William Graydon Myers: Scholar and Pioneer in Investigative Nuclear Medicine
by Jack Rall
Professor of Physiology & Cell Biology, The Ohio State University
William Graydon Myers, a faculty member in The Ohio State University College of Medicine for more than forty years, was considered to be "one of the outstanding pioneers in the fascinating history of the application of radioisotopes to diagnostic and therapeutic medicine" (1). He introduced more radionuclides into medicine than any other individual, including cobalt-60 for cancer therapy and iodine-125 for in vitro tests such as radioimmunoassays. Throughout his career he championed the importance of the cyclotron as a source of short-lived radionuclides for medical use. Dr. Myers died in 1988, less than 30 days before his 80th birthday.
Born in Toledo, Ohio in 1908, the son of a farmer who was also a part-time factory worker, Dr. Myers experienced a difficult childhood (2). He spent a period of time in an orphanage. When his father remarried, he homesteaded with his family in Alberta, Canada, where he rode ten miles to the local school on horseback, "by the light of the moon" in winter, and where temperatures could go to 400 F below zero. He lived briefly in Denver and worked there as a photographer and then joined his family in Detroit where he worked as a waiter and employee at an automobile assembly plant. Because of these difficult conditions, he did not graduate from high school until he was 21 years old, in 1930. Based on a competitive examination, he received a tuition scholarship from The Ohio State University. To make up for time lost, Dr. Myers attended Ohio State for 39 consecutive quarters and received his B.A. in 1933, M.Sc. in 1937, Ph.D. in 1939, and M.D. in 1941. During this time, he supported himself as a barber and as a teaching assistance in chemistry. After an internship at University Hospitals, he was appointed a Research Associate in 1942, Julius F. Stone Fellow in Biophysical Research in 1945, and Stone Research Professor in 1953. (Julius F. Stone donated the funds for the OSU cyclotron). Dr. Myers was a Visiting Professor of nuclear medicine at the University of California at Berkeley from 1970 to 1977. He became a Diplomate of the American Board of Nuclear Medicine in 1972. In 1979 he was granted Emeritus Professor status in the Department of Radiology at Ohio State. From 1979 to 1988, Dr. Myers was a Visiting Professor of biophysics at the Sloan-Kettering Cancer Research Institute of Cornell University.
Dr. Myers met Florence Lenahan in a neuroanatomy class in 1938 and they were married in 1940. She received her M.D. from Ohio State in 1940 and was a practicing physician in the Columbus community for more than 35 years. During World War II, Dr. Myers worked as a research chemist and studied practical chemical extractions of penicillin and streptomycin which were in limited supply. In University Hospitals, in 1944, Dr. Myers and his wife successfully used penicillin for treatment of a patient with osteomyelitis, a rare therapy at that time. This was the first use of penicillin in Columbus, Ohio. To conserve penicillin, Dr. Myers extracted it from the urine of treated patients.
It is possible to trace the origin of Dr. Myers' career-long research interests to a single event in the Autumn of 1940. Dr. John Lawrence, M.D., University of California at Berkeley, presented a lecture at Ohio State on the potential uses of the cyclotron in medicine. The cyclotron was conceived and built by Lawrence's brother, Ernst O. Lawrence, for which he received the Nobel Prize in 1939. Later Myers recalled, "I decided then that was what I wanted to spend the rest of my life doing" (2). This lecture led Dr. Myers to write a senior medical student thesis entitled "Applications of the cyclotron and its products to problems of biomedical interest." In time he became known as the "godfather of the cyclotron" in medicine (3). It was clearly his scientific "true love" for nearly 50 years. A cyclotron is an accelerator of charged atomic nuclei, usually of hydrogen or helium. The accelerated nuclei are used to bombard targets of other atoms to produce radioactive atoms or nuclei. The product nuclei formed are not isotopes of the target, but rather new elements, so that high specific activity can be achieved after chemical separation. The Physics Department at Ohio State built and installed a cyclotron in 1941.
