Notwithstanding his discovery of the Bragg peak and other research progress he made in Australia, Bragg began to find his remote location oppressive to his work. It typically took six months for news of any scientific discovery to make its way to Australia. That meant he was perpetually six months behind the scientists in less remote locations. Bragg knew that if he wanted to do cutting-edge physics, he would need to return to England. What’s more, he believed that higher educational opportunities for his sons, Willie and Bob, were lacking in Australia. He wanted them to go to Cambridge, where he had studied. So he resolved that he would try to find himself a suitable faculty position at a university somewhere in England and move his family there.
LEAVING A TRACE
In the spirit of Miescher, who believed the fundamental chemistry of life would most readily be revealed by studying the simplest body cells, the leukocytes, many geneticists came to believe that the fundamental chemistry of genes could best be learned from studying life’s simplest of organisms, the viruses. Recall that even Muller, in recognition of the limitations of his own fruit fly research, had to concede that viruses provided “an utterly new angle [from which] to attack the gene problem.” Therefore, many geneticists became virologists, and it wasn’t long before two of them, working together, were able to conclusively resolve the issue of whether genes were made of protein or DNA.
Viruses are so simple that they do not even carry the molecular machinery needed for their own reproduction. A virus must instead inject its genes into a host cell, and fool that cell into using its reproductive machinery to reproduce the viral genes as though they were its own. But does a virus inject protein or DNA into a cell? Radioactivity would provide the answer.
If you grow viruses in media containing radioactive elements, those radioisotopes get incorporated into the molecular constituents of the viruses. Just as ingested radium found its way into the spines of the radium dial painters because it chemically resembled the calcium component of human bone, radioactive phosphorus fed to viruses will find its way into the phosphate groups that comprise the “backbone” of the virus’ DNA. Likewise, radioactive sulfur will find its way into the sulfur component of proteins. Since DNA contains no sulfur, and proteins contain only small amounts of phosphorus, such radiolabeling of viruses with radioisotopes of phosphates or sulfur will specifically result in radiolabeling the DNA or the protein, respectively. This is what virologists Alfred Hershey and Martha Chase did to resolve the question of which of the two biological polymers, DNA or protein, represented the stuff of genes. They radiolabeled viruses with radioactive phosphate and sulfur and then looked to see which radioisotope the viruses were injecting into cells when they reproduced. It turned out that the cells contained radioactive phosphorus only, suggesting that the viruses were only injecting their DNA and not their protein. This conclusively proved that genes are made of DNA.13
HOME AGAIN
In 1909, the chairman of the physics department at the University of Leeds, England, decided to retire. Rutherford, who had moved on from his first faculty position at McGill University in Montreal, Canada, was now physics professor at the nearby University of Manchester. He prevailed on the Leeds selection committee to offer the vacant position to Bragg. It was the opportunity Bragg had been waiting for. He accepted the position straightaway, and booked passage to England.
Upon arriving, Bragg immediately went to visit his friend Rutherford in Manchester, where they relived their first encounter of so many years earlier. This time, Rutherford played host and showed Bragg his latest scientific marvels, including a pump that he had designed to collect radon gas emanating from a radium solution. (This radon pump’s design was similar to the one that Rutherford would later provide to Dr. Howard Atwood Kelly in Baltimore, so that Kelly could collect radon for his brachytherapy cancer treatments.14)
Willie enrolled at Cambridge University, fulfilling his father’s wish, and began studying physics at the Cavendish Laboratory. He was academically well prepared for Cambridge. In fact, he had been taking college courses at the University of Adelaide since the age of 16. When Willie arrived at the Cavendish, his father’s old mentor, J. J. Thomson, was still in charge, and would remain in charge until Rutherford succeeded him a decade later.
FIGURE 11.1. WILLIAM (“WILLIE”) LAWRENCE BRAGG. Willie Bragg realized that x-rays bounce off crystals just as light bounces off mirrors. His discovery of this phenomenon and his description of its associated mathematics (Bragg’s law) won him a Nobel Prize in Physics (1915) when he was only 25 years old. He remains the youngest scientist ever to win a Nobel Prize. (Source: Photograph courtesy of the AIP Emilio Serge Visual Archives, Weber Collection, E. Scott Barr Collection)
If Willie believed he had left behind the ignorant bullies that haunted his childhood in Australia, he was sadly mistaken. At Cambridge he encountered the same prejudice against provincials that Rutherford had experienced years before. Willie was treated as a second-rate student by his fellow classmates, who harbored the widespread misconception that Australia was a country best described as a mixture of aboriginal wasteland and British penal colony. But Willie was as academically gifted as Rutherford, and just as Rutherford had soon outshone his detractors, Willie’s tormenters were presently struggling to keep up with him. This, in turn, provided another reason for them to dislike him. Also, like Rutherford before him, Willie earned himself a prestigious scholarship. He did this by achieving a top score on a competitive mathematics exam that he took while confined to bed, battling pneumonia. And then in 1912, at the young age of 22 and in his very first year of research work at the Cavendish, Willie made a momentous discovery that further distanced himself from his peers. He discovered a property of x-rays that no one else had ever appreciated before. They bounce!
