Strange Glow

by Timothy J Jorgensen

  The term target, when used in a scientific sense, does not imply that radiation is actually aiming to damage DNA. Rather, it means that DNA is the target that must be hit (damaged) in order for radiation to produce a biological effect. Other biological molecules, including proteins, are damaged by radiation just as readily. In fact, the vast amount of molecular damage in cells occurs outside of their DNA, but only the damage to DNA is important to producing biological consequences. In retrospect, the reason seems clear. All the other molecules of the cell are replaceable, and the DNA—the cellular director that is giving all the orders—governs their replacement. But if a cell’s director is damaged, replacement is impossible, control is lost and the cell’s functions go awry, sometimes resulting in cell death and sometimes in mutation. If the mutations happen to occur in sex (germ) cells, the consequence can be inheritable mutations. If instead, those mutations happen to occur in nonsex (somatic) cells, the consequence can be cancer. The cell type and the radiation dose determine the specific type of health effect, but damage to DNA is always the mechanism.21

  THE CUP RUNNETH OVER

  Other than brother Bob, to whom he was devoted despite the unfortunate elbow incident, Willie had no close friends. Always shunned by his peers, Willie suffered profound loneliness. But all that changed when he met Rudolph “Cecil” Hopkinson. Cecil was an electrical engineering student at Cambridge, and his father was a leader in the development of England’s electric power industry, similar to what Willie’s grandfather Todd had done on a much smaller scale back in Australia. Despite his aristocratic family ties, Cecil had none of the social pretentiousness of the other Cambridge students, and he and Willie hit it off immediately. Interestingly, it was an attraction of opposites, since Cecil was bold and loved adventure spiced with danger, while Willie was relatively meek. Cecil’s personality was actually more like Willie’s brother, Bob. However, unlike Bob, Cecil was somehow able to get Willie out of his shell. Willie would later say: “What [Cecil] gave me was like water in a thirsty land. He dragged me into adventures that bolstered up the self-confidence in which I was so sadly deficient.”22 Cecil introduced Willie to skiing, hunting, sailing, and other vigorous outdoor activities. With the daring duo of Bob and Cecil in his corner, Willie was now able to enjoy pleasures of companionship of which he had been so cruelly deprived as a boy. He was lonely no more. And then war broke out.

  STRETCHING EXERCISES

  Among the biologists, DNA had become the center of attention. As both the substance of genes and the target for radiation damage, no one any longer doubted its fundamental importance to understanding how life works. Nevertheless, its physical structure was still unknown, as was an explanation of how it replicated itself, as genes were known to do.

  The next breakthrough came from another graduate of Cambridge University, William Astbury (1898–1961). Astbury was working as a textile chemist at the University of Leeds, specializing in the determination of the structures of fibrous textiles, including wool and animal hair. Wool and hair—both comprised of long fibers made of proteins—would not form crystals, and so were not amenable to x-ray crystallography in the traditional sense. Still, Asbury found that by stretching the fibers out, they would line themselves up in a more or less ordered structure that roughly approximated the highly ordered structures found in crystals. Astbury was familiar with x-ray crystallography techniques because Willie’s father had been his doctoral advisor. While studying under Bragg, he had done some x-ray crystallography work on tartaric acid, one of the main acids found in wine. Since the stretched fibers represented a simulated crystal structure, he decided to give the x-ray crystallography technique a try. He did not get the same high resolution images that resulted from real crystals; nevertheless, his x-ray photographs of the fibers were good enough to rule out some hypothetical structures as inconsistent with the x-ray data, thus shortening the list of potential structures that needed to be considered.

  The one thing he couldn’t rule out from the x-ray data was a coiled structure. In fact, by altering the force applied to the fibers, Astbury could alter the distribution of the spots on the photographic film. The movement of the spots was consistent with the notion that the added force was stretching out the coils and, thereby, separating the atoms from each other.

