From Ribosome to Royal Society Georgina Ferry Enjoys Venki Ramakrishnan’S Account of His Road to the Nobel Prize

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STRUCTURAL BIOLOGY From ribosome to Royal Society Georgina Ferry enjoys Venki Ramakrishnan’s account of his road to the Nobel Prize.

n 1968, the molecular biologist James Gene Machine: The and several others Watson electrified the staid world of Race to Decipher were contributing scientific biography by publishing The the Secrets of the key techniques to IDouble Helix, his memoir of the discovery of Ribosome improve crystal- DNA’s structure. Its irreverent style shocked VENKI RAMAKRISHNAN lization or locate

Oneworld (2018) MAX ALEXANDER/SPL and delighted readers in equal measure. And atoms. it changed how many think about science, by In 1999, Rama presenting it as a race in which winners got krishnan moved to the mecca of structural Nobel prizes and losers got nothing. biology, the Medical Research Council Lab- Fifty years later, structural biologist, Nobel oratory of Molecular Biology in Cambridge, laureate and Royal Society president Venki UK. Scientists at this one lab had already Ramakrishnan tells the story of his own garnered seven Nobel prizes. The institution marathon. In Gene Machine, he thoughtfully has now racked up 11 — more than some sci- embeds his trajectory in a wider meditation entifically advanced nations. Ramakrishnan on how scientists make the decisions that lead focused on the smaller of the ribosome’s subu- to success or failure — and on how they strug- nits, which decodes mRNA before the larger gle to solve complex problems. “Scientists will subunit assembles the protein. collaborate or compete depending on what is By 2000, he and his colleagues had solved in their self-interest,” he writes, adding that its structure, finishing neck and neck with competition can be “good for science, even if the team of Thomas Steitz at Yale, which it isn’t so great for scientists.” Venki Ramakrishnan. had solved the large subunit. Previously Ramakrishnan recognizes from the outset seen as a rank outsider, Ramakrishnan was that, although most people today have at least Yale University in New Haven, Connecticut. propelled into the limelight. A Nobel for the a vague idea that DNA is the carrier of genetic It was clear that the only way to under- ribosome work was being openly discussed. information, the ribosome barely registers. stand the ribosome was to solve its 3D There were up to six potential contenders Yet, without it, life as we know it would structure at the resolution of individ- for a prize that can be split only three ways. not have evolved. Every living cell contains ual atoms. Ramakrishnan retrained in James Watson twice told Ramakrishnan that millions of these complex structures, each X-ray crystallography, then the preferred he shouldn’t mind not being one of the three consisting of a large and small subunit and technique of structural biologists. when the time came. Yet, in 2009, the time incorporating a few dozen proteins and long Structural biologists face near-impossible did come. Yonath, Ramakrishnan and Steitz strands of RNA. They are themselves protein challenges. These include making floppy, shared that year’s Nobel Prize in Chemistry. factories. Each ribosome works along a mol- irregular proteins form crystals to bom- Ramakrishnan credits his wife, the art- ecule of messenger RNA, reading its copy of bard with X-rays; obtaining a diffraction ist Vera Rosenberry, with keeping him the genetic instructions encoded in DNA. pattern from the irradiated crystals before grounded: on hearing of his prize, she said, “I Guided by this, ribosomes assemble protein the structures disintegrate; and solving the thought you had to be really smart to win one chains that then float off to do the work of ever-present ‘phase problem’, the ambiguity of those!” He reflects on the disproportion- building and running the body. in a diffraction pattern caused by peaks in ate status such recognition brings. Suddenly, This much was already known when an X-ray wave giving the same intensity as you’re showered with other honours, and Ramakrishnan began to work on the ribo- troughs. Eventually, software generates maps expected to pronounce sagely on everything some in 1978 — although, as he writes, “we of electron density at high-enough resolu- from climate change to human cloning. had no idea how it did even one of the many tion to ‘see’ the individual atoms. For the big, Some readers might take issue with how complicated steps involved in making a complicated ribosome, many research teams events or personalities are presented in Gene protein”. The race for the ribosome would in different countries worked on each of these Machine. Yonath’s pioneering work is fully reframe it as an intricate machine with problems successively or simultaneously. acknowledged, for example. Yet, as Rama numerous working parts — which you can The acknowledged founder of the ribo- krishnan’s principal competitor, she some- now watch in action on YouTube. some field is Israeli crystallographer Ada times appears in an unfavourable light. This Indian-born, with academic parents, Yonath. She, with colleagues at the Max is not an objective history of the field, but a Ramakrishnan studied physics at the Planck Institute for Molecular Genetics in highly personal account. As such, anyone University of Baroda (now Vadodara) in Berlin, published the first successful crystal- who wants to know how modern science Gujarat. In 1971, he went to Ohio University lization of a ribosomal subunit in 1980. An really works should read it. It’s all here: the in Athens for graduate work in theoretical unwritten rule in crystallography at the time ambition, jealousy and factionalism — as well physics. By the time he had submitted his was that once someone had a crystal, every- as the heroic late nights, crippling anxiety thesis, he had decided to switch to biology. one else would leave it to them to progress and disastrous mistakes — that underlie Reading around a subject about which he to atomic resolution. Ramakrishnan writes the apparently serene and objective surface knew almost nothing, he picked the ribo- that the ribosome was different because of represented by the published record. ■ some on the strength of a Scientific American its importance, and the fact that years had article co-authored by biologist Peter Moore. gone by “without much apparent progress Georgina Ferry is the author of many Within a few years he was on the starting towards an actual structure”. By 1995, four books, including Dorothy Hodgkin: A Life. blocks, as a postdoc in Moore’s laboratory at groups around the world were in competition, e-mail: [email protected]