October 23, How EMR causes illnesses and what to do about it. prof. em. Martin Pall Washington State University

Transcription

1 October 23, 2014 How EMR causes illnesses and what to do about it prof. em. Martin Pall Washington State University 1

2 2 Problem 1: How can electromagnetic fields (EMFs) impact our biology and medicine - for better or for worse? A great puzzle: These EMFs are composed of low energy photons, with energy per photon too low to influence the chemistry of the body! How can they influence our biology through non-thermal effects? Safety standards assume that they can t - that only effects from heating need to be considered: If no thermal effects there cannot be biological effects. And yet, there are thousands of papers in the scientific literature reporting biological effects of exposures well within safety standards!

3 Problem 2: For over 30 years, it has been known that pulsed electromagnetic fields are often much more biologically active then are non-pulsed fields. That is inconsistent with the thermal/heating paradigm: Pulsed fields either produce less heating or the same amount, depending on how the experiment is set up. 3 It is also true that there are window effects where biological effects from a specific type of EMF is maximal within specific exposure ranges, while they decrease with both lower or higher exposures. So we meet again the great puzzle: 1. How can such low frequency EMFs influence our biology - for better or for worse? Energy per photon is too low to influence the chemistry of the body! 2. Can they influence our biology through non-thermal effects? There is a substantial literature reporting that they do.

4 I recently solved this important puzzle: EMFs activate voltage-gate calcium channels. It is the downstream effects of the increased Ca 2+ levels within cells that leads to the biological effects of EMF exposure. 4 The most central evidence: In a whole series of studies, all of the effects from exposures to various low frequency EMFs, could be blocked by calcium channel blockers - drugs that block voltage-gated calcium channels.

5 5 Multiple types of exposures produce biological effects that are blocked by calcium channel blockers that are, therefore, mediated by voltage-gated calcium channels (VGCCs): Extremely low frequency fields including 50 and 60 Hz fields such as produced by 220V electrical wiring Microwave, particularly pulsed microwave fields Very short nanosecond pulses Static electrical fields Static magnetic fields There may be still other types of fields producing VGCC activation, but the ones listed above are the ones that are currently documented.

6 6 Each of these several types of exposures may well be of concern, but the microwave frequency exposures are of greatest concern because of the great increases in exposures produced by various wireless communication and other devices.

7 The proofs 7 Table 1: EMF Responses Blocked or Lowered by Calcium Channel Blockers Ref EMF type Calcium Cell type or organism Response measured # channel 2 Pulsed magnetic fields L-type Human lymphocytes Cell proliferation; cytokine production 3 Static magnetic L-type Human polymorphonuclear Cell migration; degranulation field (0.1 T) leukocytes 5 ELF L-type Rat chromaffin cells Differentiation; catecholamine release 6 Electric field L-type Rat and mouse bone cells Increased Ca2+, phospholipase A2, PGE Hz L-type Mytilus (mussel) immunocytes Reduced shape change, cytotoxicity 8 50 Hz L-type AtT20 D16V, mouse pituitary corticotrope-derived Ca2+ increase; cell morphology, premature differentiation 9 50 Hz L-type Neural stem/ progenitor cells In vitro differentiation, neurogenesis 10 Static magnetic L-type Rat Reduction in edema formation field 11 NMR L-type Tumor cells Synergistic effect of EMF on anti-tumor drug toxicity

8 8 Ref EMF type Calcium Cell type or organism Response measured # channel 11 NMR L-type Tumor cells Synergistic effect of EMF on anti-tumor drug toxicity 12 Static magnetic field L-type Myelomonocytic U937 cells Ca 2+ influx into cells and antiapoptotic effects Hz L-type Mouse Hyperalgesic response to exposure 14 Single nanosecond electric pulse L-type Bovine chromaffin cells Very rapid increase in intracellular Ca Biphasic electric current L-type Human mesenchymal stromal cells Osteoblast differentiation and cytokine production 16 DC & AC magnetic L-type b-cells of pancreas, patch clamped Ca 2+ flux into cells fields Hz L-type Rat pituitary cells Ca 2+ flux into cells Hz L-type,N-type Human neuroblastoma IMR32 and Anti-apoptotic activity rat pituitary GH3 cells 19 Nanosecond pulse L-type, N-type, Bovine chromaffin cells Ca 2+ dynamics of cells P/Q-type Hz Not determined Rat dorsal root ganglion cells Firing frequency of cells to 1100 MHz N-type Stem cell derived neuronal cells Ca 2+ dynamics of cells

9 9 22 Very weak electrical fields T- type 23 Short electric pulses L- type 24 Weak static magnetic L- field type 25 Weak electric fields T- type Sharks Detection of very weak magnetic fields in the ocean Human eye Effect on electro-oculogram Rabbit Baroreflex sensitivity Neutrophils Electrical and ion dynamics This entire table is support for the conclusion that such EMFs act biologically by activating VGCCs.