Investigative Nuclear Medicine
The special research interests of Dr. Myers were in investigative nuclear medicine, especially in reducing radiation exposure to patients, and in radiation therapy. With regard to these interests, Dr. Myers introduced eleven radionuclides into medical use. Dr. Charles L. Dunham, then Director of the U.S. Atomic Energy Commission, Division of Biology and Medicine, stated in 1965 in a speech at The Johns Hopkins Medical School that Dr. Myers "has done more than any single physician to broaden the uses of radioisotopes for medicine, and the availability of radioisotopes for the medical profession" (2). His research with radionuclides, represented by approximately 140 publications, can be divided conveniently into two categories: radionuclides for radiation therapy and radionuclides for diagnostic and investigative medicine.
Radionuclides for Radiation Therapy
In June of 1948 (4, see reprint), Dr. Myers suggested that cobalt-60 would be a useful substitute for radium for treatment of radiosensitive neoplasms. The idea for using colbalt-60 as a radium-226 substitute came to Dr. Myers in the summer of 1946 at Bikini atoll, in Marshall Islands of the Pacific Ocean, where he was a radiologic safety monitor for the two atom bomb tests. It is characteristic of the dilemma of nuclear energy that while watching an atomic bomb send "a million tons of water a mile up into the air" (3), Dr. Myers was imagining how nuclear energy could be used in medicine to save lives. The Manhattan District, then controlling the atomic work at Oak Ridge, had made available a list of radioisotopes that could be secured for the asking by qualified institutions. Said Myers: "I looked the list over and cobalt-60 appeared to have the properties most desirable in the treatment of cancer" (5). These properties were gamma rays, of relatively uniform energy, and a low rate of emission for the undesirable, harmful beta ray. In studies undertaken in collaboration with Dr. Joseph L. Morton of the Department of Radiology at The Ohio State University, radioactive needles containing cobalt-60 were inserted into tumors in animals and humans. Cobalt-60 needles had several advantages over radium-226 capsules. The cobalt-60 needles: a) were malleable with no problems with breakage, b) exhibited weaker beta emission, c) allowed strength of dosage to be easily controlled, and d) were much less expensive. Dr. Myers correctly predicted that thousands of cobalt-60 units would someday be installed in cancer treatment centers throughout the world.
In 1952, Myers and Benjamin H. Colmery (6) introduced gold-198 (half life, T1/2 = 2.7 day) into medicine as a successor to radon-222 (T1/2= 3.8 day) for permanent seed implantation for cancer therapy. It was preferable to cobalt-60 (T1/2 = 5.3 years) in situations where it was not desirable to use the longer acting cobalt-60. The first reports of clinical studies for cancer therapy with gold-198 malleable seeds were performed at The Ohio State University in collaboration with Drs. Arthur G. James, a surgeon, and Ulrich K. Henschke, a radiologist, and appeared in 1953. In 1959, Dr. Myers (7) introduced chromium-51 (T1/2 = 27.8 day) into medicine as an agent for cancer radiation therapy. This radionuclide had the advantage that it emitted no beta particles and thus required no shielding from the harmful effects of these particles as did the other radionuclides.
Dr. Myers received The Lucy Wortham James Award for Research in 1966, presented by The James Ewing Society of New York "in recognition of his pioneering efforts in the clinical use of cobalt-60, gold-198 and other radioactive isotopes."
