The analytical approach is a mixture of empirical data and physical models which, hopefully, leads to laws that predict undiscovered phenomena. The physicist, unlike the biologist, approaches nature using constructs that do not exist-simple geometric models with perfect conductivity, for example-in an attempt to reduce the number of variables and establish functional relationships. This methodology has not yet been systematically applied to bioelectric phenomena, and hence there are no physicist-type explanations for EMF-induced biological effects. Despite this, evidence of the existence of many interesting molecular processes that may explain the effects has been discovered. In what follows, we present an overview of the physical mechanisms applicable to bioelectrical phenomena.
When an EMF is applied to a material, many types of molecular processes can occur (Fig. 9.2): (1) electronic excitation; (2) polarization; (3) field-generated force effects; (4) heat; and (5) other electronic and ionic effects. If the material is also alive, additional processes that are associated with cells and higher levels of structural organization can also occur. We shall regard such consequences as biological effects, in distinction to effects that occur regardless of whether the material is alive or dead (physical effects).
Fig. 9.2. Classes of physical processes in biological tissue exposed to EMFs: Types 1-4 can occur in living and nonliving tissue They are thermodynamically closed in the sense that they are directly proportional to the applied EMF. The biological consequences, if any, are thermodynamically open because they can occur only if metabolic energy is also present- that is, if the system is alive. For Type 5, in contrast, both the physical process and the biological consequence can be thermodynamically open. As an example, we have depicted a metabolically maintained superconducting region in a cell organelle. State S1 is associated with one biological function and S2 -induced by the presence of the EMF- with a different function.
Electronic excitation involves the transition of electrons to a higher energy level following the absorption of electromagnetic energy. If the electrons are bound to enzyme molecules, for example, then the excited molecules might behave differently in a metabolic reaction, thereby resulting, ultimately, in a biological effect. Since, however, the thermal energy at 37°C is about 0.02 electron volts (ev), it has traditionally been argued that photons having a lower energy would not produce electron excitation- hence, no biological effects-because molecules with energy states less than 0.02 ev would already be excited as a result of thermal motion. This view, although popular, is not correct because the thermal energy is only the average energy of a collection of molecules: at any given time, some molecules are in a state of less than 0.02 ev. The salient -and presently unexplored- questions associated with Type-I processes relate to the density of states that are hv ev (h is Planck's constant, v is the frequency of the EMF) below a specific average energy, and to the minimum change in the density of such states that would be required to produce a biological effect.
Type-2 processes involve electronic, atomic, and orientational polarizations produced when a material is exposed to an EMF: the total dipole moment of a group of molecules depends on these polarization properties and on the strength of the local electrical field. EMF-induced alterations in dipole moments could theoretically account for biological effects. For example, Figure 9.2 depicts a material containing a linear array of permanent dipoles. In the absence of an EMF, the dipoles remain randomly oriented because of thermal motion, but when the field is present a preferential alignment becomes established. If the dipoles were attached to a cell membrane, for example, then the preferential alignment might correspond to a state of altered membrane permeability. Every EMF produces some preferential alignment, but one cannot determine, before the fact, how much alignment would be biologically significant. Historically, the notion has been that something approaching saturation would be required, but this view is based on inappropriate models of living organisms (low-pressure gasses and dilute solutions of polar solutes).
In addition to permanent dipoles, which may or may not be present in a material, applied EMFs can induce a dipole moment as a result of electronic and atomic polarization. Field-generated forces (Type 3) occur when the field interacts with the induced dipole moment, and they can produce interesting orientational and translational effects in in vitro systems. One of the best known such effects, pearl-chain formation (Fig. 9.2), has been observed with many kinds of particles including blood cells (alive and dead) and plastic microspheres. Present theory suggests that field strengths needed to produce pearl-chains are of the order of 104-106 v/m, depending on particle size. If this is true of all Type-3 processes-the latest evidence suggests that it is not - they would be of little biological interest.
Heat is an ubiquitous consequence of EMFs and it has long been associated with gross, irreversible changes in tissue - the microwave oven is perhaps the latest and most familiar example. In theory, any heat input to a biological system (hence any EMF) could alter one or more of its functions. This idea, however, directly conflicts with the prominent view (at least in the West) that only heat inputs that are an appreciable fraction of the organism's basal metabolic rate can lead to biological effects. We shall have more to say concerning the implications of this view in chapter 10.
