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Medicine and War Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/fmcs19
Biological effects of low frequency electromagnetic fields I. Lee Doucet BA DipM
a
a
Research/Education Officer , Medical Educational Trust , 601 Holloway Road, London, N19 4DJ Published online: 22 Oct 2007.
To cite this article: I. Lee Doucet BA DipM (1992) Biological effects of low frequency electromagnetic fields, Medicine and War, 8:3, 205-212, DOI: 10.1080/07488009208409047 To link to this article: http://dx.doi.org/10.1080/07488009208409047
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form
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CONFERENCE REPORT
Biological Effects of Low Frequency Electromagnetic Fields Downloaded by [University of Sussex Library] at 18:14 02 February 2015
I. LEE D O U C E T BA DIPM
Research/Education Officer, Medical Educational Trust, 601 Holloway Road, London N19 4DJ
Epidemiological studies since 1979 have raised some medical and much public concern that low frequency electromagnetic fields, such as those of power-lines and in domestic and industrial electrical wiring, may have harmful biological effects. These studies are generally inconsistent, inconclusive, and difficult to replicate. Identifying biological mechanisms by which such harmful effects may occur has proved difficult, although there are several new and promising approaches. In epidemiological and laboratory studies' much greater co-ordination and standardization is needed if greater scientific knowledge of these phenomena, as opposed to mere diverse speculation, is to be achieved. KEYWORDS
Electromagnetic fields Cancer Children Epidemiology Laboratory studies
Leukaemia Biological mechanisms
In 1989 the National Radiological Protection Board issued guidelines1 on exposure to and protection from electromagnetic fields, which are currently being revised. In July 1991 the Institution of Electrical Engineers produced a report2 reviewing all then-available evidence on this controversial subject. A discussion meeting on 5 March 1992 was held by the IEE to allow comment on this report, to update it where possible, and to invite answers to the question 'where do we go from here?' The controversy was summarized thus in a guest editorial in the British Journal of Cancer: A perceived risk has evolved associating leukaemogenesis with 'excessive' exposure to alternating electromagnetic fields (EMF) at the very low frequencies of 50 or 60 Hz from electrical sources. This originated from one epidemiological study published in 1979 ... and some earlier and rather controversial biological observations on cellular calcium changes across membranes of cerebral tissues when weak electromagnetic fields were applied... Since then a vast amount of time, effort and money has been invested into the possible harmful effects of EMF. MEDICINE AND WAR, VOL. 8, 205-212 (1992)
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This has been stimulated by genuine public concern, by legal rulings in the US ordering investments in research before new overhead powerlines can be built and by a lively media debate ... there has also been concern about other cancers, suicides and psychosomatic illnesses.3 The non-ionizing radiation emitted at 50-60 Hz from electrical sources is at the lowest extreme of the electromagnetic spectrum. These extremely low frequencies are several orders of magnitude below radiowave frequencies and approximately 16 orders of magnitude below the ultraviolet spectrum, which is the nearest energy known to have harmful biological effects (skin cancers from excessive exposure to sunlight).
Epidemiology Epidemiological studies of the possible biological effects of low frequency electromagnetic fields were reviewed by Dr Ray Cartwright of the Leukaemia Research Fund Centre for Clinical Epidemiology, at Leeds University. Wertheimer and Leeper's 1979 study4 appeared to show a significant link between childhood cancer, brain tumours and the amount of electromagnetic radiation in households. This caused much interest world-wide and was followed by many studies, most of which have been inconsistent in methodology and findings, and inconclusive. However, there are some exceptions. At least twelve surveys from N America, Britain and Europe show a consistently and statistically significant relationship between acute myeloid leukaemia, other adult leukaemias and occupational exposure to electromagnetism. But all these findings could be interpreted otherwise; many of the occupations concerned, for example, welding, involved exposure to toxic and potentially leukaemogenic materials. None of them measured electromagnetic fields, and until proper dosimetry is produced a causal relationship with electromagnetic exposure remains only one of several possible explanations. There are many methodological difficulties in establishing a relationship between electromagnetic exposure and various cancers. The first difficulty concerns statistical significance. Each of the cancers being studied is extremely rare; childhood leukaemia occurs in approximately one case per 100,000 population per annum, and even myeloid leukaemia is only about three times more common; many of the rarer childhood cancers are difficult to diagnose. The number of people heavily exposed by their close proximity to overhead power-lines is only 1-2 per cent of the population. The coincidence of these two rare events makes achieving adequate statistical power extremely difficult. Moreover, many studies have examined only easily available cases rather than all cases in a particular area. Another difficulty concerns 'dose'. Exposure should be known at or up to the critical period of leukaemogenesis when significant mutational events take place which lead to induction of the disease. But in only a few types of
