At 10 times the size of the biggest molecule anyone had ever solved, the ribosome crystals demanded a stronger heavy atom signal than is provided by simple heavy atoms. As the team worked through the twinning problem, they made a derivative using a super heavy atom cluster containing 18 tungsten atoms bound very tightly to each other. “At low resolution they scatter essentially as one atom containing 2,000 electrons,” explains Steitz. “That gave a strong signal, which got us started.” Ban did much of the heavy lifting, with Steitz offering a stream of ideas. Two more postdocs signed on, Poul Nissen and Jeff Hansen, and the quintet decided to inch their way up the mountain instead of racing to the top. That is, they collected low-resolution data producing fuzzy, low-resolution images, double-checked against all available data, and then gradually sharpened the picture. They developed new techniques at low resolution without investing the huge resources needed to obtain high-resolution data.

While mapping their first low-resolution images, the team double-checked their data against ribosome images made by HHMI investigator Joachim Frank of Columbia University College of Physicians and Surgeons. Though fuzzy by crystallography standards, Frank's electron microscopy images offered proof that the new techniques developed by the Yale team were, in fact, working. They drove on.

In 1998, the Yale team published their first paper on the ribosome, a low-resolution map of the large subunit—the factory component of the machine, the part that actually builds proteins. (The other part, the small subunit, is the foreman—it receives messenger RNA and tells the large subunit what to do. Co-laureate Ramakrishnan mapped it.) The team revealed their methods, and the race was on. “Everybody changed course,” says Steitz, adopting the new methods his team had developed.

Within a year, the Yale team sharpened the image threefold. It was time for the push to the summit—a trip to the powerful beam at Argonne National Laboratory in Illinois. Data poured in. Moore remembers seeing it and thinking, “Oh my god. We went out and caught the whale. Now what are we going to do with it? How are we ever going to figure out what all that stuff means?”

Raw crystallography data resemble blobs on a gray field. “There's nothing that says, ‘I am a carbon, I am a nitrogen,’” says Moore. The team spent months interpreting the blobs, nearly hand-placing each atom—all 100,000 of them. In early 2000, the team completed a finely wrought 2.4-angstrom-resolution structure. “It was extraordinary, says Steitz. “We had no idea what the ribosome was going to look like.”

Some 31 proteins glued together the outer shell and helped with housekeeping. But deep inside, where the protein-making magic happened, there was nothing but coiled RNA, 3,000 bases of it. Here, laid bare, was the secret of life, or at least one of them: Proteins were not built by other proteins, as biologists had once assumed. RNA did the job. For several decades, starting with Francis Crick in 1968, some ribosome researchers had theorized that to be the case, but the Yale structure proved it.

The implications were profound: The ribosome structure provided deep support for the theory that the first organisms on Earth were built from RNA. “The ribosome is a prime basis for the ‘RNA world’ hypothesis” of how life began, says former HHMI president Thomas Cech.

And while the shell differs from organism to organism, the business end, the RNA center, is nearly identical across every species on the planet. For some two billion years of cellular evolution, the same heart of machine has been there churning out proteins, building life. Fortunately, there exist minute differences between bacterial and human ribosomes. That's good news for Rib-X, and bad news for bacteria.

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