Can Low-Level 50-60 Hz Electric and Magnetic Fields Cause Biological Effects

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Can Low-Level 50/60 Hz Electric and Magnetic Fields Cause Biological Effects? Author(s): P. A. Valberg, R. Kavet, C. N. Rafferty Source: Radiation Research, Vol. 148, No. 1 (Jul., 1997), pp. 2-21 Published by: Radiation Research Society Stable URL: http://www.jstor.org/stable/3579533 Accessed: 13/09/2010 00:53 Your use of the JSTOR archive indicates your acceptance of JSTOR's Terms and Conditions of Use, available at http://www.jstor.org/page/info/about/policies/terms.jsp . JSTOR's Terms and Conditions of Use provides, in part, that unless you have obtained prior permission, you may not download an entire issue of a journal or multiple copies of articles, and you may use content in the JSTOR archive only for your personal, non-commercial use. Please contact the publisher regarding any further use of this work. Publisher contact information may be obtained at http://www.jstor.org/action/showPublisher?publisherCode=rrs . Each copy of any part of a JSTOR transmission must contain the same copyright notice that appears on the screen or printed page of such transmission. JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected].  Radiation Research Society is collaborating with JSTOR to digitize, preserve and extend access to Radiation  Research. http://www.jstor.org

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VALBERG, KAVET AND RAFFERTY

Living Cells Exhibit Abundant Electrical ActivityIn addition o thermal noise, cells contain other sources

of electrical noise such as (1) "shot" noise, (2) "llf" noiseand (3) electrical signals from propagating action poten-tials in nerve and muscle cells (9, 15, 16). Shot noisederives from the fact that electrical charge comes in dis-

crete units. When a "constant" current is flowing, thenumber of charges per second will not be constant overshort time scales, but will fluctuate up and down, governedby Poisson statistics, as does any process nvolving discreteevents. An analogy can be drawn with radioactive decay,where the isotope half-life ("average current") s a precisenumber, but the actual decays in a short period of time("current luctuations") have a scatter to them. The elec-trical noise due to this fluctuating charge distribution scalled shot noise. The llf noise, or flicker noise, is funda-mental to many processes, and, unlike thermal noise, whichis "white" constant with frequency), he magnitude of 1lf

noise increases at lower frequencies; lf noise is not wellunderstood, but it appears to be inherent to any process(e.g. ion flow through a channel) that evolves and changeswith time. Finally, "action potentials" are vigorouschanges in the membrane potential of nerve and musclecells. Electric fields and currents rom normal physiologi-cal functions derive from electrical activity of cells withinthe heart, muscles and brain, as recorded n electrocardio-grams, electromyelograms and electroencephalograms,respectively. Magnetic signals from these sources also canbe measured (e.g. magnetocardiograms, magnetomyelo-grams and magnetoencephalograms). At low frequencies(<1 kHz), shot noise, llf noise and noise from electricallyactive tissues are manyfold arger than the electrical noisefrom thermal effects (15, 17).

Cells vary widely in their response to membrane pertur-bations by electrical fields. Steady electric-field gradientscan cause cells to migrate and extend processes ("galvano-taxis"), but 50/60 Hz electric fields as large as 1,200V/m intissue fluidshave not been found to affect galvanotaxis 18).Depolarization of single (15-,m-diameter) heart cells insolution requires high evels of field n the fluid,of the orderof 1,600V/m (19). Neither cellular morphology nor the dis-tribution of charged, cell-surface, ipoprotein eceptors wasaltered after application f 60 Hz, 2,300-V/m issue fields nhuman ibrosarcoma ells (20). Changes n the structure fartificial ipid layers, such as are characteristic f cell mem-branes, required 107V/m (which is much higher than thethreshold of electroporation f cell membranes, amely 105V/m) (21). Yet synchronization f Aplysia pacemaker neu-rons has been reported at 0.2 V/m (22), and reduction infibroblast protein synthesis has been reported at 0.01 V/m(23). The latter response was measured after 12 h of expo-sure, and increasing he field by over two orders of magni-tude did not increase the response. Overall, here is a vast,five-orders-of-magnitude pan between a reported "no-effect" level of 1,200 V/m in one cell system compared to

reported effects at 0.01 V/m in a different ell system.

Multicellular rganisms an exhibit exquisite ield sensi-tivity. Sharks respond o slowlyvarying issue (water) elec-tric fields of 106 V/m (24-27). Both large numbers of cellsdistributed n a large organism and complex signal amplifi-cation and processing are required to achieve this perfor-mance. The following discussion of mechanisms llustrates

why the signal-to-noise S/N) ratio s one of the central con-siderations n evaluating the implications of the reportedbioeffects of low-fieldEMFs.

MECHANISM: DIRECT ENERGY TRANSFER

Power Lines "Radiate" Virtually No EnergyUnlike a radio antenna, an electric-power ransmission

line is a very poor antenna, and the energy hat is put into aradiative form is minuscule; t is not accurate to say thatsignificant "radiation" r "emissions" ome from 50/60 Hzpower lines. A 100-m ength of transmission ine carrying500 MW of 50/60 Hz electrical

powerradiates ess than 10

pW of energy, which would be approximately 2 x 10-8W/m2at one meter from the line (28). Aside from electro-magnetic radiation, he heating effects of electric currentsinduced within the body by 1-kV/m and 0.1-mT fields canbe calculated o be about 5 x 10-8W (29), which, normal-ized to the body surface area, is also about 2 x 10-8W/m2.In comparison, he electromagnetic energy flux from thesun at noon is -1,400 W/m2; he energy flux from the fullmoon is -2 X 10-3 W/m2, about 100,000-fold greater thanthe energy luxfrom power ines.

Energy Can Appear as Accelerated Ions and Induced IonCurrentsAt the molecular evel, electric fields in tissue and 50/60

Hz magnetic fields can accelerate ions and charged pro-teins. The amount of energy that can be transferred tocharged molecules is readily calculated, and Table IIIshows how far a tenfold-charged molecule would have tobe accelerated o make a change in its energy that is com-parable to thermal kinetic energies (the average kineticenergy of each molecule is given by 3/2 k. T, which is 6.4x 10-21 J or -0.04 eV); the table shows that, even if freeacceleration were allowed over the dimensions of thebody, the 1,000-V/m and/or 0.1-mT fields would not beable to impart energy to charged molecules at a significantrate. Of course, collisionswith other molecules prevent anysingle molecule from unimpeded acceleration. The driftvelocity mposed s about 10-9 of the thermal velocity. Thusweak fields cannot modify the motions of individualmolecules n a manner hat would be biologically elevant.