Radionuclides for Diagnostic and Investigative Medicine
By 1960 Dr. Myers had shifted his interests from radionuclides for cancer therapy to the development of radionuclides for diagnostic and investigative purposes in biomedicine. In a classic publication of less than 400 words, Dr. Myers and Han C. Vanderleeden (8) introduced the medical community to iodine-125 (T1/2 = 60 day) (see Reprint). An important advantage of iodine-125 over iodine-131 is that it does not emit beta particles and thus would lead to less radiation exposure to patients undergoing diagnostic tracer applications. But the real impact of iodine-125 came from its use in radioimmunoassays. In 1960 Dr. Myers suggested to Dr. Rosalyn Yalow (Nobel Prize, 1977 for development of insulin radioimmunoassay) that iodine-125 would be better suited for radioimmunoassays because of its long half-life compared to iodine-131 (T1/2 = 6.8 days) (9). Because of widespread applications of iodine-125 in radioimmunoassay, this radionuclide now has been used in biomedicine several times more frequently than all other radionuclides combined. In a handwritten letter to Dr. Myers, Dr. Yalow stated, "To Bill Myers, a fine friend for more than three decades, with fond memories of his suggestion in 1960 of the applicability of I-125 rather than I-131 for tracer labeling, a prediction that proved most valuable" (3).
As a diagnostic tool, iodine-125 had an unfortunate disadvantage. Since radiation detectors, such as scintillation cameras, are outside the body, photons must have sufficient energy to escape the body for detection. The photons emitted by iodine-125 were of low energy and this severely limited its usefulness for monitoring events, especially, in deep-seated organs. Also while the radiation exposure to the patient was less, it was only about 50% less. Thus, Dr. Myers and Hal O. Anger suggested the use of iodine-123 (T1/2 = 13.3 hr) in diagnostic medicine in 1962 (10). The ideal radionuclide for diagnostic medicine should exhibit (11): 1) no beta emissions, 2) gamma photon energies between 100 to 200 KeV for ease of detection, 3) half-life to 1 to 1.5 times the imaging time to minimize radiation exposure to patient, and 4) chemical reactivity to allow formation of medical useful compounds. Iodine-123 was ideal in all of these regards (see Table). Radiation exposure to the patient was less than 5% of that with iodine-131. But there was a major problem. Iodine-123 must be produced in a cyclotron and because of its short half-life, the cyclotron must be nearby. Therefore Dr. Myers became an outspoken advocate for the placement of a "medical" cyclotron in every major hospital or region (see below). In 1966, he introduced iodine-121 (T1/2 = 2.1 hr) for short term studies and emphasized that repeated exposures could be performed to determine dynamic processes (12). The rest of Dr. Myers' investigative career was to be devoted to exploring the potential of short lived radionuclides in the study of normal and disease processes in humans.
In 1960 (13), Dr. Myers suggested that strontium-87m (T1/2 = 2.3 hr) could be a useful substitute for strontium-85 (T1/2 = 65 days) in bone scans. Strontium, a calcium substitute, concentrates in bones. Because of the much shorter half-life of strontium-87m, there would be a significant decrease in radiation exposure to the patient. Also, serial administration would be possible which would allow information to be gained about the dynamics of normal and disease processes. Further, an on-site cyclotron was not needed since strontium-87m could be obtained from a long-lived generator, i.e., yttrium-87 (T1/2 = 3.3 days) on-site. A radionuclide generator is a radionuclide that has a relatively long half-life that produces the desirable short lived radionuclide as a product of its decomposition. The product then is removed chemically and used immediately. The most important generator system in use today is the molybdenum-99:technetium-99m system (11). But not all radionuclides of medical interest can be produced in this fashion. In 1966 (14), Myers made and used for the first time strontium-85m (T1/2 = 70 min) for bone scans. This radionuclide emitted no beta particles and greatly limited radiation exposure to the patient. Its short half-life allowed study of metabolism by observing abnormal turnover of bone salts. There is an interesting sidelight to the announcement of strontium-85 as a medical radionuclide at an international meeting in Heidelberg, Germany, in 1966. Dr. Myers had first made the strontium-85m in a reactor in Heidelberg and used it the day before the meeting! There was light-hearted speculation that Dr. Myers "must hold the record for the fastest turn around of research into a meeting paper" (14).