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cancer do we know the latency-period, and there is no lasting biological marker by which exposure may be measured; without that knowledge investigators do not know when to focus on exposure or where to look for pathological outcomes. In many epidemiological studies distance from power-lines is used, but this has proved a poor surrogate for exposure or dose. Equipment has until recently easily allowed only spot measurements of exposure, and two recently developed personal dose meters are still too large to be carried by young children. Personal dose monitoring studies have added to the confusion about electromagnetic exposure. More may come from domestic sources than from power-lines, and this seems to vary from one part of the house to another, and between neighbourhoods. Other difficulties include variations between studies in definitions of geographical area, ages of children, and of diagnosis. Thus it has not been productive to overcome lack of statistical power of individual studies by pooling their results. More fundamentally, studies so far suffer from the twin epidemiological problems of confounding and interaction. Most take a unicausal approach, investigating only the possible link between electromagnetism and cancers while ignoring other possible causative, contributory or synergizing factors. The ideal epidemiological study would be a very large, prospective cohort study, starting at birth to measure the exposure of a very large number of subjects, then after a considerable period of time measuring the malignancies that have occurred. But this would involve many thousands of children, and a huge investment of resources, with a delay of many years. A new phase of studies promises much larger numbers and statistical power, and better measurement of exposures. In Canada a national study of all childhood leukaemias has as its prime hypothesis that low frequency electromagnetic fields contribute significantly to the disease. A similar study is being conducted in the United States, and by the International Agency for Research on Cancer. In Britain the national five-year study of childhood cancer which was announced in March this year will include measurement of electromagnetic exposure.
Modes of Exposure and Biological Mechanisms Possible modes of exposure and biological mechanisms were examined by Mr John Male of the National Grid Technology and Science Laboratories. The hypothesis, derived from epidemiological studies, that disease may be linked with long-term residential exposure to power-frequency magnetic - but not electric - fields as low as 0.2-0.3 microtesla (T) raises interesting questions about possible interaction mechanisms, as currents induced in the body by electric fields in homes are generally greater than those induced by the magnetic fields. Many in vitro laboratory studies have simulated exposure to fields by injecting current into biological samples via implanted electrodes. Others
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
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have used purely magnetic exposures. Whether reported effects are due to induced currents or to direct magnetic interactions is still disputed. The basis of most interaction models has been that induced currents may disturb molecules on the outer surfaces of cell membranes and that some form of biochemical or mechanical transductive coupling then leads to effects inside the cell. This makes it difficult to explain how the very weak currents induced by environmental fields could prevail over thermal noise. In seeking to identify any biological effects of power frequency electromagnetic fields, it is important to note other electrical and magnetic fields affecting people, and the very small size of power frequency electromagnetic fields in this context. Residential power fields are less than 1 per cent of the earth's geomagnetic field and equivalent to the electrical effect about one metre from a current of 1 to 1.5 amps. Simply moving through the geomagnetic field, for example walking at one metre per second, generates internal electrical fields ten times greater than those induced by power frequency magnetic fields. Endogenous fields associated with nerve and muscle activity are about 1 mA/m2 associated with electrical fields of 5 mV/m2 in major organs such as the brain and heart — swamping the power-frequency-induced fields by several orders of magnitude. If there are any biological effects of power frequency fields, they are likely to be purely magnetic. The possibility of direct magnetic interactions with living systems is now being investigated, with several interesting observations. Relatively strong magnetic fields of a millitesla or more can influence the kinetics of certain free-radical reactions. Other recent investigations suggest that much weaker fields may disturb the vibrational symmetry and binding energy of ions coupled to protein molecules — a mechanism which could, in principle, modify a number of biochemical pathways. The pattern and rate of genetic transcription can be changed by exposure to magnetic fields at low frequency (less than 100 Hz) and low amplitudes (about 5 microtesla). Other effects seem to depend on a combination of static and oscillating magnetic fields. Chemical Effects of Static and Varying Magnetic Fields The hunt for demonstrable and reproducible effects of electromagnetic fields in biological systems has been handicapped by the lack of any generally accepted mechanism by which they might occur, stated Dr Keith McLauchlan of Oxford University. Few investigators have realized that magnetic fields affect certain types of chemical reaction, and do so in a completely reproducible way. Of particular interest in this context, chemical reactions which proceed via free radical intermediates are affected by electromagnetic fields. Chemical bonds depend on atoms and free radicals coming together to form a pair of electrons, which constitute the chemical bond. Electrons also possess the intrinsic property of spin, which can be influenced by a magnetic source; changing the spin properties of electrons damages the chemical bond. It seems that magnetic fields appear to change the probability
