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frequently worked at the leading edge of such research and development. However, around ten years ago, more subtle and possibly more challenging internal changes were recognised within the Society itself. As a maturing society within a dynamic field, a progressive broadening of the membership occurred, further expanding the array of professional representation and member interests. Early pioneers of nuclear medicine were mainly physicians and physicists. Initially, the society only offered full membership to physicians and graduates. But with great foresight, these founders did not seek to restrict the new Australian & New Zealand Society of Nuclear Medicine to their own specific disciplines, but established a professional society that was open to all who worked within the broader scope of nuclear medicine and held appropriate tertiary qualifications. Associate membership was available to non-graduates, which included nucleographers (as they were known at that time) and ‘sustaining membership’ was offered from inception to involve the crucial support industry. As the practice of nuclear medicine subsequently evolved and expanded, the society moved to recognise and embrace other professionals including technologists, pharmacists and nurses, and those involved in research and production, and also suppliers to the nuclear industry. In 1997, Mrs Heather Hodges from Queensland became the first nuclear medicine technologist to be elected president of the ANZSNM. Her predecessors had been physicians, scientists, radiopharmacists and physicists. The society also established specific geographical groups of members, the State Branches; and then equipment user groups also developed. These groups were open to all members of the Society on an equal footing. More recently, groups have developed which reflect specific professional interests within the field of nuclear medicine. These are the Special Interest Groups (SIGs), which now represent technologists, nurses, physicists and pharmacists. Today’s membership of the ANZSNM is wide and varied. Various sources, from which this book has drawn, include available archival material and communications with several eminent pioneering professionals directly associated with the establishment of nuclear medicine and the society and its activities over the last five decades. Official publications of the society, ‘Nuclear Medicine News’, ‘ANZSNM Newsletter’ and ‘ANZ Nuclear Medicine’ and the ‘Spectator’ of the Australian & New Zealand Association of Physicians in Nuclear Medicine (ANZAPNM, established in 1969), were particularly valuable. The Australian & New Zealand Society of Nuclear Medicine Technologists (ANZSNMT, established in 1974) became a special interest group (SIG) of the society in 1992. Other vital sources included the ‘Pioneer Witness Seminars’ that were held in Melbourne, Adelaide, Sydney and Perth. These brought together pioneers representing all professions within the nuclear medicine community (including physicians, physicists, radiopharmacists, technologists and nurses). From New Zealand, ‘The Blue Book’ and thumbnail sketches of departmental histories were provided by several pioneering physicists and physicians.
References 1. ‘Atoms For Peace + 50 Nuclear Energy & Science for the 21st Century’ Conference, 22 October 2003, The Watergate Hotel, Washington, DC.
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Chapter 1
FUNDAMENTAL DISCOVERIES A ‘New Light’ Two great advances in basic physics became known during the closing years of the nineteenth century. One was the discovery of X-rays; the other, understanding the electron. Both arose from the study of electric discharges in gases at low pressure. The German physicist Plucker concluded in 1859 that fluorescence was due to something radiating from negative electrodes or cathodes. These ‘cathode rays' were closely studied during the remainder of the nineteenth century. The English physicist Crookes published the results of a series of researches on the subject in 1879. Crookes showed that cathode rays were emitted normally to a cathode surface and could be deflected by a magnet. When he focused the rays to a point, sufficient heat was developed to melt glass or platinum foil. He concluded rightly, that the rays consisted of negatively charged particles. But although his experimental results were indisputable, the conclusions he drew from them were vigorously contested. Most German physicists thought that the cathode rays were a wave motion similar to light and that there was no propagation of matter. Hertz, working at Bonn, was seeking an experimental proof of Maxwell's theories of the nature of electricity and magnetism, and he took up the study of discharges in a vacuum. Hertz found that cathode rays could pass through a thin film of gold or aluminium placed in their path. After his death in 1894, his pupil Lenard continued his work. Lenard made a tube with a thin aluminium window and succeeded in bringing cathode rays into the outside air. He found that they still produced fluorescence, but that the rays would not travel far through air at atmospheric pressure. Lenard said that the cathode rays passed through his hand, which was almost certainly an observation of X-rays produced where the cathode rays struck the window of the discharge tube. But he failed to notice that it was a different kind of ray. Sir William Crookes often made the observation that photographic plates which happened to be stored near his tubes became fogged and this must have been caused by X-rays. On one occasion, he returned some plates to the manufacturer as unsatisfactory. Many workers must have produced X-rays accidentally while studying cathode rays, but it was Roentgen who observed their presence and realised that he was dealing with a ‘new kind of ray’. Although humans have been exposed to radiant energy as a part of our environment since prehistoric days and have since studied many properties of this radiation (principally those visible to the eye), official acquaintance with what is rather generally classified today as ‘nuclear radiation’ began with newspaper accounts in early January 1896 of a "sensational scientific discovery." German physicist, Wilhelm Conrad Roentgen (1845-1923) reported that, in his researches with a Hittorf-Crooke's tube, he had observed a new form of radiation that was capable of penetrating wood, tinfoil, human flesh and other opaque objects. He referred to these rays as ‘X-rays’, with "X" denoting the unknown factor; and this ‘temporary’ name stuck. 9
