Introduction

"There is a history in all men's lives."

—Shakespeare, Henry V

"The history of science is the history of scientists."

—John Lukacs

"How can man perform that long journey who has not conceived whither he is bound?"

—Henry David Thoreau

In September 2003, the National Institutes of Health (NIH) presented to the American people the goals of the NIH for medical research in the 21st century. Dr. Elias Zerhouni, who became director of the NIH in May 2002, had been Associate Dean for Research at Johns Hopkins School of Medicine before going to the NIH as the first radiologist to head that agency. He had been trained in nuclear medicine while a resident in radiology at Hopkins.

"Molecular imaging" was to be a major focus of research in the future of the NIH. This declaration of intent by the NIH was exciting for those in nuclear medicine, because molecular imaging had been the hallmark of nuclear medicine since its beginning.

The new NIH "Roadmap" focused on (1) the presymptomatic detection of disease; (2) personalized treatment based on molecular targets; and (3) the discovery of the clinical manifestations of genetic abnormalities. These had been the goals of nuclear medicine for over half a century.

In 2002, a new institute of the National Institutes of Health, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), was created with an annual budget approaching $300 million, adding to the imaging research being carried out in other institutes, especially the National Cancer Institute. Imaging sciences had become a key focus of today's biomedical research, but this had not always been the case.

Those of us who had chosen to become specialists in nuclear medicine often encountered obstacles during the development of our careers. Many of the basic principles of our new specialty had not yet achieved acceptance by the medical establishment. Anatomy, radiology, and surgery remained the foundation of medical practice.

My first encounter with nuclear medicine took place when I arrived in London in July 1957, five years after I graduated from Johns Hopkins medical school. Nuclear medicine was not then a recognized medical specialty. The general public had heard the term

Figure 1 Elias Zerhouni trained in nuclear medicine at Johns Hopkins. At present, he is head of the National Institutes of Health in Bethesda, Maryland.

"atomic medicine" and associated it with the development of the atomic bomb. The field was based on the same scientific principles that had produced the atomic bomb. There was in those days an underlying fear of anything that had to due with radiation. These negative perceptions lingered long after the end of World War II. It would take decades before nuclear medicine would find its place in medical practice and biomedical research, before nuclear medicine defined itself as a scientific and clinical discipline, and people understood what the specialty was really all about. Nuclear medicine moved medicine beyond its focus on anatomy to a new focus on "molecular medicine." More than any other specialty, it brought together structure and function. Arthur Koestler has written: "In biology, what we call structures are slow processes of long duration; what we call functions are fast processes of short duration." They are both changes in mass as a function of time.

The story of the birth and growth of nuclear medicine is one of the most fascinating in physics and medicine, an excellent example of the precept that things don't happen; people make things happen. Nuclear medicine evolved from using the tools of physics and chemistry to solve patient problems. First, political, scientific, and technological challenges had to be faced.

The "tracer" principle was invented in 1913 by Georg Hevesy. It refers to our ability to "track" molecules as they participate in chemical processes. It is as if a molecule emitted a radio signal telling us what it was doing at all times.

Hevesy was born in August 1885 in Budapest. Working with Fritz Paneth in Vienna, he invented what he called "radioactive indicators." After his chemistry experiments in 1913, in 1923 he carried out his first radioisotope studies in biological systems, first in plants and then animals. In 1925, Herman Blumgart in Boston carried out the first human tracer studies by injecting his patients with solutions of the radioactive gas radon and timing how long it took for the radioactivity to travel from the injection site in an arm vein through the heart and lungs to reach the opposite arm.

In 1934, Hevesy left Berlin for political reasons and began to work in Copenhagen with Niels Bohr, who had first proposed the structure of the atom. In 1935, Hevesy began to work with phosphorus-32, being provided the radionuclide through the mail from Ernest Lawrence's cyclotron in Berkeley, California.

Nuclear TracerHow Nuclear Medicine MadeHow Nuclear Medicine Made

Figure 5 Measurement of the circulation time with intravenously injected tracers.

