Can a magnetic field be isolated

How magnetic fields work in human cells

For more than 50 years, pulsed magnetic stimulation at low intensity (repetitive low-intensity magnetic stimulation) has been used successfully in the therapy of diseases from depression to certain types of cancer. However, the cellular mechanisms of action have so far remained unclear. But now scientists from different disciplines are reporting on the mechanism of action of magnetic fields in cells: using cryptochrome and reactive oxygen species (ROS). Cryptochrome plays a role in the circadian rhythm of animals and plants and in magnetoreception - the perception of the earth's magnetic field in animals. When cells - including those of humans - were exposed to pulsed weak magnetic fields, this stimulated a biological stress reaction. The results are published in the journal “PLOS Biology” (see primary source).

 

Overview

     

  • Prof. Dr. Walter Paulus, Director of the Clinic for Clinical Neurophysiology, University Medical Center Göttingen
  •  

  • Dr. Daniel R. Kattnig, Senior Lecturer, Department of Physics and Living Systems Institute, University of Exeter (United Kingdom)
  •  

  • Prof. Dr. Alexander Lerchl, Professor of Biology and Ethics of Science & Technology, Jacobs University Bremen
  •  

Statements

Prof. Dr. Walter Paulus

Director of the Clinic for Clinical Neurophysiology, University Medical Center Göttingen

“In the publication, a tiny section (10 Hz, 1.8 mT) of the enormously large parameter space of possible electromagnetic fields was examined. I consider the mechanism of action within this highly specific laboratory situation to be plausible. It just has little to do with the assumed mechanisms of action for transcranial electrical and magnetic stimulation in humans. The authors' results are related to completely different parameters, both in the frequency range from static magnetic fields to high-frequency fields as well as in the amplitude range. Most noticeable here is the field strength several dimensions larger in the experiments compared to the measurable everyday exposure. In 977 French children, this was more than a factor of 1000 below 1.8 mT; The exposure was higher than 0.4 µT in only 3.1 percent of the children. The 0.8 percent of children who lived in the vicinity of a high-voltage line (less than 200 meters) did not experience any higher exposure either [1]. The authors of the French work therefore also question the measurements in some epidemiological studies [2]. "

“The specific title of the thesis correctly reflects the content - the generalizing conclusions then lack a scientific basis. Cryptochromes are found in the retina. In order to be able to function, they need light activation - which would only be possible in the brain with invasive light electrodes. Further cryptochromes can be found in the so-called circadian system, which has nothing to do with the plasticity mechanisms discussed in, for example, Parkinson's disease. The authors leave open the extent to which cryptochromes occur in the cerebral cortex. Embryonic cell cultures of human kidney cells are not helpful in answering this question. The production of oxygen radicals plays a subordinate role in influencing neuroplasticity. "

“Regarding possible side effects of electromagnetic fields: With repetitive transcranial magnetic stimulation (rTMS), attention is usually paid to side effects only a few hours after treatment. Long-term effects are extremely difficult to determine and would require very large numbers of patients. There are very good safety data in the context of examinations of brain tissue after long-term stimulation of brain tumor patients. The so-called Tumor Treating Fields double the life expectancy of patients with glioblastomas through very intense electrical fields with 200 kHz, applied to the scalp from the outside every day for 18 to 24 hours for many months. Current-specific tissue damage has not been described. Histological local examinations after deep brain stimulation in Parkinson's patients in the immediate vicinity of the electrode showed only minor tissue changes after twelve years of stimulation, despite considerably higher local current fields than are possible with transcranial stimulation [3]. "

Dr. Daniel R. Kattnig

Senior Lecturer, Department of Physics and Living Systems Institute, University of Exeter (United Kingdom)

“The authors use pulsed magnetic fields with a frequency of 10 Hz and an amplitude of 1.8 mT. Let me put that in relation: 1.8 mT is about 36 times stronger than the earth's magnetic field in Germany, but weaker than a typical refrigerator magnet (5 mT). So the magnetic fields are relatively weak. The field strength used corresponds approximately to the maximum permissible workplace exposure according to the ICNIRP (International Commission on Non-Ionizing Radiation Protection) at the selected frequency of 10 Hz. "

“However, the exact exposure conditions are of secondary importance. For the first time, the authors give insights into the mechanistic principles of the magnetic field effect. In particular, they identify the protein cryptochrome as essential. According to the current state of knowledge, this is also seen as the central component of a magnetic compass sense in some animals, such as migratory birds. Assuming that similar physical principles are used here, this leads us to assume that the results presented have a much broader validity. It is therefore entirely plausible that striking magnetic field effects of the type described are possible even with much lower field strengths and other frequencies. In particular, the underlying mechanism - the so-called radical pair mechanism - can be expected to have effects over a wide frequency range. Static magnetic fields, for example, should have similar effects. Here, frequencies up to the kilohertz range are to be regarded as quasi-static. In addition, specific resonance effects in the radio frequency range from a few to 100 MHz are conceivable. This includes magnetic field effects at the mains frequency (50 Hz) as 'quasi-static'. "

