by Thomas Hager
She enjoyed the attention not only for all the usual reasons but also because it helped to balance a growing feeling of neglect. Linda had always doted on her father and wanted to impress him. She tried to be the perfect daughter, respectful, polite, and quiet. But nothing seemed to bring her more than a perfunctory pat on the head. Pauling's attention was focused on research, Ava Helen, and politics, in that order, and Linda would always be at best a distant fourth. She tried to impress Pauling by taking an interest in science at her private prep school, working a summer job at age eighteen x-raying alloys in a Caltech lab and telling her family that she wanted to major in chemistry in college. That was fine, Pauling said. She became jealous of the time Ava Helen spent traveling with Pauling and the way he looked to her for approval and opinions. Linda would always remember the afternoon she waltzed into Pauling's study to show him a new dress she thought was particularly attractive. Pauling took a quick look, said, "You know, that dress would look wonderful on your mother," and went back to his calculations.
But now Linda was starting to get plenty of attention from her father's students, and she encouraged it. When Pauling and Ava Helen were away, Peter's and Linda's poolside gatherings sometimes turned into sometimes raucous parties.
The young visitors, a mix of students and postdocs, liked it almost as much when Pauling was there. They were the select, the privileged, the few disciples of science allowed into one of its private sanctums. There was the fun around the pool, of course, but there was also the opportunity to talk about research with Pauling in his octagonal study or to discuss science, politics, or their futures when Pauling, taking a break from his theoretical work, would stride across the lawn, sit down with that trademark grin on his face, and start up a conversation. Entire lives could be changed in the course of a brief poolside chat. It happened to Matt Meselson, a friend of Peter's up for a swim in the summer of 1952. Meselson, a talented young former Caltech student who had just spent a year in graduate school at Berkeley, was planning to switch to the University of Chicago until Pauling, fully dressed in a suit and tie, walked out into the hot yard, kneeled by the edge of the pool, looked straight at the young man as he treaded water, and asked, "Well, Matt, what are you going to do next year?" Meselson told him his plans for Chicago. "But, Matt," Pauling said, "that's a lot of baloney. Why don't you come to Caltech and be my graduate student?" The vision of the world-renowned scientist looming over him at poolside was awe-inspiring. Meselson looked up at him and said, "Okay, I will." After studying with Pauling, Meselson went on to a distinguished career in molecular biology at Harvard. It was like that, the great man appearing, dropping some tidbit of wisdom, then heading back to the house to leave them to their fun. It was exhilarating, the cutting edge, a heady mixture of unconventional politics, unorthodox science, and sparkling people, all packaged as a Southern California pool party. Pauling's house was, one remembered, "the hot spot."
Pauling was an extremely popular professor among his students. Most of them thought of him as a guru who did his thinking up in the hills, received enlightenment, then descended to share the revealed truth with the multitudes. His now-legendary freshman lectures were studded as always with parlor tricks—Pauling would calculate a needed number to six figures on a five-inch pocket slide rule, inevitably sending a group of disbelieving freshmen to a mechanical calculator to check his work (he was always right)—but they now also seemed like the free flow of pure wisdom from the greatest teacher in chemistry. A Pauling lecture was "like going to a great concert," one listener remembered.
His students began modeling themselves after him. The great trick in becoming another Pauling had something to do with recognizing what they called "the Pauling Point." "This is when you do things only up to a certain level to get the right answer—or another way, if you go further and deeper it looks much more complicated and the answer becomes more diffuse," said Martin Karplus, another Harvard professor who was once one of the young fellows sitting around Pauling's pool. "The Pauling Point is just to take the right level of approach to get the correct answer." This was the master's essential art, the ability to see the big picture, to stop worrying at just the right moment about niggling details, to achieve victory over a problem without beating it to death. It was science done with grace and timing. And, most of them found out, it was almost impossible to emulate.