Electromagnetic ields can transfer energy via currentsinduced by inductive and capacitive oupling,with resultantresistive heating (I2R heating) of body tissues. The energytransfer can be calculated, and a human body exposedsimultaneously o 50/60Hz 0.1-mT and 1,000-V/m ieldswillabsorb about 5 x 10-7W of energy (29). This rate of energy

absorption is 8 orders of magnitude (108) less than the

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MECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

TABLE II50/60 Hz EMF Energy Transfer o a Tenfold-Chargeda Molecule

External, applied ield

1,000V/m0.1 mT

Internal, nducedtissue E field

4 x 10-5V/m4.8 x 10-3 V/m

Energy achievablebover 20-pm cell

10-8 V10-6eV

Acceleration distanceb or"energy - kT - 0.04 eV"

100m0.8 m

aA molecule hat departs rom electrical neutrality with an excess of 10 positive or 10negative charges.bThese energies are calculated as if the ion could accelerate unimpeded, .e. as if in a vacuum. n fact, the charged molecule can accelerate only

about 10-12 before experiencing collision.What his means s that the tissue E field will add a small drift velocity o the thermal velocity of randommolecular motions. Thermal velocities are of the order of 1,000mph (450 m/s), whereas the drift velocity imposed by 4.8 x 10-3 V/m on a tenfold-charged on is about one inch per day (3 x 10-7m/s).

body's basal metabolic rate (-100 W). Because the wave-length of 60 Hz in tissue (-5 km) is far larger than thedimensions of the human body, the EMF energy cannot befocused nto a small portion of the body.

Some induced currents can be intenseenough

to trans-fer perceptible energy. Large time-varying magneticfields at low frequencies can produce physiologicaleffects. A rate of change, dBldt, of about 800 mT/s stim-ulates magnetophosphenes. These sensations of lightflashes in the eye, produced by changing magneticfields, are a well-established biological effect, presum-ably caused by the induced currents depolarizing cellmembranes within the retina. Magnetophosphenesrequire about 7 mT at 20 Hz, but 30 mT at 50/60 Hz (30);phosphenes can also be produced by electric currentapplied by means of electrodes at the temples (31). Fieldswith frequencies n excess of about 100 Hz are ineffectivein producing magnetophosphenes.

Electric currents nduced by time-varying magnetic ieldscan stimulate action potentials in neurons. Although theexact nature of the induced electric currents is poorlyunderstood, experimental vidence shows that a thresholdpower-frequency current density of about 10-20 A/m2 isrequired o induce action potentials n nerves (30). Even forlong neurons oriented parallel o the current-density ector,currents n excess of 1-2 A/m2are necessary. At 50/60Hz, awhole-body magnetic field of about 100 mT would berequired o achieve his level of induced current density. Aswas summarized n Table II, 50/60 Hz 0.1-mT fields pro-duce V/loooof this threshold urrent density.

60 Hz EMF Energy Cannot Break ChemicalBondsWithin living cells, collisions between molecules (pro-

teins, nucleic acids, etc.) moving with thermal energiesoccur at a high rate (1012per second per molecule) (32).Each collision results in electrical distortion of the col-liding entities. Biological molecules are constructed soas to withstand these electric fields and to resist the nor-mal buffeting of thermal energies (0.3 kcal/mol = 0.04eV). To disrupt single covalent bonds, 83 kcal/mol (3.6eV) is required, and even hydrogen bonds have an aver-

age energy of 2.4 kcal/mol (0.1 eV). A range of bond

energies is shown in Table IV, which also shows the rel-ative position of thermal energies (kT) in comparison othe strength of chemical bonds. Since the electric fieldproduced in tissue by a 1,000-V/m external 50/60 Hzelectric field is about 4 x 10-5

V/m,the maximum

energya tenfold-charged on can attain across a 10-pm-diametercell (even in a vacuum, with no collisions) is 4 X 10-9eV. Hence our benchmark evels of EMFs cannot accel-erate ions to energies that can disturb even the weakestchemical bonds.

Electromagnetic radiation, although "wave-like" innature, behaves like "particles" when being absorbed oremitted by matter. That s, absorption nd emission of radi-ation occurs n discrete energy units, photons, with energycontent E = hv, where h is Planck's constant and v is thefrequency. Table V lists photon energies, and these ener-gies can also be compared to the chemical bond energiesshown in Table IV. High-frequency radiation, e.g. X-rayphotons, have high energy content and can ionize biologicalmolecules. Photons n the visible and UV range can excitemolecules and initiate molecular hape changes or chemicalreactions. Photon energies of electromagnetic adiation n

TABLE VChemical Bond Energies Relative to Light,

Thermal and EMF Energies

Bond type

N-N, triple covalent bond0=0, double covalent bondC-C, single covalent bondPhotons of green ightATP hydrolysisaLigand-to-receptor ond (33)Hydrogen bondIsomerization f enzyme3/2kTEMF-accelerated ons"'

eV/bondkcal/mol (or per molecule)

22511883577.3

152.40.70.9

2.0 x 10-7

9.55.13.62.50.30.60.10.030.04

10-8

"ATP = adenosine riphosphate.bTenfold-charged ons (ions with 10 excess positive or negative

charges) accelerated hrough 4 x 10-5V/m field across a 20-pm distance

(cell diameter).

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VALBERG, KAVET AND RAFFERTY

TABLE VEnergy per Photon in Electromagnetic Waves

Descriptor

Soft XrayVisible light (green)Far infrared (body temperature)Millimeter radarTelevision/radio (e.g. 240 MHz)bPower-line 60 Hz

Wavelength rangea

X= 1.2 nmX= 0.5 pmX= 30 pmX= 1.2 mm

= 1.2mX= 5,000 km

Photon energya

1,000 eV2.5 eV0.04 eV10-3 eV106 eV10-12 eV

Photon effect

Ionize moleculesExcite molecules

Vibrate moleculesVibrate, rotate molecules

?

a" = wavelength; v = frequency; c = speed of light = 3 x 108 m/s; h = Planck's constant = 6.62 x 10-34 J-s; then, E = photon energy = hv = hcl/(4.14 x 10-15 V-s) x (v) = (1.24 x 10-6eV-m) X (l/X).

bv = Elh = 240 MHz; period of oscillation = l/v = 0.4 x 10-9 s = 0.4 ns.

the microwave region and above can excite vibrationalenergy levels of molecules. Lower frequencies, including50/60 Hz EMFs, have vanishingly small photon energies.

The photon energy of 50/60 Hz electromagnetic waves is notrelevant, however, to interactions which are not "radiative"or in the "near field" of sources.

The characteristics of 60 Hz EMFs that are relevant toenergy interactions with biological systems are summarizedin Table VI. These include wavelength much larger thanbody size, and extremely low levels of energy deposition inthe body.

MECHANISM: FORCE EXERTED BY EMFs, COMPAREDTO BIOLOGICAL ORCES

The function of proteins depends on their three-dimen-sional configuration. If an electric field were to change theshape of a protein anchored in the cell membrane or sus-pended in the cytoplasm, the protein's ability to function asan enzyme, a receptor or an ionic gate could be altered.Large enough electric fields could cause changes in mem-brane channels, which control fluxes of small ions andmolecules across cell membranes; enzyme conformation,which is key to an enzyme's catalytic activity in chemicalreactions; receptor protein shape, which may alter ligandbinding to the receptor protein; membrane conformation,which may modify biochemical reactions at the surfaces ofcell membranes; cell shape, which could alter secretion,

motility, phagocytosis or excitability; and shape of thecounterion cloud surrounding individual cells, which mayalter the electric-charge milieu of macromolecules.4 Effectsat internal cell membranes (nucleus, mitochondria, etc.)are unlikely since the resistive outer cell membrane shieldsthese inner membranes. The magnitude of the electric-fieldforce is the critical factor in evaluating whether protein

4The counterion cloud (also called the Helmholtz-Stern layer) is alayer (-0.8 nm thick) of mobile positive ions that become attracted tothe anionic membrane glycolipids and glycoproteins of the membranesurface. Counterion polarization occurs above the membrane surface

and is distinct from the transmembrane potential.

configuration or cell structures can be altered. The force ona charged molecule exerted by EMFs is given by Eq. (1);only part of this force will act to distort (as opposed to

translate) the molecule. For comparison purposes, weassumed that the total force is of biological relevance, andwe calculated the forces exerted by our benchmark EMFs(1,000 V/m and 0.1 mT) on molecules with 10 charges(Ca2+ has only two charges, but proteins can carry a largernumber of unbalanced charges).

