Human-Induced Radioresistance as a Possible Mechanism for Producing Biological Weapons: A Feasible Bridge between Radiore-sistance and Resistance to Antibiotics and Genotoxic Agents.

Dear Editor-in-Chief

Deliberate release of harmful biological agents such as bacteria and viruses which cause disease or death in humans, animals, or plants, an action that is usually referred to as a bioterrorism attack, is a global concern. Bacteria and viruses used in bioterrorism are typically found in our natural environment, but possibly the ability of these agents to cause illness, their resistance to current drugs, their ability for spreading into the environment (air, water and food) could be significantly increased by mutations. According to WHO, resistance of microorganisms to antimicrobial agents can lead to prolonged illness, greater risk of death and higher costs. Over the past years, investigators have generated extremely radioresistant bacterial species by directed evolution in Escherichia coli, a relatively radiosensitive bacterium (1). Radiore-sistance, a property which makes organisms capable of coping with intense levels of ionizing radiation can be found in certain extremophiles. Dein-ococcus radiodurans, one of the most radioresistant organisms known, is extremely resistant not only to ionizing radiation but also to UV, desiccation, and oxidizing and electrophilic agents. Deinococcus radiodurans can withstand acute doses of ionizing radiation on the order of 10kGy (2). In other words, Deinococci are extremely resistant to the severe DNA damage caused by irradiation and oxidizing agents probably because their survival in nature is dependent on this resistance. It is found that the mechanism of DNA repair in D. radi-odurans bacteria exposed to gamma radiation is a recA-dependent recombination process. It has been reported that D. radiodurans can mend over 100 double strand breaks (Successful repair without lethality, mutagenesis or rearrangement) following exposure to a dose of 10 kGy, while the majority of other organisms cannot mend only 2-3 double strand breaks per chromosome (3–6). We and other investigators have previously shown that pre-exposure to either small doses of ionizing radiation or non-ionizing radiation may induce resistance against subsequent exposure to high doses of ionizing radiation in plants, laboratory animals and human (7–11). Mechanisms such as alterations in the levels of cytoplasmic and nuclear proteins, increased gene expression, DNA repair and other processes may be involved in this type of induced radioresistance. Using a Co-60 source, Harris et al. (1) repeatedly exposed Escherichia coli bacteria to a dose needed for 1% survival after 1 day. They had to increase the dose each time, as radioresistance increased. The findings of this study showed that the directed evolution, a method used in protein engineering to control the natural selection to evolve proteins or nucleic acids towards a user defined specific goal, can generate extremely radioresistant bacteria. Considering the analogy of the radioresistance pattern of D. radiodurans, this kind of human-induced radiore-sistance (directed evolution) possibly makes Escherichia coli bacteria resistant to all physical and chemical agents and may generate life threatening weapons. In this light, these experiments should be conducted carefully and all applicable ethical issues must be considered.