Pauling had never been one to hover over his students and postdoctoral fellows. "It was a sink or swim environment," one remembered. But as his fame increased, the few interactions he did have with them took on the overtones of a conversation with a Zen master. Alex Rich, a recently graduated M.D. who joined Pauling's lab to try his hand at research, was having trouble settling into a project, jumping from sickle-cell work to theoretical studies of the binding of carbon. Nothing captured his imagination. Restless and unsure of what to do, he found himself one evening in 1950 in Pauling's study, having a talk about science in general and nothing in particular. Then Pauling picked up a book that had just been mailed to him, the proceedings of the transaction of a meeting of the Royal Society on quantum chemistry, a volume of nothing but the sort of theoretical calculations Rich had been sweating over. Pauling looked at it and threw the book down. "Worthless," he said. "Rubbish." When Rich asked why, Pauling said, "Well, in the thirties I worked hard to see if I could find a closed solution, to solve these equations in a way that gave you these answers. I couldn't find them, and since then people have used different kinds of approximations to try and do this or do that. There are many methods of making approximations. It's like whipping a dead horse." It was not until he was driving down the hill that Rich realized that Pauling was telling him something about his future. "Linus can't solve these problems," he said to himself. "Why do I think I can do a better job?" Based on the oblique conversation, Rich decided to learn x-ray crystallography, a career change that led to an outstanding career at MIT.
Meselson compared Pauling's style to Socrates' admonition that virtue cannot be taught; it can only be set by example. "That's the way Linus, I think, affected people."
The young men around him in the early 1950s, in the privileged group, including a number who would go on to significant careers in science, would be deeply affected and bound together by his example. They would become closer to Pauling than any students since his first batch back in the early 1930s.
The Secret of Life, Part 2
Being a father figure to budding scientists was satisfying to Pauling, but his greatest satisfaction, as always, came from research. After 1951, Pauling began applying the lessons he had learned with proteins to the structures of other long-chain biomolecules, including starches and nucleic acids. These were certainly less important than proteins in terms of the body's functions, but they also appeared to be much simpler structurally, which might make them solvable with his model-building approach.
In the summer of 1951, Pauling started reading in some depth and talking to others about deoxyribonucleic acid—everyone called it DNA—the most common form of nucleic acid in chromosomes. Astbury had done some smeary x-ray work in the late 1930s that indicated that DNA was a long-chain molecule with a repeating pattern. It might well be a helix. But it was composed of just four subunits, called nucleotides, all of which appeared to be present in all DNA from all animals in approximately equal amounts, compared to protein's twenty-some amino acids, which varied widely in occurrence in various molecules. Each nucleotide consisted of a sugar, a phosphate group, and one of four carbon-and-nitrogen ring structures called bases: adenine, guanine, thymine, and cytosine. Pauling had theorized a structure for guanine in the early 1930s as part of his work on resonance; it was a flat plate, and the other three bases appeared to be too. The key to DNA would be figuring how each base joined with a sugar and a phosphate to make a nucleotide; then how the nucleotides joined to form chains. Compared to protein structures, Pauling thought, that should not be too hard to work out.
It was not a top-priority problem in any case. DNA w
as by weight an important component of chromosomes, but so was protein, and it seemed likely to most researchers that the protein portion carried the genetic instructions. Protein had the variety of forms and functions, the subunit variability, the sheer sophistication to account for heredity. DNA by comparison seemed dumb, more likely a structural component that helped fold or unfold the chromosomes. Beadle believed it. Pauling believed it. At the beginning of 1952, almost every important worker in genetics believed it.
