Introduction: Before the Atomic Age: "Shadow Pictures," Radioisotopes, and the Beginnings of Human Radiation Experimentation

Radiation has existed in nature from the origins of the universe, but was unknown to man until a century ago. Its discovery came by accident. On a Friday evening, November 8, 1895, the German physicist Wilhelm Roentgen was studying the nature of electrical currents by using a cathode ray tube, a common piece of scientific equipment. When he turned the tube on, he noticed to his surprise that a glowing spot appeared on a black paper screen coated with fluorescent material that was across the room. Intrigued, he soon determined that invisible but highly penetrating rays were being produced at one end of the cathode ray tube. The rays could expose photographic plates, leaving shadows of dense objects, such as bone.

After about six weeks of experimenting with his discovery, which he called x rays, Roentgen sent a summary and several "shadow pictures" to a local scientific society. The society published the report in its regular journal and wisely printed extra copies. News spread rapidly; Roentgen sent copies to physicists throughout Europe. One Berlin physicist "could not help thinking that I was reading a fairy tale . . . only the actual photograph proved to everyone that this was a fact."[4]

Physicians immediately recognized these rays as a new tool for diagnosis, a window into the interior of the body. The useless left arm of German Emperor Wilhelm II was x-rayed to reveal the cause of his disability, while Queen Amelia of Portugal used x rays of several of her court ladies to vividly display the dangers of "tightlacing." [5] Physicians began to use x rays routinely for examining fractures and locating foreign objects, such as needles swallowed by children or bullets shot into adults. [6] During World War I, more than 1.1 million wounded soldiers were treated with the help of diagnostic x rays. [7]

In 1896, Roentgen's insight led to the discovery of natural radioactivity. Henri Becquerel, who had been studying phosphorescence, discovered that shadow pictures were also created when wrapped photographic plates were exposed to crystals partly composed of uranium. Could this radioactive property be concentrated further by extracting and purifying some as-yet-unknown component of the uranium crystals? Marie and Pierre Curie began laborious chemical analyses that led to the isolation of the element polonium, named after Marie's native Poland. [8] Continuing their work, they isolated the element radium. To describe these elements' emission of energy, they coined the word radioactivity[9].

As with x rays, popular hopes and fears for natural radioactivity far exceeded the actual applications. One 1905 headline captures it all: "Radium, as a Substitute for Gas, Electricity, and as a Positive Cure for Every Disease." [10] Following initial enthusiasm that radiation could, by destroying tumors, provide a miracle cure for cancer, the reappearance of irradiated tumors led to discouragement. Despite distressing setbacks, research into the medical uses of radiation persisted. In the 1920s French researchers, performing experiments on animals, discovered that radiation treatments administered in a series of fractionated doses, instead of a single massive dose, could eliminate tumors without causing permanent damage. With the new method of treatment, doctors began to report impressive survival rates for patients with a variety of cancers. Fractionation became, and remains, an accepted approach to cancer treatment. [11]

Along with better understanding of radiation's benefits came a better practical appreciation of its dangers. Radiation burns were quickly apparent, but the greater danger took longer to manifest itself. Doctors and researchers were frequently among the victims. Radiation researchers were also slow to take steps to protect themselves from the hidden danger. One journal opened its April 1914 issue by noting that "[w]e have to deplore once more the sacrifice of a radiologist, the victim of his art."[12](April 1914): 393.

Clear and early evidence of tragic results sharpened both expert and public concern. By 1924, a New Jersey dentist noticed an unusual rate of deterioration of the jawbone among local women. On further investigation he learned that all at one time had jobs painting a radium solution onto watch dials. Further studies revealed that as they painted, they licked their brushes to maintain a sharp point. Doing so, they absorbed radium into their bodies. The radium gradually revealed its presence in jaw deterioration, blood disease, and eventually, a painful, disfiguring deterioration of the jaw. [13] There was no question that radium was the culprit. The immediate outcome was a highly publicized crusade, investigation, lawsuits, and payments to the victims. Despite the publicity surrounding the dial painters, response to the danger remained agonizingly slow. Patent medicines containing radium and radium therapies continued.[14]

The tragedy of the radium dial painters and similar cases of patients who took radium nostrums have provided basic data for protection standards for radioactive substances taken into the body. One prominent researcher in the new area of radiation safety was Robley Evans. Evans was drawn into the field by the highly publicized death in 1932 of Eben Byers, following routine consumption of the nostrum Radiothor. Byers's death spurred Evans, then a California Institute of Technology physics graduate student, to undertake research that led to a study of the effects on the body of ingesting radium; this study would continue for more than half a century. [15]

Evans's study and subsequent studies of the effects of radium treatments provided the anchor in human data for our understanding of the effects of radiation within the human body. As the dangers of the imprudent use of x rays and internal radiation became clear, private scientific advisory committees sprang up to develop voluntary guidelines to promote safety among those working with radiation. When the government did enter the atomic age, it often referred to the guidelines of these private committees as it developed radiation protection standards. [16].