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that free radicals will escape from electrons; if these free radicals then encounter DNA, they increase the chance of replication errors in the DNA accumulating. The suggestion here is that cancer follows from free radical attack on DNA. Stomach cancers and ulcers are known to correlate with free radical activity. The effect of a static field increases monotonically as its magnitude is increased from zero, often reaching an asymptotic value by about 8 mT and not increasing further until fields above 1 or 2 T are reached. Below 1 mT there is a particularly interesting low field effect. Several distinct mechanisms are involved, which all involve the spin requirements of chemical bond formation, and singlet-triplet state interchange in pairs of radicals. Inside a static field, this interchange may be influenced by the application of an oscillating field. A continuous range of frequencies is effective, depending on the strength of the static field. These effects may underlie any biological effects of electromagnetic fields, but this has yet to be proved in areas other than photosynthesis, where their action is clear. At maximum, they can affect 66 per cent of product formation, but this depends on the diffusion conditions in the environments of the radicals. Biological Bases for Restricting Human Exposure
The National Radiological Protection Board's 1989 guidelines on standards1 relating to electromagnetic fields are currently under revision, with a draft expected to be circulated for comment this summer, stated Dr Sienkiewicz of the NRPB. This body issues advice to government departments and others. In issuing such guidelines the NRPB has three main criteria - that the harm to be protected against is identified, that a dose-response relationship is established, and that a mechanism of interaction is described - all on a basis acceptable to the general scientific community. The known biological effects of exposure to electromagnetic fields are surface charge effects (electrical only), and induced current effects. Surface effects include the vibration of hair and spark discharges against grounded objects. Induced current effects may be electrical and linear, or magnetic and circulating, and occur mostly in peripheral tissue and areas such as the wrist, ankles and neck. But it is known that central nervous system tissue is far more 'excitable' than peripheral tissue. That acute exposure to extremely low frequency electric and magnetic fields will result in the induction of electric potentials and currents in the body which may affect nerve or muscle cells is well established. Such effects range from direct nerve stimulation to modulation of ongoing electrical activity in the central nervous system. Biological effects of low frequency electromagnetic fields on circadian rhythms, development of the embryo and foetus, and on carcinogenesis have been reported. There is some evidence from animal studies of a dose/response relationship with regard to pineal gland activity and melatonin secretion, reduced tumour-inhibition, gonad- and mammary-cell stimulation. Adverse
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birth outcome and abnormal development has been shown in chicks but not in mammals up to quite intense fields around 200mT. In general there seems inadequate evidence at present that electromagnetic fields have effects on circadian rhythm or foetal and embryo development. So far it seems that with induced electromagnetic fields below 10 mA/m2 there is no convincing evidence of adverse health effects, while over 100 mA/m2 there are significant biological effects. It is generally accepted that such fields are not mutagenic. Present studies are looking for evidence of an effect on cell proliferation. Other data challenge conventional assumptions about dose-response relationships. Frequency and amplitude windows have been reported for various effects and a number of recent studies have reported that certain combinations of static and time-varying magnetic fields can affect some physiological or behavioural responses. However, it seems that these observations do not form a sufficiently cohesive set of data from which restrictions on human exposure can be derived. The Way Forward . . .
Dr Tony Barker of the Royal Hallamshire Hospital in Sheffield concluded the meeting by asking 'where do we go from here?' There is no doubt that electromagnetic fields can have some biological effects. Induced currents can be used to heat tissue and those produced by large magnetic field pulses can directly stimulate nerves. However, these well-established effects occur at levels many orders of magnitude higher than those to which we are normally exposed. Work on electromagnetic hazards has largely been driven by a small number of epidemiological studies which claim to show a slightly elevated risk of leukaemia at locations in the vicinity of electricity wiring, although this does not correlate well with field measurements at those locations. These epidemiological studies are inconsistent and unconvincing in methodology and findings, and difficult to replicate. Few of them present dose-reponse curves, which are essential in increasing our understanding of these phenomena; instead they simply rely on spot measurements. Epidemiological studies are unlikely to produce definitive answers, because of methodological difficulties such as disease-rarity and very large numbers needed, dose measurement problems, and the confounding factors described by Dr Cartwright. The many laboratory studies have very little in common, using different exposure levels, field waveforms and biological models, but rarely presenting dose-response data or providing adequate environmental control to eliminate or identify other factors. However, despite the lack of convincing scientific data, public concern has grown, often fuelled by sensationalist media coverage. Considerable resources are spent on research in Europe and the United States, where legislation to limit field exposures is being contemplated in some States despite the absence of dose-response data on which to base it. There are
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several positive ways forward for the scientific community, including international co-ordination of research to avoid duplication and to gain consistency of results; establishment of laboratory models robust enough to be followed at several independent centres, with the main aim of discovering dose-response curves and assessing any impact on human health; and a voluntary moratorium on publication of results of any studies until they have been replicated independently.