The x-ray question that Willie solved had been puzzling physicists for some time. It had to do with the mysterious effect that crystals have on a narrow x-ray beam passing through them. A crystal is a special type of solid in which all the individual molecules are lined up in perfect rows and columns, in three dimensions. Crystals further have the remarkable ability to self-assemble, such that if you have a pure solution of some particular chemical dissolved in water, and then you allow the water to evaporate away, the molecules left behind will tend to organize themselves in regular rows and columns as they begin to solidify. The forces that drive crystal formation are governed by the laws of thermodynamics (think entropy, enthalpy, and such), but we need not get into all that. Simply know that crystals are all around us. Table salt and sugar granules are good examples of small crystals, but crystals can also grow to large sizes as in rock candy and diamonds. The bottom line is simple. If a chemical solution evaporates into a crystal, you can be assured of at least two things: (1) It is essentially pure of molecular contaminants, because contaminants would disrupt the crystallization process; and (2) the molecules that have joined to form the crystal have a very regular structure, because if they didn’t, they wouldn’t be able to line up uniformly.
When a very narrow x-ray beam (as narrow as a laser pointer beam) is aimed at a crystal, most of the x-rays pass right through it, as x-rays tend to do, forming a spot on a photographic film placed directly behind the crystal in the line of the beam. Nothing unusual there. But some scientists had noticed that they also found multiple small spots of exposure in regular patterns, outside the line of the beam. Since it had already been established that x-rays could not be bent or focused with conventional optical lenses, what exactly was going on in crystals? No one knew.
Willie had been pondering this problem for a while when suddenly he realized something unique about the atoms in crystals, which made them different from other solids. In a crystal, because of its regular molecular structure, all of the component atoms are aligned along natural sheets, or geometric planes, like the surface of a table. For example, in common table salt (sodium chloride), there would be serial planes of sodium atoms alternating with planes of chloride atoms. In sugar
crystals (comprised of only carbon, oxygen, and hydrogen), its three types of atoms would also fall along their own planes. All right, you say, but so what?
Willie might have had the same reaction, but he had just completed his natural science exam, a large part of which was devoted to light and optics. In preparation for the exam he reviewed his lecture notes from his optical physics class; in particular, he went over some lectures by Professor C.T.R. Wilson, where Wilson described white light as behaving like a mixture of electromagnetic pulses comprising a very limited range of wavelengths.15 Just as these pulses of light could bounce off mirrored surfaces, like tennis balls off a court, Willie hypothesized that the shorter wavelength pulses of x-rays should bounce, or reflect, off the mirrorlike planes formed by the sheets of atoms within crystals. Also, he proposed that the deflection spots produced on the photographic film when x-rays passed through crystals were “due to the reflection of x-ray pulses by sheets of atoms in the crystals.”16
Willie even thought he could prove his hypothesis. Certain types of crystals tend to fracture along their atomic sheets, leaving surface planes of atoms with mirrorlike surfaces. Mica, a silicate mineral responsible for the sparkling flecks seen in many types of rocks, is one such crystal. Willie showed that x-rays bounced off mica sheets onto photographic film just like light bounces off mirrors. Furthermore, as he varied the angle of incidence, the angle of bounce varied according to the same physical laws as the reflection as light. He took his freshly developed photographic evidence, showing the mica-reflected x-ray spots, straight to J. J. Thomson. Thomson was elated. When Willie’s father learned of his son’s achievement he proudly wrote to Rutherford, “My boy has been getting beautiful x-ray reflections off mica sheets, just as simple as reflections of light in a mirror!”17 Hearing the news, the cautious Rutherford set his two latest protégés Harry Moseley and Charles Galton Darwin (grandson of the famous naturalist, and godson of eugenicist Francis Galton) to work on repeating and validating Willie’s findings, which they promptly accomplished, thus corroborating Willie’s claims. Rutherford, too, then reveled in the excitement. Just as Rutherford had once recognized that the angle at which alpha particles bounced off gold foil had profound implications regarding the size of gold’s atomic nucleus, Willie recognized that the angle at which x-rays bounce off a crystal had profound implications regarding the distances between the atom sheets within that crystal. Both were momentous discoveries.
To fully appreciate the significance of Willie’s insight to science, it is important to understand how his theory of x-rays bouncing off crystals could be practically used. Imagine you’re at home at night in a dark room with a window to the outside, and you have a laser pointer. Let the laser’s light beam simulate your narrow x-ray beam, and let the window simulate your crystal. Let’s also assume that the window is doubled paned; that is, it has two panes of glass trapping an air space in between, as is commonly done to provide heat insulation. You now shine your laser pointer out the window at a 45-degree angle aiming at a tree outside. You will see a spot on the tree where the laser light has passed through the glass, but if you now turn your attention to the wall perpendicular to the window you should also see two spots. One of these is formed from the reflection of the beam off the inner windowpane, and the other from the reflection off the outer windowpane. If the widow were triple paned, you would see three spots. This is what Willie realized was happening when x-rays passed through crystals. They were being reflected off the multilayered natural “window panes” formed by the planes of atoms within the crystal.