Because of much recent work using the "atomic forcemicroscope" and "optical tweezers," it is possible to com-pare the calculated electrical forces against the forces thatbiological molecules can generate and sense. These tinyforces (Table VII) are given in piconewtons (1 pN = 10-12

N); a milliliter of water weighs 1010pN, and a single, 20-pm-diameter cell

weighsabout 40

pN.sTable VII

comparesthe

largest forces that our benchmark EMFs can exert on acharged molecule with 10 unit charges against forces opera-tive in biological structures which are either force genera-tors or force transducers.

Table VII dramatically illustrates that EMF forces oneven tenfold-charged molecules are nearly 1 million-foldsmaller than typical biological forces. For example, 0.1 mTcan induce a maximum cell membrane field of about 14V/m, which results in a force of 2 x 10-5 pN. In compari-son, most mammalian cell membranes maintain a voltageof 50 mV across a distance of about 5 nm, giving an elec-tric field of 10 million V/m (50 x 10-3 V/5 X 10-9 m), whichyields a force of 16 pN. Hence proteins embedded in thecell membrane normally experience million-fold largerelectric forces than can be exerted on them by externalEMFs. Molecules sufficiently robust to withstand theendogenous forces in Table VII (-10 pN) would be

51t is important to distinguish between "weight," which is the forceexerted on something by gravity, and "mass," which is the quantity ofmatter. We are accustomed to express the weight of things in terms ofthe amount of mass they contain, but can do so only because, on the sur-face of the earth, there is a strict proportionality (F = mg) between thetwo. That is, a milliliter of water contains 1 g of mass, which is attracted

to the Earth by a force of about 0.01 N, which is its "weight."

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MECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

TABLE VICharacteristics of 60 Hz EMFs as They Relate to the Human Body

EMF parameters

Value Alternate units

Relevant biological parameters

Descriptor Value

Wavelength (in air)

60 Hz EMFsPhoton energy

5 million metersa

2.5 x 10-13 eV

Energy radiated by a 100-m section 10-5 W (24)of a 500-MW power line

Maximum heating rate at 0.1 mT; 5 x 10-8Wb1,000 V/m of human body

3,110 miles

2.43 X 108 J/mol

2 x 10-14of power transmittedalong the lineb

Temperature rise = 1.5 x 10-8?C/day

Body size0.5-m diameter

Molecular kinetic energy at37?C (3/2 kT)

Human basal metabolic rate

2-m length

0.04 eV

-100 W (basal)-800 W (exercising)

aWavelength in air. In tissue, the wavelength would be shorter because the speed of wave propagation is slower. Wavespeed in nonconductors isgiven by c = (Epi)-12; g is about the same in air and tissue, but since E, the dielectric constant, for muscle tissue is about 106 times that of air, the wave-length of 60 Hz waves in muscle tissue would be 50,000 m, still much greater than the dimensions of the body.

bGandhi and Chen (29) calculate currents induced be E and B fields, and maximum power can be calculated from Power = I2R. Temperature risecan be calculated from the fact that the heat capacity of 70-kg body is 3 x 105J/?C, and the heat input of 0.05 liW over 24 h is 4.3 X 103 J.

deformed by weak 50/60 Hz EMF forces (-10-5 pN) to anextremely small degree.

MECHANISM: MAGNETIC FIELDSAND MAGNETITE PARTICLES

Normal body tissues and proteins are not ferromagnetic;ferromagnetic crystals, however, have a permanent magne-tization, and magnetic fields can twist (torque) these parti-cles. Magnetic fields can also exert translational force onferromagnetic particles, but this would require magnetic-

field gradients far beyond what is available in environmen-tal fields. Just like the Earth's magnetic field can physicallyrotate the needle of a magnetic compass, this "magnetic-particle" mechanism postulates a direct interaction of mag-netic fields with microscopic magnets within the body(46-48). The magnitude of the twisting force depends onthe magnetic-field intensity, the particle magnetic momentand the angle between them. The torque, T, can beexpressed mathematically as:

T = m x B = mBsin0, (11)

TABLE VIIExternal 50/60 Hz EMF Forces Compared to Biological Forces

Force produced(pN = 10-12 N)

EMF forceElectric-field (1,000 V/m) force on a charged molecule(10+)60 Hz, 0.1-mT induced force on a molecule in the cell membraneForce on a moving molecule(10+), ue to magnetic field (0.1 mT)

Biological entityActivation of a single hair cell in the inner earSingle kinesin molecule acting against a microtubuleSingle muscle myosin molecule pulling on an actin filamentForce required to open a mechano-receptive, cell-membrane ion channelDNA transcription (RNA polymerase force)Charged molecule(10+), n cell membrane at resting potential (50 mV)Force required to stretch out a DNA moleculeProtein receptor to molecular ligand forces (molecular recognition)DNA strand-to-strand binding force, per each complementary base pairForce generated in flagellar motor (10-nm radius) of bacteria

6 x 10-11pN2 x 10-5 pN1 x 10-7pN

1 pN3 pN4pN

14 pN14 pN16 pN20 pN90 pN70 pN

100 pN

Reference

a

b

c

(5,34,35)(36-38)

(39)(40)(41)

d

(42)(33,43)

(44)(45)

aAn electric field of 1,000 V/m outside the body yields an internal E field of 4 x 10-5 V/m; if the tenfold-charged molecule is within a cell mem-brane, the force is 3,000 times larger, i.e. 1.8 x 10-7 pN.

bThe maximum electric field induced by a 0.1-mT magnetic field is 4.8 x 103 V/m (i.e. at the body periphery); the consequent E field produced inthe cell membrane is taken to be 0.0048 x 3,000 = 14.4 V/m.

CLorentz orce on tenfold-charged ion with thermal average velocity (37?C) of calcium ions (-450 m/s).d50 mV across a distance of about 5 nm is an electric field of 107V/m.

Descriptor

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VALBERG, KAVET AND RAFFERTY

where the cross product (x) between the vectors for mag-netic moment, m, and magnetic ield, B, indicates he twist-ing force is at a maximum when the two vectors are perpen-dicular o each other, and is zero when they are parallel.

Magnetic material is composed of "domains," each ofwhich defines a region wherein individual molecular mag-

nets point in the same direction. f there are more domainsoriented in one direction han in any other, the material ssaid to be magnetized. n "single-domain" articles, all themolecular moments are aligned, and the particle magneticmoment s the product of the particle volume and the mag-netization per unit volume. For magnetite Fe304), he satu-ration magnetization s 90 A-m2/kg or 4.8 x 105A-m2/m3(49). Hence a 0.2-im-diameter sphere would have a mag-netic moment of 2 x 10-15 A-m2 and would experience amaximum orque of 2 X 10-19N-m in a field of 0.1 mT. Thiscan be thought of as force of 2 pN acting on a lever arm of0.1 Mm.As can be seen from Table VII, the 2-pN twistingforce caused

bya 0.1-mT field on a 0.2-Am

phereof

mag-netic material s comparable o biological orces. The prod-uct mB also gives the energy of interaction, which in thiscase is -50 kT. Thus the motion of magnetic particles pro-duced by a 0.1-mT field could result in a detectable trans-ductive event, based on considerations f thermal noise andforce magnitude.