Figure 6 Forstman, discoverer of nuclear fission, and Seaborg.

Hevesy published more than 400 scientific articles and in 1943 won the Nobel prize. In 1959, he received the Atoms For Peace award by the U.S. Atomic Energy Commission. He died on July 5, 1966, in Freiburg, Germany.

In 1931, physicist Ernest Lawrence in California invented the cyclotron, which made possible the production of radionuclides not previously available. This invention was a major event along the path to nuclear medicine, occurring more than a decade before the start of the Manhattan Project, which was to build the atomic bomb and led to the invention of the nuclear reactor. The first cyclotron specifically for biomedical research was built in Cambridge, Massachusetts, by physicist Robley Evans in November 1940.

A cyclotron, which can be used to insert highly accelerated atomic particles, such as protons, into the nuclei of target molecules, can produce all of the most important radioactive elements needed for the study of living systems: radioactive oxygen, carbon, nitrogen, and fluorine (a substitute for hydrogen). Indeed, the element carbon defines organic chemistry.

Early studies in the 1940s focused on the thyroid. The fascination of the general public for this new approach to the chemistry of the living body is typified by an article in the June 4, 1963, issue of the Wall Street Journal, describing the construction of the cyclotron in the Physics Department at Washington University. For the first time, the economics of hospital cyclotrons were also examined.

The cyclotron was put on a back burner in biomedical research as a result of the invention of the nuclear reactor during World War II. In December 1938, Hahn and Strassman in Germany discovered fission, a process by which uranium atoms could be split into smaller elements. In December 1942, Enrico Fermi and his colleagues in Chicago built the first nuclear reactor as part of the Manhattan Project. Compared to the cyclotron, the nuclear reactor was able to provide a far wider source of radioactive elements and compounds at much lower cost. Fermi graduated from the University of Pisa in 1922 and subsequently studied in Gottingen, Germany, and the University of Florence, and then for 12 years taught at the University of Rome. When he learned that he was to receive the Nobel prize in Physics in 1938, he used the occasion to sail directly from Stockholm to New York. When the Manhattan Project began in 1942, Fermi was responsible for the study of chain reactions and plutonium research in the Metallurgical Laboratory of the University of Chicago. On December 2, 1942, he and his colleagues carried out the first production of a self-sustained nuclear chain reaction, which subsequently led to the production of the atomic bomb.

The invention of the nuclear reactor, which was a product of the Manhattan District Project of World War II, made large quantities of useful radioactive elements available to scientists and physicians throughout the world. The project was started by President Franklin Roosevelt shortly after he received a letter from Albert Einstein on August 2, 1939. Einstein had been told by E. Fermi and L. Szilard that "the element uranium may be turned into an important source of energy in the immediate future . . . that extremely powerful bombs of a new type may thus be constructed . . . You may think it desirable to have some permanent contact maintained between your administration and the group of physicists working on the chain reaction in America."

Ernest Lawrence had invented the cyclotron to make possible bombardment of atomic nuclei with high-energy sub-atomic particles, but in 1934, Frederick Joliot and Irene Curie made the startling discovery that practically every chemical element could be made radioactive by particle bombardment. Bombardment with high energy particles, such as protons, was possible in a cyclotron, because progressively high voltages of electricity could be produced conveniently, making it possible to produce hundreds of

Figure 7 Strassman and Wagner at Mainz in 1969.

Cyclotron General Electric

isotopes of different elements, including carbon, nitrogen, and oxygen, which are of enormous importance in living systems. Indeed, carbon defines organic chemistry, the chemistry of life. Lawrence and his colleagues recognized immediately the great biomedical potential of the cyclotron.