Let’s further suppose that it is important to know the actual distance between the two panes of the window, but there is no way to get a ruler into the window for a direct measurement. How would you do it? Willie realized that the distance between the two panes is related to the distance between the two spots on the wall and their angle from the window surface. Using his prodigious mathematical skills, he was able to generate a simple formula that allowed him to determine the distance between atomic planes in any crystal based on the distances between the reflected x-ray spots on the photographic film:
FIGURE 11.2. BRAGG’S LAW. When an incident x-ray (dashed arrow) enters a crystal, it can bounce off any one of the atomic layers. By measuring the angle of the bounce, the distances between the atomic layers (d) can be calculated. Bragg’s law allows atomic distances to be determined very precisely for any molecule that can be crystalized, and provided James Watson and Francis Crick with the clue they needed to discover the structure of DNA.
n λ = 2 d sin θ
where d is the distance between the sheets of atoms, θ is the angle of reflection, and λ is the wavelength of the incident x-ray. (The n is a term denoting some whole number corresponding to a wave interference concept known as the order of reflection, which is beyond the scope of our interests here.) We need not understand this equation, but it is important to appreciate its implications.
This simple mathematical relationship, now known as Bragg’s law, basically says that reflected x-rays behave a lot like reflected light, and that the degree of reflection is dependent upon the wavelength of the radiation. Should this surprise us? After all, light and x-ray radiation are both electromagnetic waves, distinguished solely by their wavelengths. Nevertheless, it was an eye opener at the time, and it had extremely important practical implications. Bragg’s law would ultimately provide a powerful tool for understanding the three-dimensional structure of any molecule that can be crystallized. In effect, the physicists had come to the rescue of the biochemists by providing a method to study molecules in three-dimensions rather than just two, even when those molecules are very large, as biological molecules tend to be.
Willie took his angle of reflection idea to his father, who was experienced in both optics and instrument-making, and together they built a device to measure the angle of x-ray reflection that emulated the original design of Newton’s instrument for measuring light refraction. But instead of measuring light refraction through prisms, as Newton had done, the Braggs’ instrument measured x-ray reflection off crystals. Then the two Braggs started irradiating different crystals and deducing their atomic structures from the angles of x-ray reflection. They spent the next two years determining one crystal structure after another, from lowly table salt to diamonds.18 In doing so, they contributed mightily to the future understanding of molecular structure and bond lengths between atoms.
Willie first revealed his discovery of the x-ray reflection properties of crystals and their similarity to the reflection of visible light by mirrors at a meeting of the Cambridge Philosophical Society. Shortly thereafter his presentation was published in their Proceedings. It is notable that Willie began his explanation on the behavior of x-rays in crystals by drawing parallels directly from a textbook with which his audience was quite familiar; this was An Introduction to the Theory of Optics, by Arthur Schuster. The book itself drew heavily from the original optical work of Newton. Thus, the study of radiation had come full circle, and returned to its original roots in optics.
The physical principle of producing multiple reflections from objects that have their internal structures organized along multiple stacked planes is now called Bragg reflection, in honor of Willie. Unfortunately, it is often mistakenly attributed to his father, who was already famous for discovering the Bragg peak phenomenon of particulate radiation. It was a perpetual problem that the father and son’s scientific contributions were often conflated, although each man made frequent attempts to set the record straight. The fact that they shared the same first name didn’t help. Some even thought they were the same person. Willie would soon start going by his middle name, Lawrence, rather than his first, to help lessen the confusion, but it was of little help. Even today, the two men are often confused in the scientific literature.19
FIGURE 11.3. X-RAY CRYSTALLOGRAPHY. The technique of x-ray crystallography entails directing a narrow beam of x-rays through a crystal. The x-rays then reflect at different ang
les off various planes of atoms within the crystal’s molecular structure (bottom). The reflected x-rays produce spots on photographic film. Analysis of the spatial distribution of the spots on the film provides the angle of reflection values, which are needed to calculate, using Bragg’s law, the distances between atomic planes in the crystal. An actual film from a simple protein purified and crystalized from chicken egg whites (lysozyme) is shown (top), but large and complex molecules can also be deduced using the same approach. (Source: Image of crystallography technique provided by courtesy of Dr. Gert Vreind)
BULL’S EYE
While geneticists had been working to identify the chemical substance of genes, radiation biologists had been busy confirming that radiation produced its biological effects by damaging genes. The evidence was overwhelming and consistent. The scientists were able to show that, in order to kill a cell with radiation, you must irradiate its nucleus, the home of its genes. And if you irradiated a whole cell, you could rescue it from death by transplanting a nonirradiated nucleus from another cell into the irradiated cell. It seemed that the only determinant of whether there would be a biological effect was whether the radiation reached the nucleus. Furthermore, it could be readily seen under the microscope that radiation was able to break chromosomes in the nucleus, and the magnitude of the biological effects was proportional to the amount of chromosome breakage. Likewise, chemicals that protected the chromosomes from breakage mitigated the biological effects as well. In short, there was a direct connection between the gene damage and the biological effects. Given that the substance of genes had now been determined to be DNA, the logical implication was obvious: DNA is the target for radiation’s biological effects.20
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