Kirschvink nd colleagues (46) reported he presence ofpure, microscopic magnetite crystals n the human brain.Because these "microscopic ar magnets" an interact withambient magnetic ields, they proposed that biogenic mag-netite may account or a variety of biological effects of low-frequency magnetic fields. However, a magnetite-contain-ing "sensor cell" is yet to be identified in mammalianspecies. In humans, he magnetite crystals were only about33 nm in diameter (46), and since the magnetic moment(and hence the magnetic orque) s proportional o particlevolume, 33-nm crystals would experience a 223-fold mallertorque (and energy of interaction) than that calculatedabove for a 200-nm phere. A large number of Kirschvink'ssingle-domain magnetic crystals need to act in concert forthe interaction energy with ambient magnetic fields toexceed the randomizing ffects of thermal agitations. Also,magnetite crystals would respond vigorously o changes nthe apparent direction of the Earth's magnetic field that

result from motion and rotation of our bodies during nor-mal activity, which would seem to swamp any effect causedby weak 50/60 Hz magnetic fields. However, Kirschvink(50) speculates hat some cellular processes may accommo-date to slow configurational hanges t > 0.1 s), yet respondto rapid 60 Hz) field excursions.

Adair (51) has calculated that, for a.c. fields less than 5pT, any a.c. field effect on magnetic particles willbe maskedby thermal noise, even given assumptions of anomalouslylarge magnetosome tructures nd anomalously mall cyto-plasmic viscosities.The high viscosity of the cytoplasm willdramatically educe the amount of response expected with

with the square of the a.c. field amplitude 54). For our 0.1-mT benchmark a.c. magnetic ield, viscosity7 times that ofwater and 0.2-gm magnetic crystals, Adair's calculationgives an energy transfer of -50 kT, but for a field of 10 pT,this would all below thermal noise (to 0.5kT). Or, f the vis-cosity of the intracellular matrix were 100 times larger, he

energy transfer would also be decreased o 0.5 kT, which sagain below the thermal noise limit, even for 0.1-mT 50/60Hz fields. In summary, benchmark a.c. magnetic fields incombination with biologically oupled magnetosomes f 0.5lim might give rise to a signal detectable by the cell; the

plausibility f this mechanism s undermined when biologi-cally reasonable alues for particle ize and cytoplasmic is-cosity are assumed. Cutting he field size 500-fold from 100iT to 0.2 ,iT) decreases the energy of interaction 250,000-fold, from 50 kT to 0.0002 kT; hat s, field evels reported nthe epidemiological tudies -0.2 jT) fall far below noise.

MECHANISM: MAGNETIC FIELDS ANDFREE RADICAL RECOMBINATION

McLauchlan 55), Scaiano et al. (56) and others haveproposed hat 50/60Hz magnetic ieldsmay extend the life-time of free radicals. Three characteristics of free radicalmolecules are relevant o this mechanism: 1) A free radical[e.g. hydroxyl radical (OH') or superoxide anion (0O-)] svery reactive chemically; ut, under certain conditions, wofree radicals can combine with each other such that theirchemical eactivity s canceled; 2) the reactivity s due to an"unpaired electron" [electrons can be thought of as tinyspinning ops, with an arrow pointing along the axis of spin;electrons n molecules usually come in pairs, one with spin"up" (t) and the other with spin "down" 1)]; and (3) theelectron spin has a magnetic moment, which can interactwith magnetic ields.

Free radicals are often formed in pairs either with theirspins parallel "triplet tate") or with their spins anti-paral-lel ("singlet tate"). Free radicals may recombine after for-mation. The quantum mechanics of the formation of achemical bond between two reacting radicals requires hatthey be in the singlet state (i.e. t J, with the two electronspins anti-parallel) ather han the triplet state (i.e. t t, withthe two spins parallel). Because the electrons have mag-netic moments, ocal magnetic fields from other electrons(in orbitals of the same or nearby atoms) or from atomicnuclei in the molecule may flip one of the electron spins sothat the two radicals change from singlet to triplet or viceversa; his changes the likelihood of recombination. Exter-nally applied magnetic fields tend to "hold" the electronmagnetic moments and to reduce the probability of a spinflip. For free radicals created in the triplet state (t 1), thisdecreases he probability f free radical recombination. Onthe other hand, this increases he probability f recombina-tion of radicals reated n the singlet state (t $).

In systems of organic radicals, riplet-singlet T-S) inter-

a.c. (60 Hz) (52, 53). Moreover, the energy transfer varies

12

change is seen to occur as a result of the radicals responding

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MECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

to different magnetic ields n their atomic environment. Anapplied external magnetic field can alter the rate of T-Stransitions 57-59). The effect does not depend on the spe-cificchemical dentity of the radicals, ut does require ieldsof the order of hundreds f gauss (tens of mT).

If the lifetime of free radicals were increased, he propor-

tion reacting chemically with cell macromolecules wouldincrease, and potentially, adverse effects on cell functionwould ensue. Free radical nteractions ccur over time scalesthat are extremely hort, e.g. nanoseconds o microseconds(56, 60), and any free radical ffects would not differentiatebetween 50/60 Hz magnetic ields and the Earth's magneticfield. That is, a mechanism based on changing ree radicallifetimes would not predict that power-line magnetic ieldsare somehow more deleterious than the Earth's naturalmagnetic ield (or other static magnetic ields).

The short time scales of free radical effects are due tothe rapid rate of collisions among molecules in aqueoussolutions

_1012per

second);after about

10,000or so colli-

sions, the initially adjacent radical pair have diffused apartand will no longer have the opportunity o recombine, andmagnetic fields can no longer have an effect on the likeli-hood of recombination. Thus escape by diffusion occurs nless than 0.1 ps,whereas one cycleof 60 Hz is 17 ms in dura-tion, more than 100,000 imes slower. That is, for free radi-cal recombination ffects, all magnetic ieldsup to about 105Hz "look" ike d.c., and this mechanism s not in any wayspecific o power-line magnetic ields.

In summary, free radical effects are not selective for50/60 Hz power-line fields, and become effective at fieldstrengths ar in excess of what is available n the environ-ment. Furthermore, he bioeffects of EMFs reported n theliterature are not obvious candidates for the free radicalmechanism. Although free radicals appear o play a role incausing genetic damage (61), the evidence for genetic dam-age induced by EMFs s generally negative 62,63).

