In March 2015, Martin Pall has announced that he has solved the puzzle of the mechanism behind the effects of the EMF. Following this announcement, several scientists, including myself, expressed reservations about this over-the-board claim.
Martin Pall didn’t do himself any experimental research on EMF. What he did is that he reviewed studies presenting effects of EMF on calcium metabolism in cells and, based on these studies, presented a hypothesis that the VGCC is the mechanism for the effects caused by EMF exposures.
In his announcement of the “VGCC calcium hypothesis” Martin pall went even further and claimed that: “Calcium channels are the main, possibly the sole target for EMFs“
While Martin Pall can be considered an experienced biochemist, he has no sufficient knowledge about the various types of EMF and, because of it, he seems to mix apples and oranges in formulating his VGCC hypothesis. This is the problem. The arena of the biological and health effects of EMF is plagued by research where scientists knew biology but did not know physics of EMF, leading to false conclusions.
Several scientists, who themselves performed experimental research on EMF bio-effects have criticized Martin Pall’s announcement of the VGCC as the major, possibly the sole target for EMFs. Here is what was said in order of appearance:
- Martin Pall announcement about VGCC mechanism
- Martin Blank responds to Pall announcement
- Dariusz Leszczynski responds to Pall announcement (#1)
- Martin Pall responds to Leszczynski
- Henry Lai responds to Pall announcement
- Dariusz Leszczynski responds to Pall (#2)
- Denis Henshaw responds to Pall announcement
- Dimitris Panagopoulos responds to Pall announcement
- Martin Pall last response to all discussants
1. Martin Pall announcement
[emphasis in bold red added below by DL]
On 2015-03-18 à 05:48, Pall, Martin L wrote:
Dear Andre Fauteux and others:
I agree that toxicology is not an appropriate model, in part because there are many dozens of targets of toxicant action, making this model unnecessarily complex. Fortunately, EMF action is much simpler. The sole target of EMFs is the voltage sensor of the voltage regulated ion channels including especially the calcium channels. This is the target in both animal cells and in plants. The reason that this is the sole target is that it is millions of times more sensitive to the fields than are other charged groups in the cell.
So we have solved this problem and it is time to move on to the many biological consequences of this mechanism of action.
Martin Pall
2. Martin Blank responds to Pall announcement
On 2015-03-18 at 19:19, Martin Blank wrote:
Andre,
Re your posting on a toxicology model, I am sending you the abstract of a study showing interaction of EMF with particular groups in DNA to initiate stress protein synthesis (i.e., initiation of the cellular response to a harmful stimulus). One would expect interactions of EMF with many cellular components, but this is the natural response of a cell, and the cell is more sensitive to EMF than to temperature (heat shock).
Journal of Cellular Biochemistry 81:143-148 (2001); Regulating Genes with Electromagnetic Response Elements. Hana Lin,1 Martin Blank,2 Karin Rossol-Haseroth,3 and Reba Goodman1*; 1Department of Pathology, Columbia University Health Sciences, New York, NY 10032, 2Department of Physiology, 3Department of Medicine,
Abstract A 900 base pair segment of the c-myc promoter, containing eight nCTCTn sequences, is required for the induction of c-myc expression by electromagnetic (EM) fields. Similarly, a 70 bp region of the HSP70 promoter, containing three nCTCTn sequences, is required for the induction of HSP70 expression by EM fields. Removal of the 900 base pair segment of the c-myc promoter eliminates the ability of EM fields to induce c-myc expression. Similarly, removal of the 70 bp region of the HSP70 promoter, with its three nCTCTn sequences, eliminates the response to EM fields. The nCTCTn sequences apparently act as electromagnetic field response elements (EMRE). To test if introducing EMREs imparts the ability to respond to applied EM fields, the 900 bp segment of the c-myc promoter (containing eight EMREs) was placed upstream of CAT or luciferase reporter constructs that were otherwise unresponsive to EM fields. EMREs-reporter constructs were transfected into HeLa cells and exposed to 8 mT 60Hz ®elds. Protein extracts from EM field-exposed transfectants had significant increases in activity of both CAT and luciferase, compared with identical transfectants that were sham-exposed. Transfectants with CAT or luciferase constructs lacking EMREs remained unresponsive to EM fields, i.e., there was no increase in either CAT or luciferase activity. These data support the idea that EMREs can be used as switches to regulate exogenously introduced genes in gene therapy. J. Cell. Biochem. 81:143-148, 2001. ß 2001 Wiley-Liss, Inc. Key words: electromagnetic field response elements; gene therapy.