Most of the Nobel prize winning discoveries in physics that provide the infrastructure of nuclear medicine were made at the time of a worldwide economic depression. In 1939, my parents took our family to the New York World's Fair in Flushing Meadow, N.Y. We were greatly impressed by the exhibit of "Man-made Lightning" at the General Electric Pavilion. A Van de Graaff generator could generate voltage up to 50,000 watts to produce an impressive 10-foot bolt of "lightning" that was spell-binding. The very next year, a group of six British scientists, called the Tizard mission, led by Henry Tizard, were sent by Winston Churchill to enlist the aid of American scientists in developing new technologically based weapons, which he believed was the key to winning the war spreading throughout Europe. They brought with them the results of all the top secret work on radar going on in England, and hastily set up headquarters in the Shoreham Hotel in Washington, D.C. On their voyage across the Atlantic, physicist John Cockcroft was asked to give a lecture on board ship. Because the work on radar was top secret, he chose to speak on atomic energy, which he believed was a safe topic "still considered years away from being realized and of no possible importance to the war." In his lecture, he stated that the energy in a cup of water could blow a fifty-thousand ton battleship one foot out of the sea.

Few people in the field of nuclear medicine know of the important relationships between the brilliant physicists who worked on both the development of radar and nuclear energy. The book Tuxedo Park, (a "must" read for everyone in the field of nuclear medicine), written in 2002 by Jennet Conant, the granddaughter of James B. Conant, President of Harvard University from 1933 to 1953 and Chairman of the National Defense Research Committee from 1941 to 1946, relates these remarkable connections between the physicists who developed radar and subsequently directed their attention and creativity to the nuclear physics foundations of nuclear medicine. The late Hal Anger was among these physicists. He had several key inventions related to radar prior to his directing his attention to nuclear instrumentation in 1948, inventing the well counter in 1951, the first of a series of basic instruments in the infant field of nuclear chemistry and medicine.

Even before the beginning of World War II, the Danish physicist Niels Bohr had lectured extensively in the United States about the destructive potential of the energy that might be released by nuclear fission. A report in Newsweek stated that atomic energy might create "an explosion that would make the forces of TNT or high-power bombs seem like firecrackers." Bohr's fears were matched by those of the Hungarian physicist Leo Szilard, who in 1939 was working with Nobel laureate Enrico Fermi on uranium fission at Columbia University.

Szilard told of his work to his 60 year old mentor, Albert Einstein, who decided immediately that the U.S. government should be warned of the possibility of making an atomic bomb, and wrote on August 2, 1939, to President Franklin Roosevelt. Szilard solicited funds to support his research on uranium from the financier tycoon and amateur physicist, Alfred Loomis, who, beginning in 1926, had built a personal research laboratory in Tuxedo Park, New York. Loomis subsequently contributed financially and helped

Ernest O. Lawrence to construct a cyclotron for the production of radioactive isotopes for research in both biomedicine and physics. With the help of Loomis and his many connections, Lawrence obtained a $1 million research grant from the Rockefeller Foundation. Loomis' consuming interest at the time was recruiting the brightest physicists to help develop advanced weapons for what he believed was certain to be a war in which the United States would become involved.

Loomis's lab would be hastily shuttered in 1940 and its research transferred to the newly established Rad Lab at MIT: "It is hard to believe that in only a few years, that bright circle (the physicists in Loomis's laboratory at Tuxedo Park) would not only build a radar system that would alter the course of the war, but would go on to create a weapon that would change the world forever."

Ernest Lawrence first visited Tuxedo Park in 1936 "to see the lab." Five years before, he had become famous for building the first cyclotron, using a radio frequency oscillator to accelerate deuterons at high speeds to bombard target atoms. As Lawrence's colleague and another Nobel prize winner, Luis Alvarez, wrote: "Lawrence had developed a new way of doing what came to be called 'big science', and that development stemmed from his ebullient nature plus his scientific insight and his charisma; he was more the natural leader than any man I've met." With the help of Arthur Loomis, Lawrence received a breathtaking $1.15 million from the Rockefeller Foundation to build a 60-inch cyclotron, far bigger than the 7-inch and 30-inch machines that had been built previously. This was long before the National Institutes of Health was even dreamed of. Nearly all scientific research was privately supported. In Loomis's words: "It was obvious from the very beginning, when he (Lawrence) was building (radioactive) isotopes, that it opened up methods for making medical measurements as well as chemical and physical measurements." After spending an enormous amount of time generating the funds, a 184-inch cyclotron was finally on the drawing board, when, on September 1, 1939, Germany invaded Poland.

