Fifty years down the line Tobacco industry strives for a cigarette which doesn’t cause cancer and when we have epidemiology, experiment and testable models for genetic interaction does this or should this inform our attitude to ELF EMFS? By Dr Chris Barnes, Bangor Scientific and Educational Consultants, LL57

Dr Barnes' Homepage Link http://drchrisbarnes.co.uk

E-mail doctor.barnes@yahoo.co.uk

Abstract

For fifty years Tobacco industries denied the risk of their products and then finally capitulated. Today electricity generators and suppliers have an inclination there could be issues with ELF EMR but are in a similar state of denial. Common reasons given for such denial are (1) ELF field quantum is non-ionising (2) ELF SAR is approximately 10^-12 W/m^2 which is less than KT i.e. energy would be thermalized in an equilibrium situation and (3) At ELF frequencies cells sample the external field over their dimensions and apply the resulting potential to the membranes with cut-off frequencies extending up to the RF range. Tissue water appears to be identical in its dielectric properties with normal water, except for a small fraction of protein bound water. The author goes on to explain the flaws in this reasoning and further to show using existing epidemiology, experiment and testable models for genetic interaction that this should inform and modify our attitude to ELF EMFS. ELF can be either geno-toxic, a co-initiator, a promoter or a co-promoter of Cancer. Our present views of ELF safety with regard to electricity distribution and electrical/electronic appliances is insufficient and ought to be revised Once properly understood ELF has the potential to be used as a powerful biomedical tool, tremendous future opportunities for UK exploitation exist .

Introduction

Public domain documents suggest that the Tobacco industry knew the dangers of its products for some fifty years yet persistently chose to deny them, see for example Bates and Rowell (1). Tobacco products, especially cigarettes were proved to be dangerous and carcinogenic by epidemiological studies and animal models. Eventually the biochemical pathways for DNA damage were also discovered and accepted.

By epidemiological relative risk context alone Tobacco is perhaps some five to ten times more dangerous than the worst estimates for ELF (Extremely Low Frequency Electromagnetic Radiation ) which come from occupational exposure studies. This is not, however, to imply there is no absolutely no risk from domestic exposure. Of some additional concern is the explosion of use of laptops and mobile phones. Laptops produce ELF as mainly as a result of electrical current flows to the Hard Drive and from frequencies in their power supplies. These magnetic fields can induce considerable currents in their users at close quarters, see Bellieni et al 2012 (2). Although concerns surrounding these devices are more usually associated with UHF/Microwave RF but it must be borne in mind that each are substantial close emitters of ELF. Laptops and their drives emit ELF of several tens of milli-gauss and similarly transmitting mobile phones due to the pulsing of the battery current in sympathy with the outgoing pulse modulated RF emission, see Sage et al 2007 (3). People may be exposed to these fields for up to several hours a day. In other words a greater and greater proportion of the population are now being exposed to ELF at levels which would have previously been described as 'occupational'.

Despite the growing body of evidence suggesting an epidemiological connection of ELF with mainly but not exclusively blood and lymphatic cancers, see Knave 1994 (4), visits to the public information websites of most energy suppliers and distributors suggest that there is absolutely no danger from emissions from their infrastructure or from, for example, house wiring. They may, however, acknowledge that contact with certain appliances such as electric blankets, hair-driers and vacuum cleaners will exposed one to larger magnetic fields which is also corroborated by Delpizzo 2005 (5). It is uncertain as to which, if any, scientific advisers these organisations use but they are certainly propagating bad science for at the very least misunderstood reasons.

Reasons why some don’t accept ELF bio- interaction, see for example Hafemeister 1996 (6)

1. ELF field quantum is non-ionising

2. *ELF SAR is approximately 10^-12 W/m^2 which is less than KT i.e. energy would be thermalised in an equilibrium situation

3. At ELF frequencies cells sample the external field over their dimensions and apply the resulting potential to the membranes with cut-off frequencies extending up to the RF range. Tissue water appears to be identical in its dielectric properties with normal water, except for a small fraction of protein bound water. Field effects on large biopolymers are indicated only at field values above 10 kV/cm, but field induced dipole effects on large cells are possible at considerably lower fields

