Saving normal tissues - a goal for the ages.

Almost since the earliest utilization of ionizing radiation, many within the radiation community have worked toward either preventing (i.e. protecting) normal tissues from unwanted radiation injury or rescuing them from the downstream consequences of exposure. However, despite over a century of such investigations, only incremental gains have been made toward this goal and, with certainty, no outright panacea having been found. In celebration of the 60th anniversary of the International Journal of Radiation Biology and to chronicle the efforts that have been made to date, we undertook a non-rigorous survey of the articles published by normal tissue researchers in this area, using those that have appeared in the aforementioned journal as a road map. Three 'snapshots' of publications on normal tissue countermeasures were taken: the earliest (1959-1963) and most recent (2013-2018) 5-year of issues, as well as a 5-year intermediate span (1987-1991). Limiting the survey solely to articles appearing within International Journal of Radiation Biology likely reduced the number of translational studies interrogated given the basic science tenor of this particular publication. In addition, by taking 'snapshots' rather than considering the entire breadth of the journal's history in this field, important papers that were published during the interim periods were omitted, for which we apologize. Nonetheless, since the journal's inception, we observed that, during the chosen periods, the majority of studies undertaken in the field of normal tissue countermeasures, whether investigating radiation protectants, mitigators or treatments, have focused on agents that interfere with the physical, chemical and/or biological effects known to occur during the acute period following whole body/high single dose exposures. This relatively narrow approach to the reduction of normal tissue effects, especially those that can take months, if not years, to develop, seems to contradict our growing understanding of the progressive complexities of the microenvironmental disruption that follows the initial radiation injury. Given the analytical tools now at our disposal and the enormous benefits that may be reaped in terms of improving patient outcomes, as well as the potential for offering countermeasures to those affected by accidental or mass casualty exposures, it appears time to broaden our approaches to developing normal tissue countermeasures. We have no doubt that the contributors and readership of the International Journal of Radiation Biology will continue to contribute to this effort for the foreseeable future.