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Discussion In discussion which followed these formal presentations, the relevance of dose-response curves was questioned. Dr McLauchlan thought that this requirement was an inappropriate carry-over from other areas of work. In contrast, electromagnetic field effects seem not to be dose-dependent—above a certain level there is no change in biological response. It seems more correct to say that one exposure may have triggered the pathological event, and increasing doses or dose-levels only increase the probability of this happening. Following Dr Barker's call for international collaboration and protocolsharing, participants noted that there exists the Committee for International Research into Powerlines, involving 46 countries. However, this has existed since 1921, concerns itself with very high voltage power-lines, and seems not to be collaborative in the fullest sense intended by Dr Barker. The national studies in Canada, the United States and Britain, and a World Health Organization international initiative, may provide the numbers and statistical robustness needed to address these issues. A participant noted that brain tumours are grossly under-researched in epidemiological terms. There is evidence of excess incidences in some industries (for example, the electrical, solvent and aerospace industries). Some of the methodological difficulties were illustrated further by a participant who pointed out that, according to some hypotheses, British Rail with its 50 Hz overhead electricity lines should experience many more affected employees than appears to be the case. But the relative inaccuracy and incompleteness of medical records for retrospective identification of causes of death may be relevant here. It seems that there has been no such health survey of BR workers. Referring to Dr McLauchlan's paper, another participant questioned why, if free radicals are carcinogenic, they do not show up in mutagenicity studies. The body eliminates DNA replication errors. Perhaps low frequency electromagnetic fields reduce this capacity of the body instead of, or as well as, increasing the number of replication errors. It seems likely that these phenomena occur most in people whose immune systems are already compromised; this might be the most interesting sub-set of the population for epidemiological studies to concentrate upon in future. Dr Male felt sure that the molecular biochemistry of these biological effects is the new and crucial focus for research in this area, from which advances in knowledge would come.
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References 1.* National Radiological Protection Board. Guidance as to restrictions on exposures to time varying electromagnetic fields and the 1988 recommendations of the International Non-ionising Radiation Committee. Document GS11. Didcot: NRPB, 1989. 2.* Institution of Electrical Engineers. The possible biological effects of lowfrequency electromagnetic fields. Public Affairs Board Report no. 10. London: IEE, 1991. 3. Cartwright RA. Low frequency alternating electromagnetic fields and leukaemia: the saga so far. British Journal of Cancer 1989; 60, 649-51. 4. Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. American Journal of Epidemiology 1979; 109, 273. * available in the Resource Centre of the Medical Educational Trust, at 601 Holloway Rd, London N19 4DJ. (17 April 1992)
Abstract Changing the Consent Rules for Desert Storm, by George J. Annas. New England Journal of Medicine 1992; 326: 770-73. The decision of the US military to seek a waiver of requirements for informed consent for the use of investigational drugs and vaccines among US troops during the Gulf War is reviewed. This raises three issues: how easily the distinction between therapy and experimentation can become blurred; differences between law and ethics; and the ethical obligations of physicians when the interests of their patients conflict with the interests of the patients' and/or physician's employer. Two agents were involved primarily: pyridostigmine bromide as pre-treatment for nerve-gas attacks, and pentavalent botulinum-toxoid vaccine to protect against botulism in biological warfare. The Food and Drug Administration granted the waiver but an action was brought in the district court to prevent their use in this way, based partly on the Fifth Amendment. The judge considered that such military decisions were not within the court's jurisdiction, but stated that if it were he would uphold the military decision; he made no reference to the Nuremburg Code. On appeal the lower court's decision was upheld but on different grounds, again with no reference to the Code. The Nuremburg Code is then considered; its first principle provides that voluntary, competent, informed and understanding consent of the subject in any human experimentation is 'absolutely essential'. Annas manages to conclude that the non-voluntary use of pyridostigmine bromide was not experimentation but treatment and therefore acceptable under the Code, and that no FDA waiver was needed in the first place; and that the military's later decision to make administration of the vaccine optional rendered this aspect of the matter acceptable also. Finally, considering 'the role of military physicians', he states 'The only justification a physician can have for participating in the administration of experimental or investigational drugs without soldiers' consent is that he or she sincerely believes the agents are therapeutic under combat conditions.' ILD
Medicine and War Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/fmcs19
Biological effects of low frequency electromagnetic fields I. Lee Doucet BA DipM
a
a
Research/Education Officer , Medical Educational Trust , 601 Holloway Road, London, N19 4DJ Published online: 22 Oct 2007.
