Linus Pauling and his DNA triple helix

Linus Pauling is remembered as one of the greatest American scientists of all time. He was awarded two undivided Nobel Prizes, and is basically the father of modern structural biology.

He's most famous for solving the 3D structure of the α-helix and the β-sheet, the two most common protein structures.

To do this, Pauling employed a technique called x-ray crystallography which basically bombards a crystal with x-rays. How those x-rays bounce off of a crystal tells you something about the shape of the item that was crystallized and the resulting 'diffraction patterns' can be used to determine key structural features of the crystallized molecules.

In his work, Pauling took this a step further and was one of the first scientists to use that information to model molecular structures with balls and sticks.

Fresh off of his foundational work with proteins, Pauling turned his attention to DNA. While Pauling famously thought that DNA was NOT the genetic material, there's a rumor that he heard that teams in the UK were close to solving DNA's structure and the ever competitive Pauling wanted to see if he could beat them.

However, Pauling didn't generate his own data and relied heavily on data and calculations derived by others in the field, namely those created by William Astbury and Florence Bell in 1938.

Unfortunately, Pauling was unaware of the most recent advancements in the diffraction of DNA by Franklin and Gosling.

But he did have access to electron micrographs of DNA and the 15 year old Astbury/Bell data which indicated the structure was helical.

Based on incorrect density calculations, he also proposed that the structure had 3 nucleotides at each position.

It was already known that DNA was composed of a sugar phosphate backbone, so all of these things taken together led Pauling to a triple helix.

In the figure above, Pauling and Robert Corey placed the phosphate backbones of 3 DNA strands at the center of the structure with the nucleotides facing out, like the spokes of a bicycle wheel.

In hindsight, we know this is totally wrong and there are 3 key errors that make this structure implausible:

1. At pH 7, the phosphate backbone is negatively charged so 3 of them packed together would repel one another

2. The model doesn't leave space for sodium and Astbury's diffractions were all sodium salts

3. Chargaff's nucleotide pairing rules were totally ignored

Fortunately, taking inspiration from Pauling and his use of modeling, Watson and Crick, armed with pristine x-ray diffraction data from Franklin and Gosling, published the correct double helical structure for DNA two months later in the April 1953 issue of Nature.