Low frequency electromagnetic (EM) fields induce increased expression of the stress response gene HSP70 [Lin et al., 1997; Goodman and Blank, 1998]. There are several parallels in the biochemical pathways induced by EM fields and heat shock, but there are striking differences as well. Both pathways involve the binding of heat shock factor 1 (HSF1) to a heat shock element (HSE), but regulation of HSP70 gene expression byEM®elds requires three nCTCTn binding sites in the HSP70 promoter that lie between ÿ230 and ÿ160, upstream from the transcription initiation site. These three nCTCTn sequences appear to act as electromagnetic field response elements (EMREs), since the ability of an EM ®eld to induce stress proteins gradually gradually disappears as the EMREs are mutated one by one [Lin et al., 1998a, 1999]. Removal of EMREs by mutation does not affect the response to heat shock, since the heat shock domain is downstream from the EM ®eld domain in the HSP70 promoter (between ÿ106 and ÿ67) [Lin et al., 1997, 1998b, 1999].
3. Dariusz Leszczynski responds to Pall announcement (#1)
On 2015-03-20 à 08:13, Dariusz Leszczynski wrote:
André and others,
I certainly and fully agree with Martin Blank when he states that stress response is activated by EMF and, especially, when he states “One would expect interactions of EMF with many cellular components”. Absolutely so. There might be many targets for interaction with EMF and Martin Blank speaks from experience of doing research in EMF area.
I absolutely disagree with what Martin Pall is saying. Calcium channels might be a target but it is not proven yet. Especially not proven that it takes place in human body. However, Martin Pall writes as if it would be a sure thing when he says “Fortunately, EMF action is much simpler. The sole target of EMFs is the voltage sensor of the voltage regulated ion channels including especially the calcium channels.” Especially his statement about “The sole target of EMFs” is not justified by any scientific data.
Martin Pall is speaking as if he would be a student that found something “new” and thinks that it is an “epicenter of everything”. I would expect somewhat more balanced scientific opinion from retired professor and not outburst like “So we have solved this problem and it is time to move on to the many biological consequences of this mechanism of action”. This is not correct. But this might be no wonder. Marin Pall did not do any research in EMF area. He did not publish any studies on EMF effects. He also did not do any research in area of calcium channels. Therefore, his claims of expertise are dubious…
What is even more concerning, is that Martin Pall goes around and speaks such unbalanced opinions to other scientists, like e.g. two lectures in Finland last week, and as expert witness in hearings before politicians and decision-makers. Any scientist, really experienced in the area of EMF research, will dismiss Martin Pall’s “sole target” claims easily. Using such out of balance opinions, e.g. as expert testimonials, might be unwise as these opinions will be easily dismissed, and rightly!
There are several potential mechanisms and all of them are to some degree plausible. Research needs to validate them and prove that they take place in human body, not just in cells grown in laboratory.
Best wishes, Dariusz
4. Martin Pall responds to Dariusz Leszczynski
Objet: RE: Calcium channels are the main, possibly the sole target for EMFs
Date: March 21 2015 05:46:46 UTC−4
Dariusz Leszinski seems to have forgotten that science is not a matter of unsupported opinion, but rather of what the evidence shows. He was present at one of my presentations in Finland last week and failed to raise any questions about the presentation, despite having ample opportunity to do so. There was widespread agreement among the other scientists present on the strong support for the view that EMFs act via VGCC activation.
We now have the following types of evidence, each of which provides strong support for VGCC activation, with the calcium channel blocker studies alone providing compelling evidence. These include the following:
There are 26 different studies showing that calcium channel blockers, agents specific for blocking the VGCCs, block or greatly lower all effects of EMF exposure that were measured in each study. These include 5 classes of calcium channel blockers, with each acting of different sites and having different structural properties. Each of these are thought to be highly specific agents and we have, therefore, no alternative interpretation to these results – the EMFs are activating the VGCCs.
The VGCCs and other voltage-gated ion channels have voltage sensors located in the plasma membranes of cells, which based in their location and structural properties, are predicted based on the physics to be exquisitely sensitive to activation by these EMFs.
There is published evidence that pulsed microwave exposures produce an almost instantaneous increase in intracellular calcium levels, strongly supporting a direct activation of the VGCCs by these EMFs, as suggested in the previous paragraph.