“A correlation between childhood leukemia and the proximity of the home to the power line is often discussed in this context. In principle, the study could be consistently relevant here, but the causality of the disease clusters and the increased exposure to magnetic fields is in and of itself controversial. More and more detailed studies are definitely warranted and given specific direction through the work of Sherrard and colleagues. On the other hand, I would like to point out that magnetic fields in the gigahertz range, such as those used in mobile telephony, do not give rise to any significant effects of this kind to be feared. "

“Transcranial magnetic stimulation makes use of significantly higher magnetic field strengths (1.5 T are typical in clinical applications) and a different mechanism of action - the activation of nerve cells through magnetic induction. The described effect already results for magnetic fields that are a thousand times smaller. "

“No direct relevance with regard to transcranial magnetic stimulation can therefore be derived from the study. However, the work - if reproducible - is of great importance in assessing the effects of electromagnetic fields on living organisms and, in particular, exposure guidelines derived from them. As far as the latter is concerned, it should be noted that these currently do not take into account the quantum effects on radical pairs that are relevant here and instead build on the induced thermal effects of the electromagnetic radiation acting, for example. This is not the result of ignorance, but rather a consequence of the unclear mechanisms of action of weak magnetic fields and the resulting difficulties of assessment. Here this study offers - again: if true - important new approaches in terms of identifying the central role of cryptochromes and biological model systems that can serve as a reference in future exposure studies (with consistently different field strengths and frequencies). "

“I am convinced that these effects will be taken into account in the exposure guidelines in the medium term. In this context, however, it must be said that the effect relevant here is in principle much more difficult to grasp than is the case for thermal or other effects. In principle, depending on the field strength and frequency, the effect can both favor and suppress reactive oxygen species. The effect can therefore develop both positive and negative effects, depending on the framework conditions. In particular, the assessment should take into account that an increase in reactive oxygen species can also be indicated throughout, for example around the immune response to pathogens (Pathogens; editor's note) to increase. Forcing these diverse aspects into the corset of a directive will not be easy. "

“In any case, the study mentioned offers important approaches to fundamentally understand the biological effects of weak magnetic fields. Regardless of this, a wide range of magnetic field exposures should and are of course subject to systematic epidemiological studies. "

“Many detailed questions remain unanswered in the publication. The only known mechanism that can fundamentally describe the effects mentioned - the radical pair mechanism and its modern developments - is not mentioned directly, but is suggested. As a proponent of the theoretical development of this field of work, I consider the results described to be entirely plausible. "

“Thanks to studies on isolated proteins and theoretical calculations, light-induced magnetic field effects of cryptochromes are now well understood. The radical pair mechanism can explain most of the effects. Radicals are unstable compounds with unpaired electrons - when they occur as pairs, their recombination depends on the strength and frequency of surrounding magnetic fields, although these interact with the radicals with minimal interaction energies. However, some of the effects described here are presumably based on radicals that arise from the oxidation of the reduced cryptochrome with oxygen. Magnetic field effects as a result of this reaction were excluded for a long time [4] because this implied species with too fast spin relaxation. However, my group recently succeeded in circumventing this paradox: In systems with three instead of two radicals, the phenomenon described can at least be explained in principle [5]. "

“Nonetheless, there are still a lot of unanswered questions. The effects in the current publication, for example, are very large - probably greater than the new and established models would predict. This discrepancy will probably occupy us for many years to come. It is also still unclear whether, for example, the human cryptochrome binds the flavin cofactor to a sufficient extent to enable the effects described. "

“My assessment here is based on an assessment of the physical possibility. So I assume that the results described are true, but this will only be known after the study has been independently reproduced. As far as the quality of the study is concerned, it can be said that the authors carried out sham controls, but not blind studies in which the exposure conditions were concealed from the experimenter. In controversial areas such as this, the latter are also advisable in quantitative sciences. In the related field of animal magnetic reception, this is now consistently common [6]. "

