab, Freeze started trying to isolate bacteria from this yellow mat.
Freeze, the undergraduate, noticed crystals accumulating in the bottoms of his test tubes and decided to look at them under the microscope. When Freeze saw “long strings of bacteria,” he experienced a thrill, realizing he was the first person in the world to see them. Brock named the organism Thermus aquaticus, that is, “warm bath water dweller.” Freeze’s first scientific publication, coauthored with Brock, was the description of T. aquaticus.
Brock deposited representative cultures of the organism in the American Type Culture Collection in Washington, D.C., a non-profit repository of microorganisms from which scientists can draw to conduct their research.
Freeze and Brock won the 2013 Golden Goose award, an award for scientists and engineers who have done federally funded research that initially seemed to be offbeat or insignificant, but ended up having important effects on science and the larger culture. The results of their research would turn out to be enormous.
A Nobel Prize
Typically in the history of science, Nobel Prize winners stand on the shoulders of previous researchers. Without Brock and Freeze's success in discovering and isolating T. aquaticus and its heat-tolerant enzyme, Taq Polymerase, biochemist Kary Mullis would never have been able to invent Polymerase Chain Reaction (PCR).
PCR and related processes like DNA sequencing use heat to allow enzymes access to the internal structure of DNA. Before the discovery of T. aquaticus, no known enzyme could tolerate the necessary heat to facilitate more than the most rudimentary research.
In 1983, Mullis was working for Cetus Corporation, a biotechnology company in Berkeley, Calif. One summer night he was driving home from work, unable to stop thinking about possibilities for DNA replication in the laboratory. Convinced he was on the right track, Mullis kept pulling the car over to make calculations on paper. When he arrived at his cabin, he stayed up all night “drawing little diagrams on every horizontal surface that would take pen, pencil or crayon until dawn, when with the aid of a last bottle of good Mendocino county cabernet, I settled into a perplexed semiconsciousness.”
Over the next few months, Mullis worked on his idea, also discussing it with colleagues and reviewing the relevant literature. He was certain that it was neither as revolutionary nor as unique as it appeared to be. But it was. He completed his first successful experiment on Dec. 16, 1983. For inventing PCR he won the 1993 Nobel Prize in chemistry, sharing the prize with British biochemist Michael Smith, who had also achieved important breakthroughs in DNA research.
In PCR, a single strand of DNA is isolated, and billions of copies can be made of it. Thus, many experiments can be performed on it without risking the loss of a researcher’s only sample of that strand. Suppose you had a small shrub in your yard, the only one of its kind. It produces a single tiny leaf, once. If you want to experiment with that leaf, after you’ve used it up you’ll never have another one. PCR would make it possible to create more exact copies of that leaf than you could experiment on in a lifetime.
PCR has revolutionized many areas of science, including medical diagnoses, genetics, law enforcement and even paleontology. It was also used to decode and map human DNA as part of the Human Genome Project.
Big money
For his discovery, Cetus awarded Mullis $10,000. Cetus later sold the patent to PCR to the Swiss multinational pharmaceutical firm, F. Hoffmann-La Roche (Roche) for $300 million. Mullis felt cheated for the rest of his life.
Roche has continued to make millions of dollars annually from its patent on PCR and the products it generates. In 2022 alone, Roche reported $5.4 billion in PCR-related sales. The National Park Service, Yellowstone National Park and the state of Wyoming have received no percentage of these revenues.
Bioprospecting
Recognizing the enormous financial and scientific potential of Yellowstone’s extremophiles, on Aug. 17, 1997, Diversa—a California-based biotechnology company—signed an agreement with the National Park Service and Yellowstone Park. The agreement allowed Diversa to take small samples from Yellowstone’s hot springs. It stipulated that Diversa would pay Yellowstone $20,000 per year for five years plus an undisclosed amount in royalties on future profits from its research, reportedly ranging from half a percent to 10 percent.