The fascinating history of X-Rays goes back to 8 November 1895, when, at the Institute of Physics in the University of Wurzburg, Bavaria, Roentgen first observed this new radiation. By 28 December he had submitted a preliminary report. When, in January 1896, the context of Roentgen's discovery, reduced to a small paragraph, was flashed around the world, it caused a sensation comparable with that resulting in recent times from the announcement of the atomic bomb. A detailed description of Roentgen's discovery was given by Sylvanus P. Thompson, late Professor of Science and Principal of Finsbury Technical College, himself an enthusiastic Xray research worker and President of the British Roentgen Society, at a meeting held on Friday 5 November 1897, at St Martin's in London. There is no doubt that Roentgen’s discovery of X-Rays is considered as one of the greater moments in history. However, the knowledge from which this advance in science was made could be found in the momentous work of a number of previous investigators. In 1837, Faraday, in England, identified dark spaces in electrified evacuated bulbs and he pioneered experiments with induction coils. It was also Faraday who, in 1853, referred to the positive electrode as the ‘anode’ and the negative electrode as the ‘cathode’. In 1851, Ruhmkorff, in Russia, produced his self-named coil. Geissler then discovered that an electric current produced vivid colours when passed through a tube containing rarefied or thin gases. Sir William Crookes, in England, was the man who laid the foundation upon which it can be said that X-Rays were discovered. In transcripts of the Royal Society, in 1874, Crookes stated that cathode rays could be brought to a focus by curving the cathode.1 He accordingly replaced the flat cathode with a concave one. In 1879, Crookes actually constructed a tube with a plate of platinum at the focus to display the heating effects of focused cathode rays. X-Rays must have been produced in abundance when the vacuum of his tubes was high enough to give a pale green fluorescence. But how did Crookes get the idea for making a Crookes-tube? This question was answered some years ago by Marshall Brucer M.D. who wrote Vignettes in Nuclear Medicine and researched the life and times of Sir William Crookes.2 William Crookes (1832-1919) was from a large family reasonably placed in society. His father was the court tailor on Regent Street in London. Crookes entered the Royal College of Chemistry and, by the time he was 19, had read his first paper to the London Chemical Society on the remarkable parallelism between sulphur and selenium. From this time, photography, spectrometry and finally metrication of any kind became his passions. To earn money, he became editor of the Liverpool and then, in 1856, London photographic journals, which were then primarily publications in practical chemistry. He purchased the copyright to the ‘Chemical Gazette’ and, as editor published the first issue of the renamed ‘Chemical News’ on 10 December 1859. For the next thirty years practically everything that went on in Science passed under Crookes' eyes. Editing was only a part-time 10
pursuit, as he maintained an extremely sophisticated laboratory for his research within his own home. On 5 March 1861, after experimenting with impure selenium he announced the discovery of a new element 'Thallium' (from ‘thallous’: a green budding twig). Following the death of his brother, Crookes became dangerously engaged in spiritualism, so much so that his scientific peers considered reading him out of the scientific society. This was a turning point in Crookes' career and, as a means of scientific endeavour he threw himself into research to purge the hurt he had encountered from his colleagues. From this work came an introduction to the atomic age. Following demonstrations to the Royal Society in 1873, 1874 and 1875 of a sensational instrument he called the ‘radiometer’, Crookes continued experimentations. The radiometer consisted of four disks of pith (black on one side; white on the other) that were attached to four arms suspended on a steel point, so as to revolve horizontally. All of this was enclosed in a glass globe evacuated to the highest obtainable vacuum. The arms revolved when exposed to visible light. The rate of revolution was proportionate to the intensity of the incident radiation. A number of scientists of the day, including Crookes, then started to develop experiments with electricity through gases in glass vacuum tubes. Other such notable scientists included Faraday, Julius Plucker and Johann Hittorf, famed for his shadow experiment of 1869. In one experiment, Hittorf put an obstruction between the cathode and glass wall of the vacuum tube. The obstruction cast a very sharp-edged shadow on the glass wall. He concluded that whatever was coming off the cathode must have been travelling in straight lines and was similar to waves of light in the luminiferous 'aether'. Crookes improved Hittorf's experiment by placing the anode asymmetrically, so as to leave the path of the cathode-ray beam free to strike the glass wall. In its path he had placed a hinged, mica, Maltese cross. During the early 1870's, Crookes' fanatic drive for precision in measuring the atomic weight of thallium led to the invention of the ‘Radiometer’. The Radiometer was converted into a ‘Crookes-tube’; then to dozens of modifications. Practically every physics laboratory in the world had at least one. A most memorable event in the history of Science occurred on 8 November 1895, when a new light, never before known to humans, was first observed. Professor Wilhelm Conrad Roentgen observed a faint, flickering, greenish illumination on a piece of cardboard he had painted with a fluorescent chemical preparation. In a carefully darkened room, from which every known kind of ray had been scrupulously excluded, he saw a line of dark shadow on the faintly luminous surface. Roentgen’s Crookes-tube was stimulated internally by sparks from an induction coil, but was carefully covered by a shield of black cardboard that was impervious to every known kind of light, even the most intense. In that darkness, especially arranged to see luminous phenomena, nothing was visible but these previouslyunrecognised rays evidently emanating from the Crookes-tube and penetrating the cardboard shield.