To cite this article: I. Lee Doucet BA DipM (1992) Biological effects of low frequency electromagnetic fields, Medicine and War, 8:3, 205-212, DOI: 10.1080/07488009208409047 To link to this article: http://dx.doi.org/10.1080/07488009208409047
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions
CONFERENCE REPORT
Biological Effects of Low Frequency Electromagnetic Fields Downloaded by [University of Sussex Library] at 18:14 02 February 2015
I. LEE D O U C E T BA DIPM
Research/Education Officer, Medical Educational Trust, 601 Holloway Road, London N19 4DJ
Epidemiological studies since 1979 have raised some medical and much public concern that low frequency electromagnetic fields, such as those of power-lines and in domestic and industrial electrical wiring, may have harmful biological effects. These studies are generally inconsistent, inconclusive, and difficult to replicate. Identifying biological mechanisms by which such harmful effects may occur has proved difficult, although there are several new and promising approaches. In epidemiological and laboratory studies' much greater co-ordination and standardization is needed if greater scientific knowledge of these phenomena, as opposed to mere diverse speculation, is to be achieved. KEYWORDS
Electromagnetic fields Cancer Children Epidemiology Laboratory studies
Leukaemia Biological mechanisms
In 1989 the National Radiological Protection Board issued guidelines1 on exposure to and protection from electromagnetic fields, which are currently being revised. In July 1991 the Institution of Electrical Engineers produced a report2 reviewing all then-available evidence on this controversial subject. A discussion meeting on 5 March 1992 was held by the IEE to allow comment on this report, to update it where possible, and to invite answers to the question 'where do we go from here?' The controversy was summarized thus in a guest editorial in the British Journal of Cancer: A perceived risk has evolved associating leukaemogenesis with 'excessive' exposure to alternating electromagnetic fields (EMF) at the very low frequencies of 50 or 60 Hz from electrical sources. This originated from one epidemiological study published in 1979 ... and some earlier and rather controversial biological observations on cellular calcium changes across membranes of cerebral tissues when weak electromagnetic fields were applied... Since then a vast amount of time, effort and money has been invested into the possible harmful effects of EMF. MEDICINE AND WAR, VOL. 8, 205-212 (1992)
206
I. LEE DOUCET
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
This has been stimulated by genuine public concern, by legal rulings in the US ordering investments in research before new overhead powerlines can be built and by a lively media debate ... there has also been concern about other cancers, suicides and psychosomatic illnesses.3 The non-ionizing radiation emitted at 50-60 Hz from electrical sources is at the lowest extreme of the electromagnetic spectrum. These extremely low frequencies are several orders of magnitude below radiowave frequencies and approximately 16 orders of magnitude below the ultraviolet spectrum, which is the nearest energy known to have harmful biological effects (skin cancers from excessive exposure to sunlight).
Epidemiology Epidemiological studies of the possible biological effects of low frequency electromagnetic fields were reviewed by Dr Ray Cartwright of the Leukaemia Research Fund Centre for Clinical Epidemiology, at Leeds University. Wertheimer and Leeper's 1979 study4 appeared to show a significant link between childhood cancer, brain tumours and the amount of electromagnetic radiation in households. This caused much interest world-wide and was followed by many studies, most of which have been inconsistent in methodology and findings, and inconclusive. However, there are some exceptions. At least twelve surveys from N America, Britain and Europe show a consistently and statistically significant relationship between acute myeloid leukaemia, other adult leukaemias and occupational exposure to electromagnetism. But all these findings could be interpreted otherwise; many of the occupations concerned, for example, welding, involved exposure to toxic and potentially leukaemogenic materials. None of them measured electromagnetic fields, and until proper dosimetry is produced a causal relationship with electromagnetic exposure remains only one of several possible explanations. There are many methodological difficulties in establishing a relationship between electromagnetic exposure and various cancers. The first difficulty concerns statistical significance. Each of the cancers being studied is extremely rare; childhood leukaemia occurs in approximately one case per 100,000 population per annum, and even myeloid leukaemia is only about three times more common; many of the rarer childhood cancers are difficult to diagnose. The number of people heavily exposed by their close proximity to overhead power-lines is only 1-2 per cent of the population. The coincidence of these two rare events makes achieving adequate statistical power extremely difficult. Moreover, many studies have examined only easily available cases rather than all cases in a particular area. Another difficulty concerns 'dose'. Exposure should be known at or up to the critical period of leukaemogenesis when significant mutational events take place which lead to induction of the disease. But in only a few types of
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
