Failla Memorial lecture. The future of heavy-ion science in biology and medicine.

Interplanetary space contains fluxes of fast moving atomic nuclei. The distribution of these reflects the atomic composition of the universe, and such particles may pose limitations for space flight and for life in space. Over the past 50 years, since the invention of Ernest Lawrence's cyclotron, advances in accelerator technology have permitted the acceleration of charged nuclei to very high velocities. Currently, beams of any stable isotope species up to uranium are available at kinetic energies of several hundred MeV/nucleon at the Berkeley Bevalac. Recently, new areas of particle physics research relating to the mechanisms of spallation and fission have opened up for investigation, and it is now realistic to search for nuclear super-dense states that might be produced in heavy nuclear collisions. The heavy ions hold interest for a broad spectrum of research because of their effectiveness in producing a series of major lesions in DNA along single particle tracks and because of the Bragg depth ionization properties that allow the precise deposition of highly localized doses deep in the human body. Individual heavy ions can also interrupt the continuity of membraneous regions in cells. Heavy ions, when compared to low-LET radiation, have increased effectiveness for mammalian cell lethality, chromosome mutations, and cell transformation. The molecular mechanisms are not completely understood but appear to involve fragmentation and reintegration of DNA. Cells attempt to repair these lesions, and many of the deleterious effects are due to misrepair or misrejoining of DNA. Heavy ions do not require the presence of oxygen for producing their effects, and hypoxic cells in necrotic regions have nearly the same sensitivity as cells in well-oxygenated tissues. Heavy ions are effective in delaying or blocking the cell division process. Heavy ions are also strong enhancers of viral-induced cell transformation, a process that requires integration of foreign DNA. Some cell lines, known to be radioresistant to X rays, have exhibited greater sensitivity to heavy ions. These radiobiological properties, combined with the ability to deliver highly localized internal doses, make accelerated heavy ions potentially important radiotherapeutic tools. Other novel approaches include the utilization of radioactive heavy beams as instant tracers. Heavy-ion radiography and microscopy respond to delicate changes in tissue electron density. Dose localization with helium ions has achieved excellent results for pituitary tumors, tumors adjacent to the spinal cord, and ocular melanomas. We are working on adapting silicon- and neon-ion beams for controlled therapy studies.(ABSTRACT TRUNCATED AT 400 WORDS)