A coalition of three environmental groups sued to prevent the research: the Edmonds Institute, the Alliance for the Wild Rockies and the International Center for Technology Assessment. In 1999 the Ecology Law Quarterly noted, “The Park Service should view this lawsuit not as a roadblock in the way of a clever deal to gain the parks needed revenue, but as an opportunity for reflection on the appropriate role of bioprospecting and other commercial scientific ventures in the national parks.” The article also reported, “Park officials present the Diversa bioprospecting agreement as an unqualified positive. Yellowstone will receive cash and research assistance as well as future royalties should the venture lead to any commercial products. The money could help close gaps in the park's chronically inadequate budget. Park officials are painfully conscious that Yellowstone has received no financial return from the discovery of Thermus aquaticus or its valuable DNA polymerase and [are] anxious not to miss the next such opportunity.”
The Diversa agreement eventually went forward, and was the first of future bioprospecting agreements between private companies and the NPS, Yellowstone and other national parks.
Of the approximately 140 research permits Yellowstone issues annually, most do not have commercial applications, but are more often oriented toward science and education. Out of the zero to two permits per year with explicit commercial applications, most are related to extremophiles.
Covid-19
Covid-19 tests and vaccines are among the most recent benefits of PCR. Because of the DNA work required to manufacture these products, and the heat that work generates, scientists use to T. aquaticus and its heat-tolerant enzyme, Taq Polymerase. Annie Carlson, Yellowstone National Park research coordinator, noted in 2020 that PCR will continue to help in the fight against future infectious diseases.
Brilliant scarlet, yellow, orange, green and blue mineral pools are one of Yellowstone’s greatest attractions. Visitors to the pools can also reflect on the enormous scientific and health-related benefits the organisms in these hot springs give us—and were the first to give to the world.
Resources
Primary Sources
- Brock, Thomas D. “The Road to Yellowstone—And Beyond.” Annual Review of Microbiology 49, 1995: 1-28, accessed Sept. 10, 2022 at https://www.annualreviews.org/doi/pdf/10.1146/annurev.mi.49.100195.000245.
- _____________. Thermophilic Microorganisms and Life at High Temperatures. Springer Series in Microbiology, edited by Mortimer P. Starr. New York, Heidelberg, Berlin: Springer-Verlag, 1978, 75, 441-449.
- Hein, Lewis. Personal interview with the author, Oct. 29, 2022. Text messages to the author, Nov. 1, 8, 2022.
- Mullis, Kary. "The Polymerase Chain Reaction." Nobel Lecture, Dec. 8, 1993, accessed Sept. 11, 2022 at https://www.nobelprize.org/prizes/chemistry/1993/mullis/lecture/.
- Veress, Linda, Yellowstone National Park Public Affairs Office. Email to the author, Dec. 16, 2022.
Secondary Sources
- “Benefits Sharing in the National Parks,” Jan. 27, 2021. National Park Service, accessed Nov. 11, 2022 at https://www.nps.gov/nature/benefits-sharing.htm.
- “Bioprospecting,” July 30, 2019. National Park Service, accessed Nov. 10, 2022 at https://www.nps.gov/yell/learn/nature/bioprospecting.htm.
- Burger, Ludwig. “Roche sees slower 2022 sales growth as COVID tests demand eases,” Feb. 3, 2022. Reuters.com, accessed Nov. 4, 2022 at https://www.reuters.com/business/healthcare-pharmaceuticals/roche-sees-slower-2022-sales-growth-covid-19-test-demand-eases-2022-02-03/.
- Doremus, Holly. "Nature, Knowledge and Profit: The Yellowstone Bioprospecting Controversy and the Core Purposes of America's National Parks." Ecology Law Quarterly 26, 1995: 401-488, accessed Oct. 27, 2022 at jstor.org. Database available to patrons at the Natrona County Public Library, Casper, Wyo.