MECHANISM: FREQUENCY-SELECTIVE, "RESONANCE"RESPONSES REDUCE THE EFFECT OF NOISE

Some mechanisms re selective for the "information" nEMFs. Such information s often envisaged as altering hetransition ates between quantum mechanical tates of thesystem. These transitions xhibit "resonance" n the sensethat the frequency band is narrow, and the noise level thatneeds to be exceeded s reduced. However, he noise reduc-tion comes at the price of additional requirements. Onerequirement or this mechanism o operate s that the sensi-tivity of the biological system spans only a narrow fre-quency range. If, for example, he interaction mechanism sfinely tuned to exactly the 60 Hz (or 50 Hz) frequency i.e."resonant"), hen the electric fields nduced n the biologi-cal system within a sufficiently narrow band of frequency(e.g. 59.5 to 60.5 Hz) may be greater han thermal noise inthis same frequency band. Another necessary ondition or

resonance-narrowing s that the resonant system be undis-

turbed for the required sample time. For example, toachieve a 1 Hz bandwidth n a 60 Hz resonant mechanismwould require at least 60 undisturbed ycles, or 1 s of per-turbation-free ntegration ime, which s difficult o achievein a fluid environment where 1012molecular collisions areoccurring very second.

Ion Cyclotron Resonance (ICR)Most mechanisms nvolving"resonance" redict hat only

specific combinations of d.c. magnetic-field trength (thesource of which s the Earth's ield) and a.c. magnetic-fieldfrequencies are biologically effective. Because magneticfieldsexert force on moving charged particles t right anglesto their direction f motion, a static magnetic ield willcausea charged particle (e.g. a Ca2+ on) to move in a circle at arate that s called he "cyclotron requency." iboffproposedthat a resonant esponse an be elicited by combining staticmagnetic ield with a parallel, ime-varying magnetic ieldwhose

frequencys tuned to the

cyclotron requency of anion (64-67). Liboff applied the equations describing oncyclotron motions in a vacuum o biology. However, sincereal cyclotron motion cannot take place in liquids, themotion was postulated o take place in transmembrane onchannels or on membrane surfaces where the ion wasassumed o be isolated from other molecular nteractions.The 50/60 Hz field s postulated o alter he movement of cal-cium ions through channels n the cell membrane; hus thecyclotron esonance hypothesis an be applied o bioeffectsthat show a strong dependence on frequency. According oICR theory, the frequency, vc,of the a.c. magnetic ield isrelated o the strength f the d.c.magnetic ield,B0,by:

qBovc = n rm,

2 am(12)

where n is an integer, and where the ion has mass m andcharge q. For example, he 60 Hz resonance n = 1) for Ca2+ions (qlm 5 x 106C/kg) occurs at a static ield of 78.4 J,T,and the similar esonance n = 1) for Mg2+ons (qlm - 8 x106C/kg) occurs at 47.5 pT. For these same ions and staticfields, resonance would also occur at 120 Hz, 180 Hz, ... (n= 2, 3, ...). Many criticisms have been made of the ICRhypothesis (8, 32, 68, 69) because:

1. The requirement hat ions in a cell or membrane chan-nel behave in a way comparable o ions in a vacuum sunrealistic.

2. In the Earth's geomagnetic ield (50 ,uT), he cyclotronorbital adius for Ca2+) s over 1 m, and thus s far largerthan he dimensions f a cell or even the organism.

3. Molecular ollisions damping) ccur at a rate of 1012 ersecond, preventing "orbital" motion.

4. The electromotive orce provided by the oscillatingmag-netic field reverses direction ach half cycle,averaging ozero. But even if rectified, he possible energy ransfer s

minute [e.g., for an ion constrained o move in an orbit

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VALBERG, KAVET AND RAFFERTY

having the diameter of an ion channel (-10 nm), thetime required to exchange kT of energy with the ionusing a 0.1-mT 60 Hz field s 44,000years].

5. Since the time that an ion spends in a transmembranechannel s less than 1 ps, it would seem impossible or theion to "resonate" o 60 Hz fields. The very term "reso-

nance" requires that the ion and field interact undis-turbed or at least a few cycles (-100,000 ps).

In addition o these flaws,a theoretical analysis of an ionconfined to a potential well and exposed to a combinationof parallel a.c. and d.c. magnetic fields failed to find reso-nant behavior at realistic values of model parameters 70).Recent experiments have failed to find resonant responses(71-78), and the ICR model lacks validity from both theexperimental nd the theoretical tandpoints.

Ion Parametric Resonance (IPR)Another resonance mechanism was

proposed byLednev

(79-81), who predicted nhanced bioeffects or certain com-binations of parallel d.c. and a.c. magnetic ield amplitudesand frequencies. He postulated a "3-D harmonic scillator"interaction f ions of mass m and charge q attached by elec-trostatic orces to a binding protein (e.g. Ca2+ ons attachedto Ca2+-binding roteins like calmodulin). The d.c. field isenvisioned to split the vibrational evels into adjacent Zee-man sublevels,and a shift n the probability f ion transitionbetween different vibrational nergy evels is postulated ooccur when an a.c. magnetic ield is applied n combinationwith a d.c. field. This, in turn, s hypothesized o affect theinteraction f the ion with the surrounding igands and, pre-sumably, he enzymatic activity of the calcium-binding ro-tein. The (unspecified) biological effect is postulated toreach a maximum (a resonant response) when the ioncyclotron resonance requency s an integer multiple of thea.c. field frequency i.e. when the applied a.c. frequency s asubharmonic (i = 1, 2, 3, ...) of the cyclotron frequency]. Thefrequency, vp, or the a.c. magnetic field, B1 (peak value),relates to the strength of the static magnetic ield, Bo,by thesame cyclotron resonance relationship noted earlier, whichwas derived or ion of mass m and charge q moving n a vac-uum, except that now appears n the denominator o desig-nate different ubharmonics:

vc 1 qBoVp . . .... (13)i i 27rm

In this case, resonance requency s interpreted s due tothe energy difference between adjacent vibrational nergylevels that characterize he binding of the ion (e.g. Ca2+) onearby ligands. Lednev's theory predicts that at fixed Bo,and at resonant conditions, he magnitude of the biologicalreaction depends on the peak amplitude of the alternatingfield, B1. That is, the optimum for transitions depends notonly on the frequency of B1 but also on its magnitude rela-

tive to Bo.The probability f transitions ccurring between

adjacent energy levels is proportional o Ji(x), where Ji isthe ith-order Bessel function and where x = iB1/Bo a recentreanalysis of Lednev's IPR theory gives this as x = 2iB1/Bo(82), although Lednev does not agree (83)].

Lednev acknowledges hat the interaction of weak mag-netic fields with biological systems s "anomalous" ecause

of the low energy content of the interacting magnetic ieldswhen compared o ion thermal nergies. However, he claimsthat his theory howschanges n the probability f transitionsbetween vibrational nergy evels without ny energy pump-ing into the system. He calls t analogous o "parametric es-onance" or the "quantum-beats ffect." Lednev (81) identi-fied the following eatures of his IPR theory:

1. Differential ransition probabilities hange sign for evenversus odd subharmonics f Vp, uggesting opposite bio-logicaleffects; e.g., cell proliferation may be increased byone and inhibited by the other.

2. Monovalent ions such asH+, Li+,

K+ and Na+ are notexpected to show any resonance effects because of theirshort duration f binding o protein igands.

3. The width of the frequency response can be expected tobe between one and several hertz of the central fre-quency, and is related to 7, the lifetime of an ion in thebinding ite.

4. Failure to find IPR indicates that the system is in thewrong "physiological tate," meaning hat the concentra-tions of Ca2+, almodulin, cofactors and activators maynot be in the correct range.

