David J. Brenner, PhD
The first objective is aimed towards understanding the carcinogenic effects of low levels of radiation. We are constantly exposed to low levels of radiation, both from natural sources such as radon, and man made sources. Consequently, it is of major societal importance to be able to make rational and credible estimates for the risks of exposure to low levels of radiation. However, these risk estimates are still very uncertain. These uncertainties arise mainly from the difficulties of applying information from the survivors at Hiroshima and Nagasaki. There, the doses were high, and exposure times short. In situations of environmental interest, the doses are low and the time of exposure long. Thus, transferring risk estimates to environmental situations requires understanding of the basic mechanisms by which radiation absorption in a living cell can ultimately lead to cancer.
As an example of research into basic mechanisms, radiation produces large numbers of double strand breaks in DNA, yet almost all of them are efficiently repaired. Just a few are repaired wrongly, and we look into the completion between DNA repair and misrepair, to understand what are the condition which make DNA strand-break misrepair more likely.
The second objective is directed towards improvements in radiotherapy treatments. In that about half a million cancer patients are treated each year in the U.S. with radiotherapy, this is an important goal, and even small improvements in treatment can result in significant increases in life expectancy or quality of life for cancer patients. An example of our work here is for treatment of cervical cancer, a disease affecting roughly 13,000 women each year in the U.S. Until recently, the treatment of choice has been insertion of low-activity radioactive sources adjacent to the cervix for several days. This presents major difficulties for patients, especially elderly women, who are immobilized and isolated for long time periods. There have been several pioneer trials with high dose rate inserts, in which the treatment is delivered in a few fractions taking only a few minutes each. This treatment had been presumed to represent a compromise between optimal treatment (long irradiation) and patient convenience (short irradiation); thus few clinicians were willing to switch to the high dose rate short irradiations. We showed, in a series of papers, that for radiotherapy of the cervix, one should actually expect better clinical results with short irradiations. This discovery has fueled an explosion of interest in high dose rate cervical radiotherapy and, within five years, most women with cervical cancer will probably be treated with this technique.
Research into the biological effects of radiation has two, interlinked, objectives, both of which require understanding of the effects of radiations on living tissue. These are:
1 Research into basic mechanisms of the carcinogenic effects of low doses of radiation;
2 Research into effects of high radiation doses, in support of radiotherapy.