On the nature of electromagnetic eld interactions with biological systems.

Allan H Frey Chapter 1 OVERVIEW AND PERSPECTIVE Allan H. Frey In recent years, a body of data on the interactions of exogenous and endogenous electromagnetic elds with biological systems has been gathered which is profoundly changing our understanding of biological function. This book is intended to provide the reader with: 1) an integration of many of the ndings from this research that bear on the nature of the interactions of electromagnetic elds with biological systems, 2) a summarization of much of the cutting edge work on the mechanisms and 3) an indication of its signicance for biology. The signicance for biology can be understood if the reader considers that if one used electromagnetic energy sensors to view the world from space 100 years ago, the world would have looked quite dim. Now, the world glows with electromagnetic (em) energy emissions

at most frequencies of the nonionizing portion of the spectrum. It would be incredible and beyond belief if these electromagnetic elds did not affect the electrochemical systems we call living organisms. And since living organisms have only so recently found themselves immersed in this new and increasingly ubiquitous environment, they have not had opportunity to adapt to it. This gives us, as biologists, the opportunity to use exogenous em elds as probes to study the functioning of living systems. We now also have a new technology to study endogenous em elds. This is exciting since new approaches to studying living systems so often provides the means to make great leaps in science. Specically, living organisms are complex electrochemical systems that evolved over millions of years in a world with a relatively weak magnetic eld and with few electromagnetic energy emitters. As is characteristic of living organisms, they interacted with and adapted to their environment of electric and magnetic elds. One example of this adaptation is the visual system, which is exquisitely sensitive to emissions in the very narrow portion of the em spectrum that we call light. Organisms, including humans, also adapted by using em energy to regulate various critical cellular systems; we see this in the complex of circadian rhythms. Fish, birds, and higher animals developed systems to

use electromagnetic elds to sense prey and to navigate. Electromagnetic elds are also involved in neural membrane function; even protein conformation involves the interactions of electrical elds. But as has often been the case in the history of science, though these were interesting observations, they were disconnected bits and pieces that made no real impact; they didn't t the frame of reference of the time. Further, the technology and techniques needed to do much with the information did not exist. Thus, the very broad importance of the interactions of electromagnetic elds with biological systems was not really recognized. But that was yesterday. Now, as James Burke
1might

put it, is (guratively) the day the Universe changed.

Organization of the chapters In the next chapter, the second, I integrate many of the above mentioned disconnected bits and pieces and show how they are expressions of a common theme. In this way, I provide a context or structure for viewing the information provided in the following chapters. The third chapter is a review, from the biophysical standpoint, of data bearing on cell mechanisms. The authors of the fourth through sixth chapters provide models for mechanisms at the cell membrane, some

data on the membrane interactions of em elds and one provides a broader view. The seventh chapter begins a description of the events that occur within the cell, from the cell membrane to the nucleus; the signal cascade. The recounting of theory and data on the signal cascade is continued through chapter ten. Chapters eleven and twelve are concerned, to a limited extent, with the immune system and its interaction with electromagnetic elds. The nal chapters, thirteen and fourteen, provide information on electromagnetic eld interactions with the nervous system. In this way, a coherent and detailed picture of the current state-of-the-art is presented. Before beginning the chapters on the nature of the interactions of electromagnetic elds with biological systems, I will rst provide a brief review of some of the relevant basic physics for the reader unfamiliar with the area; then I will discuss matters of importance for all readers bearing on this area of research; then I will briey mention minor matters of which the reader, who is motivated to read further in the area, should be aware. Incidentally, the rest of the physics and the equipment needed to do biological research in this area of research is readily

available and is no more difcult to learn than what we needed to learn to do electrophysiology. Nature of electromagnetic elds The earth is a magnet created by massive currents in the molten portion of its core. These currents induce an approximately 0.5 gauss dipolar magnetic eld which varies over the surface of the earth. This is an exogenous eld to which all living organisms are essentially always exposed. There are also a wide variety of natural and articial exogenous electromagnetic elds. The natural elds, such as light and radio frequency emissions from lightning have always been in the environment of living organisms. The articial elds, such as microwaves, radio waves and power line elds are a recent phenomena. The electromagnetic energy spectrum encompasses the wavelengths from 3 x 107meters to .003 angstroms as is indicated in Fig 1. This book is concerned with wavelengths longer than those that we perceive as light. Electromagnetic energy is generated through a change in the state of motion of an electrical charge. A change in state of motion is accompanied by the emission or absorption of em energy. The wavelength of emitted em energy is inversely proportional to the magnitude of the energy change. As an example of emission, if