Reasons why 1 and 2 above are invalid and reasons to expect ELF bio-interaction, see for instance Mae Wan Ho (2011) (7) and Goldsworthy (2012) (8) and Barnes (9)

1. ELF electric and magnetic fields can be regarded as acting separately. Heisenberg principles only relevant at much higher frequencyae

2. Biological systems operate outside of thermal equilibrium and create negative entropy

3. Biological systems operate in both space and time and often create quantum coherence

4. Biological systems create and utilise ELF fields of similar frequency and magnitude to (2*) above.

5. Biological systems are at least 70% water which has its own magnetic and physical-chemical magnetic memory storage capacity

6. Biological systems have developed since primordial times in the presence of weak static and time varying fields viz. a viz. Earth’s Geomagnetic Field and Schumann resonances

7. Brain rhythms are at or close to Schumann resonance bands.

8. DNA in humans replicates at the rate of about 50 base pairs per second (50 Hz)

9. Electric fields underneath high voltage lines could cause a second and compounding effect due to concentrate of radioactivity and air pollution

10. Water ions and electrolytic chemistry generate magnetic fields under some conditions and respond to magnetic fields under others

11. Biological systems contain natural magnetite in the form of magnetosomes.

12. DNA may imprint itself into water at about 7Hz (frequency equivalent to 1^stSchumann resonance) (see ….)

13. Magnetic effects in electrochemistry are now commonly understood, see Fahidy (2001-2008), especially for example (2002) (10) so why not in Bio-chemistry?

Bio-interactions already observed to date

The following is a summary of some of the most significant bio-interactions of tissue and whole animal systems with ELF to date and is not meant to be exhaustive.

Besides Positive Epidemiological Human Cancer Studies, frequency and power windowing in tissue interactions with weak electromagnetic fields for example extremely low frequency (ELF) fields at frequencies of 6 and 12 Hz and gradients in air of 0.1 to 0.5 V/cm show decreased calcium efflux in the brains of experimental animals by 12 to 15 per cent, see Bawin et al (11).

Weak fields have been observed to produce chemical, physiological, and behavioural changes only within windows in frequency and incident energy. For brain tissue, a maximum frequency sensitivity occurs between 6 and 20 Hz. Two different intensity windows have been seen, one for ELF tissue gradients around 10^-7V/cm, and one for amplitude modulated RF and microwave gradients around 10^-1V/cm. The former is at the level associated with navigation and prey detection in marine vertebrates and with control of human biological rhythms; the latter is at the level of the electroencephalogram (EEG) in brain tissue. Coupling to living cells appears to require amplifying mechanisms that may be based on non-equilibrium processes, with long-range resonant molecular interactions. These cooperative processes are now recognized as important in immune and hormonal responses, as well as in nerve cell excitation, see Adey, Proceedings of the IEEE ...> Volume:68 Issue:1 (12)

Naturally occurring electric fields are not only important for cell-surface interactions but are also pivotal for the normal development of the organism and its physiological functions. A further goal of this review is to bridge the gap between recent cell biological studies (which, indeed, show new data of EMF actions) and aspects of EMF-based therapy, e.g., in wounds and bone fractures, see Funk and Monsees 2006 (13).

A few animal studies on the possible carcinogenic effect of magnetic fields have been also published. They have been designed to reveal a possible tumour promotion obtained by applying continuous or pulsed alternating fields at flux densities varying between 0.5 microT and 30 mT on mice or rats initiated with different initiators. One study with 2 mT applied on MBA-initiated mice may suggest a co-promotive effect together with the promoter TPA. Another study on rats suggests an inhibitory effect by a magnetic field on rat liver foci formation, induced with DENA. Cell studies show that magnetic fields at some frequencies, amplitudes, and wave forms interact with biological systems. Thus effects have been seen, e.g., on enzymes related to growth regulation, on calcium balance in the cell, on gene expression, and on pineal metabolism and its excretion of the oncostatic melatonin. Cellular and physiologic studies thus suggest effects that may be related to cell multiplication and tumour promotion, see Holmberg 1995 (14). During the past decade considerable evidence has accumulated demonstrating that non-thermal exposures of cells of the immune system to extremely low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be relevant to in-vivo immune activity. A similar responsiveness to nonionizing electromagnetic energy in this frequency range has also been documented for tissues of the neuroendocrine and musculoskeletal system. However, knowledge about the underlying biological mechanisms by which such fields can induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca (2+)-regulated activity is involved in bioactive ELF field coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of non-thermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells and then closely examines new results that suggest a role for Ca2+ in the induction of these cellular field effects. Based on these findings it is proposed that ELF critically impinges on membrane-mediated Ca2+ signalling, see Walleczek 1992 ( 15).

