Strange Glow

by Timothy J Jorgensen

  Willie’s first scientific love was biology, and in this he was bucking a family tradition. His father, William Henry Bragg (1862–1942), was the most prominent physicist in Australia. An Englishman trained at the Cavendish Laboratory by J. J. Thomson, Bragg was offered, at a very young age, a prestigious professorship at the University of Adelaide in Australia; he had obtained this offer largely through the influence of his mentor, Thomson. The elder Bragg arrived in Adelaide early in 1886, just when laboratory training was beginning to be seen as essential to the education of scientists; so university administrators were more than happy to provide their new young professor with a state-of-the-art science laboratory. The laboratory contained the latest scientific equipment, and copious windows admitted the sunlight he needed to perform optical experiments. It also included four dozen high-quality lenses, one dozen prisms, and an assortment of mirrors. The laboratory was an ideal educational facility for teaching Newtonian optical physics, a specialty of Bragg’s at the time.2 The notable reforms that Bragg subsequently made to physics education at Adelaide won him a measure of fame throughout the scientific community of Australia, as well as a good deal of prestige within high society.

  Then there was Willie’s grandfather on his maternal side, Charles Todd (1826–1910). Grandpa Todd was an astronomer, meteorologist, and electrical engineer of even greater fame within Australia than Willie’s father. He was a contemporary of Edison’s, and like Edison, was deeply involved with introducing electricity to his country.

  So, both Willie’s father and grandfather were leading figures among the scientific intellectuals of Australia, and both foresaw great things for Willie in the field of physics. Together they would have a profound influence on Willie’s scientific career, an influence that would shepherd him in a direction that seemed, at least at the time, far afield from his beloved biology. Of this period, Willie would later recall that his father’s “bedtime stories were always the same—about the properties of atoms; we started with hydrogen and ran through a good part of the periodic table.”3 For the moment, however, Willie was indifferent toward physics and occupied his private moments exploring the natural world near his home in Australia, a country that possessed some of the most unique wildlife in the world, much of it still undiscovered.

  Willie’s interest in nature, coupled with his friendless existence, led him to take long, solitary walks on the beach, and to eventually collect seashells as a hobby. In fact, over a few short years, this young boy had amassed one of the finest collections of South Australian seashells in existence and had become well versed about all aspects of South Australian sea life.4 It therefore might not be too surprising that the first scientific discovery of Willie’s life would be a new species.

  This happened one day as Willie was combing the beach for shells and found the bone of a cuttlefish. Cuttlefishes (Sepia) are really not fish at all. Rather, they are a specific class of mollusks (Cephalopoda) closely related to octopuses. They also are the premier camouflage artists of the ocean. Somehow they have the ability to manipulate their skin texture and modify the reflection of light to the point that they can assume the appearance of virtually any object they encounter in their environment. By blending in, they escape torment from predators.

  A cuttlefish’s skeleton consists of a single, porous, and brittle bone, roughly the shape and size of a shoehorn. Most people have seen cuttlefish bones, but not on the beach. They are routinely hung in birdcages by bird fanciers, to perform the double duty of providing an object for gnawing that sharpens the pets’ beaks, while simultaneously providing a dietary source of the essential element calcium, the major constituent of bone.

  When Willie first saw the cuttlefish bone, he immediately recognized what it was, but was unable to identify the exact species. It was unlike any cuttlefish bone Willie had seen before, so he showed the bone to a local expert, who confirmed Willie’s expectation. It was from an unknown species, and Willie, as its discoverer, was entitled to give this new species its scientific name. Thus, the cuttlefish became Sepia braggi—Bragg’s cuttlefish.

  Willie was thrilled. He would have liked to continue exploring the wilds of Australia for the rest of his life, making more natural discoveries in a country that still had a largely pristine environment … but this was not to be. Willie later said, “biology rather than physics might have been my trend had there not been such a strong family tradition [in physics].”5 For better or worse, Willie, like his namesake cuttlefish, would need to blend into his environment if he were to survive as a scientist. And Willie’s scientific environment was physics, not biology.