electrons are caused to move to and fro along a conductor, the conductor acts as a transmitting antenna and emits em energy; examples of this are radio waves. When an electric current ows in a wire at extremely low frequency, a magnetic eld forms around and extends out from the wire; examples of this are power line elds. Another example is em energy that is perceived as visible light. This is generated as an electron changes energy level in moving from one orbit to another in an atom. Electromagnetic waves vary in space and time and have associated with them a transport of energy. The physically varying quantity is really a set of quantities, i.e. electric and magnetic eld vectors. There is an electric (E) eld, dened by the force that is exerted on an electric charge placed in the eld and a magnetic (H) eld, dened by the force exerted upon a small electric current element. These elds vary at any given point with time. The electric and magnetic elds in an em wave are not independent entities. Describing the basic transverse wave, they are perpendicular to each other, and they are both perpendicular to the direction of propagation. As Figure 2 illustrates, the basic transverse em wave is one in which E and H vary sinusoidally with a xed relationship to each other and to time and space.

 There are also standing waves; these are relevant to biology. When an em wave encounters a change in the properties of a medium such as tissue layers, a partial reection, absorption, and transmission occurs. The reected wave is superimposed upon the incident wave and gives rise to a standing or locally intensied wave. The energy can be polarized and the orientation of a conductor, e.g. tissue or wire, can have a signicant effect on the energy distribution. The amount of current, for example, induced in a wire by an em eld is a function of the wire's orientation with reference to the eld. A wave uctuating at a frequency of millions of cycles per second that is propagating through space can be used as a carrier for various types and frequencies of modulation. This is a signicant point from the biological standpoint, both in terms of effect and measurement. For example, photic driving of the brain occurs with appropriately modulated light, not with a constant light. The foregoing capsule review provides the basic information needed to understand the content of the following chapters. Matters of importance bearing on the experimentation As a result of this area of research having its real start because of a concern about hazards in the 1940's, the tendency has been for people

to use a toxicology model as their frame of reference in the selection, design and analyses of experiments. They have tended to set up experiments to look for a "dose-response relationship" between electromagnetic eld exposure and a biological variable. But is a toxicology model appropriate as a guide for biological research with electromagnetic elds? It's a crucial question for, as Burke 1and others have made quite clear our frame of reference determines what we look at and how we look. And as a consequence, this determines what we nd . Theory and data show that this is the wrong model 2,3,4. Electromagnetic elds are not a foreign substance to living beings like lead or cyanide. With foreign substances, the greater the dose, the greater the effect a dose-response relationship. Rather, living beings are electrochemical systems that use very low frequency electromagnetic elds in everything from protein folding through cellular communication to nervous system function. To model how em elds affect living beings, one might compare them to the radio we use to listen to music. The em signal the radio picks up and transduces into the sound of music is almost unmeasureably weak. At the same time there are, in toto, strong em elds impinging on the radio. We don't notice the stronger em signals because they are not the appropriate frequency or

modulation. Thus, they don't disturb the music we hear. However, if you impose on the radio an appropriately tuned em eld or harmonic, even if it is very weak, it will interfere with the music. Similarly, if we impose a very weak em signal on a living being, it has the possibility of interfering with normal function if it is properly tuned. This is the model that much biological data and theory tell us to use, not a toxicology model. There are other matters of importance that I would like to bring to your attention. The physiological state of the organism or specimen and individual differences among them are of consequence. This is true in many areas of biology but it is quite clearly true when using electromagnetic elds as a probe to study biological processes. Some of the authors in the following chapters provide specic examples of this fact. There are specic windows of effectiveness for certain carrier frequencies and modulation frequencies of electromagnetic energy. There are also intensity windows. These also will be seen in some of the chapters. But this is so important that it bears taking specic notice of it here.

 The nature of the geomagnetic eld in the location where the experiment is done is also of consequence as is the time of day of the exposure. This will also become clear in the course of reading several of the chapters in this book. It appears possible that an organism's response to a low frequency modulated eld is the same as its response to exposure to a high frequency eld which is acting as a carrier for low frequency modulation. Thus, I have made no attempt to separate out, as different, data from experiments using low frequency em elds, high frequency em elds and what are conventionally termed low frequency magnetic elds. For the sake of clarity in my discussion, I refer to electromagnetic elds as being generated by the organism (endogenous) or as being generated outside of the organism (exogenous). It is important to keep in mind that the organism does not make such a distinction. If the exogenous eld has the appropriate characteristics, it can substitute in a biosystem for the endogenous eld that normally interacts with that biosystem. Two somewhat analogous situations will make this clear. The nervous system doesn't care if the opioid it uses is self-generated or if it comes as heroin from a poppy plant. The heart

