On reading The Double Helix

I recently reread The Double Helix because I am interested in understanding why people began thinking that the structure of DNA was an important problem. Watson and Crick are the most famous 20th century biologists – if you ask a random person on the street to name a 20th century biologist, the most likely response is a blank stare, but the second most likely response is Watson and Crick. Why? Why did the structure of DNA turn out to be so enlightening, and why did people think it was an important problem in the early 50’s?

I first read this book in the 90’s before I became a scientist, and so I missed much of Watson’s insight into how scientists sniff out and pursue a good problem. Watson argues that only a few key people were thinking of DNA as being the key to heredity, but things clearly weren’t going to stay that way for long – DNA’s significance would soon be recognized, and so those hoping to solve the problem had to work fast before more competitors arrived.

The key to understanding The Double Helix is to figure out when Watson is accurately describing the quirky way in which scientific personalities interact in the process of pursuing hot science, and when Watson is being an asshole. (As his subsequent life has shown, in spite of his many genuine virtues he really is an assoholic, to use an appropriate word from the recent Steve Jobs bio.) Understanding when he is being an asshole is complicated, because when you reach the end of the book, you encounter his final generous comments about Rosalind Franklin, and realize that he deliberately portrays himself as an asshole throughout the book, because he never lets on until the end that the whole story finishes with him thinking highly of Franklin. It’s an interesting meta-textual twist, an asshole consciously portraying himself as an asshole. But some of the assholishness seems also to be a result of Watson’s attempt at characterization – he really tries hard to make all of the characters he describes vivid and memorable. He generally succeeds, but also come off sounding like an asshole in the process.

For example, the opening sentence, “I have never seen Francis Crick in a modest mood,” is, read in context, a positive comment, because Watson clearly sees that part of the key to Crick’s success is his outspoken, gregarious personality, and his ambition to not waste time on less significant science. On the other hand, when Watson suggests that ‘Rosy’ Franklin needs to let her hair down and stop wearing glasses, he’s simply being an asshole.

With that in mind, let’s look at the basic story: Watson entered grad school with an interest in studying genes and their physical makeup. He ended up with the brilliant Italian phage geneticist Salvador Luria at Indiana, but after completing his graduate work he still wasn’t any closer to understanding the physical makeup of the gene. Watson, Luria, and a few others were already ahead of the game in suspecting that DNA was the carrier of genetic information, and so understanding the physical structure and properties of DNA seemed key. To pursue this, it seemed advisable to pursue some nucleic acid biochemistry, which Watson reluctantly attempted to do during a fruitless postdoc in Copenhagen. His colleagues were interested in DNA metabolism, and not at all in DNA as the carrier of genetic information. After hearing Maurice Wilkins speak on DNA crystallography at a conference, Watson became convinced that crystallography was going to be crucial, and he managed to move up to Cambridge to work with leading structural biologists Max Perutz and John Kendrew, despite the fact that Watson had no skills in crystallography whatsoever.

Crick, of course, was already at Cambridge, still a PhD student, getting on in years, and with little success to his name. Crick and Watson both shared the belief that understanding the structure of DNA would be key to understanding the behavior of genes. Why did they believe this, when many others did not? Oswald Avery’s famous DNA transformation experiments seemed to them to be important, and Crick was influenced by reading Schrödinger’s What is Life?. As far as I can tell, that was about it – there weren’t many other reasons to think that the structure of DNA would be crucial for understanding how genes carried information, and how genes were duplicated.

In fact, there was soon reason to think that just determining the structure of DNA would not be very informative. Linus Pauling came out with his groundbreaking structure of a protein alpha-helix, and, while this result would later prove to be absolutely fundamental to understanding protein structure, at the time it was largely a dud, in terms of insight. Staring at the structure of the alpha helix told you absolutely nothing about how proteins worked. As Watson writes, “The alpha-helix, even if correct, had not provided any biological insights; [Max Delbrück] seemed bored speaking about it.” This same outcome would be repeated when the first protein structures of myoglobin and hemoglobin came out – the large tangled mess was generally meaningless in terms of insight. And so the worry was that the structure of DNA would be equally uninformative.

Nevertheless, Watson and Crick put that worry aside and set out to think about DNA structure. One thing they did gain from Pauling’s alpha-helix work was an appreciation of the value of playing with structural models. Nowadays, structural biologists routinely play with structural models on the computer, but back then playing with models was more unusual. Pauling played with high-precision tinker toys, and it worked, but perhaps only because he was the world’s greatest physical chemist. Other structural biologists, like Rosalind Franklin and Maurice Wilkins were skeptical of the model building approach, and believed that macromolecular structures would gradually become clear as more data were collected.

But Watson and Crick were impatient, and convinced that they could make progress by model building. This was their great strategic insight, the reason why they beat everyone else to the solution. While doing no DNA crystallography themselves, they took a scientific approach that was fundamentally different from that taken by the others working on DNA structure. They didn’t steal Franklin’s data and then beat her at her own game; Franklin’s intellectual approach wasn’t going to yield the structure of DNA any time soon, despite the fact that she collected very, very, very good data that turned out to be crucial. And Franklin’s and Wilkins’ data weren’t the only pieces of the puzzle that went into Watson and Crick’s model building; Watson and Crick relied on other results, such as Chargaff’s unappreciated rules and various facts about glycosidic and phosphodiester bonds and tautomeric forms of bases worked out by organic chemists.

The result then, was that Watson and Crick figured out the notion of base-pairing and solved the structure of DNA first, beating Linus Pauling, who probably would have also solved in 1953, if Watson and Crick hadn’t existed. What’s remarkable about the result, and why Watson and Crick’s paper indicated a coming revolution in biology in a way that Pauling’s alpha-helix paper didn’t, is that the structure of DNA was immediately informative. It was suddenly clear how information could be encoded within what had been thought to be a chemically boring molecule, and it was clear how genes could be duplicated. This result put DNA in its central spot in biology, where it remains.

Author: Mike White

Genomes, Books, and Science Fiction

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