Radiostrontium is not used often today for bone scans because as a calcium substitute it is involved in processes other than bone metabolism and thus clears relatively slowly from the blood. This has the disadvantage of increasing the background radioactivity and thus decreasing resolution of the bone scan.
Further research emphasizes Dr. Myers' interest in the short-lived radionuclides. In 1967 (15), Myers and William W. Hunter introduced carbon-11 (T1/2 = 20.3 min) for low-radiation radioscanning. Of interest here was that carbon-11-labeled metabolites could be made and their fate followed in humans.
A few years after the installation of the medical cyclotron at Memorial Sloan-Kettering Cancer Center (MSKCC) in 1967, Dr. Myers accepted the invitation of Dr. John S. Laughlin, Biophysics Chairman, to visit and give a talk. Later, Dr. Myers became a Visiting Investigator on the staff of MSKCC, working there several months each year for ten years. He was active in the criticism and design of metabolic studies being carried out with quantitative scanning with compounds labeled with position emitting nuclides produced on the MSKCC cyclotron (16, 17, 18). In 1973 (19), Myers put forward the idea that potassium-38 (T1/2 = 7.7 min) could be useful in the imaging of the heart since the half-life of potassium-38 matched the duration of processes involving rapid turnover of potassium by the heart. Ischemic regions of the heart would exhibit a deficiency of potassium uptake because of deficient energy supply to transport potassium into the heart cells. In 1986 (20), Myers introduced another radionuclide for applications in nuclear medicine: krypton-79m (T1/2 = 50 sec), a radionuclide of the noble gas krypton, generated while being inhaled and used to image lungs, trachea, and bronchi. In a letter written in 1986 concerning this last paper, Dr. Myers states: "This delightful cyclotron-generated "twinkling" atom has been lurking inactively on physicists' charts for 46 years, a long 'gestation' period indeed! This makes me wonder how many other 'goodies' are awaiting being pried off and put to use?" One can imagine Dr. Myers poring over the more than 1600 known radionuclides in the periodic table and imagining creative ways to make and use these "twinkling" atoms in medicine. In fact at the time of his death, he was working on another "twinkling" atom, xenon-127m (T1/2 = 75 sec).
As is obvious from the Table, from 1960 to the end of his career, Dr. Myers studied radionuclides with progressively shorter half-lives. His interest here was to minimize radiation exposure to patients but also to maximize the ability to follow biological processes in real time with high resolution in humans. Because many of these radionuclides could best be produced in a cyclotron, Myers championed, for years, the concept of an in-hospital medical cyclotron. In 1969 he stated: "I feel that there MUST be a small 'MEDICAL' cyclotron in every major hospital or regional medical center NECESSARILY within a decade or two." The importance of this statement has been reinforced by the development of positron emission tomography (PET) as a tool to derive functional and structural information in real time and in three dimensions in humans. PET employs radionuclides with short half-lives, like carbon-11 (T1/2 = 20.3 min), nitrogen-13 (T1/2 = 10 min), oxygen-15 (T1/2 = 2 min), potassium-38 (T1/2 = 7.7 min), and fluorine-18 (T1/2 = 110 min). As of 1983, there were about 40 cyclotron/PET facilities in hospitals worldwide. Dr. Myers liked to say, "The medical cyclotron plus PET tomography gives in vivo biochemistry." He was keenly aware that since medical imaging is primarily a radiologist function, the full use of the advantages of a tool for imaging in vivo biochemistry would require a shift in emphasis from images of morphology to images of function. PET allows visualization of changes in concentrations due to biochemical processes.
It must have been a major disappointment to him The Ohio State University Hospitals did not install a medical cyclotron during his life time. But the emergence of magnetic resonance imaging and spectroscopy which does not employ radionuclides and provides better morphological representation was found more attractive to University Hospitals. Nonetheless Dr. Myers would have been pleased to know that the new Arthur James Cancer Hospital and Research Institute plans to install a cyclotron/PET facility.