10 10 Further support: Hundreds of studies have shown that microwave EMF exposures are followed by changes in calcium fluxes, and/or changes in amount of calcium signaling. Biophysical modeling studies show that EMFs can act through their interactions with the charged amino acid residues which regulate channel opening and closing, to open voltage-gated ion channels. Panagopoulos et al, BBRC 2000 Jun 16;272(3):634-40; BBRC 2002 Oct 18;298(1): So, EMF VGCC activation is biophysically plausible, as Panagopoulos predicted from biophysical modeling.

11 11 The biophysical modeling predictions make great sense: We know that 1) these fields exert forces on charged groups, 2) opening and closing of these channels is controlled by charged amino acid residues, 3) modest changes in the charge across the plasma membrane produce weak forces that regulate the opening and closing of these channels. So it makes great sense that such weak electromagnetic fields as in the table, can target these channels! The Panagopoulos modeling studies show mathematically that this holds up.

12 12 It seems to be the calcium channels - the VGCCs - that are responsible for the biological responses to these weak fields, not any other voltagegated ion channels: Only VGCCs seem to be involved. It is not clear why. It may have to do with amplification mechanisms triggered by increased intracellular calcium. Still, the advocates of the current safety standards, claim that there is no biophysically viable mechanism for these weak field EMFs to produce non-thermal effects in our bodies. Their claim is simply wrong!!

13 13 The finding that EMF exposure acts via activation of VGCCs, provides for the first time, an answer to the puzzle of how exposure to EMFs composed of low energy photons can affect our biology and medicine. But there is more: Increased intracellular Ca2+ [Ca2+]i produced by VGCC activation can act, in turn, to stimulate NO synthesis. Pulsed microwave frequency EMF exposures have been shown to produce almost immediate increases in both [Ca2+]i and also of NO synthesis (< 5 seconds). Pilla AA. Electromagnetic fields instantaneously modulate nitric oxide signaling in challenged biological systems. Biochem Biophys Res Commun. 2012;426: Such NO increases may also have important biological effects:

14 Most physiological responses to [Ca2+]i and NO, act as follows: Microwave / low freq. EMFs Most pathophysiological effects: NO is a precursor of ONOO(-), i.e. peroxynitrite, leading to free radical generation and oxidative stress. 14 Therapeutical effects: NO increases levels of cgmp, leading in turn to stimulation of the cgmp-dependent protein kinase (protein kinase G). VGCCs [Ca2+]i NO cgmp G- kinase Superoxide +/-CO2 ONOO(-) (peroxy- Free nitrite) radicals Negative Health Impacts by Microwave Radiation Therapy Oxidative/ Nitrosative Stress

15 15 Some Relevant Papers: Pall ML Electromagnetic fields act via activation of voltage-gated calcium channels to produce beneficial or adverse effects. J Cell Mol Med Aug;17(8): This paper was honored to be included on the Global Medical Discovery site as one of the most important medical papers of Pall ML Electromagnetic field activation of voltage-gated calcium channels: role in therapeutic effects. Electromagn Biol Med Apr 8. Pall ML Microwave electromagnetic fields act by activating voltage-gated calcium channels: Why the current international safety standards do not predict biological hazard. Recent Res Devel Mol Cell Biol, 7(2014): 0-00 ISBN: , in press. Pall M. L Multiple chemical sensitivity: Toxicological questions and mechanisms. In General and Applied Toxicology, 3rd Edition, John Wiley & Sons, pp

16 16 Health Impacts by Microwave Radiation There are multiple studies showing that each of the following responses have been reported to be produced by microwave radiation exposures. There may be arguments about how strong the evidence is, but there is no question that there is substantial evidence. None of these can be explained by heating but they can all be explained by VGCC activation and downstream effects.

