‘Genetical information’: 60 years old today!

by Matthew Cobb

Sixty years ago today, an article appeared in Nature that used a form of words that was completely novel and which changed the way we think about life:

‘‘it therefore seems likely that the precise sequence of the bases is the code which carries the genetical information’

The authors of the article were James Watson and Francis Crick, but this was not their article on the double helix structure of DNA – that theoretical article appeared six weeks earlier, accompanied by two data-rich articles from Maurice Wilkins and Rosalind Franklin.

This is the second article written by the pair, entitled ‘Genetical implications of the structure of deoxyribonucleic acid’. (The first article has been cited around 4700 times; the second article ‘only’ 1400 times, and yet it is arguably the more important of the two, in conceptual terms.)

In this second article Watson and Crick explore the consequences of the precise pairing of the four ‘bases’ (A, T, G, C) in the double helix (A on one strand is always complemented by T on the other, and G with C). The principal consequence related to how the DNA molecule could copy itself. But Watson and Crick were also interested in what genes actually do, hence this powerful phrase.

It had been previously suggested by researchers such as Dounce (1952) and Caldwell and Hinshelwood (1950) that the order of the bases might in some way enable a gene to synthesise proteins, probably by acting as a physical template (Dounce even argued that three bases would correspond to a particular amino acid, which turned out to be right, but not for the physico-chemical reasons that Dounce argued). In 1950, Erwin Chargaff had suggested that a single change in a base could lead to a mutation, but again he viewed this in terms of a physical change to the DNA molecule.

The great step forward made by Watson and Crick in their second paper was to take these pre-existing ideas and reshape them in a less literal form. The sequence of bases was no longer seen in terms of a physical template for protein synthesis, but as something far more abstract – a code carrying genetical information.

What is intriguing is where this novel interpretation came from. The first person who explicitly suggested that genes contained a ‘code-script’ was the physicist Erwin Schrödinger, in 1943. Although his ideas were widely-read, there were few attempts to explore the idea of a ‘code’, because the physical nature of the gene was unknown.

The importance of ‘information’ as an abstract concept – so widespread in our modern view – was a direct product of war-time work on electronic transmissions by Claude Shannon, and on the development of control systems to guide anti-aircraft guns carried out by Norbert Wiener. In 1948, these two mathematicians each published a popular book – Information Theory and Cybernetics, respectively. (For best-sellers they contained a surprising number of mathematical formulae. Maybe people were more maths-savvy back then. Or more tolerant of things they didn’t quite understand.)

There were a growing number of meetings at which physicists, mathematicians and biologists tried to see how they could forge a new way of looking at life (the cyberneticians were particularly bold in this respect). In the end, nothing came of these attempts, but at some point along the way, the idea of seeing that genes contain ‘information’ seeped its way into Watson and Crick’s thinking, leading them to explain the implications of the double helix structure in this radically novel way.

How exactly the pair came up with the idea is not known (that’s why yesterday I asked Jerry to ask Watson this question when they met – we should get a post on this later today). We know that Crick wrote most of this article, in a terrible hurry. Did either of them read Shannon or Wiener? Or were these just terms they heard floating about on the Cambridge air, or idly discussed in the corridors at conferences? Whatever the case, today it is impossible to think about genes – or evolution – without using this powerful metaphor.

Further reading:

This is the topic of a book I am writing about the history of the genetic code, to be published by Profile Books. It should be out on both sides of the Atlantic at the end of 2014.

You can find a précis of my ideas in this article I published in Cell in April, and the role of Schrödinger in this article in The Guardian.

If you want to know more about the relation between genetic codes and information, then the best book (until mine comes out!) is Lily E Kay’s brilliantly-titled Who Wrote the Book of Life: A History of the Genetic Code (Stanford University Press, 2000). Beware, it is tough going in parts. If you want a great popular read about the ideas linked with information theory, then James Gleick’s The Information (2011) is for you.

And of course, everyone should read the original papers, which are available free from Nature. This collection includes the 1944 article by Oswald Avery, Colin MacLeod and Maclyn McCarty which shows that in pneumonia bacilli, an inherited character is composed of DNA. The conceptual and stylistic gaps between Avery et al.’s paper from 1944 and the second Watson and Crick paper give some indication of the amazing progress that was made in such a short period of time.

EDIT: Reader Pyers Symon points out that the famous picture of Watson and Crick by Antony Barrington-Brown reproduced above was not published for ten years and is just one of a number taken that day. There is an excellent article by Soraya de Chararevian about this photo session. (Soraya de Chadarevian (2003), ‘Portrait of a Discovery: Watson, Crick, and the Double Helix’ Isis 94:90-105 – PDF available here.).

Barrington-Brown was killed in a car crash in 2012. He was a student at Cambridge when he took the photo, and he later recalled:

An undergraduate friend of mine aspiring to be a journalist sought out stories on his own account. One day he gave me a tip-off that someone at the Cavendish Laboratory had made an important discovery, so could I take a picture to go with his story which he wanted to offer to Time magazine? So it was that I set off on my bicycle towing a two-wheeled trolley which carried my tripod and lights. I dragged the trolley up several flights of stairs and knocked at the door of one of dozens of similar rooms where research students worked.

I was affably greeted by a couple of chaps lounging at a desk by the window, drinking coffee. “What’s all this about?” I asked. With an airy wave of the hand one of them, Crick I think, said “we’ve got this model” indicating an array of retort stands holding thin brass rods and balls. Although supposedly a chemist myself it meant absolutely nothing to me and fortunately they did not expose my ignorance by attempting to explain it in terms I might just have comprehended. Anyway, I had only come to get a picture so I set up my lights and camera and said “you’d better stand by it and look portentous” which they lamentably failed to do, treating my efforts as a bit of a joke. I took four frames of them with the model and then three or four back with their coffee.

My ‘snaps’ came out well enough and my friend fired them with his story off to Time, but they never used it and sent me half a guinea (52p) for my pains. Several historians have spent a lot of effort trying to establish when the pictures were first published, but I have never known.”

You can read more about his life here (that’s where I got the quote from). Here are some other, less ‘iconic’ photos taken on the same day: