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A second contingent of Szostak's lab is working on the proto-cell genome. For a protocell to evolve in a Darwinian fashion its genome must replicate accurately, yet occasionally make mistakes. Bartel's team at MIT has evolved a replicase—an RNA molecule that begins to catalyze its own replication in test tubes—though better replicases are needed. In contrast, postdoc Alonso Ricardo and other Szostak lab members are devising protocells that need no replicases. They're fine-tuning chemical cousins of RNA and DNA that assemble spontaneously when provided with their respective building blocks, called nucleotides.
In 2008, Szostak's team reported in Nature that they created protocells that combine two of the essential properties of life. Fatty acid vesicles containing DNA could “feed” on nucleotides outside them, and then the ingested nucleotides could chemi-cally replicate the DNA fragment inside. The findings are crucial, Szostak says, because researchers had thought that nucleotides were too bulky to make it through a cell membrane unaided.
To be truly alive, according to the accepted scientific definition, protocells would also need to evolve via Darwinian natural selection. To do that, they'd need at least one trait specified by their genome that would let one protocell outcompete another. In 2004, Szostak and graduate student Irene Chen provided a proof of principle that such test tube evolution was possible. Physical and chemical forces alone, they found, make vesicles with more RNA grow bigger faster—and steal lipids from adjacent vesicles with less RNA. The results suggested that early cells that reproduced their RNA faster would have had a competitive advantage, and early cells with just a single gene—perhaps an RNA gene that could copy itself—could have undergone Darwinian evolution.
They also suggest that if Szostak can succeed in building a self-replicating nucleic acid and put it into a fatty acid vesicle, he'll have a living, self-replicating protocell.
At 4:45 in the morning on October 5, the phone rang at Jack Szostak's house, waking Szostak and his wife, Tel McCormick. It was Göran Hansson of Sweden's Karolinska Institute, who told Szostak that he, Carol Greider, and Elizabeth Blackburn had won the Nobel Prize for their groundbreaking early work on telomeres.
Szostak had little time to react. At 5 a.m., there was an interview with someone from the Nobel Foundation's website. By 6 a.m., a photographer from Harvard arrived, who shot photos of Szostak as he fielded call after call. When he finally made it to the lab, he saw balloons, streamers, and high-spirited lab members. There was a 10 a.m. party in the conference room with champagne, cheese, and crackers; lunch with the hospital's president; a visit to the statehouse to meet the governor, and nonstop interviews with newspaper and television reporters. It was enough to make anyone's head spin.
But not Szostak's. The next morning, Szostak rushed into his group's weekly lab meeting, where graduate student Ting Zhu would present his recent findings on lipid vesicles. An animated discussion followed, in which young chemists, biophysicists, and Szostak himself interrupted with questions and made theoretical and technical suggestions. It was a typical lab meeting.
Still, for weeks reporters and dignitaries remained in hot pursuit. There was a documentary for the BBC, a thick stack of requests for autographs, even a congratulatory note from President Obama, followed by an invitation to the White House. Nearly a month after the event, a reporter asked Szostak about his post-Nobel life. Was he eager to get back to science after the Nobel hullabaloo? Replied Szostak: “I definitely am.”