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cancer do we know the latency-period, and there is no lasting biological marker by which exposure may be measured; without that knowledge investigators do not know when to focus on exposure or where to look for pathological outcomes. In many epidemiological studies distance from power-lines is used, but this has proved a poor surrogate for exposure or dose. Equipment has until recently easily allowed only spot measurements of exposure, and two recently developed personal dose meters are still too large to be carried by young children. Personal dose monitoring studies have added to the confusion about electromagnetic exposure. More may come from domestic sources than from power-lines, and this seems to vary from one part of the house to another, and between neighbourhoods. Other difficulties include variations between studies in definitions of geographical area, ages of children, and of diagnosis. Thus it has not been productive to overcome lack of statistical power of individual studies by pooling their results. More fundamentally, studies so far suffer from the twin epidemiological problems of confounding and interaction. Most take a unicausal approach, investigating only the possible link between electromagnetism and cancers while ignoring other possible causative, contributory or synergizing factors. The ideal epidemiological study would be a very large, prospective cohort study, starting at birth to measure the exposure of a very large number of subjects, then after a considerable period of time measuring the malignancies that have occurred. But this would involve many thousands of children, and a huge investment of resources, with a delay of many years. A new phase of studies promises much larger numbers and statistical power, and better measurement of exposures. In Canada a national study of all childhood leukaemias has as its prime hypothesis that low frequency electromagnetic fields contribute significantly to the disease. A similar study is being conducted in the United States, and by the International Agency for Research on Cancer. In Britain the national five-year study of childhood cancer which was announced in March this year will include measurement of electromagnetic exposure.
Modes of Exposure and Biological Mechanisms Possible modes of exposure and biological mechanisms were examined by Mr John Male of the National Grid Technology and Science Laboratories. The hypothesis, derived from epidemiological studies, that disease may be linked with long-term residential exposure to power-frequency magnetic - but not electric - fields as low as 0.2-0.3 microtesla (T) raises interesting questions about possible interaction mechanisms, as currents induced in the body by electric fields in homes are generally greater than those induced by the magnetic fields. Many in vitro laboratory studies have simulated exposure to fields by injecting current into biological samples via implanted electrodes. Others
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
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have used purely magnetic exposures. Whether reported effects are due to induced currents or to direct magnetic interactions is still disputed. The basis of most interaction models has been that induced currents may disturb molecules on the outer surfaces of cell membranes and that some form of biochemical or mechanical transductive coupling then leads to effects inside the cell. This makes it difficult to explain how the very weak currents induced by environmental fields could prevail over thermal noise. In seeking to identify any biological effects of power frequency electromagnetic fields, it is important to note other electrical and magnetic fields affecting people, and the very small size of power frequency electromagnetic fields in this context. Residential power fields are less than 1 per cent of the earth's geomagnetic field and equivalent to the electrical effect about one metre from a current of 1 to 1.5 amps. Simply moving through the geomagnetic field, for example walking at one metre per second, generates internal electrical fields ten times greater than those induced by power frequency magnetic fields. Endogenous fields associated with nerve and muscle activity are about 1 mA/m2 associated with electrical fields of 5 mV/m2 in major organs such as the brain and heart — swamping the power-frequency-induced fields by several orders of magnitude. If there are any biological effects of power frequency fields, they are likely to be purely magnetic. The possibility of direct magnetic interactions with living systems is now being investigated, with several interesting observations. Relatively strong magnetic fields of a millitesla or more can influence the kinetics of certain free-radical reactions. Other recent investigations suggest that much weaker fields may disturb the vibrational symmetry and binding energy of ions coupled to protein molecules — a mechanism which could, in principle, modify a number of biochemical pathways. The pattern and rate of genetic transcription can be changed by exposure to magnetic fields at low frequency (less than 100 Hz) and low amplitudes (about 5 microtesla). Other effects seem to depend on a combination of static and oscillating magnetic fields. Chemical Effects of Static and Varying Magnetic Fields The hunt for demonstrable and reproducible effects of electromagnetic fields in biological systems has been handicapped by the lack of any generally accepted mechanism by which they might occur, stated Dr Keith McLauchlan of Oxford University. Few investigators have realized that magnetic fields affect certain types of chemical reaction, and do so in a completely reproducible way. Of particular interest in this context, chemical reactions which proceed via free radical intermediates are affected by electromagnetic fields. Chemical bonds depend on atoms and free radicals coming together to form a pair of electrons, which constitute the chemical bond. Electrons also possess the intrinsic property of spin, which can be influenced by a magnetic source; changing the spin properties of electrons damages the chemical bond. It seems that magnetic fields appear to change the probability
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