The only evidence to the contrary was a little-appreciated paper published in 1944 by Rockefeller Institute researcher Oswald Avery, who had found that DNA, apparently by itself, could transfer new genetic traits between Pneumococcus bacteria. For years no one paid much attention to Avery's work. Pauling knew about it—he had been in contact with Avery during the war through his work with Pneumococcus antigens and artificial antibodies—but thought it unimportant. "I knew the contention that DNA was the hereditary material," Pauling said. "But I didn't accept it. I was so pleased with proteins, you know, that I thought that proteins probably are the hereditary material rather than nucleic acids—but that of course nucleic acids played a part. In whatever I wrote about nucleic acids, I mentioned nucleoproteins, and I was thinking more of the protein than of the nucleic acids."
So the structure of DNA was simply an interesting question in modeling techniques when Pauling talked with Gerald Oster, a professor visiting Caltech from Brooklyn Poly in the summer of 1951. Oster had been looking at the effects of water content on DNA, and after returning east, he sent Pauling some of his data. At the end of one letter, Oster added a quick idea. "I hope you'll write to Prof. J. T. Randall, King's College, Strand, London," he wrote. "His coworker, Dr. M. Wilkins, told me he had some good fibre pictures of nucleic acid."
Good pictures of DNA were hard to come by. While any strand of hair could provide a decent x-ray photo of keratin, DNA had to be extracted from cell nuclei and separated from its attendant protein, a difficult process. The techniques of the day for isolating DNA in general degraded the molecule somewhat, and the final product was the sodium salt of DNA, called sodium thymonucleate. There was some mystery surrounding how the isolation process might alter the molecule's structure, and even purified sodium thymonucleate was difficult to use for x-ray diffraction. At the time, Astbury's first x-ray patterns from the 1930s—and one new photograph he had published in 1947 with his own ideas about DNA structure—were the only usable ones in print. And they were not worth much. While x-ray patterns from globular proteins provided too much data to analyze successfully, Astbury's DNA photos provided too little. Pauling could get some rough ideas of dimensions and the size of repeating units from these pictures, but they were too muddy to get much more.
He needed better x-ray photos and decided to write Wilkins. It would be somewhat uncommon for a researcher involved in an active program to give up raw data before publishing it in some form, but Oster had led Pauling to believe that Wilkins was not interested in doing much with the photos he had, which Oster thought had been taken some time ago. So Pauling took a chance and wrote to Randall's laboratory sometime in the late summer of 1951 asking if he could see what Wilkins had.
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Maurice Wilkins was not sure what to do when he read Pauling's letter.
A thin, bespectacled physicist whose career had so far failed to produce much of significance, Wilkins had succeeded a year earlier in one endeavor: finding a way to get the world's best x-ray photos of DNA. It had happened while he was working with a solution of sodium thymonucleate. When dissolved in water, the substance formed a kind of viscous solution that Wilkins found could be drawn out into spiderweb-thin fibers by carefully dipping the end of a glass rod in the solution and pulling it slowly. The very long DNA strands apparently aligned themselves along the fibers. By keeping in mind Bernal's discovery that globular proteins photographed better when wet, Wilkins kept his x-ray camera set up at a high humidity and was able to string his fibers up and take x-ray photos. The results were dramatically better than Astbury's, with a wealth of sharp spots. Wilkins's work immediately confirmed that DNA had a repeating crystalline structure and was therefore solvable.
But he could not solve it alone. Wilkins was a man of many talents—he got his start separating uranium isotopes for the Manhattan Project—but was not well trained in the interpretation of x-ray photos and was hampered by inadequate equipment for fiber x-ray work at King's College. He decided in 1950 not to publish his pictures until he had a chance to analyze his data more thoroughly and replicate them with better equipment. The delay that Oster read as lack of interest was really time spent arranging for a better laboratory setup and some help.