“Many questions regarding biological magnetic field effects are still open. Cryptochromes play a central role in the interpretation of these findings - both in this study and in the context of the better understood magnetic sense of many animals. However, it has still not been conclusively proven whether these proteins only play a role in signal transduction or whether they are the cause. I suspect that the latter is the case, but the proof of this hypothesis is still a long way off. As for the theoretical description, it is surprising that many of the biological effects clearly exceed our theoretical predictions. This demonstrates that our imagination is still incomplete. The greatest imponderables, however, arise from an epidemiological point of view. The effect can, depending on the field strength and frequency, suppress or promote reactive oxygen species. It follows that the effect opens up new possibilities in medical treatment, for example by increasing radiotherapy to cure cancer; while on the other hand it can cause or exacerbate clinical pictures, for example in the context of cancer development. This Janus-headedness holds the potential, but also causes difficulties in the correct assessment of risks. "

Prof. Dr. Alexander Lerchl

Professor of Biology and Ethics of Science & Technology, Jacobs University Bremen

"In my opinion, the paper should not have been accepted for publication, the errors and 'weirdnesses' are glaring."

“The work should be reproducible, as is explicitly mentioned in the primer. Only, for example, no one could do that: The company named 'GEM Pty LTD.' From Perth in Australia does not exist, at least no such company manufactures PEMF exposure equipment. There is no 'EC10701' model either, at least I can't find anything like it. So I couldn't reproduce such experiments at all. That is very worrying! "

“The title says 'electromagnetic' which is wrong. It is all about magnetic fields. "

“There is absolutely no technical description of the magnet coils: current, voltage, power loss, inductance, ohmic resistance, dimension. No experimenter can do anything with '9 x 5.5 cm and 200 turns'. The supplement data doesn't help either, only the current is given. "

“The position and field distribution of the experimental set-up given (in Suppl. Fig. 3a) are misleading. If the coil were 5.5 cm in diameter, it would not be to scale. The figure also suggests that there are no stray fields, which is wrong. "

“The coils used in the experiment produce heat. A magnetic flux density of 1.5 mT is not a trivial problem when it comes to temperatures. I doubt the information on page 9 of the paper ('less than 0.5 ° C between the corners') because it is not documented, and it also contradicts the general statement that there were no temperature differences (a paragraph later in the paper). Such effects must be documented with considerable care or explicitly excluded, since temperatures are an extremely important variable with regard to the probability of their presence in Drosophila (for example [7]). That should have been proven with infrared thermography. "

“Figure 2 is critical: measured with a ruler, the coefficient of variation (= standard deviation / mean) is between 2 and 5 percent. This is simply completely unusual for such experiments! Even if that were the case, the differences between the bars on the right-hand side of Figures A and B would also have to be highly significantly different, which would make the statement as a whole ad absurd. So there is probably something completely wrong in this crucial figure. The original data would certainly be helpful. "

Information on possible conflicts of interest

Dr. Daniel R. Kattnig:"No"
All other: None specified.

Primary source

Sherrard M et al. (2018): Low-intensity electromagnetic fields induce human cryptochrome to modulate intracellular reactive oxygen species. PLOS Biology; 16 (10). DOI: 10.1371 / journal.pbio.2006229.

References cited by the experts

[1] Magne I et al. (2017): Exposure of children to extremely low frequency magnetic fields in France: Results of the EXPERS study. Journal of Exposure Science and Environmental Epidemiology; 27 (5): 505. DOI: 10.1038 / jes.2016.59.

[2] NIH National Cancer Institute: Electromagnetic Fields and Cancer. Status: May 27, 2016.

[3] De Vloo P et al. (2018): Histopathology after microelectrode recording and twelve years of deep brain stimulation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. DOI: 10.1016 / j.brs.2018.05.005.

[4] Hogben HJ et al. (2009): Possible involvement of superoxide and dioxygen with cryptochrome in avian magnetoreception: origin of Zeeman resonances observed by in vivo EPR spectroscopy. Chem. Phys. Lett .; 480 (1-3). DOI: 10.1016 / j.cplett.2009.08.051.

[5] Kattnig DR et al. (2017): Radical-Pair-Based Magnetoreception Amplified by Radical Scavenging: Resilience to Spin Relaxation. The Journal of Physical Chemistry; 121 (44): 10215-10227. DOI: 10.1021 / acs.jpcb.7b07672.

[6] Schwarze S et al. (2016). Weak broadband electromagnetic fields are more disruptive to magnetic compass orientation in a night-migratory songbird (Erithacus rubecula) than strong narrow-band fields. Frontiers in behavioral neuroscience; 10 (55). DOI: 10.3389 / fnbeh.2016.00055.

[7] Sayeed O, Benzer S (1996): Behavioral genetics of thermosensation and hygrosensation in Drosophila. PNAS 93 (12), 6079-6084. DOI: 10.1073 / pnas.93.12.6079.

Further sources of research

ICNIRP International Commission on Non-Ionizing Radiation Protection: Guidelines can be found under Publications.