The VGCCs have been shown to have a universal or near-universal role in converting electrical effects into chemical changes in cells, so it should not be surprising that there appears to be a universal or near-universal role of the VGCCs in producing biological responses to EMFs.
There are extensive published studies (close to 1000) showing changes calcium fluxes and/or calcium signaling following microwave frequency exposures with each of these, including the calcium efflux studies, providing support for the VGCC activation mechanism.
There are a wide range of repeatedly reported responses to microwave EMF exposures that can be explained as being caused by downstream effects of VGCC activation and consequent increases in intracellular calcium, including:
Oxidative stress, single strand and double strand breaks in cellular DNA, other genotoxic responses including increases in 8-nitroguanine and 8-oxoguanine, cancer, cardiac effects including tachycardia, bradycardia, arrhythmia, possibly leading to sudden cardiac death, widespread neuropsychiatric effects, male and female infertility and low levels of melatonin. Many of these effects have been shown to be produced by excessive activity of the VGCCs in humans, based on genetic studies.
Microwave EMFs act in plants act very similarly to the way they act in animals, activating voltage regulated calcium channels and producing large increases in calcium signaling responses. The plant responses are also blocked by calcium channel blockers, including some the same blockers that work in animals. The plant calcium channels have voltage sensors with similar properties to the VGCCs in animals, thus providing an explanation for the exquisite sensitivity of the plant channels to these fields.
It should be obvious, that the calcium channel blocker studies provide the key piece of evidence pointing directly to the VGCCs (and plant channels) as the targets of these fields, but the other types of evidence provide powerful and extensive support for this conclusion from various types of diverse evidence.
Science is and always has been a matter of evidence, preferably evidence that examine a theory from a variety of different perspectives, such that it can be tested not just from one perspective, but from many. It is not and never has been based on unsupported opinion, Dr. Leszczynski.
Martin Pall
5. Henry Lai responds to Pall announcement
[this is the original version of Henry Lai comments; the version edited by Henry was recently published in a blog post available from this link: ‘Henry Lai: cautionary words on “calcium hypothesis” in the science of EMF‘]
Hi André,
Please forward the following to the other people of concern, Marty and Dariusz, etc. Thanks.
Henry Lai
———–
I agree with Marty Pall that “calcium channels” is an important topic of investigation on the mechanisms of EMF bio-effects. But, I am not sure that “calcium channels” is the “sole” answer to the mechanism of EMF interaction with living materials. The idea that EMF (particularly ELF EMF) affects calcium channels is not new. But, there are some concerns on how big a role it plays.
- It is quite difficult to envision how alternating EMF affects calcium channels. The channels are activated when membrane potential depolarizes. That means the change that triggers the effect is spatially directional, i.e., the outer part of the cell membrane becomes “less positive” and a cell in question has to be aligned in a certain orientation with the detection of the EMF. This may be true in in vitro experiment, but not in in vivo experiments and “human exposure situations” when an animal (human) moves in the field.
- Temporally, it is difficult to understand how oscillating EMF affects calcium channels. The time period of change when exposed to an AC-field in the environment is probably too fast for the channels to detect, for ELF field and particularly for RF field. One has to consider that RFR may exert its effect by its low-frequency modulation-component and not the carrier frequency (see the study by Ross Adey on calcium efflux). If this was true, one would expect that modulated-RFR should be more potent that continuous-wave RFR of the same frequency and SAR. The literature does not support this.
- In 1992, Liburdy published a study (which I consider to be an ingenious experimental design and concept) showing that ELF-EMF affected calcium channels by “induced current” (or electric field, and not magnetic field). What it means is that to show effect on calcium channels, one has to use very low-frequency fields (< 10 Hz) and/or high intensity. In most of the recent studies on calcium channels, relatively high fields were used (1-10 mT). How could the results from “calcium channels” explain the epidemiological effects of increased cancer risk at 0.4 uT?
- How can “power intensity” and “frequency window” effects be explained by the assumption that EMF affects calcium channels?
- It is quite puzzling that most of the effects reported have been on the L-form of calcium channels. However, there are reports showing that ELF EMF inhibited the T-form. And, ELF had no significant effect on the N-form, but RFR activated it. If change in membrane polarization by EMF is the cause, should one expect similar effects on all forms of calcium channel? Do they use the same positively-charged polypeptide domain to open the channel?