The Miracle of Tracers

In 1913, the Hungarian chemist Georg von Hevesy began to experiment with the use of radioactive forms of elements (radioisotopes) to trace the behavior of the normal, nonradioactive forms of a variety of elements. Ten years later Hevesy extended his chemical experiments to biology, using a radioisotope of lead to trace the movement of lead from soil into bean plants. In 1943, Hevesy won the Nobel Prize for his work on the use of radioisotopes as tracers.

Previously, those seeking to understand life processes of an organism had to extract molecules and structures from dead cells or organisms, and then study those molecules by arduous chemical procedures, or use traceable chemicals that were foreign to the organism being studied but that mimicked normal body chemicals in some important way. Foreign chemicals could alter the very processes being measured and, in any case, were often as difficult to measure precisely as were normal body constituents. The radioactive tracer--as Our Friend the Atom, a book written by Dr. Heinz Haber for Walt Disney productions, explained in 1956 to readers of all ages--was an elegant alternative: "Making a sample of material mildly radioactive is like putting a bell on a sheep. The shepherd traces the whole flock around by the sound of the bell. In the same way it is possible to keep tabs on tracer-atoms with a Geiger counter or any other radiation detector."[17]

By the late 1920s the tracer technique was being applied to humans in Boston by researchers using an injection of dissolved radon to measure the rate of blood circulation, an early example of using radioactivity to observe life processes. [18] However, research opportunities were limited by the fact that some of the elements that are most important in living creatures do not possess naturally occurring radioactive isotopes.

The answer to this problem came simultaneously at faculty clubs and seminars in Berkeley and Boston in the early 1930s. Medical researchers realized that the famed "atom smasher," the cyclotron invented by University of California physicist Ernest Lawrence, could be used as a factory to create radioisotopes for medical research and treatment. "Take an ordinary needle," Our Friend the Atom explained, "put it into an atomic reactor for a short while. Some of the ions contained in the steel will capture a neutron and be transformed into a radioisotope of iron. . . . Now that needle could be found in the proverbial haystack without any trouble." [19]

In 1936, two of Lawrence's Berkeley colleagues, Drs. Joseph Hamilton and Robert Stone, administered radiosodium to treat several leukemia patients. In 1937, Ernest Lawrence's brother, physician John Lawrence, became the first to use radiophosphorus for the treatment of leukemia. This application was extended the following year to the treatment of polycythemia vera, a blood disease. This method soon became a standard treatment for that disease. In 1938, Hamilton and Stone also began pioneering work in the use of cyclotron-produced neutrons for the treatment of cancer. The following year, not long before the war in Europe began, Ernest Lawrence unveiled a larger atom smasher, to be used to create additional radioisotopes and hence dubbed the "medical cyclotron." [20] The discovery that some radioisotopes deposited selectively in different parts of the body--the thyroid, for example--inspired a spirited search for a radioactive "magic bullet" that might treat, or even cure, cancer and other diseases.

In Cambridge, the age of "nuclear medicine" is said to have begun in November 1936 with a lunchtime seminar at Harvard, at which MIT President Karl Compton talked on "What Physics Can Do for Biology and Medicine." Robley Evans, by that time at MIT, is reported to have helped prepare the portion of the talk from which medical researchers at the Massachusetts General Hospital's thyroid clinic came to realize that MIT's atom smasher could produce a great research tool for their work--radioisotopes. Soon, doctors at the thyroid clinic began a series of experiments, including some involving humans, that would lead to the development of radioiodine as a standard tool for diagnosing and treating thyroid disease. [21]

In late 1938, the discovery of atomic fission in Germany prompted concern among physicists in England and the United States that Nazi Germany might be the first to harness the power of the atom--as a propulsion method for submarines, as radioactive poison, or most worrisome of all, as a bomb capable of unimagined destruction. In the United States, a world-famous physicist, Albert Einstein, and a recent émigré from Hungary, Leo Szilard, alerted President Franklin D. Roosevelt to the military implications of the German discovery in an August 1939 letter.

Assigning his own science adviser, Vannevar Bush, to the task of determining the feasibility of an atomic bomb, Roosevelt's simple "O.K.," scrawled on a piece of paper, set in motion the chain of events that would lead to the largest and most expensive engineering project in history. Soon, Ernest Lawrence's Radiation Laboratory and its medical cyclotron were mobilized to aid in the nationwide effort to build the world's first atomic bomb. In a related effort, Drs. Stone and Hamilton, and others, would turn their talents to the medical research needed to ensure the safety of those working on the bomb.