  SIMPLICITY RULES

  Despite its still unknown function, nuclein occasionally attracted the curiosity of various chemists over the first few decades following its discovery. These chemists each contributed their own small piece to the puzzle of nuclein’s chemical composition. By the late 1920s, when biologists started to show an interest, chemists had formulated a succinct chemical description, if not an exact structure. The nuclein molecule appeared to be a very long chain (i.e., a polymer) of phosphate-containing monomers, which the chemists called nucleotides to reflect their nuclear origin. Each nucleotide was comprised of just three components: (1) a nucleobase (a single- or double-ringed structure that resembled a honeycomb cell); (2) an unusual circular sugar structure (specifically, deoxyribose—a five-carbon sugar that was missing one of its oxygen atoms); and (3) a phosphate group (a phosphorus atom bound to oxygen atoms). What’s more, nucleotides used their phosphate groups like hands grabbing the sugar of their neighboring nucleotide to form the chain, similar to humans forming a conga dance line, with all the nucleotides in the chain facing in the same direction. Curiously, only four different chemical versions of the nucleotides were present in this huge biological polymer. They were called cytosine and thymine (the single-ringed nucleobase forms collectively known as the pyrimidines), plus guanine and adenine (the double-ringed nucleobase forms collectively known as purines).

  Chemists also had determined that the phosphate groups were electrically charged. That is, the phosphates were devoid of any hydrogen ions (positively charged) to neutralize their negatively charged oxygen atoms. This meant that the nucleotide chain was highly negatively charged along its entire length. Such molecules that shed their positive hydrogens to become negatively charged are called acids. Consequently, nuclein could reasonably be described as a nuclear acid polymer. To reflect this new chemical understanding, nuclein was given a new name, more fitting to its known chemistry. It became deoxyribose nucleic acid (now termed deoxyribonucleic acid), meaning an acid from the cell’s nucleus that is derived from the sugar, deoxyribose. That’s quite a mouthful, so it’s usually just called by its acronym, DNA.

  This polymer chemistry stuff might not sound all that simple. Admittedly, it is a little complicated, particularly when trying to visualize DNA’s chemical structure in three dimensions. Nevertheless, because DNA is fundamentally just a very long molecular chain with only four different types of links, it was considered much too simple to be able to encode complex genetic information. How could genes write the very story of life, if they only had a four-letter alphabet to work with?

  The easiest way to appreciate why DNA seemed too simple to be the stuff of genes is to consider the alleged superiority of protein as a potential vehicle for passing on genetic information to future generations. DNA’s linear polymer of nucleotides is somewhat analogous to the structure of proteins, except that proteins are linear polymers of amino acids rather than polymers of nucleotides. DNA has just four very similar nucleotides that differ from each other in only subtle ways. In contrast, proteins have 20 versions of amino acids to work with when forming their polymer chains. And those 20 amino acids are very different from one another in terms of their structure, charge, solubility, and so forth. So, by linking vastly different amino acids together in innumerably different orders, you can come up with highly diverse protein structures as different as a rhino’s horn is
from the lens of a human eye. Not so for DNA. The structure of DNA seemed to always be the same, both between cells and between species. How can you encode the vast genetic complexity of life on Earth with such a simple molecule that has an unchanging form?

  At first blush, it seems justified to suppose that simple molecules do simple things, and complex molecules do complicated things. It was, in fact, this intuition that led scientists to speculate that DNA must amount to some type of simple nuclear scaffold or skeleton to which the complex genes, allegedly consisting of proteins, are attached. This presumption about the informational deficit of simple things was a rather naive contention even for the time. Nevertheless, this groundless supposition about the functional limits of simple structures was taken for granted by many biologists. In a short while, however, their belief that simplicity was DNA’s greatest weakness would prove to be absolutely wrong.

