Research carried out in Baltimore wins Nobel

October 03, 2006|By Dennis O'Brien and Michael Stroh | Dennis O'Brien and Michael Stroh,Sun reporters

The year was 1997. Andrew Z. Fire, a 38-year-old Baltimore biologist, had just performed a neat trick that caused lowly roundworms to flick their genes on and off.

It was the kind of fundamental discovery that delighted Fire and his colleagues at the Carnegie Institution's Department of Embryology in Homewood. He never dreamed it would one day earn him a Nobel Prize.

But the trick - known as RNA interference - has since launched a new branch of biological research, spawning hundreds of scientific papers and potentially opening the door to new therapies for diseases ranging from cancer to macular degeneration.

Yesterday, Fire, who left Baltimore in 2003 for Stanford University, learned that he won the Nobel Prize in medicine for the work. He will share the $1.37 million prize with collaborator Craig C. Mello at the University of Massachusetts Medical School.

"Most of what we learned about basic biology has been turned on its head because of it," said William Kelly, an associate professor of biology at Emory University. "This was a field that didn't even exist six or eight years ago."

Other Nobel Prizes - the categories are physics, chemistry, literature, peace and economics - will be announced in coming days.

Fire, who is 47, learned of the award yesterday morning about 2 a.m., when he was awakened by a phone call from Sweden at his Palo Alto, Calif., home.

"Your reaction to something like that is they probably have the wrong number, and then I thought maybe I was dreaming," he said.

The announcement sent a ripple of pride among former colleagues at Carnegie and Hopkins.

"Many of us knew he was going to get a Nobel for this. It was just a question of when," said Kelly, who worked in Fire's lab at the time of the discovery.

For scientists at Carnegie's little-known Department of Embryology, nestled in the woods on San Martin Drive next to Johns Hopkins University, it's the second occasion to celebrate in the past few weeks.

Last month, the department's Joseph Gall was given a Lasker Award, the highest prize in U.S. medical research.

Allan Spradling, director of the department, said he and his colleagues planned to pop a few bottles of champagne to celebrate - "if we have any left from Joe Gall's award."

Change of plan

Fire originally planned to be a mathematician. He received a bachelor's degree in mathematics in 1978 from the University of California, Berkeley at the age of 19. (He finished high school at age 16.)

He changed his mind when some inspiring teachers at Berkeley turned him on to the world of biology.

He earned his doctorate in biology from the Massachusetts Institute of Technology in 1983 and worked as a post-doctoral fellow under Sydney Brenner, who won a Nobel for pioneering gene-sequencing in his Cambridge, England, lab.

Phillip Sharp, a Nobel-winning geneticist who served as Fire's adviser at MIT, remembers his sharp intellect. "One of the more difficult things I've ever done in my life is write a paper with him," he says. "Every word is debated."

He arrived at Carnegie's Department of Embryology in 1986.

Colleagues describe Fire as modest, somewhat shy and intensely private.

"We found out that his wife was pregnant the day after she had her baby," says Douglas Koshland, a Carnegie researcher who has known Fire since the 1980s.

At Johns Hopkins, where he remains an adjunct professor, Fire taught classes on subjects from how to critically evaluate scientific papers to patenting discoveries. He also volunteered at Polytechnic High School. "It was one of the most rewarding things I've ever done," Fire said yesterday.

Mary Montgomery, who worked in Fire's lab from 1994 to 1998, recalled that Fire also regularly volunteered for the tedious chore most scientists assign to their lab assistants - cleaning and preparing the petri dishes needed for his experiments.

As he looks back at the research that earned him the Nobel, he says, "I feel slightly guilty. It wasn't in a complete vacuum that we did our work. It was really a tapestry that was coming together."

Roots in flowers

The road to Fire and Mello's find starts, strangely enough, with flowers. Petunias, to be exact.

By 1990, plant biologists had noticed that when they tried to crank up the color of purple petunias by introducing red genes into the plant, instead of more color, they got less. In fact, the petals turned completely white.

The reason why remained a mystery until the mid-1990s, when Fire began toying with the RNA molecules inside small worms known as nematodes.

RNA, or ribonucleic acid, had long been considered mostly a boring bit player in the grand drama of cellular genetics.

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