Cornelius Anthony “Toby” Tobias, a pioneer in radiation biology who was known as the “Father of Hadron Therapy,” died of cancer on 2 May 2000 in Eugene, Oregon.
Born in Budapest, Hungary, on 28 May 1918, Toby earned his BS in physics at the Hungarian University of Electrical and Technical Sciences in Budapest. In 1939, he went to the University of California, Berkeley, to work in Ernest Orlando Lawrence’s laboratory on a fellowship. That one-year visit extended to a 45-year distinguished teaching and research career at Berkeley and Lawrence Berkeley National Laboratory (LBNL). At Berkeley, Toby received his PhD in nuclear physics in 1942; Emilio Segrè and Louis Alvarez were his academic advisers. As part of his dissertation research, Toby was the first to accelerate carbon nuclei in a cyclotron and one of the first to apply accelerated ions to the study of biology and medicine.
In 1955, Toby teamed with John H. Lawrence to work at the Donner Laboratory at Berkeley. Because of its proximity to the 60-inch cyclotron, this laboratory became the birthplace of nuclear medicine. The synergy of the Lawrence brothers and Toby ushered in a remarkable era for nuclear medicine, fundamental radiobiology research, and hadron therapy.
At Berkeley, Toby became a professor of medical physics (1955) and chair of medical physics (1967–71), and was advanced to Professor-Above-Scale (1978). He also became a professor of electrical engineering at Berkeley, a professor of radiology at the University of California, San Francisco (UCSF), and a professor emeritus of medical physics (1985) at Berkeley.
Toby was a valuable member of the Donner group, which first (in 1945) began to use radioisotope tracers to study various human physiologies. Within that group, Toby led the team that administered a radioactive isotope to humans using carbon-11–labeled carbon monoxide. The 11C tracer was used to investigate, among other phenomena, how pilots developed the “bends” at high altitudes. In 1945, Toby also formulated an analysis of tracer turnover in the human body, which led to methods for quantitating local blood perfusion and to the discovery in 1946 that inert xenon gas, under subatmospheric pressures, can be an effective anesthetic.
As soon as Ernest Lawrence completed the 184-inch synchrocyclotron in 1947, Toby performed the first biology experiments using protons. When the Bevatron was completed in 1954, Toby investigated human therapeutic exposure to accelerated protons, alpha particles, and deuterons. In 1958, he published in Cancer Research a rationale for the use of heavy charged particles for radiation therapy of human cancer. Toby’s group at LBNL also made the first heavy-ion exposures of unicellular organisms (1957), laminar cerebral lesions by accelerated protons (1958), and corpus callosum cut by accelerated alpha particles in animals (1964). These data led to clinical trials at LNBL for treating arteriovenous malformation (AVM) using accelerated protons and alpha particles, a modality now used to treat AVM at several accelerator facilities.
Soon after the 1947 discovery of high-Z primary cosmic rays in high-altitude balloon flights, Toby wrote an article in 1952 in the Journal of Aviation Medicine on the potential hazards of these rays in spaceflight. He predicted that individual heavy ions passing through the retina might produce visual effects and that a very heavy particle could kill or modify a row of cells in its path. In 1969, Edwin Aldrin and the other Apollo-11 astronauts did observe mysterious visual stars and streaks during the first lunar mission. Toby began a series of experiments at the 184-inch synchrocyclotron, and later at the Bevalac, in which he introduced individual accelerated heavy ions to eager scientists’ eyes to reproduce the peculiar flashes and streaks of light. Only Toby and a few scientists enjoyed the light show, because a human-use committee stopped the experiment.
When low-energy accelerated heavy ions became available at the SuperHILAC in 1961, Toby and coworkers began a series of heavy-ion radiobiology experiments with yeast cells and bacterial spores. These inquiries showed that the cross section for heavy-ion effects increased proportionally with the square of the linear energy transfer (LET). When dry spores were irradiated, many low-LET effects could be annealed or chemically reversed, whereas high-LET radiation appeared to produce irreversible damages. The radiobiological oxygen effect (that well-oxygenated healthy tissues are more radiosensitive than anoxic tumor cells) was eliminated when argon beams were used. Those findings provided the foundation for heavy-ion radiotherapy to treat human cancer. Toby was honored for his contributions to cellular radiation biology in 1963: He received the Ernest Orlando Lawrence Memorial Award from the US Department of Energy (DOE).
When the Bevatron and SuperHILAC were integrated to form the “Bevalac” in 1975, Toby’s group became an active center of basic radiobiological research. Their investigations culminated in an intensive heavy-ion cancer treatment program in collaboration with physicians at UCSF in 1976. Toby retired from LBNL in 1987 as a faculty senior scientist.
In addition to his work at LBNL, Toby was instrumental in the development of hadron treatment facilities in many countries, including Sweden, Russia, Japan, and Germany. Toby also was a member of the radiobiology committee of the National Research Council, president of the Radiation Research Society in 1962, and founding member of the Biophysical Society.
His recent book People and Particles (San Francisco Press, San Francisco, 1997), which he wrote with his wife Ida Lanning Tobias, is full of anecdotes and a personal account of the historical development of LBNL and the Donner Lab. An oral history of Toby’s human radiation studies can be found at the DOE Web site http://tis.eh.doe.gov/ohre/roadmap/histories/0480/0480toc.html.
Toby’s life’s work applied to many scientific disciplines, from physics to biology to medicine. The results will continue to touch the lives of the many patients who are treated at proton and heavy-ion cancer treatment centers worldwide. We will all miss Toby greatly.