Ernest's brother, John, had been in England to give a lecture on the use of P-32 to treat leukemia, and was to return on the ship, Athenia. Ernest heard a radio report that the Athenia had been torpedoed by a German submarine and was sinking off Scotland. It was 6 hours before he received word that all Americans on board had been rescued by a British destroyer.

In November 1939, Loomis moved to the Claremont Hotel in Oakland in order to carry out microwave experiments that Lawrence helped him design to complement his work on radar in Boston. The klystron tube had been invented by a physicist at Stanford, William Hanen, with the help of a former roommate, Russell Varian and his brother Sigurd. They were all working on the design of a radar device for navigating and detecting planes. These important advances were picked up for development by the Sperry Gyroscope Company. The 37-inch cyclotron was operating in the same building. Lawrence and his talented group were continuing to make plans for what eventually turned out to be the 184-inch cyclotron. On November 9, it was announced that Lawrence had won the Nobel prize for physics for his invention and development of the cyclotron.

When Ernest Lawrence returned to Berkeley after a visit to Loomis in 1939, he excitedly told his colleague Luis Alvarez of "his adventures on Wall Street with Loomis." When Loomis asked Lawrence to help him recruit for the new radar laboratory in MIT, to be opened after the closure of Loomis's laboratory in Tuxedo Park, Lawrence recom mended two of his best students in Berkeley, Luis Alvarez and Edwin McMillan, both of whom would subsequently receive the Nobel prize. They began to work on radar a year and a month before Pearl Harbor. On February 7, 1941, Alvarez and his colleagues detected an airplane 2 miles away. The head of the laboratory, Lee DuBridge, exclaimed: "We've done it, boys."

The success in Britain and the United States on the development of radar changed the course of World War II, saved tens of thousands of lives, and subsequently revolutionized air travel, navigation, and weather forecasting. The enormous value of radar was clear in 1940 when Britain was subjected to the Blitz by the German Luftwaffe. The British could only survive and prevail because of the invention of radar, which had occurred several years before, based on the original work of Dr. Robert A. Watson-Watt, then head of Britain's Radio Research Laboratory. His work led to the establishment of a chain of Radio Detection and Ranging (RADAR) stations along the south and east coasts of England to detect enemy planes and ships.

While this work on radar was progressing, Fermi and Szilard at Columbia University were working on the possibility if obtaining a chain reaction, based on the discovery of deuterium by another Nobel laureate, Harold Urey. Before he left to work on radar, in Berkeley, Ed McMillan discovered uranium-239. His work was taken up by Glenn Seaborg and Emelio Segre, who subsequently showed that another product of uranium bombardment with deuterons was the new element, plutonium-239. They too would be among the many of Lawrence's disciples to receive the Nobel prize; McMillan with Seaborg in 1951 for their discovery of plutonium and his discovery in 1940 of neptunium; Alvarez in 1968 for his work in high energy physics.

Lawrence helped recruit every physicist of consequence in the country—many of them his former students—who were on the brink of exciting careers in nuclear physics to go to the Radiation Laboratory at MIT in Cambridge, Massachusetts, and work on the development of radar. According to Conant: "In each case, they dropped what they were doing and came for the simple reason that Lawrence had asked them to . . . Roping Lawrence into the radar project had been a stroke of brilliance . . . The Manhattan Project had not yet come into being. Here were all these unemployed nuclear physicists." Lawrence picked Lee DuBridge, a protégé and Chairman of the Physics Department at the University of Rochester, to direct the radar project, and he continued modifying and enlarging his 37-inch cyclotron. By the fall of 1941, Lawrence was convinced that every effort should be made to build an atomic bomb using either uranium-235 or plutonium-239. As Nobel laureate, Arthur Compton wrote in his memoir, Atomic Quest, the unique contribution of Lawrence was "a feasible proposal for making a bomb. No one else ever proposed the possibility. He came forward with what he felt could be carried through, and had something tangible to take hold of."

