X-ray diffraction from fibrous DNA tipped off Watson, Crick to double helix
It is one of the most famous molecular structures ever determined, the now iconic DNA double helix. Although X-ray diffraction played a role in its solution by James D. Watson and Francis H. C. Crick in 1953, it was not an X-ray crystal structure. That wouldn’t come for another 20 years from the laboratory of Alexander Rich at Masschusetts Institute of Technology.
The data that inspired Watson and Crick’s breakthrough wasn’t from a crystal; Rosalind Franklin and her student R. G. Gosling produced diffraction patterns from fibrous DNA. Franklin, a serious crystallographer, didn’t even know that Watson and Crick had access to her X-ray diffraction data on two distinct forms of DNA, dubbed A and B. The data had come to them in a somewhat roundabout way through the agency of Max F. Perutz, who directed the University of Cambridge lab in which they both worked.
The data clearly indicated to them that B DNA was a double helix and provided key information about its dimensions. They also knew from the work of Erwin Chargaff that, regardless of the provenance of the DNA, adenine and thymine bases and guanine and cytosine bases were always present in approximately equal amounts.
That information was enough for them to build their model, which suggested immediately how DNA encoded genetic information and how it could replicate (Nature 1953, DOI: 10.1038/171737a0). It eventually earned them the 1963 Nobel Prize in Medicine or Physiology, which they shared with Maurice Wilkins, a colleague of Franklin’s. Franklin had died in 1958 at the age of 37 from ovarian cancer.
Wilkins and Franklin and Watson and Crick weren’t the only scientists chasing the structure of DNA. Looming over them was the towering figure of Linus C. Pauling, who only three years earlier had used X-ray diffraction data and model building to correctly deduce the α-helix and β-sheet secondary structures of proteins.
Many people have suggested that, had Pauling had access to Franklin’s X-ray data, he would have very likely deduced the correct structure of DNA. Pauling, however, didn’t have access to Franklin’s data. Because of Pauling’s political activism, the U.S. State Department denied him a passport in 1952 and prevented him from making a planned trip to London.
In the 20 years that followed Watson and Crick’s Nature publication, X-ray crystal structures of simple DNA structures had called into question their hypothesis. In May 1973, however, Rich and coworkers reported they had solved the X-ray crystal structure of the dinucleoside phosphate adenosyl-3′,5′-uridine phosphate, noting that it “crystallizes in the form of a right handed antiparallel double helix with Watson-Crick hydrogen bonding between uracil and adenine” (Nature, DOI: 10.1038/243150a0). Other DNA X-ray crystal structures would follow, but Rich’s team had settled the question once and for all.—Rudy Baum