A major difficultywith the IPR mechanism derives romthe fact that the vibrational nergy evels for ion binding othe protein ligand are likely in the infrared range of thespectrum. The central requency of infrared pectral ines is-1013 Hz, and f Zeeman splitting f these lines by 10 to 100Hz is to be relevant, hen the infrared pectral ines must beextraordinarily narrow (Q = flAf > 1011).Lednev's IPRmechanism has been criticized (84), and the same com-ments, listed below, apply to the Blanchard and Blackman(82) version of the IPR mechanism. Major riticisms nclude:

1. IPR can be relevant only to electromagnetic ransitions.The rate of energy radiation from a charged object isproportional o the square of its acceleration 85). For acharged particle of a given energy moving n a potentialwell, the acceleration will be inversely proportional othe mass; e.g., an electron will radiate nfrared photonsat a rate 109 times faster than a calcium ion. The timerequired or electric-dipole radiation rom an object asheavy as an ion (e.g. 40Ca2+)s of the order of 8 s, but theradiative process will be interrupted y collisions n 10-12s; that is, the resonant ystem willnot be left undisturbedfor the time necessary o exhibit resonance narrowing.

2. The IPR effect relies on the phase relationship betweenthe excited states and the applied oscillating field (B1)

being fixed. However, if Bo and B1 are not turned on

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MECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

synchronously elative to each excited state, the appli-cation of B1 at random times to a pre-existing excited-state phase must both increase and decrease the decayprobability for equivalent numbers of ions, and therewould be no net effect.

3. IPR requires igorous patial ymmetry n the binding of

the ion in its orbit for the energies of the two overlap-ping (degenerate) states to be split only by the appliedmagnetic ield.Due to the characteristically omplex andasymmetrical nvironment of ions in biological systems,the perfect spherical symmetry of the binding energiesrequired by Lednev's mechanism s not possible.

Numerous experiments have failed to find resonantresponses (71-78, 86). Observation of Lednev-like reso-nance behavior n response to applied magnetic fields hasbeen reported n mitogen-activated ymphocytes 87). Neu-rite outgrowth experiments (88) have shown agreement

with Blanchard and Blackman's adaptation of Lednev'smodel, but given the limitations cited above, the actualbasis of this agreement s unclear.

Larmor PrecessionA Larmor precession mechanism has been described by

Edmonds 89) and has also been proposed by Male (90). Inthis mechanism, an ion is envisioned to be vibrating n ashielded cavity under he influence of a strong central orce.Larmor's heorem predicts hat applying a magnetic ield tothis ion imposes axial symmetry n the original motion andleads to precession f the ion's orbital motion at a frequencywhich s one-half of the

cyclotron requency,vc.If Larmor

precession n the Earth's tatic ield is combined with appli-cation of an alternating magnetic lux n parallel o the staticfield, the energies of interaction with the ion-protein bondsthat constrain he ion could conceivably be altered. How-ever, in a general discussion f resonance phenomena, Polk(91) has shown that, for an applied a.c. field of 0.1 mT, thetime required o accumulate even one-tenth of the energyassociatedwith a weak onicbond (0.1 eV) would be 7 years.

SummaryThe utilityof the "resonant" MF mechanisms s compro-

mised because of serious physics problems and because aspecific ink has not been established o the biology of thecell. The distribution f ions among hermal ibration evels,the orientation of the ion orbital angular momenta and theorientation of nuclear magnetic moments are not known toinfluence rotein hemistry n the body.

MECHANISM: SPATIAL AND/OR TEMPORALAVERAGING REDUCE THE EFFECT OF NOISE

Biological responses can result from the integration ofmultiple single-cell effects. In higher-level organisms, manyneural pathways converge onto neurons where presynaptic

activity in any one of the incoming neurons is not sufficient

to alter activity n the postsynaptic neuron, but simultane-ous activity in a large number of incoming neurons canmarkedly ncrease the firing rate of the postsynaptic neu-ron. For example, f the presynaptic neurons are firing n arandom ashion stochastic noise in individual eurons), heinput s random over time and there s little net effect in the

output neuron. However, coherent effects (e.g. of externalEMFs) may simultaneously push a substantial number ofthe presynaptic neurons into firing coherently and hencegive rise to an "EMF signal" n the postsynaptic neuron.Thus the single-cell analysis,which would seem to disallowdetection of low-level EMFs, may not preclude detection ofweak fields by multicellular ggregates.

Neural ntegration has been postulated o be responsiblefor the acute electrosensitivity f certain cartilaginous ishes(25-27, 92,93). In elasmobranch lectroreceptors, smany asfive integrating, ignal-enhancing echanismsmay operate:(1) The canals of the ampullae of Lorenzini have walls that

are poorly conducting, and thus allow the weak seawaterfieldoccurring cross everal centimeters o be concentratedover a single ayer of sensory cells. (2) Tight unctions at theapical face of each receptor cell concentrate he resultingelectrical urrent ver a small portion of the cell membrane.(3) As many as 10,000 sensory cells per canal provide thebasis or spatial averaging,with a possible 100-fold nhance-ment of the signal-to-noise atio. (4) The six afferent nervesper ampulla ire periodically n a pacemaker ashion, o that"phase-locking" o this signal may increase sensitivity. 5)Ampulla pairs may function as differential amplifiers oreject electrical oiseendogenous o the fish tself.

Insummary,

wotypes

of strategies may enhance he sig-nal-to-noise atio. In the first, electrically onnected cells orlong processes uch as those seen in shark ampullae oncen-trate the effect of the applied electric fields across arestricted portion of the cell membrane, ather han incre-mentally across many cell membranes; Weaver and Astu-mian (16) have shown that signal-to-noise ratios can beexpected to go up as the 5/6power of the number of electri-cally connected cells. In the second strategy, he signal tselfis integrated, rectified or phase-locked o that the cumula-tive effects of the signal can be distinguished rom randomnoise (94). In such a process, the nervous system may beused to extract signal from noise by recognizing spatialcoincidence r temporal oherence6 94-96).

Neural systems that are postulated to sum theirresponses over space and time take advantage of the factthat, in contrast to electrical noise, external EMFs are instep (spatially coherent) over a large number of cells andare steady in time (temporally oherent) (97). In this case,for N neurons, incoherent noise increases by a factor of

6F. S. Barnes, Possible mechanism by which biological systems can

separate coherent signals from noise. Presented at the First WorldCongress for Electricity and Magnetism in Biology and Medicine, June

15

1992,Orlando, FL.

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VALBERG, KAVET AND RAFFERTY

(N)12 n the average across the population, while the com-mon stimulus s additively nhanced by the factor N.

Extrapolation of neural integration to 50/60 Hz EMFdetection schemes, however, s based on theoretical modelsand numerical imulations, nd have yet to be found n realorganisms. There is presently no evidence in mammals or

the existence of groups of cells that exhibit he correct mor-phology (e.g. electrically connected loops of cells) or sen-sory modality (e.g. narrow requency response or rectifica-tion) for detecting ow-level50/60Hz EMFs.

PLAUSIBILITY MUST BE TESTED REGARDING BOTHPHYSICS AND BIOLOGY

What are the steps by which we can judge the plausibilityof a mechanism? A plausible candidate must link EMFexposure by a biophysical mechanism o the beginning of acellular ignaling hain (Fig. 1). That is, the plausibility f a

mechanisman be

judgedn two

steps:Step 1, Physics: Does the underlying physics makesense? Do the assumptions bout the physicsof the biologi-cal system make sense? And how robust s the link betweenthe EMF metric and the physical phenomenon t producesin the cell?

