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In the cold, mechanistic, clockwork universe of the physical scientist, the phenomena of love, compassion and empathy are driven into exile. There is no mechanism that can account for these experiences. When I am hit, I suffer alone. You standing beside me remain untouched by my misery. This state of affairs, however, is not true to the human experience. In the world of relatedness and relationship, when I am hit, you beside me bleed. Reclaiming mechanistic science from out-of-touch abstraction is biology, the study of life. This is the metaphorical significance of the recently discovered “bystander effect,” a second intriguing biological phenomenon that calls into question current assessments of risk from exposure to low doses of radiation.
Up until the closing years of the twentieth century, research in radiation biology was guided by the foundational assumption that radiation-induced damage to cells was a direct consequence of the transfer of energy to cellular molecular structures, DNA being the primary target. Those cells “hit” by radiation were damaged at the instant of exposure or shortly thereafter, and the consequences were expressed within one or two cell generations. Those cells not hit by radiation escaped damage altogether. Within the physicist’s paradigm, there was no mechanism by which non-targeted cells could receive injury from radiation. Discovery of the bystander effect dashed this shortsighted, unfounded assumption. In the realm of the living, cells hit by radiation communicate the assault to cells in their immediate vicinity, and the non-targeted cells respond by undergoing similar destructive transformations as if they had actually received the blow themselves.
The ‘bystander effect’ is the name given to a cell-to-cell communication process by which the damage created in cells hit by radiation is communicated to non-hit cells. These cells in turn manifest damage — often very extensive damage — similar in kind to that received by the targeted cells. “The radiation-induced bystander effect is a phenomenon whereby cellular damage (sister chromatid exchanges, chromosome aberrations, micronucleation, transformation, gene expression) is expressed in unirradiated neighboring cells near to an irradiated cell or cells” [1]. Besides immediately observable genetic damage and mutations, bystander damage may also include genomic instability which manifests only after many generations of cell divisions among populations of non-targeted cells. The mechanisms responsible for the bystander effect are not currently known. Two separate pathways seem to be involved. In cells which are in direct contact with each other, chemical communication from the irradiated cell to unirradiated neighbors occurs through channels called gap junctions. For communication with more distant cells, the prevailing hypothesis is that the hit cell releases damage-response chemical signals into the intercellular medium which are then absorbed by cells not directly targeted by the radiation.
The bystander effect shakes the foundation of orthodox dogma as to how radiation interacts with living systems and calls into question the adequacy of current models of radiation risk. Although as yet unproven, it suggests that internal exposure to low doses of radiation may be more hazardous than currently assumed. Further, it poses a serious challenge to the reigning assumption that the effects of low doses of radiation can be determined by a simple linear extrapolation from high doses.
"[The bystander effect] would have significant consequences in terms of radiation risk extrapolation to low doses, implying that the relevant target for radiation oncogenesis is larger than an individual cell, and that the risk of carcinogenesis would increase more slowly, if at all, at higher doses. Thus a simple linear extrapolation of radiation risk from high doses (where they can be measured) to lower doses (where they must be inferred) would be of questionable validity" [2].
"The bystander effect does not demonstrate a linear relationship to dose. It is maximally induced by very low doses, suggesting a switch on/off mechanism for its activation" [1].
"On the basis of this [bystander] effect and its possible contribution to cancer induction in body tissues via the induction of DNA damage, the authors question the assumed linearity of low dose carcinogenic response for alpha particles; this assumption is an important element in radiological protection" [3].
"The main report [CERRIE Majority Report] notes that the existence of genomic instability together with the bystander effect draws attention to the existence of organization levels for cell communication midway between the cell and the organ. Sonnenschein and Soto have recently suggested that such cell communities are pivotal in the development of cancer as it is cell communication from local cells that tends to prevent any cells in a community from running away from growth control. They see replication as a default state and quiescence as a response to control by local cells. This suggests that damage to such a cell community results in transformation and may be critical in the ultimate expression of cancer. For this reason sublethal damage from multiple decays from hot or warm particles would confer risks not accommodated within presently accepted paradigms" [4]
It is interesting to note that the existence of the bystander effect lends support to the idea put forth in Exhibit A that radiation effects cannot be adequately modeled by the simple concept of a transfer of energy. “Because of bystander effects, the distribution of energy in cells is not related to the distribution of cellular damage" [5].
Bibliography
[1] Belyakov O.V., Folkard M., Mothersill C., Prise K.M., Michael B.D. Bystander Effect and Genomic Instability-Challenging the Classic Paradigm of Radiobiology. Timofeeff- Ressovsky Centennial Conference, "Modern Problems of Radiobiology, Radioecology and Evolution." Joint Institute for Nuclear Research. Dubna, Russia. 2000.
[2] Hall E.J. Genomic Instability, Bystander Effect, Cytoplasmic Irradiation and other Phenomena that may Achieve Fame without Fortune. Physica Medica. Vol. XVII, Supplement 1, 2001.
[3] Zhou H., Randers-Pehrson G., Waldren C.A., Vannais D., Hall E.J., Hei T.K. Induction of a Bystander Mutagenic Effect of Alpha Particles in Mammalian Cells. Proceedings of the National Academy of Sciences. 2000; 97:2099-2104.
[4] CERRIE Minority Report. Minority Report of the UK Department of Health / Department of Environment (DEFRA) Committee Examining Radiation Risk from Internal Emitters (CERRIE). Aberystwyth: Sosiumi Press; 2005.
[5] Brooks A.L. Bystander Effects from High-LET Radiation. Powerpoint Presentation. US Department of Energy Low Dose Radiation Research Program. www.tricity.wsu.edu/faculty/brooks/Bystander-WEB.ppt
