Health & Medicine

August 28, 2012

UCD professor Michael Turelli finds biomathematics work 'ridiculously satisfying'

Overlooking a sunny courtyard, UC Davis professor Michael Turelli sits at a desk with a yellow legal pad, scientific papers and a computer. Next to a chalkboard covered with mathematical scrawlings, books written by his colleagues line the walls of his office.

Overlooking a sunny courtyard, UC Davis professor Michael Turelli sits at a desk with a yellow legal pad, scientific papers and a computer. Next to a chalkboard covered with mathematical scrawlings, books written by his colleagues line the walls of his office.

Stacked on a table are music books and CDs, each with an explanatory sticky note, borrowed from a friend he's known since high school.

Turelli, whose colleagues last spring honored him with the UC Davis Distinguished Faculty Lecture Award, said his is a "ridiculously satisfying occupation."

He cites brilliant students and insightful collaborators – but also chance.

"Luck has played a great role in my career," he reflected recently.

Through his studies of bacteria living inside California fruit flies, he has helped to develop a disease-control strategy. Surprisingly, it's for dengue fever, a disease spread by mosquitoes – not in the arid climate of the Central Valley, but in the tropics. How his research focused on a disease that threatens great populations half a world away is a story he unfolds.

In the 1970s, Turelli's long, white beard was nonexistent. He had worked his way through UC Riverside to complete an undergraduate degree in mathematics and was "dead keen to not worry about making money anymore."

So he went to graduate school. Instead of studying pure math, he applied it to biology, as an article in Newsweek had persuaded him to do.

He got his doctorate – and a job at the University of California, Davis – in 1977.

"I was a Ph.D. on Thursday, and a professor on Monday," he recalled.

He leaned back in his chair and crossed his Birkenstock-clad feet.

"Someone like me would never get a job now – I'm too slow," he said, again tapping a sense of humor that draws on self-deprecation.

As a professor, Turelli ventured from the pure theory of his University of Washington graduate studies – "esoteric mathematical objects" that could be applied to ecology – into experiments.

He was motivated by his wife, who told him to work on something "real," and by his Ph.D. adviser, who had told him he "would make a fool of myself if I tried to do experiments."

To make sure he didn't, Turelli hired his first postdoctoral scholar, Australian Ary Hoffmann, now a professor at the University of Melbourne.

"Even though he was my postdoc, I learned much more from him than he learned from me," wrote Turelli in an email.

Hoffmann confirmed with a laugh that he did teach Turelli some experimental methods.

"He really got excited about all the experimental things," he said.

The two studied fruit flies.

"You're a geneticist; what else are you going to study?" said Turelli. "They're so easy to manipulate."

They wanted to learn how Northern California apple-eating fruit flies, and citrus-eating Southern California ones, were adapted to their environments.

Because flies love rotting fruit, Turelli and Hoffmann set out buckets of it. Days later, they'd use nets to swoop up hundreds of flies.

As Hoffmann mated the flies to understand their genetics, all embryos died when Southern California males mated with Northern California females. The reverse worked just fine. It turned out to be because of a genus of bacteria called Wolbachia that lived inside only southern, not northern, fruit flies.

Wolbachia are known from other insects. Passed on only by females, they had an effective way of spreading through a population.

A noninfected female can have offspring only with a noninfected male. But an infected female can mate with any male. So if a Wolbachia infection is common enough, females with it can have more offspring, and pass it to them.

"All of a sudden Michael and I had an interesting project on our hands. We not only discovered this Wolbachia, but we stumbled across a unique situation where (they) were spreading," said Hoffmann.

"I did not come to California to work on Wolbachia," he joked. Yet they continued.

The two witnessed Wolbachia spread from Southern into Northern California fruit flies, and to all of North America, in a matter of years.

"My role switched to a mathematician," explained Turelli, who used mathematical models to better understand the spread of Wolbachia. Those models were motivated by "no practical interest whatsoever," but by "making predictions about how nature should work."

Others, though, were intrigued by Wolbachia's potential for disease control. If the bacteria could spread so easily among insects, maybe they could spread along with other things that stopped those insects from carrying diseases.

Believing that "the role of math is to guide experimentalists," Turelli told them over the years that their disease-control strategies were too "intimidating," and wouldn't work.

He shook his head at the memory, saying: "But Scott O'Neill wouldn't give up."