  When Astbury published his findings with these proteins, others scientists were impressed, and some noted that DNA was also a fibrous material that could be stretched into alignment. So Astbury obtained a purified DNA sample from a colleague and repeated what he had done with the wool. Surprisingly, he got comparable results. Again the data suggested a regular structure that could be altered by stretching, but the data was not good enough to determine atomic distances. Nevertheless, others were inspired to pick up the ball and try x-ray crystallography on more highly purified samples of DNA.23

  THE WELL RUNS DRY

  When World War I broke out, Cecil, Bob, and Willie, all joined the British army and went to the front. Cecil and Bob were given combat duties, but because of his scientific background, Willie was assigned to work on a technical project, the goal of which was to determine the exact location of enemy cannon by triangulation of the sound waves they generated when fired.24 This involved scrambling around the front lines and placing microphones at various locations to collect the sound wave data. So all three men did their service on the frontlines of battle, fully in harm’s way.

  Under horrific battle conditions and mounting casualties, Willie conscientiously performed his duties, although his melancholy was steadily on the rise. Then came a devastating blow. News arrived that his beloved brother, Bob, had died in the Battle of Gallipoli, in Turkey. He had his leg blown off by enemy cannon fire and died shortly thereafter. He was buried at sea from a hospital ship. Willie was devastated.

  Soon Willie received better news. He and his father had been jointly awarded the 1915 Nobel Prize in Physics for their work with x-ray crystallography. The announcement was a surprise to everyone because the rumor had been circulating that Edison and Tesla would share the Nobel for their multiple electrical inventions based on DC and AC currents, respectively. The relatively unknown Braggs, and the little x-ray reflection instrument they fabricated, had displaced two of the most famous inventors in the world. But Willie, in light of the ongoing war, now found such awards somewhat banal, a viewpoint shared by his fellow soldiers who were not impressed with their illustrious trench mate. They started contemptuously referring to Willie as “The Nobbler.”25 Once again, the only thing that Willie’s intellectual skills had earned him from his peers was disdain. His superiors, however, did take notice. Willie, in a letter home, amusingly noted that now “generals humbly ask my opinion about things.”26

  As Christmas approached, the war seemed no closer to an end, but Christmas itself was peaceful enough for Willie and his fellow soldiers to enjoy a modest Christmas dinner that even included plum pudding sent from their families back home. Nevertheless, as they ate, there was a continuous rumble of guns in the distance, reminding them that not everyone was able to enjoy their pudding.27

  The new year brought no relief from the fighting. The war dragged on and on. Then one day came the news that Willie had so dreaded. Cecil was dead. He had been at the Battle of Loos, France, when poison gas released by the British had blown back onto their own lines. He survived that debacle, but was severely wounded a few days later in combat outside of Loos. Transported back to England, he lingered in agony and died ten weeks later, on February 9, 1917, at his family’s home.28 He was 25 years old. Cecil’s death was a tragic blow to Willie’s psyche. Of Cecil, Willie remembered: “He was the warmest-hearted and most loyal friend it was possible to imagine.”29 To his mother, Willie wrote: “I am in such despair over it.”30 Willie would never have another friend so dear.

  Willie himself survived the war. He returned to Cambridge University, but it too had suffered great losses. Of its graduates from the five years immediately preceding the war, half had been wounded and a q
uarter had been killed. Everyone at Cambridge after the war had someone they mourned. The grief was palpable. Rutherford had no sons, but was grieving for his young protégé Harry Moseley who, like Bob Bragg, had lost his life in Gallipoli. Rutherford maintained that the loss of the brilliant Moseley was a national tragedy. American physicist Robert Millikan would later say of Moseley: “Had the [war] no other result than the snuffing out of this young life, that alone would have made it one of the most hideous and irreparable crimes in history.”31 That Willie had survived was nothing short of a miracle. As a second lieutenant, he had certainly dodged his share of bullets. At one point during the war, the survival time for a second lieutenant on the front lines averaged just six weeks.32 Willie had been at the front for over two years.

