Mayo Alumni Magazine 2002 Spring - MC4409-0402 - Mayo Clinic

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sample. Because each DNA copy serves as a template for producing yet another copy of DNA with each heating and cooling cycle, the amount of DNA is increased exponentially, so eventually there is enough DNA available to run further tests on it. In the final step, the amplified DNA is probed for evidence of the organism’s presence. Historically, each of these steps has required hours to complete. Speeding up PCR technology Jim Uhl, a member of the microbiology team that developed the rapid anthrax test, demonstrates how the device works. “We spend a great deal of our time searching the genomes of microorganisms,” says Dr. Cockerill. “Humans evolved from these organisms and some of their DNA is the same as ours. So we need to find their fingerprints — unique segments of DNA that specifically identify them.” The second step incorporates PCR technology — using an enzyme called Taq polymerase to copy the DNA. This chemical reaction is repeated 30 to 40 times by heating and cooling the The key to producing a rapid PCR test was the development of a new technology, trademarked as the LightCycler, and its application to clinical microbiology diagnostic testing. It was a feat that evolved from international, multidisciplinary collaboration between its inventor, Carl Wittwer, Ph.D., a University of Utah chemist with an engineering background; researchers at Boehringer Mannheim, a Bavarian chemistry plant that later merged with the Swiss company Roche Applied Science; and the Mayo microbiology team. Mayo Clinic was the first institution in the United States to use the LightCycler when, in February 1998, the microbiology team procured it for a 30-day trial. Roche Applied Science was marketing the tool to research laboratories, but Lester Wold, M.D., chair of the Department 4 Mayo Alumni Spring 2002
of Laboratory Medicine and Pathology, credits the team with envisioning the LightCycler as a tool that could be used for clinical assays as well. “That’s the beauty of the LightCycler,” says Dr. Wold. “We can use it today to identify the presence of anthrax in a research laboratory, but tomorrow it can be used to diagnose strep throat in a physician’s office.” The LightCycler is a modest-looking instrument. “It looks like a coffee maker and acts like a sophisticated hair dryer,” quips Dr. Cockerill. “It contains a heating element and a fan that blows air on the sample to heat and cool it much faster than the old heating blocks were capable of doing. It also incorporates a mechanism to detect if a probe attaches to the DNA, indicating that an infectious agent is present.” Changing the microbiology landscape The team began by prioritizing the list of disease-causing microorganisms they slated for developmental activities using the LightCycler. They focused on common diseases, such as streptococcal sore throat, whooping cough and chicken pox. The anthrax bacillus was well down the list because anthrax cases had not been seen in the United States for decades. For each targeted microorganism, team members reduced the DNA extraction step to a few minutes or less. Then, using the LightCycler technology, they combined the second and third steps — amplification and probing — into a single, 30-minute analysis. The entire test eventually took less than one hour. By September 11, the Mayo laboratory stopped using culture tests for several common infectious diseases. The rapid PCR tests were faster, cut costs in half and were more accurate. “The rapid PCR test can diagnose 219 percent more cases of whooping cough than conventional culture,” says Dr. Cockerill. “With increasing emphasis on molecular diagnostic testing, patients can soon expect results from their infectious disease tests on the same day — just as they do now for a blood glucose test.” September 11, the anthrax outbreaks and the final sprint “September 11 revealed a fundamentally different level of terrorism that caused us to turn the focus of our development efforts toward biologic agents,” says Dr. Wold. Dr. Cockerill was scheduled to teach at Mayo Medical School on the morning of September 11 but canceled classes when he saw the level of distress among the students. “Instead, I met with Tom Smith and Jim Uhl,” he explains. “As soon as we saw the second plane hit the World Trade Center, we knew that anthrax attacks would be a possibility.” “The LightCycler contains a heating element and a fan that blows air on the sample to heat and cool it much faster than the old heating blocks were capable of doing. It also incorporates a mechanism to detect if a probe attaches to the DNA, indicating that an infectious agent is present.” — Franklin Cockerill, M.D. Spring 2002 Mayo Alumni 5
Page 1 and 2: Spring 2002 Mayo Alumni Mayo Clinic
Page 3 and 4: Letter from the Secretary-Treasurer
Page 5: Members of the microbiology team th
Page 9 and 10: Testing in the Rochester field By O
Page 11 and 12: From left to right, Judy Dokken, Ph
Page 13 and 14: then went on, but I won’t forget
Page 15 and 16: Left: Mayo Clinic Sports Medicine C
Page 17 and 18: “It is a great thing to make scie
Page 19 and 20: A profile of Dr. Michele Halyard: T
Page 21 and 22: compassion and creativity merge to
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Page 25 and 26: esource Central Mayo Graduate Schoo
Page 27 and 28: Dr. Gunderson received his medical
Page 29 and 30: Therapy Program at Mayo, Dr. Bender
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Page 35 and 36: Mayo Medical Alumni Association Off

Mayo Alumni Magazine 2002 Spring - MC4409-0402 - Mayo Clinic

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