  A TOUGH BREAK

  Even before Willie discovered his cuttlefish, he had already made scientific history, although he would have much preferred if the honor had befallen someone else. Willie has the distinction of being the first person in Australia to receive a diagnostic x-ray. His story is not unlike that of Toulson Cunning, the hapless Montreal gunshot victim, who had his wounded leg imaged by the local physics professor with a Crookes tube just days after Roentgen had discovered x-rays.

  In Willie’s case, however, his assailant was his younger brother, a tricycle was the weapon, and the professor with the x-rays was his father. Six-year-old Willie was riding his tricycle when his younger brother Bob decided it would be good sport to take a running jump onto the back, and so he did, thereby toppling the tricycle and crushing the bones in Willie’s left elbow. The family doctor ruled the break beyond repair, suggesting immobilization of the arm in its least obstructive position and allowing it to set stiff. Willie’s father, the great Professor Bragg, and his mother’s brother “Uncle Charlie” Todd, himself a physician, decided the stiff-arm plan was unacceptable. Instead, they pooled their professional talents to try and save Willie’s arm.6

  It was early 1896, and Professor Bragg had just recently learned of x-rays, which had been discovered by Roentgen a few months earlier. In fact, Bragg had been using a Crookes tube to reproduce Roentgen’s results, just as so many of his fellow physicists had already done months before in less scientifically remote parts of the world. The professor had tested the device on himself and produced some quality x-ray photographs of the bones in his hand, so he knew that x-rays from Crookes tubes could reveal bone structure.7 As for Uncle Charlie, he provided expertise in ether anesthesia. The two brothers-in-law collaborated to design a therapy plan that combined anesthesia, physical manipulations, and x-rays. The idea was to anesthetize Willie every few days and, while the boy was unconscious, manipulate the bones in his elbow and flex the arm in all directions. This was intended to coax the bones into aligning properly and to prevent the elbow joint from fusing into a stiff position.

  Progress was assessed with regular x-rays of the elbow. Although Willie dreaded the arm manipulations, the x-rays equally frightened him once he saw the sparking Crookes tube with its strange glow. Nevertheless, after his fearless little brother, Bob, volunteered to have his own elbow imaged as a demonstration of safety, Willie suppressed his cowardice and submitted to the x-rays.

  Ultimately, success was achieved. Willie’s elbow function was preserved, although his left arm did end up slightly shorter than his right. Still, the whole experience had been traumatic for him. Even though he was very young at the time, Willie was able to faithfully recount the details of the incident many decades later. It had made a big impression on him, and it was his introduction to the power of x-rays to reveal hidden structure. It was also his first inkling into how physics and biology might cooperate to reveal both form and function.

  SEX IS OVERRATED

  That genes resided in the nucleus, and specifically on chromosomes, had been generally accepted ever since 1915, when Morgan had linked gene transmission to chromosome transmission in fruit flies. It was also well known that genes could be passed from one generation to the next during reproduction. But, in 1928, bacteriologist Frederick Griffith (1877–1941) discovered something about gene transmission that shocked geneticists. He showed that when he mixed a heat-killed strain with a live strain of bacteria, the progeny of the live bacteria would assume some of the genetic traits of the dead bacteria. It was as though autonomous free-floating genes within the detritus of the dead culture were being taken up by the living bacteria and altering their genetic makeup. Not only did it amount to gene transmission without sex; it was gene transmission without life. These genes were strange things indeed! What were these naked genes, viable even apart from their cells? Presumably they were some type of protein particles, but the question remained open.

  THE SCIENTIFIC OUTBACK

  Professor Bragg’s foray into x-rays with the Crookes tube, fortuitous as it was for poor Willie’s arm, had actually interrupted the physicist’s ongoing work with radio waves, his main scientific interest at that time. In fact, in August 1895, just four months before x-rays would be discovered and less than a year before Willie would shatter his elbow, Bragg was working in his laboratory, preparing a demonstration of radio waves for his physics course. Unannounced, the 24-year-old New Zealander Ernest Rutherford paid him a visit.

