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Winter 2004

Running Straight Up: UM Scientist May Have Found Missing Link in Evolution of Flight

GIS For All: UM Project Spreads the NASA Technology Gospel

Easing the Pain: UM Professor Helps People Cope After Surgery

Precious Crab Blood: University Breakthrough Stands the Test of Time

Moss Unmasked: Researcher Finds Benefit of Common Forest Plan

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MICROBIOLOGY

Precious Crab Blood
University Breakthrough Stands the Test of Time
Most researchers dream of producing something that benefits humankind. UM scientist Jon "Tony" Rudbach did just that in 1976.

Tony Rudbach
UM's Tony Rudbach helped develop the standard to test a lifesaving chemical made from horseshoe crab blood.

Rudbach now is UM's assistant vice president for research and economic development, but back then he led a team of scientists in the University's Department of Microbiology. His laboratory at that time was asked by the U.S. Food and Drug Administration to create a new substance -- or reagent -- to test an innovative chemical that protects vaccines, drugs and other injected substances from dangerous endotoxin.

"We received an $18,000 grant, which was a lot of money in those days," Rudbach says. "Since the reagent we produced became the international standard, I think it was money well spent."

Endotoxin is all around and inside us. It is a potent toxin created by the breakdown of bacteria cell walls. Human beings can ingest endotoxin without symptoms, but if even microscopic amounts get beyond our digestive tracts into other parts of our bodies, the results can be fever, low blood pressure, shock, organ failure and death. Boiling or cooking can destroy bacteria but not endotoxin.

Drug companies and hospitals once tested for the presence of endotoxin contaminates by injecting samples into rabbits. If the rabbits got a fever or died, the drug was discarded.

Then researchers at the Woods Hole Oceanographic Institute in Massachusetts discovered that the sapphire-blue blood of horseshoe crabs contains a chemical called Limulus Amebocyte Lysate (LAL), which clots in the presence of endotoxin. The compound is a thousand times more effective at detecting the toxin than rabbit testing.

Once considered junk fish, horseshoe crabs now have blood that's precious as gold, since the compound inside these living fossils is found nowhere else on Earth. Science still hasn't figured out a way to make synthetic LAL.

But how do you test the potency and effectiveness of LAL? That's where Rudbach came in. His Montana lab tested LAL with endotoxin generated from a variety of bacteria. This resulted in the discovery of a "typical" endotoxin with average biological potency -- not the most toxic or least toxic. This average endotoxin, which has excellent properties of stability and solubility, was produced from Escherichia coli, though at least 16 other types of bacteria also were tested during the UM research.

Rudbach says the standard endotoxin they produced looks like a white powder. People could eat the stuff, but if it was injected, they wouldn't last long. But it was perfect for testing lifesaving LAL supplies around the world, and the UM-created endotoxin became the standard for testing the miracle horseshoe crab compound. It also established a set sensitivity for LAL stocks around the globe, and the standard endotoxin remains stable for decades under normal storage conditions.

"We developed the standard," Rudbach says. "The reagent we designed is still in use today."

The FDA has required an LAL test for all drugs used by humans since 1987, and UM's endotoxin standard went international in 1997 when it was adopted by the World Health Organization.

LAL is used to find contaminants in every injected drug and vaccine, every artificial joint and implanted device, and every intravenous drip in every hospital in America, as well as in many health-care facilities worldwide. Blood supplies generally aren't tested by LAL, but almost anything else injected or placed in the human body must pass muster with the chemical.

Thomas Novitsky is the former president and CEO of Associates of Cape Cod Inc. of Massachusetts -- one of the world's leading LAL producers. He says, "It is a tremendous credit to Tony that his standard has withstood the test of time and is still in use today. I have been extremely fortunate in my career to have personally known most of the major players in modern endotoxin research. Tony is definitely one of these."

Rudbach says developing the standard endotoxin for the LAL test was an exciting time in Missoula. The eight-member team in his lab included graduate and undergraduate students who made important contributions to the research -- students who later went on to successful careers in a variety of fields.
Rudbach's UM success catapulted him to the head of Infectious Disease and Immunology Research at Abbott Laboratories in Illinois during 1982-85. He also taught at Chicago Medical School before working as an administrator at Ribi ImmunoChem Research Inc. in Hamilton from 1985 to 1995. During that time he also returned to UM as an adjunct professor of microbiology and formed his own consulting firm, Technology Resources International. He also was an officer for six years in the International Endotoxin Society.

In his current position as UM assistant vice president for research and economic development, Rudbach works to stimulate Montana's economy by transforming UM research into private-sector businesses -- a process called technology transfer.
It's a role he relishes because one never knows when the fruits of Montana university research will cast far greater shadows than those of the surrounding Rocky Mountains.

-- By Cary Shimek


Rita Munzenrider, Director
University Relations
The University of Montana-Missoula
32 Campus Drive | Missoula, MT 59812
phone 406-243-2522 | fax 406-243-4520
© 2007 The University of Montana

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