Although Ernest himself devoted all his efforts to physics, he appointed his brother, John Lawrence, to be Director of the University's Medical Physics Laboratory. The first application of a radioisotope in clinical medicine was the use of phosphorus 32 to treat certain blood disorders, including leukemia and polycythemia vera.

With most of the world, I heard about the atomic bombing of Hiroshima on August 6, 1945. I was aboard a three-masted, full-rigged training ship, Danmark, of the U.S. Coast Guard, that had fled to the United States at the beginning of World War II instead of returning to its homeport in Denmark. We sailed under a bridge spanning the Thames

River in New London, Connecticut, and docked at the dock of the Coast Guard Academy. I was one of 100 first year cadets who had entered the Academy in June 1945 after I had finished the first year of college at Johns Hopkins University in Baltimore. The news of the bombing of Hiroshima and Nagasaki was a tremendous shock, greater than the invasion of France on D-Day and the saturation incendiary bombing of Tokyo and other Japanese cities. The atomic bombings led to the sudden surrender of the Japanese within days.

The public had been kept in the dark about the development of the atomic bomb during the two and a half years of its development by the Manhattan Project. Some secrets had leaked out, but most people had never even heard of "radioactivity," a word that was for decades to incite fear in the minds of people all over the world. "Radioactivity" would hang as a cloud over the lives of those of us who chose to dedicate our professional lives to developing the "peaceful uses of atomic energy" in biology and medicine.

Radioactive elements, especially carbon-14, were key products of the Manhattan Project, and could be produced in large quantities by the newly invented nuclear reactors. They would provide the world with new tools for chemical and biomedical research. Radioactive "tracers" were able to "broadcast" their presence in "radiolabeled" molecules as they participated in the "chemistry of life". Being able to measure the chemical processes in every part of the body of living organisms would revolutionize biology and medicine. The radionuclides, chiefly carbon-14 and phosphorus-32, led to the birth of biochemistry.

Martin D. Kamen started working at the radiation laboratory of Dr. Ernest Lawrence at the University of California in Berkeley in 1937. He discovered carbon-14 but had the misfortune of suspicions arising from a dinner he had with two officials from the Russian consulate in 1944. He was fired by the University of California at Berkeley. He spent decades trying to prove his innocence. With the help of friends, he became Professor of Biochemistry at Washington University in St. Louis in 1945. He moved to Brandeis University in 1975, and was influential in the founding of the Universisty of California in San Diego in 1957. In 1996, he won the prestigious Enrico Fermi Award given by the U.S. Department of Energy. Among his discoveries was that the oxygen produced by the process of photosynthesis originates from water molecules, not from carbon dioxide as had been previously thought.

The American government made the decision after the war to make radioactive tracers available to qualified scientists all over the world. Before radioactive tracers could be used in human beings, the patients had to be convinced that it was safe to have "radioactivity" injected into their veins as part of the diagnostic process or medical treatment. Fear was understandable.

"Fallout" was another cause of fear. It can occur when radioactive debris that has accumulated in the atmosphere after the testing of atomic bombs falls to the earth. Radioactive particles are sucked up in millions of tons of earth, rising to altitudes greater than 40,000 feet, attaching themselves to vapor and dust that would be carried around the world because of the winds and rotation of the earth, and then falling back to earth as rain. The potential carcinogenic effects of fallout were described in newspapers all over the world. Especially fearful was that radioactive particles are invisible and cannot be detected by the natural senses. Another fear was environmental contamination from accidents during shipments of radioactive materials to hospitals and research laboratories around the country. Nuclear power plants were being built all over the country, which increased concerns about the possibility of accidents resulting in huge areas of contamination. Some feared (erroneously) that nuclear power plants could explode in the same way as atomic bombs. The greatest fear was "proliferation" of nuclear weapons by hostile countries.