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Roentgen traced back the shadow to the object that caused it and verified the source of the rays to be the Crookes-tube. These newly-discovered rays, which were invisible until they fell upon a chemically painted screen, were found to have a penetrative power previously unimagined. They penetrated cardboard, wood and cloth with ease and even went through a thick plank and a book of 2,000 pages to light up the luminous screen placed on the other side. But metals such as copper, iron, lead, silver and gold were found to be less penetrable. Strangest of all, while flesh was very transparent, bones were fairly opaque. So, interposing his hand between the source of the rays and his luminescent cardboard, Roentgen saw the bones of his living hand projected in silhouette upon the screen. A great discovery was made.2 When Roentgen first came upon this new light, so powerful that it could pass through opaque objects, he told his good friend Boveri, "I have discovered something interesting, but I do not know whether or not my observations are correct." Except for this remark, he talked to no one about what he had found. For days he locked himself in his laboratory and, without sleep or food, worked out his experiments again and again. Roentgen first reported his findings in a paper, ‘A New Kind of Ray’, which he presented to the Physical Medical Society of Wuzburg. His paper was published almost immediately, at the end of the Society's 1895 ‘Transactions’. The news of this new discovery electrified the world. Perhaps the best known X-ray of all time is that of Roentgen’s wife’s hand captured on photographic film (figure 1). Newspapers around the globe printed a host of X-ray images of the hands and feet of living persons and extolled the mysterious power of those strange rays which could "see" through almost anything. Media saturation provoked common scepticism, fear and public ridicule. A Bill was introduced into the House at Trenton, New Jersey, prohibiting the use of X-rays in opera glasses at theatres and, in England, a firm "made prey of the ignorant women by advertising the sale of X-ray proof underclothing." Roentgen's scientific contemporaries weren't completely without scepticism either, but there were also strong believers in the value of his discovery. The majority of the medical fraternity could vividly foresee how the sufferings of mankind might be lessened by the use of these new rays. Figure 1. An X-ray image on photographic film of the hand of Roentgen’s wife, Anna Bertha. It is perhaps the most famous Xray image of all time.
A general article published 30 January 1896 in ‘The Nation’ said in part:-
.....the importance of this discovery in its application to surgery as an aid to diagnosis in cases of disease or fracture of the bones is apparent. The photograph would reveal immediately and unmistakably the nature of the disorder without the long and often painful examination which the patient is now obliged to endure. In a case of complicated fractures another photograph can be taken after the
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bones have been set in order to ascertain whether the dislocation has been properly reduced or the broken parts have been rightfully replaced. The exact location of a bullet or the splinter of a shell can also be easily found without the use of a surgeon's probe. In all probability the progress can be perfected and modified so as to photograph the heart, lungs, liver and internal organs and thus determine their precise condition.
Such acclaim made Roentgen famous overnight. He was showered with honours, though he sought none and turned down many. As a result of his demonstration before Kaiser Wilhelm 11, Emperor of Germany and King of Prussia, he received a high Prussian decoration. A government decree bestowed upon him the title of ‘Excellency’, boulevards and streets were named for him, and monuments were erected in his honour. In 1901, the first Nobel Prize for Physics was awarded to Professor Wilhem Conrad Roentgen for his discovery of X-rays. This was the only monetary gain he received from his great discovery, and even this well-earned prize money was given by him to the University of Wurzburg ‘to support scientific research’. After about five years or so of intense work following up and further establishing his 1895 discovery, Roentgen's career became more and more hidden from the public eye. He devoted much of his time to teaching, which was always a foremost activity for him. Roentgen refused to patent any part of his discovery and rejected indignantly all ‘commercial’ offers. His wife's chronic illness and ultimate death in 1919 cast a shadow over his professional life. World War 1 and its immediate aftermath threw additional burdens on him. Roentgen died on 10 February 1923 at the age of 78 with a carcinoma of the rectum, which had remained unsuspected to the very last. He is buried at his wife's side in the family grave in Giessen. HERR PROFESSOR DR ROENTGEN, I PRESUME Scene: The Town Hall of Worchberg, in 1896. Enter a gentleman dressed in cape and top hat. Official: May I help you? Gentleman: My name is Wilhelm Conrad Roentgen. I am here to enquire about the status of my application for the new machine which I submitted to the health systems agency of Greater Worchberg. Official: Yes, Doctor Roentgen; we received your application and have examined it in great detail. There are, however, many questions left unanswered. Dr Roentgen: Yes, I found it as quite difficult for me to complete your application. Official: Well, Doctor Roentgen; we anticipate that your new machine will cause many problems. You claim that your new ray permits physicians to look inside the human body and to evaluate bones prior to surgery. We feel that there may be some slight merit to your invention. However, to consider this a medical necessity and expend huge capital sums will raise the cost of the medical care here in Worchberg. In addition to the equipment think of the personnel needed to run each of these units. We would also have to purchase X-ray plates and record these images and then store this information.
