News

Ewen Callaway’s News Feature in Nature on September 9, 2015 “The revolution will not be crystallized: a new method sweeps through structural biology” is astounding in its ignorance and disregard of historical facts. It disqualifies him as a serious science journalist. David DeRosier attempted to set the record straight in a Letter to the Editor, but his submission was dismissed by Nature, and relegated to the comments section of the journalistic masterpiece.

Here is David’s letter in full:

2015-11-29 10:55 PM

Callaway’s news feature in Nature (1) identifies the current excitement in cryo-electron microscopy but needs to be corrected because it provides an erroneous perspective of the historical antecedents of the field. Notable omissions are the introduction of single-particle methods by Joachim Frank (2) and the introduction of ice embedment by Taylor and Glaeser (3) and subsequently by Dubochet and colleagues; only the latter work is cited by Callaway in his article. Frank and collaborators developed single-particle methods over the years (2) and showed that by combining images from many particles and identifying their relative orientations, they could increase the signal-to-noise ratio and visualize structures in 3D. The amazing results cited by Callaway used single-particle methods. The revolutionary work of Unwin and Henderson, cited by Callaway, showed that we could see the biological molecules themselves and not just the negative stain castings. The difficulty was that it worked for crystals but not single particles because the density of the sugar embedment matches that of the particles. Thus one could neither see the particles, much less align them. Following the work of Taylor and Glaeser (3), who embedded samples in crystalline ice and showed preservation of high-resolution detail, Dubochet and his colleagues (4) revolutionized the embedment by rapid freezing yielding vitreous not crystalline ice. Because the density of ice is less than that of proteins and nucleic acids, single particles were easily seen in micrographs and aligned. Moreover, the method preserved features to atomic resolution, and the low temperature provided protection against radiation damage permitting more information per image. Thus one could study non-crystalline samples using single particle methods. The improvements in EM hardware are essential (1) as are improved computer programs to process images. There are several suitable programs; it is unclear which is best. What is true is that all incorporate elements introduced by Frank in his pioneering single-particle program SPIDER (2).

1. Callaway, E. Nature 525, 172-174, (2015).
2. Frank, J., Shimkin, B. & Dowse, H. Ultramicroscopy 6, 343-357, (1981).
3. Taylor, K.A. & Glaeser, R.M. Science 186, 1036-1037, (1974).
4. Adrian, M., Dubochet, J., Lepault, J. & McDowall, A.W. Nature 308, 32-36, (1984).