Brilliant Blunders: From Darwin to Einstein - Colossal Mistakes by Great Scientists That Changed Our Understanding of Life and the Universe (20 page)

There was yet another important piece of information concerning DNA that Pauling had been made aware of but either had forgotten or at least had not internalized. This evidence was related to the bases in the nucleotides. The following anecdote demonstrates how emotional responses may interfere even with processes that are supposed to be governed by pure scientific reasoning.

The day after Christmas 1947, Pauling and his family had been on their way to Europe for Pauling’s six-month visit to Oxford. They traveled on board the famous
Queen Mary
. Coincidentally, Erwin Chargaff, who had been interested in nucleic acids since the war years, happened to be on board the same ship, and Pauling soon ran into him. Unfortunately, Chargaff was,
in the words of biologist Alex Rich, a “very intense individual.” This did not suit Pauling, who was generally easygoing and, in this particular instance, was looking forward to a relaxing vacation. Consequently, Pauling not only paid little attention to Chargaff’s animated description of his research results but also later seemed to have ignored Chargaff’s important paper on nucleic acids.
In that paper, published in 1950, Chargaff discovered a remarkable relation between the amounts of the bases in DNA. He showed that whatever the number of adenine molecules (usually abbreviated “A”) in a certain section of DNA, the number of thymine (abbreviated “T”) molecules was equal.
Similarly, the number of guanine units (“G”) was equal to the number of cytosine (“C”) units. This meaningful clue to the structure of DNA—that the amount of A is equal to the amount of T, and the amount of G equals the amount of C—completely escaped Pauling’s attention. If it hadn’t, perhaps the discovery of DNA’s structure would have played out differently.

Following his trip to England and France in the summer of 1952, Pauling returned to Caltech in September. However, even then he was not ready to plunge back fully into the DNA problem. A conversation he had with Crick in England that summer gave him an idea of how he could finally resolve the puzzle of the protein reflection at 5.1 angstroms. As often happens in science, Pauling and Crick solved that problem independently, each showing that the alpha-helices could form coiled, ropelike structures around one another, those giving rise to the enigmatic signature. This had a nice ring of finality to it, but even though Pauling didn’t know it at the time, the “race” to solving DNA was entering the homestretch.

Pauling’s visit to France provided him with an additional clue to the fact that it was probably DNA, after all, that was the primary genetic material. The American microbiologist Alfred Hershey presented the evidence in a talk at an international meeting on viruses in Royaumont, near Paris.
Hershey and his collaborator, Martha Chase, labeled the DNA and protein of the T2 phage (a virus) with radioactive phosphorus and sulphur, respectively. They then allowed the phages to infect bacteria, and were able to demonstrate that the genetic material that infected the bacteria was most probably DNA and not protein. The viral protein coat remained outside the bacterial cell and played no role in the infection. But not everyone was convinced. Indeed, Hershey himself remarked cautiously that it was not yet clear whether his result had any fundamental significance. James Watson, on the other hand, who was also at Royaumont and who had DNA in his crosshairs, was fairly convinced.

Pauling finally came back to DNA work toward the end of November 1952. This return was spurred by an intriguing seminar at Caltech by biologist Robley Williams.
Williams showed amazingly detailed electron-microscope images of a nucleic acid salt—a chemical relative of DNA. To Pauling, the images of the long, cylindrical strands, coupled with Astbury’s X-ray diffraction photos, seemed to provide definitive evidence, if he needed any, for a helical molecule. Pauling also knew from the work of the organic chemist Alexander Todd that the backbone of the DNA molecule contained repeating phosphate and sugar groups.

Armed with Astbury’s photos, which showed strong reflections with spacing of about 3.4 angstroms, Pauling started to perform calculations of DNA structure on November 26. Based on
the density measurements of Astbury and Bell and the diameter of the strand as measured by Williams, he estimated that the length of one residue along the fiber axis was 1.12 angstroms—almost precisely one-third of the spacing in the X-ray photo (of 3.4 angstroms). This led him to a surprising conclusion:
“The cylindrical molecule is formed of
three chains,
which are coiled about one another . . . each chain being a
helix
.” In other words, having convinced himself that a two-stranded helix would yield too low a density, Pauling opted for a three-stranded helical architecture. This structure became known as the triple helix.

The next problem that he had to tackle concerned the nature of the very core of the three-chain helical design—that part of the molecule closest to the axis. The question was, which of the three known components of the nucleotides (bases, sugars, or phosphate groups) formed the core? Pauling and Corey went through a mental process of elimination:

Because of their varied nature, the purine-pyrimidine group [the bases] cannot be packed along the axis of the helix in such a way that suitable bonds can be formed between the sugar residues and the phosphate groups . . . It is also unlikely that the sugar groups constitute the core of
the molecule . . . the shape . . . is such that close packing of these groups along a helical axis is difficult, and no satisfactory way of packing them has been found . . .
We conclude that the core of the molecule is probably formed of the phosphate groups
[emphasis added].

The arrangement now looked like this: The phosphate groups were arranged about the axis of the helix, with the sugars surrounding them and the bases projecting radially outward. The three-stranded molecule was held together by hydrogen bonds between the phosphate groups of different strands.