- Fergus, Charles. “Discovering a New Life Form in the Hot Springs of Yellowstone,” July 20, 2007. Nasa.gov, accessed Oct. 6, 2022 at https://astrobiology.nasa.gov/news/discovering-a-new-life-form-in-the-hot-springs-of-yellowstone/.
- Haley, Jarrett. “The Missing Link: Completing the Triton story of Taq and PCR,” Dec. 22, 2021. Tritonmag.com, accessed Oct. 27, 2022 at http://tritonmag.com/freeze/.
- “Hydrothermal Systems,” Feb. 2, 2021. National Park Service, accessed Nov. 2, 2022 at https://www.nps.gov/yell/learn/nature/hydrothermal-systems.htm.
- Kate, Kerry ten, Laura Touche, and Amanda Collis. "Benefit-Sharing Case Study: Yellowstone National Park and the Diversa Corporation." Paper submitted to the Exceutive Secretary of the Convention on Biological Diversity by the Royal Britanic Gardens, Kew (London), April 22, 1998, accessed Nov. 2, 2022 at https://www.cbd.int/doc/case-studies/abs/cs-abs-yellowstone.pdf. The final two pages are an inventory of microoganisms first isolated at Yellowstone Park, 1969-1994.
- “Life in Extreme Heat,” Oct. 5, 2020. National Park Service, accessed Nov. 7, 2022 at https://www.nps.gov/yell/learn/nature/life-in-extreme-heat.htm. Includes a good video about Yellowstone's thermophiles.
- McClain, Dylan Loeb. “Kary B. Mullis, 74, Dies; Found a Way to Analyze DNA and Won Nobel,” Aug. 15, 2019. New York Times, accessed Oct. 25, 2022 at https://www.nytimes.com/2019/08/15/science/kary-b-mullis-dead.html.
- Milstein, Michael. "Yellowstone managers eye profits from hot microbes." Science 264, no. 5159 (April 1994): 655, accessed Nov. 2, 2022 at https://www.science.org/doi/10.1126/science.8171315.
- Repanshek, Kurt. “National Park Service Finalizes ‘Benefits-Sharing Agreement’ That Could Benefit Parks,” April 6, 2010. National Parks Traveler, accessed Nov. 12, 2022 at https://www.nationalparkstraveler.org/2010/04/national-park-service-finalizes-benefits-sharing-agreement-could-benefit-parks5661.
- Sandomir, Richard. “Thomas Brock, Whose Discovery Paved the Way for PCR Tests, Dies at 94,” April 22, 2021. New York Times, accessed Sept. 10, 2022 at https://www.nytimes.com/2021/04/22/science/thomas-brock-dead.html.
- Shea, Marybeth. "Discovering Life in Yellowstone Where Nobody Thought it Could Exist," Nov. 8, 2018. National Park Service, accessed Nov. 2, 2022 at https://www.nps.gov/articles/thermophile-yell.htm.
- Sherer, John. “Yellowstone enzyme may be key tool in creation of Covid-19 vaccine,” April 14, 2020. KBZK.com (Bozeman, Mont.), accessed Oct. 6, 2022 at https://www.kbzk.com/news/local-news/yellowstone-enzyme-may-be-key-tool-in-creation-of-covid-19-vaccine. Includes video interview with Annie Carlson, Yellowstone National Park Research Coordinator.
Illustrations
- The photo of Kary Mullis is from Wikipedia. Used with thanks.
- The photos of Mushroom Pool in the Yellowstone’s Lower Geyser Basin and the closeup of Thermophilic bacteria are from the National Park Service. Used with thanks.
- The image of Thermus aquaticus is from Wikipedia. Used with thanks.
- The University of Wisconsin photo of biologist Tom Brock and the video of him talking about his early work in the Yellowstone hot pools, “Rediscovering Yellowstone,” are from his 2021 obituary on a University of Wisconsin website. Used with thanks.