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Dr Roentgen: But, just think of what this X-ray means to patients. For the first time we may diagnose fractures intelligently; and I am working on a new application of my ray that will permit a doctor to look inside the chest and abdomen and visualise the stomach, colon and others areas of the body. Diseases may be found earlier, when they can be corrected. Official: Even if those procedures were possible, and they have certainly not been proven so as yet, we can't do very much about those diseases, so why find them earlier. If we do find these diseases we will only have a proliferation of surgical procedures and other ancillary medical tests. We must consider that our budget is limited and we must put our health care dollars into more useful areas. Dr Roentgen: But think of – Official: If we don't limit the use of the new modality each and every hospital will then want one of your units. What will happen to the cost of medical care then. If you are correct and your unit will allow physicians to see other parts of the body, not just bones then no doubt there will be a third and fourth generation X-ray unit. How can we stop this proliferation, no Dr Roentgen the agency will only approve one of your units for the greater Worchberg area. If we don't place these restraints on the unit then the use of the X-ray will increase and everyone with a headache or a stomach-ache will demand to have an X-ray. Dr Roentgen: Just think of the improved patient care with my X-ray. Official: The Worchberg HSA has decided that X-ray is still an experimental modality. We will not have our third-party payers reimburse any hospital for the use of X-ray on any part of the body but bones. Uses in the stomach, chest must be considered experimental and will not be reimbursed. I also would like to caution you to prevent your unit from falling into the hands of private practitioners. Who knows how many private X-ray offices would spring up if we did not include physicians’ offices as part of our certificate of need legislation? Perhaps you could find some other use for your new ray. Try shoe-stores.
Natural Radioactivity On 24 February 1896, only a few months after Roentgen's announcement, Henri Becquerel (1852-1908), a distinguished French physicist with equally distinguished physicists as father and grandfather, first reported his observations of natural radioactivity from pitchblende, an ore considered valuable because it was also associated with gold and silver. On Monday, 20 January 1896 the regular meeting of the French Academy of Sciences featured a demonstration of Roentgen's new photography by Henri Poincare. The Roentgen story had been leaked to the press two weeks earlier, as Roentgen didn't read his first paper until 23 January 1896. But the newspaper article had been well written and most physicists had a Crookes tube available for a quick check. Poincare had verified the news story immediately. His confirmation of the story's validity was published that day in ‘Comptes Rendus’. Henri Becquerel attended the meeting (as had his father Edmond before him, and his grandfather Antoine before him). The subject matter was of intense public interest and the distinguished occupant of the chair in physics at the Musee d' Histoire Naturell had to know what all this newspaper talk was about. Henri held the chair at that time (as Edmond and Antoine had before him, and his son Jean would also after Henri died). 14
Becquerel's analysis and report on 24 January 1896 were apparently triggered to a certain extent by Roentgen's discovery. Becquerel had noted that, as in the case of X-rays, air would be ionized by ‘emanations’ from his pitchblende ore. This was later found to be because of radiation from uranium and the minute quantities of radium and polonium in the ore. In July 1896, Pierre and Marie Curie (1859-1906 and 1867-1934), a husband and wife team in France, announced the concentration of the small fraction of radium in this ore, thus discovering a very highly-radioactive material. Henri Becquerel received the Nobel Prize in 1903. Twelve years after the death of Becquerel on 25th August 1908, William Crookes wrote the obituary of his old friend for the Royal Society. He described the excitement in 1896: [I] visited Henri Becquerel's laboratory one memorable morning when experiments were in progress which culminated in the discovery of the 'Becquerel rays’ and of 'spontaneous radioactivity’. Uranium salts of all kinds were seen in glass cells, inverted on photographic plates enclosed in black paper, and also the resulting images automatically impressed on the sensitive plates. Becquerel was working on the phosphorescence of uranium compounds after isolation; starting with the discovery that sun- excited uranium nitrate gave out rays capable of penetrating opaque paper and then acting photographically. He had devised another experiment in which, between the plate and the uranium salt, he interposed a sheet of black paper and a small cross of thin copper. On bringing the apparatus into daylight the sun had gone in, as it was put back into the dark cupboard and there left for another opportunity of isolation. But the sun kept persistently behind clouds for several days and, tired of waiting (or with the unconscious prevision of genius), Becquerel developed the plate. To his astonishment, instead of a blank as expected, the plate had darkened under the uranium as strongly as if the uranium had previously been exposed to sunlight; the image of the copper cross shining out white against the black background. This was the foundation of a long series of experiments which lead to the remarkable discoveries which have made 'Becquerel rays' a standard expression in science.