This structure looked promising, but Pauling still saw some problems. The center of the molecule now appeared to be so jam-packed by the three chains of phosphates that it resembled the “telephone booth squash”—the competition to cram as many people as possible into a telephone booth. Pauling knew that the phosphate ion was tetrahedral in shape, with the central phosphorus atom surrounded by four oxygen atoms positioned at the vertices of a pyramid. Throughout the month of December, he, Corey, and chemist Verner Schomaker were continuously trying to squeeze, warp, and twist those tetrahedra so that they would fit better. In this process, Pauling was following the same instincts that had led him previously to triumph with the alpha-helix. He believed that if he could find a structural chemistry solution that was generally consistent with the X-ray data, all other problems would sort themselves out later. For instance, there was a question of how the model allowed for the existence of a sodium salt of DNA, since there was definitely no room for sodium ions in the core. Pauling did not have an answer, but he assumed that one would be found once the main architecture was figured out. The pace of the work was frantic.
Pauling even had a small group of scientists in his lab for an informal presentation of the model on Christmas Day. By the end of the month, he thought he had gotten it to be essentially right. Pauling and Corey submitted the paper, “A Proposed Structure for the Nucleic Acids,” for publication on the last day of 1952. The paper started, “The nucleic acids,
as constituents of living organisms, are comparable in importance to the proteins.” A few phrases with a more cautious tone followed:

We have now formulated a promising structure for the nucleic acids . . . This is the first precisely described structure for the nucleic acids that has been suggested by any investigator. The structure accounts for some of the features of the x-ray photographs; but detailed density calculations have not yet been made, and the structure cannot be considered to have been proved to be correct.

In other words, even if some of the wrinkles still had to be ironed out, Pauling wanted to establish priority.

Contrary to the somewhat tentative spirit of the scientific paper, in his personal communications about the proposed model, Pauling expressed more confidence and was extremely upbeat. In a letter to the Scottish biochemist (and eventual Nobel laureate) Alexander Todd, dated December 19, 1952, Pauling wrote:
“We have, we believe, discovered the structure of the nucleic acids. I think that it will be about a month before we send off a manuscript describing the structure, but I have practically no doubt about the correctness of the structure that we have discovered . . . The structure is really a beautiful one.” In a letter
sent on the same day to Henry Allen Moe, president of the Guggenheim Foundation, Pauling repeated the same sentiment: “I have now discovered, I believe, the structure of the nucleic acids themselves.”

Another person with whom Pauling was corresponding regularly was his son Peter, who, as luck would have it, had arrived at Cambridge just a few months earlier to work as a research student with John Kendrew. Peter’s desk was in an office with four other colleagues. In Peter’s words:
“To my left, near the window, was a rather noisy fellow named Francis Crick. On my right was a desk occasionally occupied by Jim Watson. Also in the room was a visiting scientist, Jerry Donohue, whom I knew well from his long association with Caltech, and Michael Bluhm, John Kendrew’s research
assistant.” In a pre-email era, Peter, through his frequent exchange of letters with his father, became the main line of communication between Caltech and Cambridge. Consequently, as soon as Linus informed Peter of his paper on the structure of DNA, the latter asked for a copy. This was on January 13, 1953. Peter added in his letter a brief comment that spoke volumes about the pressure the British scientists were feeling:
“I was told a story today. You know how children are threatened ‘You had better be good or the bad ogre will come get you.’ Well, for more than a year, Francis [Crick] and others have been saying to the nucleic acid people at King’s ‘You had better work hard or Pauling will get interested in nucleic acids.’ ”

Under these conditions, it was only natural that the news from Peter that Pauling had discovered the structure of DNA hit Watson and Crick like a thunderbolt. With the memory of Pauling’s previous victory with the alpha-helix still fresh in the minds of everybody at Cambridge, the two young men were wondering if this was a catastrophic case of déjà vu. On January 23 Peter sent Linus another letter, this time complaining only that
“I wish Jim Watson were here [Watson was on a quick visit to Milan, Italy]. It is rather dull now. Nothing to do. No interesting girls, just young affected little things only interested in sex, in an indirect manner.”

The weeks between Peter’s request for a copy of Pauling’s paper, and the manuscript’s arrival on January 28, felt like an eternity to Watson and Crick. When Peter finally brought the paper, Watson quickly pulled it out of Peter’s outside coat pocket, and instantly devoured the summary and the introduction. Then, after staring at the illustrations for a few minutes, he couldn’t believe his eyes. Pauling’s structure, with the phosphates in the center and the bases on the outside, was strikingly similar to his and Crick’s abortive model. The model was preposterously wrong!

Calamities are of two kinds: misfortunes to ourselves, and good fortune to others.

—AMBROSE BIERCE

W
atson did not conclude that Pauling’s DNA model was wrong just because it had three strands. Pauling’s nucleic acid molecule was simply not an acid at all. That is, it could not release positively charged hydrogen atoms when dissolved in water, the very definition of an acid. Instead, the hydrogen atoms were bound firmly to the phosphate groups, rendering those electrically neutral, while every elementary chemistry book (including Pauling’s own book!) stated that the phosphates had to be charged negatively (the acid is highly ionized in aqueous solution). There was no way to extract those hydrogen atoms, either, since they were actually the key links holding together the three strands through hydrogen bonds.

This blunder was just too much for Watson and Crick to swallow. The world’s greatest chemist constructed a completely defective model, and the model was wrong not because of some subtle biological feature but because of a major blooper in the most basic chemistry. Still incredulous,
Watson rushed to Cambridge chemist Roy Markham and to the organic chemistry laboratory to check with them whether there was any doubt that DNA, as it occurs in nature,
was indeed the salt of an acid. To Watson’s satisfaction, they all confirmed the unthinkable: Pauling had utterly botched the chemistry.