2 Americans, Israeli share Nobel

Their independent work, published in 2000, provides fundamental information about the workings of the cellular machinery at the atomic level and is already being exploited by pharmaceutical companies working to make new, more effective antibiotics.

The $1.4 million prize will be shared equally by Thomas A. Steitz of Yale University; Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology in Cambridge, England, who was born in India but is now a US citizen; and Ada E. Yonath of the Weizmann Institute of Science in Rehovot, Israel.

Yonath is the only one of this year’s nine science winners who is not an American citizen, either native or naturalized. She is the first woman to receive the chemistry Nobel since Dorothy Crowfoot Hodgkin of Britain received the 1964 prize, and who was also honored for her contributions to X-ray crystallography. Yonath is also the first Israeli woman to receive a Nobel.

“It’s true that a woman hasn’t won since 1964,’’ she told Israeli radio. “But I don’t know what that means. Does it mean that I’m the best woman since then? I don’t think gender played a role here.’’ Her radio chat had to be cut short because of a call from Israeli President Shimon Peres.

On Monday, Elizabeth Blackburn of the University of California, San Francisco, and Carol W. Greider of Johns Hopkins University School of Medicine shared the medicine Nobel with Jack W. Szostak of Harvard Medical School, marking the first time that two women had won that prize in the same year.

X-ray crystallography is a time-consuming and tedious science that requires excruciating patience and care to produce crystals of cellular proteins and then sophisticated mathematics to analyze the X-ray patterns that arise when an X-ray beam is focused on such crystals. This is a difficult process with small proteins from cells, and many researchers thought it would be impossible with the ribosome, which is one of the largest proteins in living organisms.

The ribosome translates the cell’s genetic information into the proteins that actually make the cell function. It has a large and a small subunit, each of which contains thousands of the nucleotides that comprise RNA and thousands of the amino acids that comprise proteins. Getting such a large, amorphous molecule to form precise crystals was something that had never been attempted before.

Undaunted, Yonath began trying to grow crystals in the early 1970s, working with a bacterium that can grow under harsh environmental conditions on the assumption that its ribosomes would be more stable and thus more resistant to degradation during the process of inducing crystals to form.

After 20 years of work, it became apparent that she could finally produce such crystals, and other researchers such as Steitz and Ramakrishnan joined the race to complete the work.

The X-ray images produced directly from a crystal are insufficient to reveal its structure. They lack crucial mathematical information that researchers call phase angles. This information is typically obtained by seeding the crystals with heavy metal atoms, such as mercury. But ribosomes are so large that obtaining the phase angles was exceedingly difficult. Steitz’s contribution was to determine how the ribosomes were oriented within the crystal. That, combined with the information from heavy metals, finally made it possible to determine phase angles and, in 1998, Steitz published the first crude crystal structure of the ribosome’s large subunit.