An even earlier study by Foster 1974 (16) discusses the following topics: exposure versus dose; known mechanisms; thermal effects vs. nonthermal effects; membrane excitation; electric fields (charge interactions; permanent dipole interactions; induced dipole interactions); magnetic field effects; free radical effects; human perception of 60 Hz magnetic fields; cyclotron resonance; microwave auditory effect and blood-brain barrier effects

The question of whether or not non-thermal (sub-T)) electromagnetic fields in the non-ionizing frequency range (from extremely low frequency (ELF) to microwave) can influence the function of biological systems is currently of extreme interest and the subject of both ongoing experiments and controversial discussions. In this review, a brief presentation of some of the most prominent experimental results is given, and the principal problems are discussed from both physical and biological points of view. The necessary requirements for modelling approaches are described, including the entire sequence from the primary physical interaction via the secondary biological mechanisms (transductive steps) to the final response. Very small changes in the underlying non-linear kinetics caused by very weak coherent signals and noise can lead to strong, but reversible, alterations in the internal non-linear processes and associated biological function. The results of many detailed investigations are given. These include ELF field influences on G-protein activation dynamics, magnetic field influences on radical pair recombination reactions and weak signal amplification by stochastic resonance. All processes are incorporated within Ca⁺ s signal pathway models. The concept and models presented describe frequency-dependent and frequency-coded influences of very weak fields. The relevance of this is shown by sophisticated biological experiments, see Kaiser (1996) Bio-electrochemistry and Bioenergetics Volume 41, Issue 1 (17). Where laboratory studies have tested a spectrum of EM fields for bio- effects at cell and molecular levels, focusing on exposures at athermal levels. A clear emergent conclusion is that many observed interactions are not based on tissue heating. Modulation of cell surface chemical events by weak EM fields indicates a major amplification of initial weak triggers associated with binding of hormones, antibodies, and neurotransmitters to their specific binding sites.

Calcium ions play a key role in this amplification. These studies support new concepts of communication between cells across the barriers of cell membranes; and point with increasing certainty to an essential physical organization in living matter, at a far finer level than the structural and functional image defined in the chemistry of molecules. New collaborations between physical and biological scientists define common goals, seeking solutions to the physical nature of matter through a strong focus on biological matter. The evidence indicates mediation by highly non-linear, non-equilibrium processes at critical steps in signal coupling across cell membranes. There is increasing evidence that these events relate to quantum states and resonant responses in bio-molecular systems, and not to equilibrium thermodynamics associated with thermal energy exchanges and tissue heating, see Adey Published 1993 Wiley-Liss Inc. (18).

In 2003 Ivancsits (19) et al showed dose dependent 50 Hz single and double strand DNA breaks in human diploid fibroblasts of great significance towards the increased risk of cancerous disease. In 2005, similarly but using rabbit ligament fibroblasts, Ross showed a number of frequency, amplitude and DC magnetic field amplitude effects from inhibition to stimulation to proliferation and all using ac frequencies including those typically used for power transmission i.e. at 50Hz and 60Hz. He concluded that this is very relevant and warrants investigation by the power generators.

Further 50 Hz fields at subtle strength levels (2.5mT) have been shown by Paradisi et al (2005) (20) to have induce sub-lethal cellular alterations and membrane damage. Such effects could have impact on Calcium transport, for example.

Yokus et al (2005) observes oxidative DNA damage and lipid per-oxidation in rats and appears to be the first to positively associate ELF as a promoter or co-promoter of cancer (21).

Various types of Lymphoma and Leukaemia have often been associated with ELF,EMF and RF in multiple epidemiological studies, some with more significant results than others. It would thus seem logical to explore the effect of these types of fields on animal and human lymphocytes and leukaemia cells. There have been several studies since 1992, all producing effects. For example, Walleczek and Budinger (1992) (22) demonstrated that 3Hz PEMF ( pulsed field) alters calcium ion signalling in lymphocytes but at levels greater than normal human environmental exposure at these low frequencies.

