Research, Adventure, and the Thrill of Discovery Theme Analysis

As I hope this book will show, science seldom proceeds in the straightforward logical manner imagined by outsiders. Instead, its steps forward (and sometimes backward) are often very human events in which personalities and cultural traditions play major roles. To this end I have attempted to re-create my first impressions of the relevant events and personalities rather than present an assessment which takes into account the many facts I have learned since the structure was found. Although the latter approach might be more objective, it would fail to convey the spirit of an adventure characterized both by youthful arrogance and by the belief that the truth, once found, would be simple as well as pretty.

I feel the story should be told, partly because many of my scientific friends have expressed curiosity about how the double helix was found, and to them an incomplete version is better than none. But even more important, I believe, there remains general ignorance about how science is “done.” That is not to say that all science is done in the manner described here. This is far from the case, for styles of scientific research vary almost as much as human personalities. On the other hand, I do not believe that the way DNA came out constitutes an odd exception to a scientific world complicated by the contradictory pulls of ambition and the sense of fair play.

I have never seen Francis Crick in a modest mood.

Though he was generally polite and considerate of colleagues who did not realize the real meaning of their latest experiments, he would never hide this fact from them. Almost immediately he would suggest a rash of new experiments that should confirm his interpretation. Moreover, he could not refrain from subsequently telling all who would listen how his clever new idea might set science ahead.

As a result, there existed an unspoken yet real fear of Crick, especially among his contemporaries who had yet to establish their reputations. The quick manner in which he seized their facts and tried to reduce them to coherent patterns frequently made his friends’ stomachs sink with the apprehension that, all too often in the near future, he would succeed, and expose to the world the fuzziness of minds hidden from direct view by the considerate, well-spoken manners of the Cambridge colleges.

The real problem, then, was Rosy. The thought could not be avoided that the best home for a feminist was in another person's lab.

Knowing he could never bring himself to learn chemistry, Luria felt the wisest course was to send me, his first serious student, to a chemist.

He had no difficulty deciding between a protein chemist and a nucleic-acid chemist. Though only about one half the mass of a bacterial virus was DNA (the other half being protein), Avery’s experiment made it smell like the essential genetic material. So working out DNA’s chemical structure might be the essential step in learning how genes duplicated. Nonetheless, in contrast to the proteins, the solid chemical facts known about DNA were meager. Only a few chemists worked with it and, except for the fact that nucleic acids were very large molecules built up from smaller building blocks, the nucleotides, there was almost nothing chemical that the geneticist could grasp at.

I proceeded to forget Maurice, but not his DNA photograph. A potential key to the secret of life was impossible to push out of my mind. The fact that I was unable to interpret it did not bother me. It was certainly better to imagine myself becoming famous than maturing into a stifled academic who had never risked a thought.

In place of pencil and paper, the main working tools were a set of molecular models superficially resembling the toys of preschool children.
We could thus see no reason why we should not solve DNA in the same way. All we had to do was to construct a set of molecular models and begin to play—with luck, the structure would be a helix.

The wrong person had been sent to hear Rosy. If Francis had gone along, no such ambiguity would have existed. It was the penalty for being oversensitive to the situation. For, admittedly, the sight of Francis mulling over the consequences of Rosy’s information when it was hardly out of her mouth would have upset Maurice. In one sense it would be grossly unfair for them to learn the facts at the same time. Certainly Maurice should have the first chance to come to grips with the problem. On the other hand, there seemed no indication that he thought the answer would come from playing with molecular models. Our conversation on the previous night had hardly alluded to that approach. Of course, the possibility existed that he was keeping something back. But that was very unlikely—Maurice just wasn’t that type.

Most annoyingly, her objections were not mere perversity: at this stage the embarrassing fact came out that my recollection of the water content of Rosy’s DNA samples could not be right. The awkward truth became apparent that the correct DNA model must contain at least ten times more water than was found in our model. This did not mean that we were necessarily wrong—with luck the extra water might be fudged into vacant regions on the periphery of our helix. On the other hand, there was no escaping the conclusion that our argument was soft. As soon as the possibility arose that much more water was involved, the number of potential DNA models alarmingly increased.

Sir Lawrence had had too much of Francis to be surprised that he had again stirred up an unnecessary tempest. There was no telling where he would let loose the next explosion. If he continued to behave this way, he could easily spend the next five years in the lab without collecting sufficient data to warrant an honest Ph.D. The chilling prospect of enduring Francis throughout the remaining years of his tenure as the Cavendish Professor was too much to ask of Bragg or anyone with a normal set of nerves.

[…]

The decision was thus passed on to Max that Francis and I must give up DNA. Bragg felt no qualms that this might impede science, since inquiries to Max and John had revealed nothing original in our approach.

My first X-ray pictures revealed, not unexpectedly, much less detail than was found in the published pictures. Over a month was required before I could get even halfway presentable pictures. They were still a long way, though, from being good enough to spot a helix.

The moment was thus appropriate to think seriously about some curious regularities in DNA chemistry first observed at Columbia by the Austrian-born biochemist Erwin Chargaff. Since the war, Chargaff and his students had been painstakingly analyzing various DNA samples for the relative proportions of their purine and pyrimidine bases. In all their DNA preparations the number of adenine (A) molecules was very similar to the number of thymine (T) molecules, while the number of guanine (G) molecules was very close to the number of cytosine (C) molecules. Moreover, the proportion of adenine and thymine groups varied with their biological origin. The DNA of some organisms had an excess of A and T, while in other forms of life there was an excess of G and C.