Honors for Dr. Myers' research are numerous. Besides the James Ewing Society Award, Dr. Myers received an Alumni Achievement Award from the OSU College of Medicine in 1961. In 1973, he received the first annual Paul C. Aebersold Award presented by The Society of Nuclear Medicine for his "outstanding achievement in basic science applied to nuclear medicine." In 1977 he received an honorary degree from Bucknell University for "contributions to the development of radioactive isotopes in the diagnosis of disease and the treatment of cancer." In 1981, The Society of Nuclear Medicine honored Dr. Myers with the Hevesy Nuclear Medicine Pioneer Award. This award is named for Georg C. de Hevesy who performed the first biomedical studies with artificial radioactivity. Hevesy won the Nobel Prize in 1943 for his work on the use of isotope tracer elements. Dr. Myers is one of only three people to receive both the Aebersold and Hevesy awards from The Society of Nuclear Medicine.
Educational Nuclear Medicine
Dr. Myers was a dedicated teacher. He taught Radiation Biophysics in the Physiology Department at The Ohio State University for nearly 30 years. During that time over 1,000 resident physicians, medical students, and graduate students in the life sciences attended his lectures. He also taught the course Advances in Theoretical Biophysics at the University of California at Berkeley as a visiting professor from 1970 to 1977. The cyclotron at the University of California allowed Dr. Myers to pursue research interests that were not possible at The Ohio State University because of its obsolete cyclotron. He was the historian of The Society of Nuclear Medicine from 1973 through 1986, during which time he wrote numerous historical articles for the society's journal. For his achievements, Dr. Myers was given the Distinguished Educator Award by The Society of Nuclear Medicine in 1983.
Scientific Philosophy
Dr. Myers was outspoken and sometimes controversial. He held some views that would be considered highly unusual and very challenging today. For example, on the subject of grantsmanship, Myers said, "I used to get money from the National Cancer Institute, and after a while I began to recognize that I wasn't doing science -- I was managing money. Money gets in the way, and it's got very sticky strings attached to it." One of Dr. Myers' favorite aphorisms, published under his name in Who's Who in America, summarizes his philosophy of scholarly pursuit, "Savoring the past enriches the present and presages the future. In FUNdamental research, the zest is in the conquest -- but only the first three letters count!" Henry N. Wagner of the Johns Hopkins Medical Institutions paid a fitting tribute to Dr. Myers on the occasion of the presentation of the Hevesy Nuclear Medicine Pioneer Award (3):
"You can know that there will be continuing benefits long after your efforts have ceased. You have had the pleasures of discovery; the opportunity to spend your life doing what you wanted to do; the freedom to study and investigate, to develop friendships all over the world, and to know that your teaching and research have helped all mankind. All these satisfactions are yours. No one could ask for more."
Acknowledgements
The author would like to thank Florence Lenahan Myers, John S. Laughlin, and J. Robert Dahl for informative discussions and for supplying invaluable information.