The professor at Australia's Monash University wanted to control dengue fever, a sometimes deadly tropical disease caused by a virus spread by mosquitoes.

O'Neill and his team of researchers found a variety of Wolbachia that, unlike others, shortened the life of the insect. A mosquito with this type of Wolbachia would die before it could transmit dengue fever.

Since Wolbachia don't naturally occur in mosquitoes that transmit dengue, it took years of effort to finally get the bacteria into them in 2009.

Decades after Hoffmann and Turelli's fruit fly discovery, it seemed perfect: Mosquitoes couldn't transmit dengue if this version of Wolbachia could be spread to all of them.

"Michael had done quite an elegant job of modeling Wolbachia spread" in fruit flies, said O'Neill. He wanted to learn whether it would spread in mosquitoes.

But based on his own calculations and some of O'Neill's experiments, Turelli found that this version of Wolbachia wouldn't easily spread.

In 2010, Turelli thought the control measure was doomed.

"Again, Turelli has spoiled the party," O'Neill said, building the suspense.

But around the same time, another scientist found that Wolbachia, even more spreadable kinds, could themselves make insects able to withstand viruses such as dengue.

"So forget shortening life," exclaimed Turelli. "The project went from disaster to elation."

"It was one of those things in science that can happen fortuitously," said Hoffmann.

"Dumb luck," Turelli called it.

Mosquitoes with Wolbachia could be introduced into the wild, the bacteria would spread, dengue transmission could stop.

Turelli, with biologist Nicholas Barton of the Institute for Science and Technology Austria, then developed models for introducing them.

Through some "numerical hackwork," the two found "an extraordinarily pretty result," said Turelli, animatedly gesturing to a graph on his Mac.

They had to release mosquitoes "over an extended area, not all in one big heap," explained Barton.

"It provided us with a framework to think about the numbers that we could start with," said O'Neill.

A year ago August, O'Neill and his Eliminate Dengue team of more than 60 people successfully released mosquitoes with Wolbachia into several isolated areas of northern Queensland in Australia. They spread and could block dengue.

"All predicated on (Turelli's) predictions," said O'Neill.

Last year's test releases were like "a big outdoor cage," said Turelli. Wolbachia are so common among insects that there may be other versions of the bacteria better at spreading and blocking dengue.

"We're still working on what are the best strains (of Wolbachia), and what's the best methodology to employ," said O'Neill.

O'Neill expects more from Turelli, such as "helping us to decide which wine to drink at our annual meeting," he joked before turning serious – and "helping us to refine our thinking around each of the deployment strategies."

The team is setting up trials in Vietnam, Indonesia and Brazil, where dengue is endemic.

In the future, there could be help to manage insect-borne diseases such as West Nile virus or malaria.

For now, "dengue is keeping us preoccupied," said O'Neill.

"When you work as a team together, with a bunch of really good people, you're going to achieve an awful lot," said Hoffmann.

"We have a certain synergy and it works well," he said of his work with Turelli, whose theory informs his experiments, and vice versa. "That's why we make a good team."

Yet, there's more to a successful collaboration. You "need to have a personality in order to be able to work together effectively," O'Neill said. "(Turelli) is a very special person."

"He always gets you inspired by whatever you're working on," said Barton. "He carries people away with his enthusiasm."Dengue fever

Every year, 50 million people are infected with the dengue virus. People of Indonesia, South and Central America, Southeast Asia, sub-Saharan Africa and some parts of the Caribbean (nearly 40 percent of the world's population) are at risk.

The virus that causes dengue fever is transmitted by a type of mosquito.

Dengue fever is aptly nicknamed "breakbone fever." For a week or more, a person with it can sustain a high fever of up to 105 degrees, a severe rash, joint pain and extreme discomfort. The most severe infections and complications can result in death.

There is no vaccine or treatment, and those with dengue have to wait it out.

Professor Michael Turelli

Born: 1950 in Brooklyn, N.Y. ("It's always easy for me to calculate my age," he says.)

Education: 1972 graduate of the University of California, Riverside, with a degree in mathematics; 1977 earned a doctorate in biomathematics from the University of Washington.

Career: Joined the University of Calfiornia, Davis, faculty in evolution and ecology in 1977.

Home life: He lives between Davis and Winters amid an arboretum with more than 500 trees with his wife and 9-year-old grandson, who accompany him when he visits collaborators in Australia and Austria. He makes olive oil, listens to chamber music, goes to art openings and does "the usual stuff that people do."

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