Since heat is always produced when an organism is exposed to an EMF, one cannot experimentally determine whether a resulting biological effect could occur in the absence of heat production. (Conversely, although it is a heavy burden for such a humble process, it is always possible to assert that any EMF-induced biological effect is due to heat.) Thus it seems pointless to relate heat -a thermodynamic concept that is independent of the precise details of molecular activity- to observed biological effects which can, ultimately, be explained in more fundamental terms.
The most fertile ground for understanding the physical basis of EMF-induced biological effects involves those processes that we have lumped together in Type 5. They are quantum mechanical and classical processes and include, for example, superconductivity, Hall effect, converse piezoelectric effect, cooperative dipole interactions, Bose-Einstein condensation, and plasma oscillations. Type-s processes have sensitivities as low as 10-9 µW/cm2 and 10-9 gauss, and, therefore, are theoretically capable of serving as the underlying physical mechanism for any known EMF-induced biological effect. Some direct evidence for Type-5 processes has already been described in previous chapters; other developments in this area that also deserve mention are the initiative of Pilla, Frolich, Zon, and Cope.
Pilla's model originated with his and Bassett's work regarding the effects of localized pulsed magnetic fields on bone growth in dogs (2) and humans (3). Pilla reasoned that there must exist generalized mechanisms by which diverse electrical stimuli could alter cell function. He proposed a theory of electrochemical information transfer in which field-induced changes in the ionic microenvironment were responsible for alterations in cell permeability (4, 6). The theory allows for three non-faradaic electrochemical processes: the binding of specific ions; the passage of ions through the membrane; and changes in the membrane double-layer. Because the kinematics of each process differed -measured in impedance studies of the cell's cytoplasmic membrane- it would be possible, in theory, to couple to either of the three processes by choosing an appropriate magnetic pulse. The theory has been successfully applied to the study of the rate of limb regeneration in the salamander (7): it was found that the degree of dedifferentiation could be accelerated or decelerated (depending on the spectral characteristics of the magnetic field) as predicted.
The ideas of resonant absorption and resonant interactions have also been proposed as an explanation for the marked sensitivity of living systems to EMFs. Zon speculated that the electrons in cell mitochondria constituted a plasma state (8). He calculated that the frequency of resonant absorption would be in the gigahertz range for typical values of the dielectric constant and the density of charge carriers. This would make the mitochondria extremely sensitive to microwave EMFs. Zon's idea could also apply to other biostructures and other frequency ranges.
Frolich has proposed another form of resonance. Biological structures frequently consist of electric dipoles that are capable of vibratory motion-hydrogen bonds in DNA and proteins, for example. Long-range coulomb interactions between the oscillatory units produce a narrow band of frequencies corresponding to the normal modes of electromagnetic oscillations. Frolich showed that when energy is supplied to such a system-either from metabolism or from external sources-above a critical rate, it is automatically channeled into the lowest frequency mode, thereby resulting in coherent excitation of the vibratory components (a phenomenon known as Bose-Einstein condensation) (9). Theoretically, such electromagnetic oscillations could affect cell dynamics, and the sharp frequency resonances in biological effects predicted by Frolich have been observed in studies of the rate of yeast growth (10) and the rate of cell division (11). The latency of the biological effect is an important parameter, because the biological effect is associated with the condensed phase which occurs a finite time after irradiation has begun. It is not yet clear to what extent the observed time thresholds are consistent with theory. Future work may lead to an extension of Frolich's concept to higher systems.
A Josephson junction consists of a thin (approximately 10Å) insulating barrier between two superconducting regions. The current through a Josephson junction is highly sensitive to applied EMFs, and this has been exploited in the design of EMF detectors (SQUIDS). Theoretical and experimental evidence for the existence of superconductivity in biological tissue has already been discussed (chapter 4); it suggests the existence of fractional superconductivity in which the superconducting regions are dispersed in tissue that has normal macroscopic electrical characteristics (a concentration in the order of parts per million). As Cope has pointed out (12), the existence of Josephson junctions in biological tissue would provide a physical mechanism of sufficient sensitivity to explain the observed biological effects of applied EMFs. Antonowicz has observed what seems to be a room temperature Josephson effect in carbon films (13), but there are no similar reports involving biological tissue. This may only mean, of course, that the right measurements have not yet been performed.