Nuclear reactors at universities could also lead to nuclear weapons. Even today, five university nuclear reactors—the University of Wisconsin, Oregon State, Washington State, Purdue, the University of Florida—are fueled with weapons-grade uranium. More than 99% of naturally-occurring uranium is U-238, not suitable fuel for bombs. U-235, which makes up about 0.7% of naturally-occurring uranium, splits easily and can be used for making atomic bombs. The Department of Energy has spent large amounts of money to develop low-grade uranium fuel for university and other reactors. By July 30, 2004, 39 of 105 research reactors all over the world were to have been converted to U-235. Energy Secretary Spencer Abraham tried to have all of these reactors converted to U-235 by 2014.

Since World War II, proliferation of nuclear weapons has hung over the heads of everyone in the world. Some believed that the developing knowledge of the relationship between brain chemistry and behavior might help us to better understanding of the emotions of fear, rage, and insecurity that plague the human race.

Since the Cold War ended in December 1991, the greatest fear has been nuclear terrorism that could end civilization as we know it today. Those who have benefited professionally from the peaceful uses of nuclear energy have an obligation to help diminish the potential danger that could result from misuse of nuclear reactors used in research and in providing the necessary radioactive tracers on which our specialty is based. We must help face the challenge of keeping the world's nuclear materials out of the hands of the world's most dangerous people.

The pioneers of "atomic medicine" had to confront all these fears. Only their understanding, dedication, persistence, and ingenuity made success possible. They were able to convince their colleagues and the public of the benefits that radioactive materials can provide in medical diagnosis and treatment. They had to educate their colleagues about the "tracer principle," and its potential role in the practice of medicine and biomedical research.

We can see the spirit of the times right after World War II in the book, From Hiroshima to the Moon, by Daniel Lang. He quoted Dr. Willard F. Libby, a commissioner of the civilian U.S. Atomic Energy Commission, charged in 1946 with directing and controlling atomic energy, including atomic bomb production. Libby did not reassure the public when he said:

"In the event of a thermonuclear attack on the United States, a large fraction of the bombs would explode high above the earth, so that fallout of radioactivity would be minimized by the enemy's attempt to maximize the blast and thermal effects." This hardly made people feel better!

Would nuclear medicine have reached the widespread use in health care that exists today if the atomic bomb had not been developed by the expenditure of billions of dollars of government money? My answer is "yes," but the process would have taken far longer. Support by the U.S. government in promoting "peaceful uses of atomic energy"

in medicine and other scientific fields played a major role in the development and growth of nuclear medicine all over the world. Most of the support for research in nuclear medicine at Hopkins came from the National Institutes of Health (NIH) Over the past decades, the Department of Energy (successor to the Atomic Energy Commission) has played a major role in development of instruments and radionuclides as part of intra-and extra-mural AEC programs. The NIH has emphasized support of biomedical research, while AEC research provided the tools. The efforts of both government agencies—the AEC (now called Department of Energy) and the NIH—have been synergistic. An example is the Human Genome Project.

After I had finished college, medical school, a three-year residency in internal medicine at Johns Hopkins, and two years as a Clinical Associate at the National Institutes of Health in Bethesda, Maryland, Professor Mac Harvey, Chairman of the Department of Medicine at Hopkins, told me that I had been selected for the highly desirable position of Chief Resident in medicine on the Osler Medical Service at Johns Hopkins Hospital.

The Osler residency was the first modern residency in the United States, begun in 1890 with assistant residents and a chief resident in each specialty. In 1897, an internship was added when Johns Hopkins medical school graduated its first class. Osler established the sleep-in-residency system where "house staff" physicians lived in the Administrative Building of the Hospital. The house staff lived an almost monastic life, many with rooms on the third floor of the building overlooking a large statue of Christ in the lobby. It was said jokingly that the house staff could look down on God, just as God looked down on them. Susequently, when administrators took over the house staff quarters which became offices, an elevator was soon installed.

Osler introduced the clinical clerkship, having third and fourth year medical students work on the wards. They would "follow a case day by day, hour by hour." Patients welcomed the house staff without whom they could not be cared for efficiently and effectively. Unlike today, in those days there was no scheduled time off. When the patients did not require immediate care and did not present specific problems, one could "sign out" to one's house staff colleague and spend a few hours at home.

