'Hot Zone' led Wisconsin scientist to Ebola research

University of Wisconsin-Madison scientist Yoshihiro Kawaoka was researching influenza viruses that were killing chickens in the mid '90s when he picked up a new bestseller, "The Hot Zone."

Richard Preston's 1994 novel dealt with the genesis of viral hemorrhagic fevers, particularly Ebola and Marburg. It described a secret Army mission to wipe out a colony of sick African monkeys housed in Reston, Va. — monkeys that had been imported for research, but that arrived infected with a mysterious rain-forest virus thought to be the deadliest ever known.

A professor of pathobiological sciences at UW-Madison's School of Veterinary Medicine, Kawaoka realized while reading "The Hot Zone" that he could advance the world's understanding of the little-known virus. He could apply to Ebola his knowledge about how influenza replicates in the cells of chickens and how their bodies respond to being infected.

"I knew the pathology," Kawaoka said in an interview. "I've done lots of dissection of chickens infected with highly pathogenic viruses."

Kawaoka, who is best known for avian flu research, contacted the federal Centers for Disease Control and Prevention in Atlanta, telling the nation's top health officials that he wanted to work on Ebola.

Kawaoka first had to figure out how to alter the deadly virus so it was safe enough by federal government standards to work with in a Madison lab that, in terms of safety and security, is one notch below the CDC's top lab in Atlanta. He consulted with a scientist in Tennessee who had figured out how to disarm a deadly swine influenza. Kawaoka became the first scientist using the same reverse genetics to render Ebola incapable of replicating and binding to cells.

The federal government, after initially rejecting the safety level Kawaoka proposed, reversed its position.

He published his first Ebola paper in 1997, and went on to develop a candidate vaccine that never made it to clinical trials when government funding ran out in 2012 after about 10 years of vaccine research.

The vaccine protected two monkeys from Ebola — the gold standard — but Kawaoka never got to expand the number of monkeys given the vaccine to determine why it protected them. He needed that information to make a case for clinical trials.

When government funding dried up, he could have been upset.

"In this business, I don't put any emotion into it. Frustration doesn't help," he said.

Had the funding been there, Kawaoka said, "I would have known by now whether it was a promising candidate."

Kawaoka's research has explored how many mutations — and which ones — could make the jump from birds to people happen. His work is so sensitive, it was briefly in the news because of fears it could fall into the wrong hands and pose a threat.

On the Ebola front, Kawaoka is leading a team of researchers that last year received an $18 million grant from the NIH to develop a detailed molecular understanding of what happens when lethal viruses such as Ebola, influenza and West Nile infect their hosts. That's useful for developing anti-viral drugs. Scientists also can use that knowledge to potentially enhance the body's immune response and develop better treatments and prevention, he said.

At the time "The Hot Zone" was written, three of Ebola's seven known proteins were vaguely understood and four were "completely unknown." Their structure and function were a mystery.

Today, Kawaoka said, "we know the functions of most of the proteins to some extent, but not completely. We are looking for additional proteins made by Ebola virus, but not found yet."

The U.S. Department of Health & Human Services announced it is accelerating support for an Ebola vaccine under a one-year, $5.8 million contract with a Baltimore company. The clinical-state biotechnology company will manufacture vaccine for use in animal safety studies and future clinical trials, and conduct animal studies.