- How does “cyclotron resonance” fit into this? There are many reports on calcium cyclotron resonance and EMF (probably as many as the “calcium antagonist” studies.) Much lower field intensity is needed for the cyclotron resonance effect (and 7 Hz).
In general, I think it is not a good idea to make very definite conclusion on scientific matters as stated in the title of André’s e-mail: “Calcium channels are the main, possibly the sole target for EMFs”. As Einstein said, “who can be so sure about nature?”, particularly, for scientists.
Best, Henry Lai
6. Dariusz Leszczynski responds to Pall (#2)
From: “Dariusz Leszczynski”
Objet: RE: Martin Pall responds to Dariusz Leszinski
Date: 22 mars 2015 13:34:38
André,
Here is my response to Marin Pall and Henry Lai and others. Please, pass it along to all interested.
Best, Dariusz
************
Henry Lai explained in detail what the problem is, with statements made by Martin Pall. In comparison with me, Henry was more elaborate, I was very brief but the conclusion is similar do not jump to premature conclusions about biological systems, as Martin Pall does.
I remain unconvinced by the below seen response of Martin Pall to my message and I stick firmly to what I said before. I am now highlighting some fragments of my earlier e-mail using red bold fonts, to make sure that my points are understood and not misunderstood.
In my earlier message, responding to Martin Pall claims (seen towards the bottom of this e-mail chain), I said as follows:
I certainly and fully agree with Martin Blank when he states that stress response is activated by EMF and, especially, when he states “One would expect interactions of EMF with many cellular components”. Absolutely so. There might be many targets for interaction with EMF and Martin Blank speaks from experience of doing research in EMF area.
I absolutely disagree with what Martin Pall is saying. Calcium channels might be a target but it is not proven yet. Especially not proven that it takes place in human body. However, Martin Pall writes as if it would be a sure thing when he says “Fortunately, EMF action is much simpler. The sole target of EMFs is the voltage sensor of the voltage regulated ion channels including especially the calcium channels”. Especially his statement about “The sole target of EMFs” is not justified by any scientific data.
Martin Pall is speaking as if he would be a student that found something “new” and thinks that it is an “epicenter of everything”. I would expect somewhat more balanced scientific opinion from retired professor and not outburst like “So we have solved this problem and it is time to move on to the many biological consequences of this mechanism of action”. This is not correct. But this might be no wonder. Marin Pall did not do any research in EMF area. He did not publish any studies on EMF effects. He also did not do any research in area of calcium channels. Therefore, his claims of expertise are dubious.
What is even more concerning, is that Martin Pall goes around and speaks such unbalanced opinions to other scientists, like e.g. two lectures in Finland last week, and as expert witness in hearings before politicians and decision-makers. Any scientist, really experienced in the area of EMF research, will dismiss Martin Pall’s “sole target” claims easily. Using such out of balance opinions, e.g. as expert testimonials, might be unwise as these opinions will be easily dismissed, and rightly!
There are several potential mechanisms and all of them are to some degree plausible. Research needs to validate them and prove that they take place in human body, not just in cells grown in laboratory.
I also fully agree with Henry Lai that explaining the “sole target” as calcium channels might be difficult, based on our current knowledge.
Table of the “26 studies” referred by Martin Pall and published in his article in 2013 (attached) shows his inexperience in EMF research. Table is a mixed-bag of all possible electromagnetic fields (see column 2) and it fits well with what Henry Lai is saying “difficult to imagine how the calcium channel would be affected and how important it might be as mechanism”.
As Henry Lai wisely quoted Einstein: “who can be so sure about nature?”
I consider the statements, by Martin Pall concerning, calcium channels and EMF as the sole mechanism for all of the EMF types (sic!) as mostly unfounded and misleading and his expertise in EMF research as insufficient for providing expert testimonials.
Best wishes, Dariusz
7. Denis Henshaw responds to Pall announcement
On 2015-03-21 à 09:08, D L Henshaw wrote:
Andre
Re: Exchanges between Daruisz and Martin Pall
I am very confused by these exchanges, so I have one question I would like to ask and then to make a simple point.
Martin have you actually said: “The sole target of EMFs is the voltage sensor of the voltage regulated ion channels including especially the calcium channels.” ?
If so, the claim of “sole target” in the context of the interaction of magnetic fields with biological systems is clearly not correct.