  After the war, Willie became a professor at the University of Manchester, taking the position that Rutherford had vacated when he assumed directorship of the Cavendish upon J. J. Thomson’s retirement in 1919.33 Perhaps because of their shared grief over the loss of Cecil, Willie found a soul mate in Cecil’s cousin, Alice Hopkinson. They courted, married, and had four children, two boys and two girls. The couple lived a tranquil existence of a college professor and his wife for nearly two decades. And then another death changed all that.

  THE KING IS DEAD, LONG LIVE THE KING

  It’s said there is no such thing as minor surgery. True enough. Rutherford died in 1937 at the relatively young age of 66, while still a highly productive scientist. He died from complications of surgery for a strangulated hernia—a procedure that was considered routine even in 1937. It was a shame. He was a kind and generous man, and left a loving wife, as well as many devoted friends, colleagues, and former students.34 Despite his good-natured jibes at theoretical physicists, he had good personal relationships with most of them. Einstein was an admirer, calling Rutherford the “second Newton.”35 Appropriately, Rutherford’s ashes were buried in Westminster Abbey, very near the grave of Isaac Newton, the man whose study of radiation in the form of visible light started it all, more than 200 hundred years earlier.

  Rutherford’s unexpected death left the Cavendish’s leadership position open. It was offered to Willie. He assumed directorship of the laboratory in 1938, again succeeding Rutherford as he had at Manchester. But he wasn’t there long before Germany invaded Poland, and England was again at war. With another war in full swing, Willie was called back into service by the British army to resume his work of locating enemy cannon by sound wave triangulation. Meanwhile, his father, still spry in his late 70s, became famous for his visits to the bomb shelter beneath the Royal Institution during German air raids, conversing with the frightened inhabitants and trying to boost their morale.

  The war was not going well for England. The allies were taking a beating while the United States remained on the sidelines, trying to maintain an isolationist policy. Then the Japanese attacked Pearl Harbor and America was all in, declaring war on both Japan and Germany on December 8 and 11, respectively, of 1941. The entry of the United States would eventually turn the tide against the Axis powers, but Willie’s father would never see that. He suddenly became ill and died on March 10, 1942, three long years before the war’s end. With his father’s death, all of Willie’s confidants, other than his wife, were now gone, but Willie had become accustomed to personal loss. He would persevere.

  By the time the United States dropped its atomic bombs on Hiroshima and Nagasaki, thereby bringing World War II to a complete end, Rutherford and the elder Bragg had been dead for eight and three years, respectively. Rutherford had once refused to shake the hand of Nobel Prize winning chemist Fritz Haber (1869–1938),36 because he had worked on the development of chemical weapons during World War I, even though his own British army had used such weapons against the Germans. We can only wonder how Rutherford, a great humanitarian, would have felt had he lived to see his beloved nuclear fission put to use as a weapon.

  WORTH A THOUSAND WORDS

  World War II disrupted research on the structure of DNA, and it wasn’t until the early 1950s that work resumed in earnest. One might expect that the Cavendish, with its expertise in x-ray crystallography, would have taken the lead, but two factors inhibited DNA research. First, the biologists at the Cavendish had already committed themselves to determining protein structures through x-ray crystallographic techniques. They were on the verge of great breakthroughs in that area; however, their focus was on the structures of myoglobin and hemoglobin, the body’s oxygen carriers, rather than on genes, since no proteins had yet been (or ever would be) shown to be genes. Solving these protein structures would ultimately earn the Cavendish more Nobel Prizes, but it certainly turned the laboratory’s attention away from genetics. Also, x-ray crystallographic studies of DNA structure were already underway by Maurice Wilkins (1916–2004) and his colleague Rosalind Franklin (1920–1958) at nearby Kings College, in London. British social protocol at the time called for scientists to respect each other’s research turf, so Cavendish scientists interested in DNA structure had to settle for persuading the Kings College scientists to reveal any data they might be willing to share.

  It turned out that the only two Cavendish scientists with a passion for studying DNA’s structure were newcomers to the laboratory. These were an American postdoctoral fellow James Watson (born 1928), with a background in genetics, and a Cavendish graduate student Francis Crick (1916–2004), who had migrated into the study of biochemical structures from a prewar dabbling in physics. Both were passionate about the importance of DNA structure to understanding genetics, and both were frustrated at the lack of attention to this at the Cavendish and the slowness of the Kings College scientists in producing DNA crystallography data.