Photographic images of uranium had been seen previously. Forty years earlier, William Crookes had been editor of one of the first photographic journals. He remembered that, in 1857, a French photographer, Niepce de St Victor, had reported the storing up of energy by uranium. A sheet of paper impregnated with uranium nitrate and exposed to light would affect a photographic plate in the dark. This phenomenon was then considered to be a simple chemical reduction of silver salts. However, in reminiscing in 1910, in a speech to the past presidents of the Chemical Society, Crookes considered the first autoradiograph (and all Becquerel's pictures were autoradiographs) to be his own. By the end of 1899 five elements were known to be radioactive. The Curies The oppression of the Polish people by the Russian government of the Tsars caused Marie Sklodowska, a gifted young chemist to escape to France. Despite her youth, she had already obtained high academic honours. But she found it difficult to obtain employment and suffered extreme poverty while studying for a degree in Paris. 15
In the course of her work at the Ecole Polytechnique, where Becquerel headed the physics department, she met Pierre Curie, a French Scientist and personal friend of Becquerel who was engaged in experimental work in physics. Becoming friends through the common interest of their work, the two scientists married. Thus was formed one of the historic and fruitful partnerships of science, broken, unfortunately, eleven years later in 1906 by the tragic death of Pierre Curie in a street accident. As the Curies were extremely poor, they carried out their experimental work in makeshift laboratories in damp underground rooms and in leaking shanties. Nevertheless, they obtained results that were to transform science and medicine. The Curies' discovery was the result of Marie's belief that the ore pitchblende might contain another more active substance than uranium, which had been described several years earlier by Henri Becquerel. By 1898, Marie Curie had isolated two previously unknown and radioactive elements, 'polonium' which she named after her native country, Poland; and radium, in response to its intense radioactivity. The Curies received many honours in recognition of their great pioneer work. Madame Curie was twice awarded the Nobel prize; jointly with her husband in 1903 and again in 1911. In ‘Australian Doctor’, 30 June 1995, Dr George Biro précised her life and times that culminated with her remains being moved to the Pantheon, to become the first women in history honoured in this way. MARIE CURIE LIT UP THE WORLD WITH HER STUDY Imagine a derelict shed with a bitumen floor and a cracked skylight that lets in the rain. It was a dissecting room, but is no longer fit for corpses - stifling in summer and freezing in winter. Outside in the courtyard, a woman battles with a huge, heavy iron-rod; stirring a large cauldron brimming with a boiling volatile liquid. Occasionally, she stops to pour the liquid into a jar. When all the jars are full, she joins a man inside. Marie and Pierre Curie toiled like this for years. Born in 1867, Marie (Manya) Sklodovska was the youngest daughter of well-educated Polish patriots. Marie's mother was dying from tuberculosis. Only much later did Marie understand why her mother never kissed her. Russia ruled their part of Poland. Her father, a physics professor, was demoted when the Russians found him quietly teaching his Polish students their own language. He lost his life savings just when Marie was about to enrol at the Sorbonne in Paris. So Marie first worked for five years to support her elder sister Bronya while the latter studied medicine. After graduating, Bronya in turn helped Marie. In 1893, living on tea, bread and butter, Marie topped her class and got her masters. For her wedding to another physicist, Pierre Curie, she chose a dark suit which would not show the stains of lab work. It was an exciting time in physics. Soon after Roentgen's discovery of X-rays, Antoine Henri Becquerel found that uranium emitted mysterious rays and penetrated solids. For her doctorate, Marie explored other sources of radiation, which she named ‘radioactivity’. Marie found that the radiation emitted by pitchblende (the main ore of uranium, mined in Bohemia) far exceeded that expected from its uranium. Hence, she said pitchblende had to contain traces of another very radioactive, but still
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unknown, element. In fact, the Curies discovered not one, but two new radioactive elements (both breakdown products of uranium): polonium (named after Poland) and radium. Radium was one million times more radioactive that its parent, uranium. It took several years to realise that the Curies' gamma rays were identical to Roentgen's X-rays. But to isolate radium was another matter. So poisoned was the atmosphere in the derelict dissecting room that the Curies' notebooks are still dangerously radioactive. Pierre's hands became so scarred that he could not even knot his tie. He was treated for a malignancy. In 1901, the Curies lent their friend Becquerel a tube of a radium derivative. After carrying it in his pocket for only six hours, Becquerel found it had burned his skin, just like a burn from X-rays. This triggered interest in radium's therapeutic effects. Finally, in 1902, after four years of effort, the Curies isolated one-tenth of a gram of radium from eight tonnes of pitchblende. Marie and Pierre shared the 1903 Nobel Prize in Physics with Becquerel. The world cheered. A farmer wanted to put radium into his chicken feed so his hens would lay hard-boiled eggs. An academic said radium-fertilised soil would yield more and tastier crops. Pierre and Marie could have taken out patents and become rich, but passed on their findings for others to apply. Life was looking up when, in 1906, Pierre was run over by a lumbar wagon. Marie worked on despite this bereavement, the first symptoms of radiation sickness and the insults of the French. As a foreigner and a woman, she never won over the French authorities. Very reluctantly, they awarded her Pierre's professorship and asked her to give his lectures at the Sorbonne. Marie was the first woman to do so. She found that the luminous substance she and Pierre had called radium was actually a salt of radium. But Marie finally did isolate radium itself. She produced the first international standard of radium. The ‘curie’ became a unit of measurement of radioactivity. In 1911, Marie won her second Nobel Prize (this time for chemistry), but still the French Academy of Science would not admit the ‘foreign woman’. When World War I came, she invented mobile X-ray vans (‘little Curies’) to locate shrapnel in wounded troops. She trained 150 people as X-ray technicians, raised money to equip the vans and even drove one herself. By the end of the war, her 20 vans and 200 radiology posts had examined more than one million men. In 1921, Marie went to the US, where President Harding presented her with one whole gram of radium (worth $100,000) for medical use in Europe. Marie's eldest daughter, Irene, worked with her on the medical applications of radioactivity. Warsaw set up a radium institute, with Marie's sister as director. It was radium, the element to which she had devoted her life, that killed Marie. When she died in 1934 of leukaemia and aplastic anaemia, her body joined Pierre's at a cemetery. But this year the French 3 moved her remains to the Pantheon. Finally, Marie Curie rests with the foremost sons of France.
