Clockwise: Frank Mello, Craig Mello, Roger Mello, Jeanne Day, Jim Mello, Sally Mello

Mello, an HHMI investigator at the University of Massachusetts Medical School, has spent his life searching for answers. And the discoveries he's brought back from his explorations have helped change how biologists think about the functioning of cells, with profound scientific and medical implications. On October 2, 2006, Mello's work was accorded the ultimate honor when he and his colleague Andrew Fire (of the Stanford University School of Medicine) learned they were to be awarded the Nobel Prize in Physiology or Medicine for their discovery of the remarkable biological effect called RNA interference.

Last November, Mello and his parents and siblings gathered on a rainy Sunday afternoon at the parents' farm in the Blue Ridge foothills. The Mellos are an unusually close family, but they hadn't all been together since the Nobel announcement. Amidst hugs and congratulations, the family discussed who would be going to Stockholm in December for the Nobel ceremonies and who would be staying home to take care of the farm. "It's the busiest time of the year for us," said the family patriarch, James Mello.

Jim, an open and cheerful man who sets the tone for the family's conversations, was a paleontologist at the Smithsonian Institution in Washington, D.C., until the last of his four children graduated from college. He and his wife Sally then built a log house on property they had bought near Culpeper, Virginia, and began raising cut-your-own Christmas trees and organic vegetables that they sell in the local farmers' market. Over the next two decades, all their children except Craig moved to their own farms within a quarter mile of their parents' house. The oldest, Jeanne Day, is a librarian and artist who sells her hooked rugs in the area. The second-oldest, Frank, is an engineer and metalworker whose wrought-iron sconces decorate his parents' home. The youngest, Roger, is principal of the local high school, renowned for both his discipline and the poetry he quotes to his students.

For two hours that Sunday afternoon, as clouds scudded across the ridgeline opposite the Mellos' hilltop house, the family talked about school, sports, science, and the Nobel Prize (see Media Box). In many ways, the Mellos were a typical suburban family while the kids were growing up. Jeanne rode horses and the boys joined their high school wrestling and football teams. Craig and his siblings spent hours wandering through their neighborhood catching snakes, toads, and salamanders. (Craig once brought some of the toads to his high school biology class to dissect.)

		Listen as Craig Mello, his siblings, and his parents reminisce about times past. Play Audio

Once Craig built a crossbow in the family workshop and convinced his younger brother to lie with him in the backyard while they shot arrows into the air. "The game was to shoot an arrow as straight up as you could," said Craig, an experimentalist even then. "It was fun to watch it go up, and then it would turn around and come down. But no matter how hard you tried, you could never make it come straight back down. So I told [Roger] we were totally safe, just stay next to me. And sure enough nobody got hurt."

"We figured Craig was either going to win a Nobel Prize or a Darwin Award," said Roger.

The Mellos also exhibited a fierce devotion to education, achievement, and clear thinking. Jim and Sally both attended Brown University in the 1950s, and Sally—a painter in the time she could spare from raising four children—oversaw an intellectually rich household. After she prepared dinner, the family would sit down together and devote their mealtime conversation to the topic of the day.

Jim*: I worked in the museum, and I would bring home stuff about what was going on in science. We would talk about it at the dinner table. Craig was the one who would always challenge me. Do you remember those days, Craig?

Craig: My favorite line was, "That's the most ridiculous thing I've ever heard."

Jim: I remember when the first tube worms were discovered. We actually got specimens—these big six-foot-tall, encased worms—at the museum. I was always interested in this sort of thing, and maybe some of the enthusiasm that I had for it carried over.

Jeanne: I remember the blue-tailed skink conversation. Dad had just given us a nice talk about lizards, and he said, "You could always tell a blue-tailed skink because it always has a blue tail." And Craig said, "But that's not necessarily true, because you just told us that sometimes they lose their tails."

Craig: One time, when I was really into astronomy, I said Sirius was a southern star, and you couldn't see it from North America because it was in the southern hemisphere. Jeanne pointed out that she had seen it, so I must be wrong, because she had never been to the southern hemisphere. That was such a crushing argument.

Those conversations were great for our self-esteem. You [Jim] would listen to what we had to say and never put us down. If you disagreed with what we said, you would argue with us, and you didn't get upset if I said, "That's ridiculous."

Jim: No, I was delighted.

*This conversation has been edited for the Bulletin.

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