By January 1951, Wilkins had his new equipment and someone to run it, Rosalind Franklin, a talented young crystallographer who had earned a reputation for her meticulous x-ray work with hard-to-study coal derivatives. Unfortunately, the relationship between Wilkins and Franklin got off to a rocky start. Wilkins thought Franklin had been hired to assist him and turned over to her his photos, his fiber x-ray setup, and one of his graduate students. Franklin, however, was under the impression that she had been hired to work independently. By the time Pauling's letter arrived, the two had had a falling-out, leaving the question of how to proceed with DNA somewhat up in the air and making it more difficult to answer Pauling's request. Franklin had taken a proprietary interest in solving DNA's structure from the steadily better photos she was taking, and Wilkins was also interested in solving the structure—with, he hoped, Franklin's help. Wilkins was well aware that given his photos, Pauling would probably beat them both to it. His fears were increased by his suspicion that DNA might be a helix, the form that Pauling had already used to embarrass the English. He held on to Pauling's letter for a week while he mulled over alternatives. Then he wrote back that he was sorry but he wanted to look more closely at his data before releasing the pictures.
Undeterred, Pauling wrote Wilkins's superior, J. T. Randall, with the same request. Randall was sorry, too, replying, "Wilkins and others are busily engaged in working out the interpretation of the desoxyribosenucleic acid x-ray photographs, and it would not be fair to them, or to the efforts of our laboratory as a whole, to hand these over to you."
That was in August. Pauling put DNA aside until November, when an article on its structure by a fellow named Edward Ronwin was published in the Journal of the American Chemical Society (JACS). With a glance, Pauling decided that some of Ronwin's ideas about structure were wrong. The molecule's phosphate groups, which should have consisted of a phosphorus atom surrounded by a tetrahedron of four oxygens in Pauling's opinion, showed each phosphorus connected to five oxygen atoms. Pauling had just finished reviewing phosphorus chemistry for a paper of his own, and it seemed to him that Ronwin's model was nonsense. He wrote a letter to the JACS about it. Pauling, as it turned out, was right.
More important, it started him thinking about how DNA might be built. Ronwin had put his phosphates down the middle of the molecule, with the flat bases sticking out to the sides. This was certainly possible—Astbury's x-ray photos did not rule out such an arrangement— and it would solve a major problem. The four bases of DNA came in two different sizes: two double-ring purines and two smaller pyrimidines with single rings. Say that it was a helix, as Astbury's photos indicated it might be. Trying to arrange the different-sized bases on the inside of a long helical molecule would create all sorts of fitting and stacking problems. Facing the bases out would make the molecule easier to solve, just as facing the amino-acid side chains away from the center of the protein spiral had made the alpha helix much easier to work with.
If the bases faced out, Pauling hypothesized, then the core of the helix would be packed with phosphates. Phosphates up the middle, bases facing out. It fit the available x-ray data. After Ronwin's paper, the problem of the structure of DNA began reducing itself in Pauling's mind to a question of packing phosphates together.
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He
had gotten that far when Pauling put DNA aside again. In the fall of 1951 he received an invitation to a special meeting of the Royal Society designed specifically to address the many questions British researchers had raised about his protein structures. The date was set for May 1, 1952.
Pauling was eager to go. In preparation, through the end of 1951 and on into the first months of 1952, he and Corey tested, refined, and rethought their structures, especially muscle and collagen. Part of the problem with muscle was that it rarely gave clear x-ray patterns, so Pauling collected and dried two hundred samples himself, mostly from mussels gathered at the Caltech marine station at Corona del Mar. He concluded from his new pictures that muscle was mostly composed of alpha helixes, with about 10 percent of something else that gave an odd look to the x-ray patterns; he and Corey would later try to figure out what that was. As for collagen, Corey prepared a twenty-page in-house review of data supporting their three-helix cable structure. Corey also redoubled his efforts on a multistage attack on lysozyme, working to become the first person to determine the complete structure of a globular protein. Here again, Pauling's lab was racing with Bragg's, with Corey pitted against Perutz and Kendrew, who were doing the same thing with hemoglobin and myoglobin.
In January 1952, Pauling began making arrangements for a spring European trip that would include the May Royal Society meeting, an honorary doctorate from the University at Toulouse, and a tour of Spanish universities. He sent in an application to renew his passport.