Radium Following her isolation of plutonium in July 1898, Marie Curie was soon to isolate another radioactive element (radium) some two months later. It had been apparent that the biologic 17
effects of the radiations emanating from radium were witnessed by Becquerel, and were to eventually cause Marie and her daughter Irene's ultimate deaths from leukaemia. Radium occurs in small quantities in many different minerals found in different parts of the world and also in the water of various mineral springs. For practical purposes it is extracted from pitchblende. In 1901, Becquerel was travelling to a lecture in London with a sample of his colleagues' radium in his vest pocket. After his return to Paris he consulted a physician about the reddened area on his abdomen beneath the pocket. In his 1910 publication: ‘Medical Electricity and Roentgen Rays’, S. Tousey reported: 0.2 gram of radium (of high activity) carried in the pocket of a flannel shirt for six-hours produced an ulcer without any pain and which took over a month to heal. This had been preceded by erythema which developed after a fifteen-day period of incubation. This accident was a personal experience of Becquerel. An accident of the same nature occurred to Mme Curie; and M. Curie, Dr Oudin, and M. Giesel have made experiments upon themselves and 4 upon animals.
The first medical applications of radium came only a few years later. During this period, radium therapy consisted most commonly of the application of a radium preparation applied as directly as possible to a local lesion and leaving it in contact for selected periods of minutes, hours, or days, according to the radioactivity employed and the extent of the tissue changes desired. Celluloid needles were coated with radium of various strengths and inserted into the substance of tumours. This would cause sloughing of tissue to enable extrusion of a tumour en masse. Such needles were left in place for up to 3-4 days depending on the radium activity that had been applied to the needle. It was observed that cancer cells were more susceptible than normal cells to the influence of radium. However, the effect appeared to be confined to tumour cells within a half-inch radius of each needle. Carcinomas of the breast, and especially large tumours, were targeted in this way. Under a general anaesthetic, the breast was punctured in a number of different places to obtain the desired effect of reducing the tumour and curing the disease. British Scientific Investigations While the discovery of natural radioactivity was emerging in France, English scientists were beginning to identify the constituent components of atoms. Thompson identified the electron in 1897 as a negatively-charged particle with a mass almost 2,000-times smaller than the lightest atom, hydrogen. He postulated that the electron might be a constituent of atoms, indicating that the atom was not indivisible, as Dalton had suggested a century before. The divisibility of atoms had been suggested by an intuitive English physician, Prout, in 1816. He had hypothesised that the basic building-block of all elements might be an entity identical to the hydrogen atom. In 1911, Rutherford demonstrated that the principal mass of an atom was concentrated in a dense, positively-charged nucleus. Then, with Soddy, Rutherford ascribed radioactivity to a process involving the spontaneous disintegration of atoms. Together with the Curies and 18
Villard, Soddy and Rutherford were able to identify (by behaviour in magnetic fields) three distinct types of radioactive emissions: 1. positively-charged alpha particles, identical to the helium nucleus, 2. beta particles, consisting of negatively charged electrons, and 3. non-particulate and highly-penetrating electromagnetic gamma-ray emissions. Following general acceptance by the wider scientific community of Rutherford's atomic model, it seemed clear that these emanations had their origin in the nucleus of the atom. Irene Curie and her husband, Frederic Joliot, were the first to demonstrate that nuclear bombardment could induce transmutations of some light elements to radioactive forms of other elements. In a short article in ‘Nature’, on 10 February 1934, they announced their discovery: Our latest experiments have shown a very striking fact: when aluminium foil is irradiated on a polonium preparation, the emission of positrons does not cease immediately when the active preparation is removed. The foil remains radioactive and the emission of radiation decays exponentially as for an ordinary radioelement. We observed the same phenomenon with boron and magnesium.
