Craig Mello '82 felt "total disbelief" as he stood in his bedroom before dawn the morning of Oct. 2. At 4:40 a.m., a man with "a very dignified accent" had called to tell the former biochemistry concentrator he'd won the 2006 Nobel Prize in Medicine.
"I just couldn't believe it," Mello, who is 45, told The Herald. "My first words were, 'you've got to be kidding.'"
In December Mello and fellow researcher Andrew Fire will be awarded science's top international honor - and will share the accompanying $1.37 million cash prize - for discovering a process that researchers might use to cure cancer and other diseases.
The so-called "RNA interference" technique enables scientists to perform "gene silencing," which allows researchers to test what every gene in the human body does, and, potentially, pinpoint which genes make people sick.
"It's like a dream come true," Mello said of receiving the prize. "If you're a religious person, it's a gift from God."
Professor of Biology Kenneth Miller '70 P'02, who taught Mello in the fall of 1980, described the discovery as "revolutionary."
"It has affected the course of research everywhere," Miller said. "I'm convinced it's going to lead to significant medical breakthroughs in the decades ahead."
How it worksGenes tell cells how to behave; when a person has cancer, genes instruct cancer cells to multiply.
Thanks to Mello's discovery, which was published eight years ago, researchers now may be able to determine specifically which genes trigger that undesirable cell growth.
The breakthrough allows scientists to de-activate isolated genes and observe whether cells behave differently when those genes aren't functioning.
"If you want to know what a particular gene does, you get rid of it," explained Professor of Medical Science John Sedivy, who chairs the Department of Molecular Biology, Cell Biology and Biochemistry.
To simplify, he likened the cell to a car.
"If you put a nail in the tire, the car won't roll," Sedivy said. "That tells you something about what the tire does."
Prior to Mello's 1998 discovery, the only methods available for disabling - or "silencing" - genes were cumbersome and inconsistent.
Professor of Medical Science Michael McKeown said the discovery will allow scientists to "go off and test every gene." That means scientists might be able to not only identify cancer-causing genes, but also turn them off, thereby curing certain forms of the disease.
Mello said he is trying to help people understand the possible applications of his findings. "This creates a new opportunity to help people who are suffering from diseases that have no other cure," he said.
While the medical community is abuzz with excitement, biologists are applying Mello's discovery in different ways. They can use it in myriad organisms, from plants to fungi.
Miller said thousands of labs worldwide have been using Mello's method since shortly after his findings were published.
"Almost everybody in biology thought, 'Wow, I can use this to help solve my particular research problem.'" Miller said.
Scientists typically wait much longer than the eight years Mello did before their discoveries are recognized by the Nobel Assembly. At 45, Mello is considered a young Nobel recipient.
Miller said the assembly likely recognized Mello's work so soon after his findings were published because they had already had a cataclysmic impact on the scientific community.
The moment of discoveryAs a professor of molecular biology at the University of Massachusetts Medical School, Mello experimented for four years with RNA interference before developing his breakthrough. RNA interference is the method by which scientists silence genes. Because RNA strands carry messages from DNA strands, which control the makeup of genetic material, scientists can indirectly yet precisely de-activate genes by altering a cell's RNA.
In 1995, still paying off his Brown student loans, Mello began manipulating RNA sequences in nematode worms. The breakthrough came three years later, though at the time neither he nor Fire knew how to interpret the results.
"It was mind-boggling," Mello said. "We spent long hours on the phone discussing what all these could mean."
The two published their findings in 1998, but it wasn't until 1999 that the pair discovered that their results were applicable to humans.
"That to me was the most exciting moment," Mello said.
How the technology is used in the future hinges largely on how much funding is available. Miller said major pharmaceutical companies have invested hundred of millions of dollars in RNA-interference technology. He wants the federal government to finance similar testing.
"If we don't, other countries will," he said. "This is an opportunity we can't afford to pass."
Fond memories of BrownIn the fall semester of 1980, Mello earned an A in Miller's BI 105: "Eukaryotic Cell Biology." Miller remembered Mello as "intense" and "inquisitive."
The native of Fairfax, Va., whose parents met at Brown, attended the University at the same time as three of his siblings. He recalled his days on College Hill with great nostalgia.
"Brown was a fantastic place for me, and the education I got there just prepared me so well for my future," he said. "It was a wonderful home away from home."
Mello wanted to attend Brown because of his family's ties to the school as well as the fact that it was near his grandparents' house in Warren. He kept his Sunfish sailing boat there and often sailed with friends from Brown on Narragansett Bay.
Now a resident of Shrewsbury, Mass., Mello remains an avid sailor, though his vessel might be due for an upgrade. The Nobel laureate still glides down the bay in a precarious Hobie Cat he bought more than 20 years ago, right after he graduated from Brown.
"It's a fun boat," he said. "But maybe now I can get a little bit bigger, drier boat."