Literature Cited
| 1. | DeLand, F. H. In memoriam. William Graydon Myers (1908-1988). J.Nuclear Med. 30: 1129-1130, 1989. |
| 2. | "Pioneering" in medicine with Dr. William Myers. College of Medicine Journal, Ohio State University. 24: 2-3, 24, 1974. |
| 3. | Wagner, H. N. Hevesy nuclear medicine pioneer lecture. J. Nuclear Med. 22: 573-576, 1981. |
| 4. | Myers, W. G. Radioactive needles containing cobalt 60. Science. 11: 621, 1948. |
| 5. | New weapon in war on cancer: Ohio State leads in "cobalt 60" research. The Ohio State University Monthly. 39: 3-5, 1948. |
| 6. | Myers, W. G. and B. H. Colmery. Radioactive Au-198 in gold seeds for cancer therapy. Cancer Research. 12: 285-286, 1952. |
| 7. | Myers, W. G. Radioactive chromium 51 gamma ray sources. Am J. Roentgenology, Radium Therapy Nuclear Med. 81: 99-106, 1959. |
| 8. | Myers, W. G. and H. C. Vanderleeden. Radioiodine I-125. J. Nuclear Med. 1:124, 1960. |
| 9. | Myers, W. G. Radioiodine-125 in biomedicine: 1959-1984. J. Nuclear Med. 25:1389-1391, 1984. |
| 10. | Myers, W. G. and H. O. Anger. Radioiodine-123. J. Nuclear Med. 3: 183, 1962. |
| 11. | Kowalsky, R. J. and J. R. Perry. Radiopharmaceuticals in Nuclear Medicine Practice. Appleton and Lang: Norwalk, 1987. |
| 12. | Myers, W. G. Radioiodine-121. J. Nuclear Med. 7: 390, 1966. |
| 13. | Myers, W. G. Strontium-87m. J. Nuclear Med. 1: 124, 1960. |
| 14. | Glos, M. B. Nuclear Medicine. Nucleonics. December, 1966. |
| 15. | Myers, W. G. and W. W. Hunter. Radiocarbon-11 for scanning. J. Nuclear Med. 8: 305, 1967. |
| 16. | Laughlin, J. S., Gelbard, A. S., Benua, R. S., Myers, W. G., Reiman, R. E., Bigler, R. E., Hopfan, S., Dahl, J. R., Lee, R. Recent results concerning diagnostic and therapeutic evaluation of tumors with cyclotron-generated, short-lived, positron-omitting radionuclides. Proceedings of the Annual Meeting of the International Society of Nuclear Medicine, September, 1980, Nuremberg, Germany. |
| 17. | Myers, W. G., Benua, R. S., Yeh, S. D. J., Bigler, R. E., Graham, M. C., Lee, R;, Reiman, R. E., Bading, J. R., Laughlin, J. S. Kinetics of potassium-38 in the heart intercompared by means of a position-electron transmutation (PET) tomograph and a rectilinear high-energy gamma (HEG) scanner. Proceedings of the International Symposium on Medical Radionuclide Imaging, Heidelberg, Germany, September 1-5, 1980. |
| 18. | Myers, W. G., Bigler, R. E., Benua, R. S., Graham, M. C., Laughlin, J. S. PET tomographic imaging of the human heart, pancreas and liver with nitrogen-13 derived from 13N-L-glutamate. Eur J Nuclear Med. 8: 381-384, 1983. |
| 19. | Myers, W. G., Radiopotassium-328 for in vivo studies of dynamic processes, J. Nuclear Med. 14: 359-360, 1973. |
| 20. | Myers, W. G., J. R. Dahl and M. C. Graham. Krypton-79m: a new radionuclide for applications in nuclear medicine. J. Nuclear Med. 27: 1436-1441, 1986. |
Table
Radionuclides introduced into Medicine by W. G. Myers
| Radionuclide | Date | Beta Decay | Half-Life | Photon Energy (KeV)
| | Cancer Therapy |
| Cobalt-60 | 1948 | Yes | 5.3 year | 1173,1332 |
| Gold-198 | 1952 | Yes | 2.7 day | 411 |
| Chromium-51 | 1958 | No | 27.8 day | 320 |
| |
| Nuclear Medicine |
| Iodine-125 | 1960 | No | 60.0 day | 36 |
| Strontium-87m | 1960 | No | 2.3 hr | 388 |
| Iodine-123 | 1962 | No | 13.3 hr | 159 |
| Iodine-121 | 1966 | Yes | 2.1 hr | 213,575 |
| Strontium-85m | 1966 | No | 70.0 min | 231,150 |
| Carbon-11 | 1967 | Yes | 20.3 min | ann. rad. |
| Potassium-38 | 1973 | Yes | 7.7 min | ann. rad. |
| Krypton-79m | 1986 | No | 50.0 sec | 130 |
|