They had discovered that the bombarded boron had been transmuted into radionitrogen-13, and the aluminium into radiophosphorus-30. With the discovery of ‘artificial radioactivity’ the ‘classical period’ of nuclear medicine ended. Nuclear Fission X-Rays and naturally radioactive substances were the principal radiation sources available for general use until the discovery of nuclear fission in 1939 by German chemists Otto Hahn (1879-1968) and Fritz Strassman (1902-1980), and the development of the first nuclear reactor prototype in 1942 under the leadership of Italian physicist Enrico Fermi (1905-1954) in a squash court under the west stand of Stagg Field at the University of Chicago
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1
. Subsequently the first harnessing of the atom for practical purposes culminated in the first nuclear weapon, which was exploded in 1945. These developments and their subsequent large-scale use for both war and peace usheredin an exciting nuclear age. They have also produced extensive sources of radiation, primarily from the accompanying large scale production of radioisotopes, both incidentally and by design. These include neutrons as well as alpha, beta and gamma radiations from a bewildering variety of materials made artificially radioactive. Radioactivity and Tracer Techniques The first phenomenon of radioactivity observed was the blackening of photographic plates by uranium minerals. Although this effect is still used to some extent in research on radioactivity, the property of radioactive substances that is of greatest scientific value is their ability to ionize gases. Under normal conditions, air and other gases do not conduct electricity. If they did, power lines and electrical machines could not operate in the open, as they do. But under some circumstances, air molecules are broken apart into positively and negatively charged fragments called ions. Air thus ionized does conduct electricity. Within a few months after the first discovery of radioactivity, Becquerel found that uranium had the power to ionize air. Specifically, he found that the charge on an electroscope leaked away rapidly through the air if some uranium salts were placed near it. (The same thing happens to a storage battery if sufficient radioactive material is placed nearby.) Ever since that time, the rate of discharge of an electroscope has served as a measure of intensity of radioactivity and nearly all present-day instruments for studying radioactive phenomena still depend on this ionization effect, directly or indirectly. In 1908, the physicist Hans Wilhelm Geiger produced the first cathode ray tube with a centrally wired anode and 5 years later reported counting beta particle emissions with his charged tube. This was to become the now commonly used Geiger-Mueller (G-M) tube, which was used to ‘trace’ radioactivity throughout the body in the ensuing decades2. Wilhelm Mueller, co-inventor and associate of Geiger, is noted by Millard N Croll, a nuclear medicine historian, as “unfortunately, Wilhelm Mueller...immigrated to Australia, and his further activities are entirely lost to history”8. Curie and Joliot’s findings stimulated similar experiments all over the world. In particular, Fermi reasoned that neutrons, because of their lack of charge, should be effective in penetrating nuclei, especially those of high atomic number which repel protons and alpha particles strongly. He then verified this prediction almost immediately; finding that the nucleus of a bombarded atom captured the neutron to initially produce an unstable nucleus and then achieved stability by emitting an electron. The resultant stable nucleus was one unit higher in mass number and one unit higher in atomic number than the initial target nucleus. As a result of innumerable experiments carried out since 1934, radioactive isotopes of nearly every element in the periodic table can now be produced. Some regain stability by the emission of positrons, some by the emission of electrons, some by a process known as electron-capture, and a small number (probably three) by alpha-particle emission. 1
The University of Chicago was to become a key training site for Australian nuclear medicine physicians in the 1970s and 80s (see chapter 2). 2 For example, Hermann Blumgart & Otto Yens from Boston used radium to measure arm-to-arm circulation times using such a detector in 1927.
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Altogether, some five hundred unstable nuclear species have been observed and, in most cases, their atomic numbers and mass numbers have been identified. These artificially-radioactive elements play an important role in medicine, in ‘tracer’ chemistry and in many other fields of research which can hardly be overestimated. Artificial Production of Radioisotopes During 1931-1932, a team led by Professor Ernest Lawrence at the University of California, in Berkley, built a particle accelerator which they named cyclotron. Eventually the cyclotron produced a range of radioactive nuclides by suitable nuclear reactions between accelerated ions and elements in the target. The team’s major interests lie in those radionuclides which could be used for medical purposes. On Christmas Eve in 1937, Lawrence’s brother John gave the first dose of the radioisotope phosphorous-32 to a patient with chronic lymphatic leukaemia.5 The nuclear reactors established in Hanford, USA, could be used to produce relatively large quantities of radioisotopes likely to have valuable applications in medicine. Of these, phosphorus-32 and iodine-131 were of particular medical interest. It may seem ironic to some that the reactors built to produce material required for the manufacture of the earliest 'atomic' bombs should also have made possible the development of completely new clinical methods of diagnosis and treatment which have been of great benefit to patients in hospitals and clinics throughout the world. The Manhattan Project The Manhattan Project was a secret military project established in 1942 to produce the first US nuclear weapon. Fears that Nazi Germany would build and use a nuclear weapon during World War II triggered the start of the Manhattan Project, which was originally based in Manhattan, New York. US physicist Robert Oppenheimer and General Leslie R. Groves served as directors of this project, which recruited some of the