At High Table John kept the conversation away from serious matters, letting loose only the possibility that Francis and I were going to solve the DNA structure by model building. Chargaff, as one of the world’s experts on DNA, was at first not amused by dark horses trying to win the race. Only when John reassured him by mentioning that I was not a typical American did he realize that he was about to listen to a nut. Seeing me quickly reinforced his intuition. Immediately he derided my hair and accent, for since I came from Chicago I had no right to act otherwise. Blandly telling him that I kept my hair long to avoid confusion with American Air Force personnel proved my mental instability.

It was from his father. In addition to routine family-gossip was the long-feared news that Linus now had a structure for DNA. No details were given of what he was up to, and so each time the letter passed between Francis and me the greater was our frustration. Francis then began pacing up and down the room thinking aloud, hoping that in a great intellectual fervor he could reconstruct what Linus might have done. As long as Linus had not told us the answer, we should get equal credit if we announced it at the same time.

The instant I saw the picture my mouth fell open and my pulse began to race. The pattern was unbelievably simpler than those obtained previously (“A” form). Moreover, the black cross of reflections which dominated the picture could arise only from a helical structure. […] The real problem was the absence of any structural hypothesis which would allow them to pack the bases regularly in the inside of the helix. Of course this presumed that Rosy had hit it right in wanting the bases in the center and the backbone outside. Though Maurice told me he was now quite convinced she was correct, I remained skeptical, for her evidence was still out of the reach of Francis and me.

Though I kept insisting that we should keep the backbone in the center, I knew none of my reasons held water. Finally over coffee I admitted that my reluctance to place the bases inside partially arose from the suspicion that it would be possible to build an almost infinite number of models of this type. Then we would have the impossible task of deciding whether one was right. But the real stumbling block was the bases. As long as they were outside, we did not have to consider them. If they were pushed inside, the frightful problem existed of how to pack together two or more chains with irregular sequences of bases. Here Francis had to admit that he saw not the slightest ray of light.

My aim was somehow to arrange the centrally located bases in such a way that the backbones on the outside were completely regular—that is, giving the sugar-phosphate groups of each nucleotide identical three-dimensional configurations. But each time I tried to come up with a solution I ran into the obstacle that the four bases each had a quite different shape. Moreover, there were many reasons to believe that the sequences of the bases of a given polynucleotide chain were very irregular. Thus, unless some very special trick existed, randomly twisting two polynucleotide chains around one another should result in a mess. In some places the bigger bases must touch each other, while in other regions, where the smaller bases would lie opposite each other, there must exist a gap or else their backbone regions must buckle in.

Despite the messy backbone, my pulse began to race. If this was DNA, I should create a bombshell by announcing its discovery. The existence of two intertwined chains with identical base sequences could not be a chance matter. Instead it would strongly suggest that one chain in each molecule had at some earlier stage served as the template for the synthesis of the other chain. Under this scheme, gene replication starts with the separation of its two identical chains.

As the clock went past midnight I was becoming more and more pleased. There had been far too many days when Francis and I worried that the DNA structure might turn out to be superficially very dull, suggesting nothing about either its replication or its function in controlling cell biochemistry. But now, to my delight and amazement, the answer was turning out to be profoundly interesting. For over two hours I happily lay awake with pairs of adenine residues whirling in front of my closed eyes. Only for brief moments did the fear shoot through me that an idea this good could be wrong.

However, we both knew that we would not be home until a complete model was built in which all the stereo-chemical contacts were satisfactory. There was also the obvious fact that the implications of its existence were far too important to risk crying wolf. Thus I felt slightly queasy when at lunch Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.

Rosy’s instant acceptance of our model at first amazed me. I had feared that her sharp, stubborn mind, caught in her self-made antihelical trap, might dig up irrelevant results that would foster uncertainty about the correctness of the double helix. Nonetheless, like almost everyone else, she saw the appeal of the base pairs and accepted the fact that the structure was too pretty not to be true. Moreover, even before she learned of our proposal, the X-ray evidence had been forcing her more than she cared to admit toward a helical structure. The positioning of the backbone on the outside of the molecule was demanded by her evidence and, given the necessity to hydrogen-bond the bases together, the uniqueness of the A-T and G-C pairs was a fact she saw no reason to argue about.

Fortunately, by the time my letter reached Cal Tech the base pairs had fallen out. If they had not, I would have been in the dreadful position of having to inform Delbrück and Pauling that I had impetuously written of an idea which was only twelve hours old and lived only twenty-four before it was dead.

Pauling’s reaction was one of genuine thrill, as was Delbrück’s. In almost any other situation Pauling would have fought for the good points of his idea. The overwhelming biological merits of a self-complementary DNA molecule made him effectively concede the race. He did want, however, to see the evidence from King’s before he considered the matter a closed book. This he hoped would be possible three weeks hence.

For a while Francis wanted to expand our note to write at length about the biological implications. But finally he saw the point to a short remark and composed the sentence: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”