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that free radicals will escape from electrons; if these free radicals then encounter DNA, they increase the chance of replication errors in the DNA accumulating. The suggestion here is that cancer follows from free radical attack on DNA. Stomach cancers and ulcers are known to correlate with free radical activity. The effect of a static field increases monotonically as its magnitude is increased from zero, often reaching an asymptotic value by about 8 mT and not increasing further until fields above 1 or 2 T are reached. Below 1 mT there is a particularly interesting low field effect. Several distinct mechanisms are involved, which all involve the spin requirements of chemical bond formation, and singlet-triplet state interchange in pairs of radicals. Inside a static field, this interchange may be influenced by the application of an oscillating field. A continuous range of frequencies is effective, depending on the strength of the static field. These effects may underlie any biological effects of electromagnetic fields, but this has yet to be proved in areas other than photosynthesis, where their action is clear. At maximum, they can affect 66 per cent of product formation, but this depends on the diffusion conditions in the environments of the radicals. Biological Bases for Restricting Human Exposure
The National Radiological Protection Board's 1989 guidelines on standards1 relating to electromagnetic fields are currently under revision, with a draft expected to be circulated for comment this summer, stated Dr Sienkiewicz of the NRPB. This body issues advice to government departments and others. In issuing such guidelines the NRPB has three main criteria - that the harm to be protected against is identified, that a dose-response relationship is established, and that a mechanism of interaction is described - all on a basis acceptable to the general scientific community. The known biological effects of exposure to electromagnetic fields are surface charge effects (electrical only), and induced current effects. Surface effects include the vibration of hair and spark discharges against grounded objects. Induced current effects may be electrical and linear, or magnetic and circulating, and occur mostly in peripheral tissue and areas such as the wrist, ankles and neck. But it is known that central nervous system tissue is far more 'excitable' than peripheral tissue. That acute exposure to extremely low frequency electric and magnetic fields will result in the induction of electric potentials and currents in the body which may affect nerve or muscle cells is well established. Such effects range from direct nerve stimulation to modulation of ongoing electrical activity in the central nervous system. Biological effects of low frequency electromagnetic fields on circadian rhythms, development of the embryo and foetus, and on carcinogenesis have been reported. There is some evidence from animal studies of a dose/response relationship with regard to pineal gland activity and melatonin secretion, reduced tumour-inhibition, gonad- and mammary-cell stimulation. Adverse
Downloaded by [University of Sussex Library] at 18:14 02 February 2015
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birth outcome and abnormal development has been shown in chicks but not in mammals up to quite intense fields around 200mT. In general there seems inadequate evidence at present that electromagnetic fields have effects on circadian rhythm or foetal and embryo development. So far it seems that with induced electromagnetic fields below 10 mA/m2 there is no convincing evidence of adverse health effects, while over 100 mA/m2 there are significant biological effects. It is generally accepted that such fields are not mutagenic. Present studies are looking for evidence of an effect on cell proliferation. Other data challenge conventional assumptions about dose-response relationships. Frequency and amplitude windows have been reported for various effects and a number of recent studies have reported that certain combinations of static and time-varying magnetic fields can affect some physiological or behavioural responses. However, it seems that these observations do not form a sufficiently cohesive set of data from which restrictions on human exposure can be derived. The Way Forward . . .
Dr Tony Barker of the Royal Hallamshire Hospital in Sheffield concluded the meeting by asking 'where do we go from here?' There is no doubt that electromagnetic fields can have some biological effects. Induced currents can be used to heat tissue and those produced by large magnetic field pulses can directly stimulate nerves. However, these well-established effects occur at levels many orders of magnitude higher than those to which we are normally exposed. Work on electromagnetic hazards has largely been driven by a small number of epidemiological studies which claim to show a slightly elevated risk of leukaemia at locations in the vicinity of electricity wiring, although this does not correlate well with field measurements at those locations. These epidemiological studies are inconsistent and unconvincing in methodology and findings, and difficult to replicate. Few of them present dose-reponse curves, which are essential in increasing our understanding of these phenomena; instead they simply rely on spot measurements. Epidemiological studies are unlikely to produce definitive answers, because of methodological difficulties such as disease-rarity and very large numbers needed, dose measurement problems, and the confounding factors described by Dr Cartwright. The many laboratory studies have very little in common, using different exposure levels, field waveforms and biological models, but rarely presenting dose-response data or providing adequate environmental control to eliminate or identify other factors. However, despite the lack of convincing scientific data, public concern has grown, often fuelled by sensationalist media coverage. Considerable resources are spent on research in Europe and the United States, where legislation to limit field exposures is being contemplated in some States despite the absence of dose-response data on which to base it. There are
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several positive ways forward for the scientific community, including international co-ordination of research to avoid duplication and to gain consistency of results; establishment of laboratory models robust enough to be followed at several independent centres, with the main aim of discovering dose-response curves and assessing any impact on human health; and a voluntary moratorium on publication of results of any studies until they have been replicated independently.