best US scientists, engineers and mathematicians; and a number of European scientists, including Albert Einstein, Enrico Fermi and Leo Szilard. Under the auspices of the Manhattan Project, three main research and production facilities were established at Oak Ridge, Hanford, and Los Alamos. The Oak Ridge Laboratories in Tennessee provided uranium-235; while weapons-grade plutonium was produced at Hanford, Washington; and nuclear weapons were assembled at Los Alamos in New Mexico. Los Alamos produced four weapons, two of which (‘Little Boy’ and ‘Fat Man’) were used against Japan in August 1945. The building of nuclear reactors at Oak Ridge, Tennessee, eventually led to a new, cheaper source of medical radioisotopes after the war ended in 1945. The Atomic Energy Act, passed by Congress on 1 August 1946, created the Atomic Energy Commission; and the Manhattan Project officially ended in 1946, when it became part of the AEC. The Act enabled the peaceful production of medical isotopes in an Oak Ridge reactor; and the modern era of nuclear medicine had begun. Oak Ridge, Tennessee was to figure again much later in nuclear medicine as one of the main sites in the development of positron 21
emission tomography (PET), due to the abundance of nuclear technology infrastructure and human resources which was a legacy of the original Manhattan Project. In 1986, Josephine Wiseman was accepted into a course run by the Radiation Emergency Assistance Centre Training Site in Oak Ridge, Tennessee; and had this to say about the sleepy town: Oak Ridge was a small rural settlement before the war and was chosen as a nuclear research site, as it was relatively hidden in a valley. During the war, it became a secret city not recorded on any map, although its population swelled to 90,000 with scientific and military personnel. This was considered unfortunate by the population at the time, although one nurse on the REACTS staff, who would have been 20 at the time, relished fond memories of the invasion. This influx of people was housed in pre-fabricated huts which still stand, mostly untouched, giving one the impression of stepping back in time to a southern movie set of the 1940's. The famed bluegrass seemed as green as any I had ever seen, but all the locals complained of the terrible drought which had turned the grass as brown as they had ever seen it. I stayed in the old Guesthouse, renamed the Alexander Motor Inn, where Einstein, 6 Fermi and Oppenheimer had stayed when they visited to work on the Manhattan Project.
It was from here that P-32 was first procured arriving in Brisbane, Australia in 1944.7
References 1. Gardiner, J. H., ‘The Origin, History and Development of the X-Ray Tube’, Journal of the Roentgen Society, May 1909. 2. Brucer, Marshall MD, Vignettes in Nuclear Medicine (No.93), Mallinckrodt, St Louis, 1979. 3. Biro, George. ‘Marie Curie lit up the world with her study’, Australian Doctor, 30 June 1995. (Further reading: Pflaum, Rosalynd, Grand Obsession: Madame Curie and Her World, Doubleday, 1989.) 4. Tousey, Sinclair, Medical Electricity & Roentgen Rays, W. B. Saunders, 1910. 5. Brucer, M., ‘Nuclear medicine begins with a boa constrictor’, Journal of Nuclear Medicine, 19, 1978. 6. Wiseman, J., ‘Medical Planning and Care in Radiation Accidents’, ANZ Nuclear Medicine, Vol. 17, No. 4, 1986. 7. http://www.atomicmuseum.com/tour/nuclearmedicine.cfm 8. Croll, M.N. Nuclear medicine instrumentation. Historic perspective. Semin Nucl Med. 1994;24(1):310
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Chapter 2
ADVANCES IN AUSTRALIA Early Use of Radium in Australia According to Sydney Hospital’s Radium Registrar, Sylvia D. Bray, who on 18 May 1939 wrote to the Medical Journal of Australia, the first reported medical use of radium in Australia was on 5 May 1911. I would like to state that on 17 February 1911, twenty one pieces of radium, consisting of twenty plates of various strengths and one fifty milligram tube, were purchased by Dr Langloh Johnston for the Sydney Hospital, in all a total of 252.5 milligrams. This radium was first used on 5 May 1911, and from this date onwards was used continuously in the treatment of all grades of skin carcinomata, and the tube was used for carcinoma of the female genital tract, breast cases and glands, as well as many other types of lesions, superficial and deep. In the eight months of 1911, 163 new cases alone were treated at the clinic, and between 1 1912 and 1922 the annual total of new cases treated varied between 180 and 250.
Radium was first purchased by the Commonwealth Government in 1928 and the department of health established the Commonwealth Radium Laboratory to act as both custodian of the radium and as the centre from which it could be distributed on loan to approved hospitals as required. However, in a clinical context, the value of radium treatment for cancerous conditions was first demonstrated in France in 1901 and the first radium treatments in Australia were reportedly performed by a Melbourne dermatologist in 1903. At the Royal Hobart Hospital, radium needles were used for the first time to treat patients suffering from tumours and ulcers in 1912, just eleven years after the action of radium on human tissues first became known. But the initial results were far from encouraging. In 1913, encouraging results were obtained from radium treatment of certain cancer cases at the London Radium Institute, which issued its first report covering 539 cases treated from the opening of the institute on 14 August 1911 to 31 December 1912. In the same year, Senior Resident Surgeon and Radiologist of the General Hospital Hobart, E. J. Roberts M.D., presented a paper to the Tasmanian Branch of the British Medical Association entitled ‘The therapeutic value of secondary rays produced from metal by the action of the Rontgen rays.’ Roberts’ paper was then published in the Australasian Medical Gazette on 13 September 1913. I have not had an opportunity of practically comparing the therapeutic action of the secondary rays with that of the radium emanations, but a careful study of the radium literature has led me to think that for definite prognosis, convenience of manipulation and expense of instalment, the secondary rays are decidedly superior, while the therapeutic effects seem to 2 be more reliable and satisfactory.
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