It now seems certain that the amino acid sequence of any protein is determined by the sequence of bases in some region of a particular nucleic acid molecule. ~ Francis Crick
Continuous research of nucleic acids followed the typical path of scientific inquiry: mistaken hunches and endless experimentation to suss structure and function, until insight puts the pieces together and fills the evidentiary gaps.
By 1929, Russian American biochemist Phoebus Levene had identified the components of DNA & RNA and coined the term nucleotide, though his ideas about the structure of DNA were wrong.
English chemist and X-ray crystallographer Rosalind Franklin managed the first snapshots of DNA in 1951 via X-ray diffraction imagery. With her wealth of accumulated image data and analysis, Franklin significantly furthered understanding of DNA’s intricate structure.
Franklin correctly surmised that DNA was a double-stranded helix, with each helix having 4 nucleobases (nucleic acid bases) attached to a phosphate-sugar backbone. The DNA bases are adenine (A), cytosine (C), guanine (G), and thymine (T).
These results she shared at a seminar attended by American biologist James Watson and English biologist Francis Crick, who were graduate students at Cambridge University. Franklin worked at nearby King’s College.
Watson & Crick completed figuring out the 3-dimensional structure of DNA in 1953, after building innumerable physical models. Their first models were quite off: a triple helix, not double; and the bases on the outside, not inside where they belonged.
Watson & Crick got an advance publication copy of DNA work by American chemist Linus Pauling from Peter Pauling, Linus’ son, who worked in the same lab as Watson & Crick. Pauling’s paper wrongly had the triple helix, wrongly put the bases on the outside, and wrongly characterized the phosphate groups by not ionizing them. Pauling, then a world-renown chemist, made careless schoolboy blunders in his DNA work.
Watson & Crick had previously made equally obtuse mistakes, including ignoring water’s role in the DNA molecule. But, determined to secure their career prospects, Watson & Crick persevered post haste.
A crucial piece of the puzzle was handed to them by John Griffiths, a mathematics postgraduate student: that nucleobases A & T paired, as did C & G.
Linus Pauling had heard that years before, on a sea cruise where Griffiths and Pauling were on the same boat. But petulant Pauling, peeved at having his vacation interrupted, ignored Griffiths’ input.
In the finale, Watson & Crick put the matching bases inside, and flipped the negative phosphorous ions so they wouldn’t touch. The result was a tight-fitting double helix that checked out.
DNA comprises a double helix of paired molecules, joined by hydrogen bonds. The helix is like a twisting ladder, each rung a bonding of 2 complementary nucleobases.
Watson & Crick’s triumph, shortly before others hot on the same trail, came solely from the chemical and physical observations done by others, without doing any original research themselves. Obsession paid off in a Nobel prize.