Step 2, Biology:How likely s it that, n the cell, the physi-cal phenomenon produced by EMFs can result n a biologi-callysignificant hange? Does the biological nd point makesense? And how likely s it that the physicalphenomenon slinked o a cell signaling amplification) ystem?

For example, body fluids are electrically onducting, ndFaraday's law predicts that a 0.1-mT 50/60 Hz field candrive a flow of ions. Thus, for Step 1, there is a physicallylogical link between the applied EMFs and ion flow, but,for Step 2, the link between this weak ion current and possi-ble changes in cell function is highly uncertain. Likewise,magnetic resonance imaging (MRI) is a procedure thatrotates magnetic nuclei of some molecules n biological is-sue, so Step 1 of the transduction rocess s known o occur.However, nuclear spins have extremely weak links to cellchemistry, nd thus the nuclear resonance has no significanteffect on cell function or homeostasis, and a Step 2 effectthat causes disease via the nuclear pins s implausible.

Conversely, f we propose that an EMF opens or closes atransmembrane, oltage-sensitive on channel, hen Step 2,the biological link to a cell signaling system, is unambigu-ous. However, Step 1 is implausible; n the absence of a spa-tial or temporal averaging mechanism, our benchmarkEMFs produce physical forces on cell membrane proteinsthat are many orders of magnitude weaker than the elec-tric-field forces needed to modify channel proteins. Like-wise, if we could propose a mechanism wherein EMFscould damage DNA, Step 2, the biological link betweenDNA damage and alterations in cell progeny, would beclear, but Step 1, the physical delivery of the amount ofenergy that is required o disrupt DNA, is not possible with

0.1-mT or 1,000-V/m xternal EMFs.

Physical ConsiderationsTables I and II summarize he fields, orces, currents nd

energy transfer hat would be generated within he body byeither 1,000-V/m electric fields or 0.1-mT magnetic fields.Electric fields induced in the body are calculated, and thestrength of the physical ide of the mechanism Step 1) can

be assessed by comparing hese values to general noise lev-els for each parameter under consideration. Can molecules,membranes, tructures, tc. distinguish hese induced elec-trical effects from endogenous, random, stochastic varia-tions? As discussed earlier, or many of the possible physi-cal interactions, he electrical ffects appear o be buried nthe noise. For example, the fields induced in tissue by the1,000-V/m external electric field (4 x 10-5V/m) and thelargest possible electric field induced by the 0.1-mT 50/60Hz magnetic field (4.8 x 10-3 V/m) are small compared othermal electric fields across the whole cell (0.02 V/m).Using microprobe echnology n living rats, Miller and col-

leagues (98)have

measured ndogenouselectric-field oise

in the 60 Hz frequency range to be 0.006 to 4.5 V/m peak-to-peak, and 0.0002 o 0.04V/m rms.

Biological ConsiderationsThe biological aspect of mechanisms (Step 2) can be

evaluated by considering whether he changes n the targetsystem are known to have functional consequences. Livingsystems are self-regulating (homeostasis), and smallchanges n function are not likely to have a big effect. Someions (Na+, CI-, K+,HCO3, etc.) and some proteins (actin,myosin, albumin, etc.) are so ubiquitous that changes inindividual molecules are not likely to control rate-limitingprocesses, and thus small changes will not be amplified. Onthe other hand, enzymes, receptor proteins, hormonemolecules, second-messenger molecules (e.g. Ca2+ ons),nucleic acids (DNA and RNA), membrane channels andmembrane potential all represent "control points" wheresmall changes n function may lead to larger consequences.Here again, living organisms exhibit reserve capacity andfeedback control, which act to restore normal physiologicalfunction after perturbation. Thus transient hanges or low-level changes may not lead to long-term effects. Moreover,there is a normal variability n the concentration f biologi-cal molecules over which physiological function does notchange. If baseline calcium currents hrough a cell mem-brane are increased by a few percent, or if secretion of agiven hormone s decreased by a few percent, neither short-term nor long-term malfunctions re likely.

In Table VIII, a summary f this two-step analysis s pre-sented for mechanisms discussed earlier in this review.Some qualitative assessments are also made regarding howthe benchmark evels of a.c. fields may relate to biologicalconsequences. Some of the field magnitudes hat might beexpected to be effective lie at or below our benchmarkmagnetic field (0.1 mT). Yet Table VIII also shows thateach of the mechanisms has limitations as an explanation

for the reported bioeffects of EMFs. The most solidly sup-

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17ECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

TABLE VIIIComparison of Several EMF Mechanisms

(Considering 50/60 Hz Fields of Magnitude either 1,000 V/m Electric or 0.1 mT Magnetic)

Mechanism

Energy input: radiation,photons, induced I, ionredistribution

Force on ions and oncharged: cell proteins,cell organelles, cellmembranes, cellglycocalyx

Ferromagnetic rystals(magnetic-field orce)

Modulation of free radicallifetimes (magnetic-fieldspin flip)

ICR, ion cyclotronresonance

IPR, ion parametricresonance

Noise reduction(frequency selectivity,multicell ntegration,time averaging)

Step 1, physical nput

Radiative flux, photonenergy, I2R heating,iontophoresis, electro-osmosis are all extremelysmall; magnitude of inducedchemical potentials is verysmall

Force due to E fields and B-induced E fields on fixed andmoving charges readilycalculated; high dielectricconstant of biological tissueyields greater electricpolarization han for H20

Magnetic fields can twistferromagnetic particles; wistmotion is resisted by cellviscosity; small particlesexperience random thermal,kinetic rotations, a "noisy"competing motion

Large magnetic fields canmodify free radicalrecombination and hencelifetime; effects not specific to50/60 Hz frequencies; imeconstants of free radicalrecombination are extremelyshort

Very serious inconsistencieswith basic physics areapparent or this mechanismat a fundamental evel

Effect on transition ratesbetween ion-ligandvibrational evels as aconsequence of applied60 Hz magnetic fields isimplausible because ofcollision damping, and lackof coherence of thequantum states

Detection of signals belowbroadbrand noise levelsclearly possible if signals havespatial, temporal orfrequency features thatdistinguish hem from noise;the noise-reduction systemmust have an adequate timespan to perform the averaging

Step 2, biological output

The energy perturbations areundetectable; nduced ioncurrents are belowendogenous currents and arenot likely to depolarize cells

No established electric-forceeffect on messenger proteins,gene transcription proteins,receptor proteins, membranepores, voltage-sensitivechannels

Behavioral evidence in somespecies suggests magnetite-based sensory systemsadapted to detect theEarth's field

Chemical reactions with freeradical can damagemolecules important o cellfunction; ncreased freeradical damage has not beena reported EMF bioeffect

Perturbation of receptor-ligand binding or of ion-channel flux not established;biological function not yetshown to respond topredicted resonanceparametersNo demonstratedphysiological relevance ofionic thermal vibrationallevels for cation binding tochannels or to receptorproteins

Neural networks have thecapability o achieve long-term averages of weaksignals; ensory ampullae ofLorenzini n the shark maybe an example; for mammals,neither EMF detection norplausible link to diseases isknown

Typical "effective"field magnitudes

60 Hz thermal heatingvirtually nil at any practicallevel; magnetophosphenes at30 mT may be due to ionfluxes, which are known totrigger neuron firing at -100mT but are below noise at-0.1 mT

