Historical review: Viruses, crystals and geodesic domes

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Abstract

In the mid 1950s, Francis Crick and James Watson attempted to explain the structure of spherical viruses. They hypothesized that spherical viruses consist of 60 identical equivalently situated subunits. Such an arrangement has icosahedral symmetry. Subsequent biophysical and electron micrographic data suggested that many viruses had >60 subunits. Drawing inspiration from architecture, Donald Caspar and Aaron Klug discovered a solution to the problem – they proposed that spherical viruses were structured like miniature geodesic domes.

Section snippets

Virus crystallography in the mid 1950s

Originally trained as physicists, both Caspar and Klug came to study spherical viruses via earlier investigations into the structure of rod-shaped tobacco mosaic virus (TMV). In 1953, after studying physics at Cornell University (Ithaca, NY, USA), Donald Caspar began his PhD in biophysics at Yale University (New Haven, CT, USA). His goal was to pass X-rays through an oriented fibre of TMV particles and then analyze the diffracted X-rays to infer how the virus is structured. In the same year,

The Crick–Watson theory of virus structure

At the end of the summer of 1955, Caspar traveled to England, where he met Franklin and Klug. In Cambridge, Caspar began to analyze BSV and, a little later in London, Klug began to analyze turnip yellow mosaic virus (TYMV), another well-studied spherical virus. Results came quickly for Caspar, but they were unexpected and novel. He discovered ‘spikes’ in the BSV diffraction pattern that indicated fivefold symmetry [6]. Max Perutz coined the term ‘spike’ while helping Caspar refine his

Caspar and Klug's collaboration

Caspar and Klug's collaboration began during great sorrow. In August 1958, Franklin was scheduled to talk in Bloomington (IN, USA) at a plant pathology meeting organized to celebrate the 50th anniversary of the American Phytopathology Society. She would have spoken on her recent work on TMV. Tragically, Franklin died of ovarian cancer in April 1958 at the age of 37. Under these unfortunate circumstances, Caspar was invited by the committee to speak in Franklin's place, and he suggested Klug's

Caspar and Klug's famous paper of 1962

Back in the USA, while considering hexagonal nets, Caspar derived a simple selection rule that described all the possible icosahedral quasi-equivalent structures (Eqn 1). In the meantime, Klug was invited to speak at the 1962 Cold Spring Harbor meeting (NY, USA). The invitation sparked a further collaborative paper. The transatlantic collaboration was extremely fruitful and Casper and Klug soon had too much material for one paper. They literally cut up Caspar's original notes and reassembled

Summary

To recapitulate, the biophysicists Caspar and Klug began their respective virology careers by working on the rod-shaped TMV. For Caspar, his TMV work brought him into professional contact with Watson. Crick and Watson argued, using theoretical principles, that small spherical viruses, such as BSV and TYMV, were constructed out of identical subunits in identical environments. They thought of viruses as ‘point-group crystals’. This analogy is perhaps not too surprising, as Crick and Watson

Acknowledgements

I thank the many people who kindly agreed to share their knowledge of the period, including Sydney Brenner, Carolyn Cohen, Francis Crick, John Finch, Alfred Gierer, Ken Holmes, Robert Horne, Hugh Huxley, Vittorio Luzzati, Max Perutz, Alex Rich, James Watson, Jo Wildy and especially Don Caspar and Aaron Klug. My colleagues Peter Achinstein, Angela Creager, Lindley Darden, Ed Lattman, and Bob Olby provided useful comments. The Novartis Foundation (formerly Ciba) allowed me access to their

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