A colleague of mine, Dr. Wilbur Mattison, had also been selected for the position of Chief Resident in medicine, but since there could be only one chief resident at a time, Professor Harvey said: "You and Wilbur decide who will go first." We literally flipped a coin. The result determined that I would go second, thereby giving me a free year before returning from the NIH to the Chief Residency at Hopkins. I decided to go to Hammersmith Hospital in London in 1957 to work under the direction of Professor Russell Fraser, head of endocrinology, the most exciting field in internal medicine at that time.

After my year at Hammersmith Hospital, I returned to Johns Hopkins Hospital. On August 24, 1867, Johns Hopkins, a Baltimore merchant, who provided the funds and inspiration for the founding of Johns Hopkins University and Hospital, wrote: ". . . It will be your duty, hereafter, to provide for the erection, upon other ground, of suitable buildings for the reception, maintenance and education of orphan colored children . . . It will be your special duty to secure for the service of the Hospital surgeons and physicians of the highest character and greatest skill . . . The Active Staff . . . shall regularly practice a hospital-based specialty." Johns Hopkins was among the earliest hospitals to have a fulltime faculty. The Hospital and School of Nursing began operations in 1889, and the medical school, closely linked to the Hospital opened in 1893. Today, greatly expanded in size, the Hospital is still at this site, despite occasional temptations to follow other hospitals to the more affluent suburbs of Baltimore.

Two years before I went to Hammersmith Hospital, the Medical Research Council of the United Kingdom had built a cyclotron dedicated to biomedical research. Soon after I arrived, I recognized immediately the potential that radioactive isotopes could play in medicine. They could be measured by radiation detectors directed from outside of the patient's body. These new techniques might help solve many problems of patients that I had seen since my graduation from medical school five years before. One of the physicians at Hammersmith who was active in the use of radioiodine in diagnosis and therapy beginning in 1969 was Dr. A.W.D. Goolden. I often saw patients with him, as well as with Professor Fraser. Goolden subsequently published an article in 1971 on the use of tech-netium-99m for the routine assessment of thyroid function.

The "tracer principle" was to become the focus of my professional life for the next half century. After a year at Hammersmith, I returned to Johns Hopkins as Chief Resident in medicine, and then joined the full time faculty of internal medicine at Hopkins in 1958, with the goal of establishing a nuclear medicine division with John McAfee. We visualized the division as a joint effort of radiology and internal medicine. I still wonder why internal medicine never viewed nuclear medicine as an important part of internal medicine.

Beginning in those early days, which subsequently extended to almost half a century in the field of nuclear medicine, I felt that I was walking up the upward-moving escalator of nuclear medicine, an escalator powered by the discovery of radioactivity, the

Figure 8 Measurement of the accumulation of radioactive iodine with a Geiger-Mueller counter placed at different points indicated by a plastic grid over the patient's neck.

cyclotron, nuclear reactor, radiochemistry, rectilinear scanner, Anger camera, computer, positron emission tomography (PET), single photon emission computed tomography (SPECT), PET/CT, and SPECT/CT. The combining of PET and SPECT with CT (computed tomography) brought anatomy and biochemistry together.

In 1958, when I told Professor Harvey, Chairman of Internal Medicine,that I wanted to work full time at Hopkins on the application of "radioisotopes" in medicine, he recommended that I consider an alternative, that is, to join Dr. Lawrence Shulman in the field of arthritis and rheumatology. At the time, I thought this was a curious recommendation, but in retrospect I believe that he knew of the work going on at that time in the laboratory of Dr. Dewitt Stetten at the NIH. In the summer of 1957, a young biochemist named Marshall Nirenberg had just come to the NIH and with his colleagues in the National Institute of Arthritis and Metabolic Diseases carried out research that was to win the Nobel prize for his work in molecular biology. He and his colleagues discovered that RNA consisted of chains of four nucleotide bases that served as templates for the synthesis of proteins containing 20 kinds of amino acids.