I refer of course to the near-explosion of research in recent years into animal magneto-reception and navigation in the Earth’s static magnetic field. If I may remind you, evidence suggests exquisite MF sensitivity to MF changes – some would say as low as 10 nT, but not to overstate it, let’s say below 50 nt. To name just three areas, such sensitivity includes animal orientation, navigation and effects on pain threshold.
In the field of animal magnetoreception, two primary MF interaction mechanisms are well-discussed: (i) magnetic particles in the body and (ii) the ability of low intensity MFs to alter chemical reaction pathways by operating on the spin states of pairs of radicals – the so-called Radical Pair Mechanism. This mechanism is deemed to take place in cryptochrome protein molecules in the eye, functioning as the magnetic compass in birds and other species.
Whether ion channels are part of the process of magnetoreception downstream of magnetic particle and/or RPM interactions is a separate question.
I cite no references here. There are many, those interested may do a Google search
Regards, Denis Henshaw
8. Dimirtis Panagopoulos responds to Pall announcement
From: “Dimitris Panagopoulos”
Object: Dariusz Leszczynski responds to Martin Pall
Date: March 22 2015 20:18:13 UTC−4
Attached is a biophysical mechanism (Panagopoulos et al 2000; 2002) in very good agreement with what Dr Pall says….Irregular gating of electrosensitive channels on plasma membranes by EMFs is a most plausible direct mechanism. The rest effects like stress response, DNA damage, etc, are secondary effects.
It is shown by physics and molecular data that the lower frequency fields (ELF) and the pulsed fields are more bioactive, which explains many observed effects. A key point is that all man-made EMFs are polarized in contarst to natural ones. Polarized oscillating EMFs induce parallel forced-oscillations in all charged molecules in biological tissue, especially in the mobile ions. The combined polarized (parallel and in phase) movement of several ions in the vicinity of the voltage-sensors of an electrosensitive channel, exerts combined forces that cause the irregular opening or closing of the channel. This causes alteration in the physiological ion concentrations within the cell, which initiates secondary effects that Dr Pall very well describes in his papers, and which finally disrupt cell function.
The above biophysical mechanism seems to be the only one which is verified by numerical test in computer (Halgamuge 2011).
Thanks, Dimitris J. Panagopoulos
9. Martin Pall last response to all discussants
From: “Pall, Martin L”
Objet: EMFs act largely, possibly entirely via VGCC activation
Date: 26 mars 2015 18:43:28 UTC−4
My email crashed and just got back on line. With regard to the subject line, that was written by Andre Fauteux not by me, my subject line was that EMFs act largely, possibly entirely via VGCC activation.
I challenged Dariusz Leszczynski to produce some evidence that supports his claims and his response is to give more completely undocumented rhetoric. If you look through each of his statements, you see not one iota of evidence – and evidence is always the basis of good science. All he does is repeat the completely undocumented claims he made before.
If he has an alternative interpretation for how in 26 different studies, calcium channel blockers can block or greatly lower each of the EMF responses studied, then he needs to provide such an alternative. And it is necessary to add into the mix the fact that 5 distinct blockers were shown to have these effects, blockers that are all thought to be highly specific and are known to have different structures and to act at different sites. Is he arguing that these highly specific calcium channel blockers block EMF effects by some other mechanism than via blocking the VGCCs, and if so, what is the evidence for that? It is sheer nonsense to say there are no scientific data when the data have just been presented to you.
When Dr. Leszczynski states that there is no VGCC activation shown to occur and is “Especially not proven that it takes place in human body” – he sounds awfully like an apologist for industry. Yes we have it going on in cells in culture, including human cells and we have it going on in experimental animals, but for some reason when those cells get into the human body, you argue that they behave completely differently. In other words, you are claiming, in effect, that the NIH is wasting billions of dollars studying the effects of physiological/pathophysiological processes in cells in culture and in experimental animals. Are you really arguing that your own cell culture work is clearly irrelevant to what goes on in the human body?
Mobile phone radiation causes changes in gene and protein expression in human endothelial cell lines and the response seems to be genome- and proteome-dependent
R Nylund, D Leszczynski – Proteomics, 2006 – Wiley Online Library
Abstract We have examined in vitro cell response to mobile phone radiation (900 MHz GSM signal) using two variants of human endothelial cell line: EA. hy926 and EA. hy926v1. Gene expression changes were examined in three experiments using cDNA Expression Arrays …
But even that argument, however weak it clearly is, fails to consider the various downstream effects of VGCC activation that have been demonstrated in humans exposed to microwave fields. Those include studies demonstrating oxidative stress and also therapeutic effects. The therapeutic effects have been shown to occur via calcium/calmodulin-dependent increases in nitric oxide (NO) and consequent NO signalling increases. Maybe Dr. Leszczynski wants to argue that the roughly 7000 papers on therapy in response to controlled microwave exposures don’t exist or that they work via a different mechanism, but that would require him to look at some real data.