The work of Belyaev and Alipov (2001) observed frequency dependent effects on chromatin conformation in both human lymphocytes and e-coli . Some overlap in excitation frequencies between the two was observed, suggesting common targets. Their model identified cyclotron resonance frequencies of some common biological ions including Calcium. Sub-harmonic effects confirmed cyclotron resonance (23). Lyle (2005) showed that even at more subtle field strengths at 13.6 Hz and the environmentally relevant US 60 Hz mains frequency calcium uptake was increased in both normal and leukaemic lymphocytes.

Grassi at al (24) showed 50Hz UK mains frequency was capable of causing cellular proliferation and DNA damage at environmental exposure levels in both normal and tumour cells. They conclude that their results ought to be of value in appraising the patho-physiological consequences of ELF-EMF.

Another study, Cho and Chung (2003) (25) evaluates the effect of ELF on human lymphocytes in the presence of a known carcinogen, namely benzo(a)pyrene (BP) (also found in cigarette smoke). The conclusion is that ELF could act as an enhancer of the initiation process of BP. This is not inconsistent with the work of Yokus et al.

On the other hand Tofani at al (26) using human lymphocytes and 32 Hz at 75 uT provide evidence of a direct genotoxic effect of the ELF. Similarly Fatigoni et al (2005) showed geno-toxicity of 50 Hz using a specific bio-assay.

Mechanisms

Despite all the evidence that low level ELF EMFS do, in fact produce, measurable bio- effect, and even cancer, sceptics might point to the observation that no single mechanism has been identified which accounts for all bio-coupling. Liburdy (2000) positivity identifies the calcium site in thymic lymphocytes as being influenced by 60 Hz in real time. The present author sees this as a particularly relevant and valuable observation given ELF, EMF and RF are often associated epidemiologically with Lymphoma. (27)

The present author has recently advanced three new mechanisms for RF interaction with tissue which remain untested. The present author has also shown that pulsed RF emissions are more dangerous than CW and FM emissions and has advanced reasons for the same. The pulse repetition frequencies of modern RF communication systems often fall in the ELF. Energetically, RF packs more punch all round than ELF but because of the experiential observations of frequency and field specific windows associated with the latter then perhaps different or multiple mechanisms are at work.

The most common two recorded effects of ELF are the modulation of the membrane calcium ion channel and the presence of or in increase in ROS (reactive oxygen species). A favourite mechanism for ELF, particularly magnetic interaction is ion cyclotron resonance. Few people are perhaps aware that this mechanisms is more than just a theory and has recently been validated in a biological model system which was exploited by Smith et al (1987) (28 ) using diatom mobility as the model. Diatoms are organisms which move or don't move depending how much Calcium is transported across the cellular membrane. Smith et al also prove a dose dependent response a requirement suggested by Hafemeister (1996 ) as a pre-requisite for convincing others of the dangers of ELF. The present author has previously commented on ROS as a common link in bio-damaged in plants and animals due to RF. There is growing evidence in the bio-chemical and biomedical literature of an intimate link between endogenous and exogenous ROS and Calcium channel signalling.

Ion cyclotron resonance has been demonstrated for free ions and for amino acid solutions (Zhadin 1998) and Alberto et al (2008) but for some there are difficulties in explaining the low field strengths and seemingly very large path lengths for membrane bound ion channels, (Kinouchi et al 1997). Mae Wan Ho (ref) provides a comprehensive explanation and way around this. Further using artificial membrane vesicles Koch et al (2003) (29) provide very significant experiential confirmation of protein calcium channel modulation and confirm the quantum mechanical model proposed by Blanchard. Further cellular membranes may in some regards be thought of as ion exchange media. Significant magnetic field effects have been demonstrated for artificial ion exchange media, see Zaidi (2014) (30) and Baran and Degtyarev (2000) (31) . The Zhadin experiment was reproduced and improved upon by Comisso et al (2005) showing that electrode polarisation state could be important (32) . Cell membranes have their own polarisation sheath and the authors point out the biological importance of their observations. Calcium channel effects and ion cyclotron resonance in response to ELF has been observed in a huge number of in-vitro experimental situations with human and animal cell lines.