When political leaders such as Senator Lister Hill and Congressman John Fogarty responded to NIH director James Shannon's request for funds to "fight arthritis," they didn't realize at the time that they were helping to found molecular biology, a principal component of modern "molecular" medicine. Nirenberg received the Nobel prize for his work in 1968. The great accomplishments of investigators at the NIH were the result of Shannon's vision that clinical progress would come only through fundamental research.

I had no knowledge of this exciting work in molecular biology at that time, so I stuck with my plan to join John McAfee to co-found the Division of Nuclear Medicine at Hopkins. This new division was a combination of a new Division in Radiology, directed by John, and one from Internal Medicine, directed by me. My mental image at that time was that I was standing with one foot in each of two rowboats, one being Radiology, the other Internal Medicine, hoping that I would not fall in the water. We faced many hurdles over the next half century, all of them taking place against the background of the Cold War with the Soviet Union, the arising Red Chinese dragon, the rebuilding of Europe, the resurrection of Germany and Japan, the Korean, Vietnamese and Iraqi wars, and the tragedy of September 11, 2001.

My professional and personal life for the past 55 years has depended on the love, companionship, intelligence, and wonderful personality of my wife, Anne. We married on February 3, 1951, and began the spartan life that we lived during my last year of medical school, the house staff days at Hopkins, and subsequent the two years at the NIH. We were fortunate that we were able to enjoy those days without ever reflecting on how things would be better in the future.

When we moved to a two bedroom apartment at 120 Center Drive on the grounds of the NIH, we believed that our living conditions were luxurious compared to our three rooms on the 2nd floor of a row house at 1900 McElderrry Street across from the Woman's Clinic at Johns Hopkins. There was very little likelihood that I would be called to the Clinical Center during the night, as I had been almost every night when I was on the house staff at Hopkins.

After 2 years at the NIH and one year at Hammersmith Hospital in England, we returned to Baltimore, and lived for 10 months in the "Compound" on Monument Street across the street from the main building of the Hopkins Hospital. "Broadway Apartments" was the name of the rows of two-story dwellings owned by Hopkins. The two acres of green lawn enclosed in a high chain-link fence was a great playground for the children, all of whom were under 6 years of age. We on the married house staff enjoyed the proximity to the Hospital and the congeniality of other young married couples.

After 10 months living in the "Compound," Anne, our four children and I moved to 3410 Guilford Terrace to a row house built during World War I. Each three-story house in the block was different. Our next door neighbor was Paul Menton and his family; Paul was famous as sports editor of the Evening Sun for decades. Many of the people in the neighborhood were elderly, but beginning in the 1970s the neighborhood attracted doctors, lawyers, stock brokers and other professionals, including Dr. John Walton, chairman of the education department and President of the Baltimore City school board. Johns Hopkins University was only a few blocks away. Walton said: "I think it (our neighborhood) compares favorably with Georgetown." We decided to purchase our house as soon as it was shown to us by our realtor, who really understood what we wanted. We belonged to the Baltimore Protective and Improvement Association, which (among other activities) managed to block the granting of a liquor license for the dining room in the Marylander apartment house nearby until 1966 when the opposition ceased under the condition that there be no stand-up bar or cocktail lounge on the premises and that liquor would be served only at meals.

One of our neighbors, John Young, a retired stock broker said: "If it's a question of a broken curb or hole in the street, I get on the phone to City Hall. It's been my experience that if you call the right people down there, you get results."

On July 20, 1969, on her 40th birthday Anne and I, together with a friend, the late Bishop Frank Murphy, watched the first landing on the moon on television. After living 22 years on Guilford Terrace, we moved to Mt. Washington to live with Anne's parents in a carriage house remodeled by Anne's father during WWII. Our son-in-law, an architect, tripled the size of the original house before we moved in.

We had returned with our four children to the house where Anne and I had had our first date, several days after meeting on March 11, 1948 in Levering Hall on the campus of Johns Hopkins University. I was then 20 years old and Anne was 18. A great adventure lay ahead.

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