With regard to my research in this area, my Journal of Cellular and Molecular Medicine article on this topic was honored by being placed on the Global Medical Discovery web site as one of the top medical papers of 2013 and it has been cited now 28 times in the short time it has been out and seems to be on an exponential upward trajectory, as these things often are. So obviously, many would disagree with you on what constitutes research here.
By failing to provide even one iota of evidence in support of any of your claims, you have, Dr. Leszczynski, provided a very important function. You have shown that beyond any doubt, there is no evidence supporting your views. So I am profoundly grateful for that and thank you very much for your help in this matter.
Now for the others on this list, I wanted to provide a figure showing how the various downstream effects of VGCC activation act in the cell:
So you can see how such responses as oxidative stress and therapeutic responses to microwave field exposures are generated as downstream effects of VGCC activation.
Now I believe that Martin Blank raised the issue of stress responses, including heat shock responses following exposure to microwave EMFs and specifically raised the issue about whether these responses suggest that there are multiple targets of the EMFs. It has long been known that high levels of intracellular calcium [Ca2+]i can activate the heat shock transcription factor leading to raises in heat shock and other proteins controlled by that transcription factor:
Proc Natl Acad Sci U S A. 1990 May;87(10):3748-52.
In vitro activation of heat shock transcription factor DNA-binding by calcium and biochemical conditions that affect protein conformation.
Mosser DD1, Kotzbauer PT, Sarge KD, Morimoto RI.
The transcription of heat shock genes in response to physiological stress requires activation of heat shock transcription factor (HSF). Although the transcriptional response is most commonly induced by temperature elevation, the biochemical events involved in HSF activation in vivo can also be triggered at normal physiological temperatures by chemicals that inhibit metabolic processes. We have used a HeLa cell-free system in which HSF DNA-binding is activated by conditions that affect protein conformation, including increasing concentrations of hydrogen ions, urea, or nonionic detergents. Treatment with calcium ions also results in a concentration- and time-dependent activation of HSF in vitro. Pretreatment with each of these biochemical conditions reduces the temperature dependence for HSF activation in vitro. These results suggest that HSF is activated either directly by undergoing a conformational change or indirectly through interactions with unfolded proteins.
There is also a mechanism by which products of oxidative stress also activating the heat shock transcription factor:
Chem Biol Interact. 1992 Sep 28;84(2):97-112.
In vitro activation of heat shock transcription factor by 4-hydroxynonenal.
Cajone F1, Crescente M.
In the activation of eukaryotic heat shock genes, the acquisition of a binding ability to specific DNA sequence by a transcriptional activator, heat shock factor (HSF), is believed to be a crucial step. The induction of this new DNA binding activity of HSF is also obtained in a cell-free system (in vitro activation) by hyperthermia or at physiological temperature by calcium ions, low pH, urea, or non-ionic detergent. We report here the in vitro activation of HSF by treating at 0 degrees C a HeLa cell-free system with the aldehyde 4-hydroxynonenal (HNE), a highly cytotoxic product of lipid peroxidation. The in vitro activation of HSF by HNE occurred only if some components of the cell-free system were not sedimented at 100,000 x g. The reason for this is unclear but the release of active HSF from nuclei of unshocked cells and the involvement of Ca2+ contained in the mitochondria and ER have been excluded. Although HNE is known to be a sulfhydryl blocking agent, the results obtained with N-ethylmaleimide suggest that different mechanisms might be involved in the in vitro activation of HSF by HNE.
There are similar mechanisms occurring in many different eukaryotic organisms including not only many mammals and other vertebrates, but also Drosophila, C. elegans, yeast and many plant species. It follows that these responses to microwave frequency EMFs not only do not imply additional targets of such EMFs, but may be viewed as support for a widespread role of VGCC activation in producing biological effects of such fields.
Now I want to raise one other important issue, that of the Sheppard et al article which argues that there cannot be a biophysically plausible mechanism of action of these weak EMFs:
Health Phys. 2008 Oct;95(4):365-96. doi: 10.1097/01.HP.0000319903.20660.37.