  It didn’t help matters that Nobel Prize winner Linus Pauling was taking a strong interest in DNA. Pauling was one of the most brilliant protein structural chemists in the world and the discoverer of the alpha helix, a major structural feature of almost all proteins. In his work on the alpha helix, he had used a combined approach of model building and x-ray crystallography to correctly deduce the alpha helix’s structure, and there was no reason to believe that he would not be successful using that same approach for DNA. The fact that Pauling had actually written to Wilkins, asking to see some of his x-ray photographs of DNA, had sent a shiver down Wilkins’s spine. But Pauling was no more successful in getting a look at Wilkins’s films than Watson and Crick had been.

  The reason why neither model building nor x-crystallography alone could produce a definitive answer was because in model building, there were just too many possible conformations to consider, with no clear way to discern which conformations might be correct. For x-ray crystallography, the data for stretched fibers were just not good enough to calculate all the bond angles required to define the exact structure. But the x-ray photographs were good enough to eliminate some theoretical models as being contrary to the x-ray reflection data. In that way, the crystallography limited the number of models that needed to be considered, and thus aided deduction of the correct structure. This, essentially, was the scientific landscape that existed in 1951, the year Watson and Crick teamed up to discover the structure of DNA.

  The molecular structure that Watson and Crick were most curious about was also a helix. The structure of a helix is analogous to a spiral staircase. For DNA, the helix structure would amount to the nucleobases (i.e., the “stairs”) spiraling around themselves. Pauling had found that proteins formed helixes, in which amino acids were the spiraling stairs. There was also a prevalent theory, subscribed to by Watson, that helical structures were the most efficient structural conformation for all polymers.37 Watson and Crick wanted to know whether the x-ray photographs of DNA were consistent with a helical conformation. Once they confirmed that, they could discard all other molecular conformations and focus on playing with the models of nucleotides, which the Cavendish machine shop had made for them from sheet metal, until a workable helical structure was found. How would they know when they had found the corr
ect structure? They weren’t quite sure, but they had the strong belief that “the truth, once found, would be simple as well as pretty.”38

  This delicate dance between the Wilkins laboratory in London, and Watson and Crick in Cambridge, went on for some time. Meanwhile, Watson and Crick considered data generated by Erwin Chargaff (1905–2002) that suggested the nucleobases in DNA were paired with each other; that is, adenine (A) paired with thymine (T), and guanine (G) paired with cytosine (C). They also considered the possibility that multiple polymer strands of DNA were twisted around each other, similar to the way a rope is formed. But how many strands were in this “rope”? If they were lucky it would be a small number, ideally no more than three.

  Then their worst fear was realized. Pauling reported that he had discovered the structure of DNA! His proposed structure had three strands wrapped around themselves, with the nucleobases facing outward and the phosphate backbones on the interior. But Watson quickly realized that Pauling had it wrong. The phosphate groups were ionized and negatively charged. If they were on the inside, their negative charges from the different backbone strands would repel each other and force the strands apart. Also, Pauling’s DNA structure did not account for the base pairing suggested by Chargaff’s findings. Pauling had gotten close to the correct answer, but his proposed structure for DNA was, nevertheless, completely wrong. Watson and Crick still had time to find the correct answer before Pauling realized his mistake and went back to work on the problem.

  Then Watson got the information he needed. In discussing the folly of Pauling’s proposed structure with Wilkins at Kings College, Wilkins let his guard down and showed Watson one of Franklin’s x-ray photographs of DNA. Watson was no crystallographer. As he would later quip, “I was even ignorant of Bragg’s law, the most basic of all crystallographic ideas.”39 Nevertheless, he knew enough. Crick had described to him what an x-ray photograph of a helical structure of DNA should look like, and Franklin’s photograph matched Crick’s description. The bottom line was that Franklin’s crystallography data suggested a helical structure with a diameter consistent with two, not three, intertwined strands—a double helix.