Benchmark EMFs produce-14 V/m cell membrane field;natural membrane E field is107V/m; so benchmark Eforce is very weak

>10 pT Bac equired npresence of expected 50 uTBdc o be above noise, evenwith large particles andlow cytoplasmic viscosity

-10 pT or greater (notexpected to be specific to50/60 Hz fields)

Experiments (reporting bothpositive and null results)usually have BC,, Bd,50 uT; most experimentsnegative, positive reportshave not been reproducible

Experimental results overallequivocal; maximal effectsexpected at Bac -

Bdc, andexperiments have used -10-100 uT; as Ba, becomes muchlarger than Bdc, heory predictsdiminishing effects

Averaging plausibly enhancesS/N ratio in the range of 100to 1,000-fold; ampullae ofLorenzini n the shark maybe sensitive to seawaterelectric fields -105 V/m;neural processing may bringsignal out of the noise

Summary critique

Neurons, sensory cells andelectrically active cells are themost sensitive, but EMFs atbenchmark evels do nottrigger action potentials;currents n shark electro-receptor cells may be anexception

Biologically generated forcesbetween cell proteins andstructures appear to be fargreater than any forcegenerated by EMFs

Plausible mechanism, but notspecific for 50/60 Hz EMFs,viscous damping of particlemotions at 50/60 Hz a seriousproblem inside cell or onthe cell membrane

Any effect at benchmark50/60 Hz levels would also beexpected from the Earth'smagnetic field

Overwhelming scientificimplausibility of ions inbiological solutions movingin cyclotron orbits effectivelyrules out the physicalbasis of this mechanism

The problems with collisiondamping, quantumcoherence time and lowenergy input point to null orminimal perturbation ofchemical bonds; ink tobiological function isimplausible

Stability requirements oncells for detection oftemporal or spatial coherencevery stringent; requencyselectivity of cells for exactly50 or 60 Hz (or harmonics)unexpected and withoutbiological basis

ported experimental example of a weak bioeffect of EMFs For some mechanisms, consideration of higher fieldis electroreception in fishes. Even so, many details of this levels does not resolve the problems identified, in whichprocess remain unknown (25-27, 92, 93). case the mechanism cannot be endorsed as having useful

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VALBERG, KAVET AND RAFFERTY

explanatory or predictive value. Other mechanisms can-not be ruled out on the basis of magnitude alone because,in some occupational settings, environmental fields canrange up to >0.5 mT and can have complex temporalcharacteristics hat encompass a frequency range from 0to 100,000Hz (99).

If we consider the magnetic-field values that have beeninvestigated n the epidemiological iterature below 1 uT,albeit by surrogate measures), the problem of selecting aplausible mechanism becomes even more difficult. All ofthe mechanisms roposed o date fall short of being able toexplain 50/60 Hz-specific magnetic-field effects at typicalenvironmental ields.

How might biological systems cope with the problemof detecting 50/60 Hz fields? Perhaps living systems candesign a biological polymer of substantial ength and highconductivity 100), which might function as a loop of wirethat could detect induced EMF signals. Electrical noise is

proportionalto the

squareroot of the

resistivityof the

medium, and the resistivity of tissue (2 Qf-m) s 100 mil-lion times greater than the resistivity of copper (1.7 x10-8 -m). The thermal noise in a biological polymer withthe conductivity of copper would be reduced by 10,000times. Similarly, he performance of magnetic particles as50/60 Hz magnetic-field sensors is limited if they areembedded in viscous media, such as the cytoplasm of aliving cell. A 50/60 Hz magnetic-field sensor using ferro-magnetic particles would operate more efficiently ifenclosed in a low-viscosity fluid or in air, with the parti-cles attached to a vibration-sensitive ciliary bundle, likethat of a hair cell in the fluid-filled cavities of the innerear. A sensor could consist of hair cells loaded with ferro-magnetic particles and affixed to a tectorial membranetuned to give maximal amplitude response in the 50/60Hz range. Thus the question of finding an EMF transduc-tion mechanism is a challenge for both the theoreticalphysicist and the experimental biologist.

CONCLUSIONS

Several epidemiological tudies have posed the challengeof understanding f and how weak 50/60 Hz EMFs cancause biological effects in humans. Interpretation of the

results requires hat we integrate epidemiological and bio-logical observations with the fundamental hysicsof EMFs.Some weak-field biological effects (at frequencies ess than50/60 Hz) are reproducible, namely electro-sensitivity nsharks and rays (25-27, 92, 93) and magnetic-field ensitiv-ity in honeybees (101-103). These behavioral esponses areattributed to specialized neuroreceptor cells and neuralprocessing, but many biophysical and physiological aspectsof these systems remain o be elucidated.

We identified and analyzed everal classes of interactionmechanisms with respect to their ability o explain biologi-cal effects at benchmark 0/60 Hz field levels of 0.1 mT and

1. Relative to the kinetic energies of molecular thermalmotions, direct EMF energy effects are very small. TheEMFs present in normal environments are not capableof energetically altering biological structures, whichremain robust in the face of buffeting by far strongerthermal mpacts.

2. Electric-field orces on charged molecules and cell struc-tures are much smaller han forces typically xperiencedby biological tructures.

3. Direct force on magnetic particles can be comparable otypical biological forces, but microscopic erromagneticparticles would have to be attached o low-viscosity ens-ing structures. Magnetite has been isolated from the tis-sues of animals and humans, but associated sensorystructures ave not been found.

4. Magnetic-field interaction with free radical magneticmoments can alter radical ifetimes and therefore modifytheir availability or chemical reaction. So far, modifica-tion of free radicals

byEMFs has not been observed n

biological ystems or shown to operate at environmentalfield evels.

5. Resonant mechanisms, although widely analyzed andinvestigated xperimentally, ave not been shown eitherto be theoretically valid or to be supported by experi-mental indings hat are reproducible cross aboratories.

6. Spatial and temporal averaging processes provide ameans to increase the sensitivity of biological detectionby the above mechanisms. Averaging processes are, infact, used by electronic nstruments hat measure 50/60Hz EMFs; no biological structures n humans hat havesimilar capabilities for measuring 50/60 Hz EMFs areknown o exist. Extraordinary lectrosensitivity n sharkslikely occurs due to specialized sensing systems, whichuse integrating nd averaging rocesses hat are, to date,only partially described.

The hypothesis that the epidemiological associationsobserved between 50/60 Hz EMFs and disease reflect acausal relationship is not supported by what is knownabout mechanisms. In addition to the mechanisms wehave discussed, a number of other theories of EMF inter-actions have been proposed. Most of the available theo-ries do not predict a priori, specific biological effects as a

function of a well-defined EMF exposure metric, nor dothey identify specific experimental results that would ruleout that mechanism. A good theory is amenable to directexperimental testing; i.e., it clearly provides the proce-dures for its own disproof. Also, a good theory differenti-ates between the influence of power-line EMF exposureand the influence of EMFs normally present in biologicalsystems. More rigorous approaches are needed to developthe theoretical basis by which "EMF mechanisms" mightprovide plausible explanations for possible biologicaleffects of low-level EMFs.

1 kV/m (and below):

18

Received: August 27, 1996; accepted: March 24, 1997

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MECHANISMS OF EMF: INTERACTIONS WITH BIOLOGICAL SYSTEM

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