From Radioisotopes to Medical
Imaging, History of Nuclear Medicine
Written at Berkeley

September 9, 1996

By Jeffery Kahn,

For six decades, this Laboratory has been acknowledged as the birthplace of nuclear medicine. During Berkeley Lab's 65th anniversary celebration, pioneering researcher Tom Budinger documented the
John Lawrence, the father of nuclear medicine
extent to which Berkeley Lab has remained the cradle of invention in this field, right on up to the present moment.

Budinger, who heads the Center for Functional Imaging here, chronicled the preeminent role of the Lab in nuclear medicine -- in the diagnosis and treatment of diseases, in imaging, and in safety. Berkeley Lab researchers have provided an ever-clearer window for doctors to view and image disease within the human body. They have provided physicians new and more effective ways to treat diseases. And they have devised treatments for diseases that had been untreatable.

The contributions of nuclear medicine extend to surprising horizons. World War II aviators, who suffered the bends when flying at high altitudes, were able to overcome this obstacle thanks to Lab researchers. Radiobiologists here resolved the mystery of the ghostly flashes of light being observed by spooked astronauts. Today, researchers are establishing radiation limits for human space travel.

Radiobiology has further extended these contributions. Melvin Calvin's Berkeley team resolved the riddle of photosynthesis, discovering the path of carbon as it travels through a plant, using the tracer carbon-14 (also discovered at Berkeley). Today, radioisotope tracers are a fundamental tool of biology.

Budinger, whose Building 50 auditorium audience included many pioneers of nuclear medicine, started his talk by describing the beginning of the field.

Ernest Lawrence about the time he came to the University of California at Berkeley in 1928.
Ernest Lawrence, inventor of the cyclotron, recognized the possibilities for medicine, and persuaded his brother John to join the Laboratory. John Lawrence started Donner Laboratory circa 1936. Treating a patient with leukemia, he administered a radioactive isotope of phosphate. It was the first time that a radioactive isotope had been used in the treatment of a human disease as well as the start of a career-long contribution from John Lawrence. He became known as the father of nuclear medicine and his laboratory is considered the birthplace of this field.

In 1937, Joseph Hamilton was the first to use these tracers to study circulatory physiology. Using radioactive sodium, Hamilton studied how fast that which we eat enters and traverses the human body.

Hamilton realized that radioisotopes with a short half-life -- a property which allows them to be used without medical side effects -- were needed. He asked the Lab's Glenn Seaborg for help. Seaborg and Jack Livingood bombarded tellurium with deuterons in the Lab's 37-inch cyclotron, creating iodine-131, with a half-life of eight days.

Iodine-131 was the beginning of the Lab's ongoing role in the discovery and use of radioisotopes. In 1938, technetium-99m which remains the most commonly used isotope in medicine, was discovered by Emilio Segre. Other important isotopes in which the lab played pivotal roles in the discovery and application include tritium, carbon-14, fluorine-18 and thallium-201.

During the war, John Lawrence and his colleagues used radioisotopes to help pilots deal with the consequences of high-altitude flying. Pressurized cabins did not exist at that point. Donner Lab researchers used radioisotopes of inert gases to study decompression sickness and other maladies. These tracer studies made fundamental contributions to the understanding of the circulation and diffusion of gases. This research led to the development by the laboratory's Cornelius Tobias of aircraft oxygen measurement equipment. As a result of this work, an automatic parachute-opener was developed.

Numerous advances were recorded during this era of nuclear medicine at the laboratory. People suffering from polycythemia vera, a rare disease characterized by an over-abundance of red blood cells, were treated with doses of radio-pharmaceuticals. It was the first disease to be controlled with radioisotopes. In 1940, a pioneering treatment procedure debuted to treat leukemia. That was also the year in which hyperthyroidism first was diagnosed and treated using Seaborg and Livingood's iodine-131.

In the 1950s, Hal Anger conducted seminal studies on medical imaging. From 1952 to 1958, he gradually developed the scintillation camera, also known as the Anger Camera, which enables physicians to detect tumors and conduct other medical diagnoses by imaging gamma rays emitted by radioactive isotopes. Developed forty years ago by Anger, these techniques remain the most commonly used tools in nuclear medicine today.

Hal Anger , shown with his invention, the positron scintillation camera
Over time, Anger's scintillation camera evolved into modern imaging systems such as PET (positron emission tomography) and SPECT (single photon-emission computed tomography). The evolution of this technology was shaped by Anger, his colleagues and successors here. Their contributions include the multi-crystal whole body scanner (1970), gated heart single gamma tomography (1974), dynamic, gated PET (1978). Today, there are 160 PET cameras operating in hospitals, medical and research facilities worldwide. The highest resolution PET scanner in the world -- the 2.6 millimeter-resolution camera -- was built by Budinger's colleagues Steve Derenzo and Ronald Huesman, and resides here.

Many of the applications of the Anger camera and its descendants were pioneered here. In the 1960s, researchers used the Anger Positron Camera to diagnose bone tumors. In 1972, Yukio Yano devised a technetium-99m/phosphate system for bone scanning. In 1979, rubidium-82 was used for dynamic PET diagnosis of heart disease. Currently, an effort led by Budinger, Derenzo, Huesman, and Bill Moses is on the verge of creating a 2 millimeter-resolution, three-dimensional PET camera that can image brain chemistry.

Just as Ernest Lawrence's cyclotrons made possible the creation of radioisotopes, these accelerators also made possible the use of beams of neutrons, protons, and heavy ions for the treatment of disease.

In the 1940s here at this Lab, researchers first investigated the use of neutron beams for cancer radiotherapy. Here in the 1950s, helium and protons beams first began to be used. Later, in the 1980s, medical researchers here were the first to begin using heavy ion beams to treat cancerous tumors as well as a deadly brain disorder known as AVMs, or arteriovenous malformations (AVMs). AVM is a disease characterized by abnormal growths in the brain of blood vessels. Heavy ion beams can be precisely focused to obliterate these growths which, unless treated, can cause lethal or disabling brain hemorrhages and seizures.

Charged particle beams generated by Lawrence's accelerators have vital medical uses.

At the Bevalac, which closed in 1993, scores of patients benefited from the pioneering experimental use of heavy ions to treat cancerous tumors. The success of this program is responsible for the recent opening of the charged particle patient treatment facility in Chiba, Japan. This commercial facility uses a Berkeley Lab accelerator design. A second commercial charged particle facility is scheduled to start patient treatments in Darmstadt, Germany this year.

Much of the book on radiation safety was written here.

The Lab's Will Siri literally wrote the first textbook on the safe application of radioisotopes in biology and medicine. From 1945 to 1979, researchers developed and refined a model of the effects of inhaled radioactive particulates. Researchers here have been instrumental in promulgating guidelines that define the radiation limits of space travel. These findings have important implications for future interplanetary space travel by humans.

Budinger is among those whose work is part of the ongoing history of nuclear medicine. The very day of his talk, Laboratory Director Charles Shank, Life Sciences Division Director Mina Bissell, and Director of DOE's Office of Energy Research Martha Krebs joined to praise Budinger at the dedication of the Lab's new Biomedical Isotope Facility.

Shank said the new facility, which can produce the short-lived radioisotopes indispensable in many areas of research, would not have been possible without a stubborn 10-year-effort by Budinger and his chemist colleagues Chet Mathis and Henry Van Brocklin. As with the nuclear medicine program begun by John Lawrence, over time, the payoff from persistence and vision can be of historic dimensions.

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