  Rutherford was en route to England to begin studies at Cambridge.8 He had been a runner-up for a Cambridge scholarship offered to students in the British provinces, as New Zealand was at the time. But the original nominee was unable to commit to the terms of the award, so it was offered to Rutherford at the last minute. Rutherford had been working in the potato patch of his family’s farm when news of his scholarship arrived. He is said to have thrown his shovel into the air proclaiming, “That’s the last potato I’ll ever dig!”9 Within days, he set sail for England, but used the opportunity of his ship’s stopping in Adelaide, Australia, to look up the famous Professor Bragg and say hello.10

  Bragg was actually tinkering with his Hertz wave oscillator at the moment Rutherford showed up. Coincidently, Rutherford had brought along his own toy. He showed Bragg an electromagnetism detector that he had built himself. It was the device that he would ultimately employ in Cambridge to ring bells at long distances without wires, just as Édouard Branly had first demonstrated four years earlier. The two men talked radio waves all afternoon. They found a kindred spirit in each other and became lifelong friends. It is unlikely that Rutherford encountered six-year-old Willie during his brief sojourn in Adelaide. If he had, the loud and gregarious New Zealander would never have imagined that this quiet and shy little boy would eventually become his scientific successor at the Cavendish Laboratory.

  Enjoyable as it was for Bragg, Rutherford’s visit had underscored the virtual impossibility of staying in the forefront of science while working in the scientific backwater that Australia was at the time. In fact, with no central electricity in his laboratory, Bragg had to electrically power his experiments with his own small generator. And while Bragg was just beginning to take his first x-ray photographs with his Crookes tube, Edison was already demonstrating his newly invented fluoroscope at the National Electric Exposition in New York, showing rapt crowds the real-time moving x-ray images of internal bones, rather than just still x-ray photographs.11 The sad truth was that Bragg’s research had thus far amounted to little more than reproducing the findings of Newton, Marconi, and Roentgen, with light, radio waves, and x-rays, respectively. And he had only belatedly become aware of the discovery of radioactivity by Becquerel.12 Nevertheless, Bragg’s relative isolation had forced him, through necessity, to become a master instrument maker. He and his technical assistant, Arthur Rogers, both had very high standards for design and construction of their homemade scientific instruments, a skill that would later serve Bragg extremely well.

  Rutherford sympathized with the predicament of his friend back in Australia, and for many years exchanged regular corre
spondence with him about the latest scientific developments and shared experimental reagents whenever he could. And Bragg achieved some progress despite the obstacles. Following up on an observation by Marie Curie that alpha particles have a limited range that is dependent upon their energy, Bragg discovered that the rate of ionizations produced along the alpha particle’s path reaches a maximum just before the particle exhausts all of its energy and comes to a complete stop. This peak level of ionizations, releasing an energy burst at the very end of a particle track, is now called the Bragg peak. The Bragg peak has been used over the years in a number of applications, most recently in radiation therapy. This type of therapy strategy uses a proton accelerator, of similar design to that used at the Cavendish to first split the atom, to treat tumors. Since the range of the protons in tissue is energy dependent and well defined, the beam can be positioned and the particle energy adjusted so that the protons stop within the tumor itself, rather than in the normal tissue beyond the tumor. This means that the cell damage caused by the Bragg peak is predominantly restricted to the tumor, which should result in better tumor-cell killing. Grubbe, Kelly, Kaplan, and other early researchers of cancer radiation therapy, could only have dreamed of the day when tumor-destroying radiation doses could be delivered so precisely as to demolish internal tumors without also decimating the surrounding normal tissues. In fact, because of the efficiency of the Bragg peak in killing tumor cells while sparing normal tissue, proton accelerators are currently being installed in many radiation therapy clinics around the world.