Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields

Abstract

We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental hazards. Understanding necessary conditions for such effects can be based on a unified approach: quantitative comparison of the estimated chemical change due to a particular electromagnetic field exposure to that due to competing influences, with both estimates based on a biophysical mechanism model within the context of a model of a biological system.

Photoreceptor-based magnetoreception: optimal design of receptor molecules, cells, and neuronal processing

“…In the decade following, a significant body of work, both experimental and theoretical (Stass et al 2000;Weaver et al 2000;Timmel et al 2001;Woodward et al 2001;Weaver 2002;Cintolesi et al 2003;Henbest et al 2004;Ritz et al 2004Ritz et al , 2009Vink & Woodward 2004;O'Dea et al 2005;Rodgers et al 2005Rodgers et al , 2007Thalau et al 2005;Vaughan & Weaver 2005;Shakirov et al 2006;Solov'yov et al 2007;Woodward & Vink 2007;Efimova & Hore 2008;Maeda et al 2008;Miura & Murai 2008;Solov'yov & Schulten 2009;Hill & Ritz 2010;Lau et al 2010), has advanced our information and understanding of how a putative radical-pair magnetoreceptor should be designed so as to be well suited to detect the geomagnetic field. Behavioural studies have provided more information about the functional properties of magnetic compasses in a variety of animals (Rappl et al 2000;Wiltschko et al 2000aWiltschko et al ,b, 2001Wiltschko et al , 2002bWiltschko et al , 2003aWiltschko et al , 2004aWiltschko et al ,b, 2005Wiltschko et al , 2006Wiltschko et al , 2007aÅ kesson et al 2001;Phillips et al 2001Phillips et al , 2002Muheim et al 2002Muheim et al , 2006Irwin & Loh...…”

Gauging the strength of power frequency fields against membrane electrical noise

“…It is also possible for this energy to not be dissipated completely and to be partially converted into ''work'' on a metabolic chain. Metabolic flows can be affected and the effect can accumulate over time [Vaughan and Weaver, 2005].…”

Quantitative Evaluations of Mechanisms of Radiofrequency Interactions With Biological Molecules and Processes

“…The kinetic energy associated with random motions of atoms and molecules results in background electromagnetic noise that, depending on context, is called blackbody radiation or Johnson noise (Wannier 1966). Biological systems have additional noise sources (Vaughan and Weaver 2005). In order to affect molecular function, incoming RF energy must either "pump" existing vibrational, rotational, or electronic modes of resonant absorption, or affect non-resonant energy absorption processes in a way that overcomes the molecular level noise resulting from fluctuating temperature, concentration, mechanical stress, and background electric fields (Vaughan and Weaver 2005).…”

“…On a prima facie basis, any exogenous signal has to overcome this in-band background signal if there is to be a plausible interference with ongoing biological processes. A S/N of Ͻ0.1 is considered a conservative threshold for RF to be effective in changing a biochemical process (Vaughan and Weaver 2005).…”