The conclusive, elegant and yet presumably little known experiment to prove calcium cyclotron resonance as a feature of static and ELF MF interaction in biology was of course performed far earlier by Smith et al (1987) (28) by using diatom mobility as the model. Diatoms are organisms which move or don't move depending how much Calcium is transported across the cellular membrane. Smith et al also prove a dose dependent response a requirement suggested by Hafemeister (1996 ) as a pre-requisite for convincing others of the dangers of ELF.

As an alternative to ion cyclotron resonance within channels themselves, Panagopoulos et al (2000) (33) and later, have proposed that the magnetic vibration of ions exterior to the membrane my promote disruption of cellular electrochemical balance. This may tie in better with the effects of infrasound and LFN on biological systems which are very similar in many way to those of ELF, see Martirosyan et al (2011) (34). Physical-chemical and electromagnetic effects involving extra-cellular water are also likely, see Chaplin (2013) (35). Such effects can generate raised levels of exogenous ROS (Barnes 2013)(36) . Finally for the bio- safety argument magnetic isotopes have been shown to have effect on DNA synthesis via an ion -radical mechanism (see Buchachenko et al 2013). The authors predict that if properly controlled the effect may have substantial bio-medical implications.

ROS and radicals seem to be a repeated theme in ELF mechanism. As a potentially related issue Torres-Duran et al (2007) have found whole body exposure alters rat liver lipid levels thought to be linked to Nitric Oxide Synthase levels. The present author sees a link with ROS. Here we are reminded that Yokus et al (2005) observes oxidative DNA damage and lipid per-oxidation in rats and appears to be the first to positively associate ELF as a promoter or co-promoter of cancer.

This view point based on ROS is backed up by Barnes (2013) (36) and for ROS and redox modulation by Simko and Myrtill (2007) (37) which the authors state is responsible for the very diverse observed effects of electromagnetic fields in biology as a whole.

The new science of trans-cranial magnetic stimulation, see for example Chen et al 1997 (38) and the recently released magnetic migraine stimulator, see Lipton 2010 ( 39) is indisputable proof that ELF fields interact with the human bio-system and that health and safety implications of their use present and future needs to be far more carefully considered than has been in the past.

Conclusions

The present author has reviewed and part summarised an incredibly extensive literature spanning back some two decades or more.

Previous scientific panels have dismissed an association between ELF ( primarily due to 50/60 Hz

power fields) and Cancer on the grounds of unconvincing epidemiology studies, too many negative in vitro and in-vivo biological experiments and no convincing models to back up such experiments.

The present author believes it has been shown here that the situation has certainly moved on some what.

Results of experiments have been compounded in a logical manner to show historic and present conclusions. By considering some of the conditions in this plethora of experimentation it is possible to see how epidemiology would be somewhat randomised. For example experimentation

shows ELF to be either genotoxic, a co-initiator, a promoter or a co-promoter (refs). Other valid and concurrent mechanisms of interaction such as surface ion vibration and altered water structure cannot be ruled out. Following from the above, one would expect to see different epidemiology in different geographical areas according to, for example, local dominant socio-economic status and air pollution etc. The present author has recently shown how this can applied when considering the effects of TV transmitters (Barnes 2013).

It would appear that the mechanism of ion cyclotron resonance causing altered calcium ion channel behaviour in both human and animal cells has now being convincingly proven. The frequencies for ion cyclotron resonance lie at or close to 50 Hz and 60 Hz but overall effect depends on AC field strength and background DC field strength. Notwithstanding, of course, that exogenous ROS could bring about membrane per-oxidation and altered calcium ion mobility. Taking environmental considerations into account the AC field strength will depend not only on the proximity of external electrical installation and phase configuration i.e.- US twin, UK 3-phase Delta or 'Y' but also on the type of internal house wiring. Human exposure will vary between work and home and with occupation. DC field strength will vary according to local geomagnetic anomaly, underlying rock type, housing type and geomagnetic field a function of the solar system – earth- ionosphere system. All these factors will 'tune' bio-effect to individual locations, places of employment and living accommodation, even down to the position in a house where a person sleeps. Based on the above it might even be possible for a person with a new neoplasm to have it placed into a cancero-static mode one day or an accelerated mode the next or vice versa based purely on the precise electromagnetic environment and exposure time. We are looking at a critically complex science here.

