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Mello, Fire, and their colleagues published their results in Nature in 1998, calling the effect RNA interference (or RNAi) after polling other worm researchers for an appropriate name. Their paper triggered an avalanche of new findings. Mello, Fire, and other researchers soon uncovered a cellular mechanism that explains not only the original findings but other unexplained occurrences of gene silencing in organisms such as petunias.
Furthermore, the mechanism they discovered turned out to be part of a much larger system that regulates the expression of many genes in multicellular organisms, including humans. When double-stranded RNA is introduced into a cell, a protein known as Dicer cleaves it into double-stranded fragments 20 to 25 base pairs long. The fragments are then incorporated into a molecular structure known as RISC (RNA-induced silencing complex), which degrades messenger RNAs that have the same nucleotide sequence as the RNA fragments, blocking the action of the gene that produced the messenger RNA.
As soon as it was discovered, RNAi was put to work as a powerful research tool. Researchers use it to silence genes one by one to determine the effects of each gene on a cell's growth and function. The same technique can block the action of genes that have gone awry in disease. Today, RNAi is being tested for its ability to treat respiratory infections, macular degeneration, hepatitis, cancer, and other illnesses.
The insulin gene, which first attracted Mello to biology, has continued to influence his life. Four years ago, his daughter Victoria, who is now six, was diagnosed with type 1 diabetes. Mello's wife Edit, whom he met at a dance the same year the Nature paper was published ("It was a good year," Mello says.), is a nurse, and the two of them meticulously monitor Victoria's blood sugar level as a part of a daily regimen of insulin injections. "Our pediatrician recommended that we check her every night in the middle of the night," Mello says "Usually we check her about 1 a.m., and if all is well we can sleep for the rest of the night. But if at 1:00 her blood sugar is high, we have to give her insulin, and then we have to check her later to make sure that everything is okay."
When the call from the Nobel committee came on October 2, Mello was actually in Victoria's room checking her blood sugar. Edit didn't know that the prize was being announced that night and hung up on the first call. "She thought it was a crank call, because who calls at that time, anyway?" But Mello's father had mentioned to him the previous day that the prize was being announced that night.
Craig: [As the phone rang again] I said to her, in a calm voice, "Yeah, but they're announcing the Nobel Prize tonight, so I'd better pick it up."
Jim: He called me after he got the news. At first I was elated, and then I said, "Craig, are you sure this isn't a joke." And [Craig] said, "I'm watching the Nobel screen right now; and, yup, there comes Andy's and my name at the top of their Website."
Craig: It was just amazing.