responds to the signal from a man-made pacemaker as well as to a signal from its own. The ubiquitousness of em elds is also a matter of concern to us from another standpoint, as experimenters. It is relevant to the question of controls needed in many biological experiments that seemingly have nothing to do with electromagnetic elds. Look about the lab and consider the em elds now being imposed on test specimens by all the electrical devices in use. How do they inuence the results of biological experiments? This is incidentally touched on in a later chapter. Minor matters of which one should be aware Since this area of biological research had its origin in the physics and engineering communities' concern about the hazards of their high power equipment in the 1940's, most of the literature on em eld interactions published before the mid 1980's is irrelevant to us as biologists. Little attention was paid to the variables that are important in biology. But out of this history came some notions that are not seen in other areas of biological research. If this book motivates the reader to read more extensively on the subject, he will come across the residue of these notions. Thus, I will briey discuss them here.

 Thermal vs non-thermal. From the 1940's through the 1970's there was a great deal of heated discussion concerning whether biological effects of exogenous em elds were all "thermal" or some could be "non-thermal". This led to much fruitless experimentation. As I noted in one of my papers 5, the thermal vs non-thermal controversy was one of semantics, not science. There was no common denition of the words and the proponents talked past each other. Some were dening thermal in terms of core temperature measured with a rectal thermometer, whereas others were talking about molecular motion. Further, since the technology did not exist to measure molecular motion, for example, at a membrane interface during exposure to an em eld, this was a fruitless argument. In addition, the words thermal and nonthermal are labels, not specications of biological mechanisms. As an interesting aside though, one implication of the dopamineopiate hypothesis discussed in the next chapter is that em energy exposure would likely affect the hypothalamic set-point for body temperature regulation. The mechanism that sets the body's temperature is located in the hypothalamus and the dopamine-opiate systems are believed to play an important role in the adjustment of this mechanism
6,7. With

all the supporting data on em eld effects that have now been

collected, it seems likely that exposure to low intensity em energy could inuence the hypothalamic set-point via the dopamine-opiate systems. The consequence would be a body temperature shift and this has been reported 8. This is an ironic twist. SAR. In the 1970's there was a well meaning effort to work out a dosimetry. The desire was to be able to specify the exposure to em energy at a relevant point within an organism. Thus, the specic absorption rate (SAR) concept was developed. In essence, the SAR is a calculated energy absorption in an assumed homogenous mass of tissue. All of us are more comfortable when we can quantify in a neat sort of way. Thus, obtaining a number for dose by use of the SAR concept is satisfying. But does the SAR concept have any value in the context of living breathing organisms or is it misleading in that context? If, in fact, the SAR was a point measurement within an organism of the strength of the eld at the locus of an identied biological mechanism, then everything would be ne. But it is not that. It is a calculated value from calorimetry or incident eld measurement, resting on a foundation of assumptions. In addition, it is assumed that an average calculated value for a homogenous whole body mass of tissue is relevant to what

the eld is at a point at the locus of a biological mechanism of an effect. But the mechanism and its locus are also unknowns. I can see the SAR concept having value now with very simple cell suspension systems. But it has been indiscriminately used to provide what amounts to a very precise appearing, but pseudo-exposure number in reports of all sorts of biological experiments - right up to man. That is the problem and is what the reader has to be alert to. Living organisms are not a homogenous mass, a cup of tea. It matters where the energy is deposited. One example is all that is needed to illustrate the problem. If a bullet is red into the calf of a person's leg, there will be a deposition of energy and he will be most unhappy. He might require a day of hospitalization. If the bullet was red through his brain, there would be the same deposition of energy, but the result would be quite different. Thus, might it not be best at this time to report measured incident energy, possibly with a "tentative SAR". Then, at such time as we can exactly specify mechanism, locus of effect, and a non-perturbing means of making a point measurement in an organism, we can then go back and use the reported incident energy to calculate a relevant number. For now,