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Discussion In discussion which followed these formal presentations, the relevance of dose-response curves was questioned. Dr McLauchlan thought that this requirement was an inappropriate carry-over from other areas of work. In contrast, electromagnetic field effects seem not to be dose-dependent—above a certain level there is no change in biological response. It seems more correct to say that one exposure may have triggered the pathological event, and increasing doses or dose-levels only increase the probability of this happening. Following Dr Barker's call for international collaboration and protocolsharing, participants noted that there exists the Committee for International Research into Powerlines, involving 46 countries. However, this has existed since 1921, concerns itself with very high voltage power-lines, and seems not to be collaborative in the fullest sense intended by Dr Barker. The national studies in Canada, the United States and Britain, and a World Health Organization international initiative, may provide the numbers and statistical robustness needed to address these issues. A participant noted that brain tumours are grossly under-researched in epidemiological terms. There is evidence of excess incidences in some industries (for example, the electrical, solvent and aerospace industries). Some of the methodological difficulties were illustrated further by a participant who pointed out that, according to some hypotheses, British Rail with its 50 Hz overhead electricity lines should experience many more affected employees than appears to be the case. But the relative inaccuracy and incompleteness of medical records for retrospective identification of causes of death may be relevant here. It seems that there has been no such health survey of BR workers. Referring to Dr McLauchlan's paper, another participant questioned why, if free radicals are carcinogenic, they do not show up in mutagenicity studies. The body eliminates DNA replication errors. Perhaps low frequency electromagnetic fields reduce this capacity of the body instead of, or as well as, increasing the number of replication errors. It seems likely that these phenomena occur most in people whose immune systems are already compromised; this might be the most interesting sub-set of the population for epidemiological studies to concentrate upon in future. Dr Male felt sure that the molecular biochemistry of these biological effects is the new and crucial focus for research in this area, from which advances in knowledge would come.
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References 1.* National Radiological Protection Board. Guidance as to restrictions on exposures to time varying electromagnetic fields and the 1988 recommendations of the International Non-ionising Radiation Committee. Document GS11. Didcot: NRPB, 1989. 2.* Institution of Electrical Engineers. The possible biological effects of lowfrequency electromagnetic fields. Public Affairs Board Report no. 10. London: IEE, 1991. 3. Cartwright RA. Low frequency alternating electromagnetic fields and leukaemia: the saga so far. British Journal of Cancer 1989; 60, 649-51. 4. Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. American Journal of Epidemiology 1979; 109, 273. * available in the Resource Centre of the Medical Educational Trust, at 601 Holloway Rd, London N19 4DJ. (17 April 1992)
Abstract Changing the Consent Rules for Desert Storm, by George J. Annas. New England Journal of Medicine 1992; 326: 770-73. The decision of the US military to seek a waiver of requirements for informed consent for the use of investigational drugs and vaccines among US troops during the Gulf War is reviewed. This raises three issues: how easily the distinction between therapy and experimentation can become blurred; differences between law and ethics; and the ethical obligations of physicians when the interests of their patients conflict with the interests of the patients' and/or physician's employer. Two agents were involved primarily: pyridostigmine bromide as pre-treatment for nerve-gas attacks, and pentavalent botulinum-toxoid vaccine to protect against botulism in biological warfare. The Food and Drug Administration granted the waiver but an action was brought in the district court to prevent their use in this way, based partly on the Fifth Amendment. The judge considered that such military decisions were not within the court's jurisdiction, but stated that if it were he would uphold the military decision; he made no reference to the Nuremburg Code. On appeal the lower court's decision was upheld but on different grounds, again with no reference to the Code. The Nuremburg Code is then considered; its first principle provides that voluntary, competent, informed and understanding consent of the subject in any human experimentation is 'absolutely essential'. Annas manages to conclude that the non-voluntary use of pyridostigmine bromide was not experimentation but treatment and therefore acceptable under the Code, and that no FDA waiver was needed in the first place; and that the military's later decision to make administration of the vaccine optional rendered this aspect of the matter acceptable also. Finally, considering 'the role of military physicians', he states 'The only justification a physician can have for participating in the administration of experimental or investigational drugs without soldiers' consent is that he or she sincerely believes the agents are therapeutic under combat conditions.' ILD