Quantitative evaluations of mechanisms of radiofrequency interactions with biological molecules and processes.
Sheppard AR1, Swicord ML, Balzano Q.
The complexity of interactions of electromagnetic fields up to 10(12) Hz with the ions, atoms, and molecules of biological systems has given rise to a large number of established and proposed biophysical mechanisms applicable over a wide range of time and distance scales, field amplitudes, frequencies, and waveforms. This review focuses on the physical principles that guide quantitative assessment of mechanisms applicable for exposures at or below the level of endogenous electric fields associated with development, wound healing, and excitation of muscles and the nervous system (generally, 1 to 10(2) V m(-1)), with emphasis on conditions where temperature increases are insignificant (<<1 K). Experiment and theory demonstrate possible demodulation at membrane barriers for frequencies < or =10 MHz, but not at higher frequencies. Although signal levels somewhat below system noise can be detected, signal-to-noise ratios substantially less than 0.1 cannot be overcome by cooperativity, signal averaging, coherent detection, or by nonlinear dynamical systems. Sensory systems and possible effects on biological magnetite suggest paradigms for extreme sensitivity at lower frequencies, but there are no known radiofrequency (RF) analogues. At the molecular level, vibrational modes are so overdamped by water molecules that excitation of molecular modes below the far infrared cannot occur. Two RF mechanisms plausibly may affect biological matter under common exposure conditions. For frequencies below approximately 150 MHz, shifts in the rate of chemical reactions can be mediated by radical pairs and, at all frequencies, dielectric and resistive heating can raise temperature and increase the entropy of the affected biological system.
This is a serious paper and needs to be taken seriously by each of us that is convinced that the basic inference here is wrong. Sheppard et al do make a strong case that most charged structures in the cell are insufficiently responsive to these weak fields to produce substantial biological effects. We do know, of course, that there are thousands of studies showing such effects, so that their basic inference must be wrong, but the question is why is it wrong, when the arguments are so substantial? It is very important, therefore, that the voltage-sensors of the VGCCs and also other voltage-gated ion channels are predicted to be exquisitely sensitive to these weak fields, several orders of magnitude more sensitive to EMFs than would be any non-plasma membrane located target, based on the physics. When one argues that there must be multiple targets of EMFs, one needs to have, at a minimum, specific identified targets where there is substantial evidence that it is a direct target of such EMF exposures and where the change in the target can cause biological effects produced by EMF exposures. The only such targets that we have in mammals at present are the VGCCs. It is a mistake, in my view, to argue for multiple targets of EMFs unless and until those minimum needs are met for additional such targets.
Now I want to thank Dr. Panagopoulos and Dr. Belyaev for their comments and for the information that they each provide for earlier studies that pointed towards VGCC-like mechanisms of action for EMF exposures. Dr, Panagopoulos has, of course, provided important biophysical modeling studies on the voltage-gated ion channels predicting that they may be targets of these EMFs. Dr. Belyaev showed on pp 57-58 in his review, that a number of studies implicated plasma membrane targets of EMFs and specifically ion channels. He cites the 20 year old Kaiser et al paper suggesting that Ca2+ oscillation may be produced by EMF exposures. Each of these are important for pointing in the direction of possible VGCC activation and provide substantial early support for the view the VGCCs are the primary targets of the EMFs. I have been greatly impressed by an additional finding on this, that I have quoted in one paper that I have currently under review. W.R. Adey’s prescience is most clearly shown by his statement that “Collective evidence points to cell membrane receptors as the probable site of first tissue interactions with both extremely low frequency and microwave fields for many neurotransmitters, hormones, growth-regulating enzyme expression, and cancer-promoting chemicals. In none of these studies does tissue heating appear to be involved causally in the responses” (italics added, from a talk at the Royal Society of Physicians, London May 16-17, 2002). Elsewhere Adey had reviewed changes in calcium fluxes and signaling in response to EMF exposures. It can be seen from this paragraph that we were on the verge of discovering the VGCC mechanism at least 12 years ago and I think it is tragic that it was not clearly discovered until two years ago.
Martin L. Pall
Finally, the claim by Martin Pall, that the VGCC is the sole target for EMF is not only not proven but the ultimate proof, as claimed by Martin Pall, is not the proof at all but a lacking logic misunderstanding of science. About this “proof” and about the negative consequences of Martin Pall’s outlandish claim in the next blog on BRHP.