Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid

Sixty years ago yesterday the journal Nature published a letter by James Watson and Francis Crick titled Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid (Volume 171, Pages 737-738), announcing the discovery of the double helix structure of DNA.

The 4th edition of Intermediate Physics for Medicine and Biology doesn’t discuss the structure of DNA much. As Russ Hobbie and I say in the preface, “Molecular biophysics has been almost completely ignored: excellent texts already exist, and this is not our area of expertise.” Yet, we do mention DNA occasionally. In the first section of our book, about distances and sizes, we say

Problem 2 in the first chapter analyzes the volume of DNA

A problem in Chapter 3 considers errors in DNA in the context of the Boltzmann factor.

“Problem 25 The DNA molecule consists of two intertwined linear chains. Sticking out from each monomer (link in the chain) is one of four bases: adenine (A), guanine (G), thymine (T), or cytosine (C). In the double helix, each base from one strand bonds to a base in the other strand. The correct matches, A–T and G–C, are more tightly bound than are the improper matches. The chain looks something like this, where the last bond shown is an ‘error.’

A  T  G  C  G

T  A  C  G  A (error)

The probability of an error at 300 K is about 10⁻⁹ per base pair. Assume that this probability is determined by a Boltzmann factor e^−U/k_BT, where U is the additional energy required for a mismatch.

(a) Estimate this excess energy.

(b) If such mismatches are the sole cause of mutations in an organism, what would the mutation rate be if the temperature were raised 20° C?”

We discuss DNA again in Chapter 16, when considering radiation damage to tissue.

The story of how the structure of DNA was discovered is nearly as fascinating as the structure itself. James Watson provides a first-person account in his book The Double Helix. It begins

“I have never seen Francis Crick in a modest mood. Perhaps in other company he is that way, but I have never had reason so to judge him. It has nothing to do with his present fame. Already he is much talked about, usually with reverence, and someday he may be considered in the category of Rutherford or Bohr. But this was not true when, in the fall of 1951, I came to the Cavendish Laboratory of Cambridge University to join a small group of physicists and chemists working on the three-dimensional structures of proteins. At that time he was thirty-five, yet almost totally unknown. Although some of his closest colleagues realized the value of his quick, penetrating mind and frequently sought his advice, he was often not appreciated, and most people thought he talked too much.”

The Double Helix is one of those iconic books that everyone should read for the insights it provides into how science is done, and for what is simply a fascinating story. The tale is also told from a more unbiased perspective in Horace Freeland Judson’s book The Eighth Day of Creation: The Makers of the Revolution in Biology. Let us end with Judson’s discussion of Watson and Crick’s now 60-year-old letter.