the reader must be wary in reading the interpretations of experiments in which only SARs are given. Implicit assumptions. I can think of no better way to start this section than with a quotation from James Burke 1 "Today we live according to the latest version of how the universe functions. This view affects our behavior and thought, just as previous versions affected those who lived with them. Like the people of the past, we disregard phenomena which do not t our view because they are 'wrong'.... Like our ancestors, we know the real truth. At any time in the past, people have held a view of the way the universe works which was for them similarly denitive.... And at any time, that view they held was sooner or later altered by changes in the body of knowledge." An example will illustrate his point. In 1915 a German meteorologist named Alfred Wegener, noting the shape of the continents and the distribution of fossils, proposed that the continents drifted apart. He suggested that they oated on a sea of heavier basaltic material. To paraphrase Burke, the proposal was greeted with universal scorn. The naysayers said that there was no known mechanism which could move the continents. The soft land masses obviously could not

plow through the hard ocean oor. The problems Wegener had posed were called pseudo-problems. The bio-geographical similarities of the fossils were explained away as due to land bridges and blown seeds. Since the continents did not t exactly, his proposal had to be wrong. For thirty years Wegener's view was ignored. In the 1950s, the newly invented magnetometers had shown that the earth had a magnetic eld which was parallel to the axis of rotation. By 1966 magnetic proles showed that the ocean oor was spreading outward from the mid-ocean ridges, and it was clear that this mechanism had slowly pushed the continents apart. This was a mechanism that had not, and until magnetometers were invented, could not have been envisioned by the naysayers; besides, they already knew the "real truth". Or leaving Burke, consider that it used to be a rmly held dogma of physics that the basic laws of nature are symmetric under reection. The quantity conserved by virtue of reection symmetry is called parity. Every physicist accepted the "law" that parity is conserved. Then, some particle-collision experiments done by high-energy physicists resulted in puzzling data for which there were only two possible explanations: either there were two particles, or else parity was not conserved in nature. Since violation of a "law" of physics was

considered absurd, physicists were left with the "tau-theta puzzle"; the data was in limbo. But then an incredible proposal was made by two physicists, T. D. Lee and C.N. Yang, they proposed that parity is in fact not conserved; nature is not symmetric under mirror reection. The rst reaction of most physicists to the Lee-Yang proposal was incredulity. Wolfgang Pauli, discoverer of the neutrino, electron spin, and the Pauli exclusion principle, ridiculed the idea of nonconservation of parity in the weak interactions. The simple conrming experiments were done by C. S. Wu; and Lee and Yang were awarded the Nobel Prize. So why have I presented this brief discourse? This area of biological research is not privileged, it also has its few naysayers who imagine that they are the possessors of "real truth". The reader who is motivated to venture into the literature will nd them. They like to talk about the dogma, the "laws of physics". If the data do not conform to the dogma, then the data must be wrong. But one does not challenge data with the current dogma. That's upside down, its the dogma that is tested by data obtained with constantly increasing precision of measurement and observation.

Observations improve, particularly the ability to measure more and see more. The test of data is additional, more precise data or data obtained with new techniques. This is the great leap in thinking that created Science out of the thinking of the Medieval Age. It is to be expected that theories conceived at one level of observation will have to be modied as observational ability improves. This is what some scientists ignore. They implicitly assume that they have reached a "fundamental" level of understanding, which leaves no room for even more fundamental levels of understanding. References 1. Burke J. The day the Universe Changed. Boston: Little and Co, 1985. 2. Frey A H. Electromagnetic eld interactions with biological systems. FASEB Journal 1993; 7:272-281 3. Frey A H. Evolution and results of biological research with lowintensity nonionizing radiation. In: A. A. Marino, ed. Modern Bioelectricity New York: Marcel Dekker, Inc 1988: 785-837.

 4. Frey A H. Biological function as inuenced by low power modulated RF energy. IEEE Trans on Microwave Theory and Techniques 1971; MTT-19:153-164 5. Frey AH. Behavioral biophysics. Psychol Bull 1965; 63:322-337 6. Weiss J, Thompson ML, and Shuster L. Effects of naloxone and naltrexone on drug-induced hypothermia in mice. Neuropharmacology 1984; 23(5):483-489 7. Glick SD and Guido RA. Naloxone antagonism of the thermoregulatory effects of phencyclidine. Science 1982; 217(24): 1272-1273 8. Lai H, Horita A, and Chou C et al. The pharmacology of post exposure hyperthermia response to acute exposure to 2450 MHz pulsed microwaves. Bioelectromagnetics Society Sixth Annual Meeting, Atlanta, GA, 1984.

Figure captions Fig. 1 Electromagnetic eld spectrum. ELF refers to extremely low frequency waves in a broad sense; this includes power line frequencies. X refers to ionizing radiation such as x-rays. This book is primarily concerned with the portion of the spectrum from infrared through ELF. Fig. 2 Spatial variation of E and H in a simple TEM wave.