Given all of the above it is hardly surprising then that epidemiological evidence is limited and much weaker, for example, then that associated with Cancer and Cigarette Smoking.

The best epidemiological evidence at all is the reverse case! Consider the Amish religious community in the USA who do not use mains electricity or electrical appliances. The Amish being a small community with limited gene pool ought, theoretically, to suffer from more cancer due to inherited mutations. In fact, the reverse is true, they only suffer about half the cancers than the rest of the US population. It may be possible to attribute the absence of electromagnetic fields to at least part of this absence. If we attribute all the absence then a RR (relative risk) factor of about 2 is comparable with that, for example, for Leukaemia reported elsewhere.

There are more than 5000 references in the present world literature linking bio-effects and electromagnetic radiation. Most of the epidemiological studies linking ELF radiation to cancer consider Leukaemia, Lymphoma and CNS cancers. Most reported RR 's are low,

most likely for the reasons outlined above, but also for the same reasons far more significant than has previously being given credance.

The power generators and distributors of the World clearly make huge profits from their product, otherwise they would not be in business. One would think that rather than fuel bad science and scepticism they would take the lead from the Tobacco industry in seeking ways of improving safety, maybe by better screening or by switching to higher frequency transmission or all DC systems.

One would further think they would be proud to fund cutting edge medical research since there is the possibility that appropriately manipulated fields might be able to cure as well as cause human disease.

It is apparent that electromagnetic manipulation might become an important tool of tomorrow's genetic engineers and of medicine in general. General interest websites would suggest that Russian scientists are extremely enthusiastic in this direction. It would be a tragedy if British Science were to miss out on such an opportunity.

The author has previously published an article urging caution in the use of all forms of ELF/EMF.

This work only serves to reinforce that believe. Laptops and mobile phones too emit pulsed ELF, the former do so even when their wireless signal is switched off. The fear remains that there might be an explosion of medically related problems within the near to mid-term future associated with the use of these devices. Thus additionally, it may be necessary to consider improved screening of these devices.

To sum up:

1. Epidemiological studies of ELF and cancer have associations which are moderately weak but significant

2. Some dose dependent biological effects are reported

3. Calcium ion channel disturbance and ROS are most widely reported

4. These mechanisms have now been tested in model agents

5. Both of the above can make ELF to be either genotoxic, a co-initiator, a promoter or a co-promoter of Cancer

6. The Amish who do not use electricity have about 50% of the cancer of the rest of the US

7. Once properly understood ELF has the potential to be use as a powerful biomedical tool, tremendous future opportunities for UK exploitation exist

8. Our present views of ELF safety with regard to electricity distribution and electrical/electronic appliances is insufficient and ought to be revised

Further work

There is some evidence to suggest that UHF and microwave signals amplitude and pulse modulated at ELF or sub-audio frequencies might be more biologically damaging then ELF alone. It is hoped to provide a balanced critique/view of the evidence and present any new conclusions required in the very near future. Use will also be made of the latest Cancer statistics from ONS to support some authors of existing epidemiological studies and make a striking revelation concerning TV and pulsed emission technologies.

References

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2. http://www.tandfonline.com/doi/abs/10.1080/19338244.2011.564232#.Ut-WCtFFC1s

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5. http://onlinelibrary.wiley.com/doi/10.1002/bem.2250110205/abstract

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7. http://www.paolobellavite.it/files/1107quantumwaterho.pdf

8. http://www.thermoguy.com/pdfs/Biological_Effects_of_Weak_Electromagnetic_Fields_2012_By_Andrew_Goldsworthy.pdf

9. http://www.drchrisbarnes.co.uk/

10. http://link.springer.com/chapter/10.1007/0-306-46916-2_5#page-1

11. http://magdahavas.com/wordpress/wp-content/uploads/2011/02/THE_PHYSICAL_BASIS_OF_ELECTROMAGNETIC_INTERACTIONS_WITH_BIOLOGICAL_SYSTEMS.pdf#page=83