New Medical Specialty

"The history of the living world can be summarized as the elaboration of ever more perfect eyes within a cosmos in which there is always something more to be seen." Nuclear medicine provides new ways to look at the function and biochemistry of all parts of the living human body. People try to pinpoint the "birth of nuclear medicine" to a specific date or event, but it is difficult to do so. Nor did nuclear medicine develop along a continuous growth curve, but rather was the result of "revolutionary" discoveries, some of which had difficulty in being accepted.

The story begins one night in 1895, when the German physicist Conrad Roentgen noticed that certain crystals, inadvertently left near a highly evacuated electric discharge tube, became luminescent even when the tube had been enclosed in a light proof box. He found that the invisible radiations, which he dubbed x-rays, ionized the air through which they traveled, and, moreover, exposed x-ray film. The x-ray "shadowgraphs" could reveal the internal structures of objects opaque to light. He realized the potential medical applications immediately, and took the famous x-ray picture of his wife's hand.

Two months later, the French physicist, Henri Becquerel, was exploring the consequences of Roentgen's discovery, and placed a phosphorescent uranium salt in a light-proof envelope containing an unexposed photographic plate and set it in the sunlight. He reasoned that if the plate showed black spots where the salt was, this would be due to x-rays excited by the sun. He was gratified to find the black spots. Then there was a period of cloudy weather. By force of habit, he developed some photographic plates that had been lying in a dark drawer with bits of uranium salt on them without any exposure to the sun. To his astonishment, the darkened areas were again observed where the uranium salt had been. As has often been said, discovery depends on a "prepared mind." Becquerel concluded that the uranium salts were giving off penetrating x-rays, even when in their natural, unstimulated state. Radioactivity had been discovered.

Becquerel was a professor of physics at the Ecole Polytechnique. One of his most promising students was Marie Sklodowska, bride of Pierre Curie, a good friend of Becquerel. Marie had emigrated from Poland to Paris, and eagerly accepted the suggestion of Becquerel that she try to find out what in uranium was responsible for the radiation that he had discovered.

Using a radiation detector invented by her husband, Pierre, Marie (who coined the term "radioactivity") set out to isolate the active fraction of pitchblende, and that was so interesting that Pierre dropped his own research and joined Marie in her efforts. Their first discovery was that there was another source of radioactivity in

pitchblende in addition to uranium. It turned out to be another element, thorium. Even more intriguing was the finding that the radiation did not emit low energy x-rays, but far more energetic and penetrating rays.

As they isolated fractions of pitchblende, they found some that contained more radioactivity than pure uranium. They concluded correctly that there must be other radioactive sources present besides uranium. By a series of remarkable and laborious chemical separations, involving tons of pitchblende, in July of 1896, they discovered an element with a radioactivity 400 times greater than an equal amount of uranium. They named the newly discovered element polonium, after Marie's native Poland. Later that same year, they discovered another new element, radium.

Soon thereafter, they discovered that the radiation from radium produced biological effects. Among the first observations was that made by Becquerel himself in 1901. Traveling to London from Paris to deliver a lecture, he carried a sample of radium in his vest pocket. After returning to Paris, he noticed a reddened area on the skin beneath the pocket. This led to great interest in the biological effects of radioactivity. In 1903 the American inventor Alexander Graham Bell suggested that placing vials of radium near cancerous skin lesions might cure them.

In 1913, the most important principle of nuclear medicine—the tracer principle—was invented in Vienna by Hevesy and Paneth. They monitored the movement of radioactive lead from the soil into plants and then back into the soil when the plants died. In this way, they could monitor dynamic processes that characterize life. Early instruments for measuring radioactivity included the piezoelectric device used by the Curies, photographic plates used by Rutherford, the cloud chamber, invented in 1895 by the Scottish physicist Wilson, the gold leaf electroscope, and the Geiger counter, perfected in 1928. Hevesy and Paneth relied on the gold leaf electroscope for their experiments. This instrument was so sensitive that radioactive lead could be given in such small amounts that there were no toxic effects of the lead on the plants. This is another important characteristic of the "tracer" principle: radioactive tracers in small amounts have no biological effects on biochemical processes within the organism being studied. These early experiments were forerunners of what lay ahead—a new branch of medicine based on the use of radioactive "indicators," as they were called by Hevesy, to reveal the biochemical pathways of molecules labeled with radioactivity as they moved through the biological system. If larger amounts of the tracer atoms or molecules were given, the biological process could be suppressed, which provided a basis for treatment.

An amusing historical anecdote occurred when Hevesy began to suspect that his landlady was returning food to the dinner table that was left over from previous meals. So he spiked his uneaten food with radioactive lead. At the next meal, he quietly pocketed a sample of the food, which he put under his gold leaf electroscope. Sure enough, the specimen was radioactive! He confronted his landlady with the evidence. Shorter in temper than in scientific vision, she promptly evicted him.

In these early days, the studies were limited to the use of the few naturally radioactive materials that were available. These were uranium, thorium, radium, polonium, bismuth, and lead, elements that had little biological significance. Blumgart and his colleagues conducted the first clinical studies with radioactive tracers in Boston in the late 1920s. They injected solutions of radium C (bismuth-214) into an arm vein, and measured the time it took for the tracer to go through the heart and lungs and be detected in the opposite arm. This took about 18 seconds in people who did not suffer from heart disease. They called their measurement the "velocity of the circulation," which was abnormally slow in patients with heart failure.

In the 1940s, the first reports of the use of radioactive iodine to treat diseases of the thyroid, and radioactive phosphorus to treat leukemia were greeted with great enthusiasm by the medical profession and the public. These classic findings were immediately recognized as forerunners of a whole series of similar uses of radioactive "magic bullets" to seek out and destroy diseased tissues within the human body. They predicted what has proved to be true: radioactive "tracers" have helped in the diagnosis or treatment of millions of patients with overactive or cancerous thyroids, and many other types of diseases. It is estimated that today one of three patients admitted to a hospital has a radioactive tracer procedure as part of the diagnostic process or treatment.

Radioiodine accumulation is blocked by the administration of triiodothyronine (T3) in normal thyroidal tissue but not in autonomously functioning nodules. Nuclear medicine was recognized as a medical specialty in 1971 by the American Medical Association. Today, over 5,000 hospitals in the United States provide nuclear medicine services to their inpatients and outpatients.

The specialty is based on the creation of images of the spatial and temporal distribution of radiolabelled molecules to reveal the chemistry and function of the organs of the living human body in health and disease. The specialty provides the unique ability to examine both the location and site of these process to reveal regions that are abnormal.

Nuclear medicine was the 22nd medical specialty to be recognized by the American Medical Association, being incorporated on July 28, 1971 when nuclear medicine was recognized as a medical specialty. The American Board of Radiology (ABR) recommended that radiology residents obtain 6 months of training in nuclear medicine. The

BEFORE T3

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BEFORE T3

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