17 Table 1. Apparent Mechanisms of Action for Microwave Exposures Producing Diverse Biological Effects (See Fig. 1) Reported Biologic Response Oxidative stress Single strand breaks in cellular DNA Double strand breaks in cellular DNA Apparent Mechanism(s) Peroxynitrite & consequent free radical formation Free radical attack on DNA [1-3] Same as above Cancer Single and double strand breaks, 8- nitroguanine and other pro-mutagenic changes in cellular DNA; produced by elevated NO, peroxynitrite Breakdown of bloodbrain barrier Male and female infertility 17 Peroxynitrite activation of matrix metalloproteinases (MMPs) leading to proteolysis of tight junction proteins Induction of double strand DNA breaks; Other oxidative stress mechanisms; [Ca2+]i mitochondrial effects causing apoptosis; in males, breakdown of blood-testis barrier Citation(s)/Comments [1-3]; detected via a large number of oxidative stress markers Same as above; detected from micronuclei and other chromosomal changes [3] and this paper [3] [3]

18 18 Male and female infertility Induction of double strand DNA breaks; Other oxidative stress mechanisms; [Ca2+]i mitochondrial effects causing apoptosis; in males, breakdown of blood-testis barrier Therapeutic effects Increases in [Ca] i and NO/NO signaling [1-3; 13] Depression; diverse neuropsychiatric symptoms VGCC activation of neurotransmitter release; other effects?; possible role of excess epinephrine/norepinephrine Melatonin depletion; sleep disruption Cataract formation Tachycardia, arrhythmia, sometimes leading to sudden cardiac death VGCCs, elevated [Ca] I leading to disruption of circadian rhythm entrainment as well as melatonin synthesis VGCC activation and [Ca] I elevation; calcium signaling and also peroxynitrite/oxidative stress Very high VGCC activities found in cardiac (sinoatrial node) pacemaker cell; excessive VGCC activity and [Ca2+]i levels produces these electrical changes in the heart [3] These were reported in occupational exposures [21]; also reported in people living near cell phone towers [3] This paper These are not the only pathophysiological effects of such EMFs, but these are among the best understood in terms of mechanism. And they give you some idea of the breadth of the effects seen. [3]

19 Microwave/ low freq. EMFs VGCCs [Ca2+]i NO cgmp G- kinase Superoxide +/-CO2 ONOO(-) (peroxy- Free nitrite) radicals Therapy Oxidative/ Nitrosative Stress Pathophysiological effects 19

20 20 Electromagnetic HyperSensitivity (EHS) I believe that EHS can also be explained as being produced by downstream effects of VGCC activation, The mechanism I have proposed is still speculative and there are little data that are available to test it. The psychiatric speculations on EHS has no empirical support - And they don t recognize the demonstrated mechanism of EMF action via VGCC activation.

21 21 Overall conclusions: 1) The heating/thermal paradigm of action of microwave and lower frequency EMFs should be replaced by VGCC activation. VGCC activation may not be the whole story of such action, but it is clearly most of the story. 2) A large number of reported microwave health effects can be understood as being caused by downstream effects of VGCC activation. 3) EHS can be explained as a biological mechanism.. 4) The current safety standards have been based on the now discredited heating/thermal mechanism, so one can have no confidence in safety of devices based on those safety standards.

22 Some sources of concern: Cell phones & cell towers Cordless phones (DECT) Cordless phone bases Wi-Fi / wireless routers Computers/tablets Smart meters Radar units Other wireless communication systems Dirty electricity Digital power supplies Digital inverter boxes Hair dryers Resistance heaters Electric motors 22

23 23 Two phase approach: 1. Decrease exposures by 100 to 1000-fold 2. Develop biologically-based safety standards for second phase assessment

24 Technicalities as to the fast and cheap way to test: The main approach to developing biologically-based assessment is to use cultures of cells with high densities of VGCCs. Reactions to field exposures can be measured either by using NO synthesis as a measure or by using fluorescent intracellular Ca2+ probes to measure changes in intracellular Ca2+ levels In these ways, fields with different pulsation patterns, different intensities and different wavelengths can be compared to determine their relative biological effects. These should help with design of new devices with lowered biological effects. 24

25 25