The Influence of Magnetic Fields including the Geomagnetic Field of Earth on Complex Life Forms: A Silent “Partner” in Human Health and Disease?

1. Introduction

1.1. Purpose

Early life on Earth evolved in the context of temperature, available elements and molecules (including water), as well as the biophysical boundary conditions of the planet. The later include gravity (1 g), exogenous and endogenous radiation from particles emanating from beyond Earth and due to radioactive elements on Earth, and magnetic fields due to the geomagnetic field of the planet and local concentrations of molecules such as iron. Thus, evolution of life within the boundary conditions of Earth for millions of years, even with fluctuations and variations due to solar system cycles and solar events, could not have anticipated life as we know it today with the advent of electromagnetic fields from modern devices, and going beyond such boundary conditions via space flight.

The altered conditions of Low Earth Orbit (LEO) space flight have already exposed astronauts to severely decreased gravity and elevated risk for exposure to radiation, and spending time in such conditions has led to a number of biological responses, particularly due to the loss of the 1 g gravity. However, the influence of increased risk for radiation exposure has not yet been documented in detail, likely in part due to the small number of individuals who have spent time at LEO.

It should be noted that one boundary condition of Earth that has not yet been exceeded by space flight is that of the geomagnetic field of Earth. At LEO, the geomagnetic field is still evident, and perhaps even at the distance of the moon, some of its influence could still be evident [discussed in 1–3].

Thus, humans have not ventured beyond the geomagnetic field of Earth and since some of the central systems of humans (i.e. cardiovascular and neural systems) generate and respond to magnetic fields, this boundary condition likely deserves more study as humans plan to travel to Mars and beyond the geomagnetic field of Earth for the first time. Thus, this article attempts to discuss the various aspects of magnetic fields on life, the potential involvement of magnetic fields on cellular and integrated biological processes, and how a lack of this boundary condition for a protracted time frame could lead to loss of function. Thus, we know that we live in magnetic fields (i.e. the geomagnetic field and local concentrations of magnetic elements), but it is mostly a silent boundary condition and we as yet do not ascribe and functions to it in our daily life. However, as we venture beyond its influence, we likely need to be prepared to understand the potential consequences and anticipate solutions to such consequences as we were not designed for space travel.

1.2. Background

Life on Earth evolved slowly from simple single cell entities that could eventually reproduce themselves using information storage molecules such as DNA. Initially as prokaryotes, and eventually as eukaryotes with subcellular organelles including mitochondria, such cells adapted to a variety of environmental conditions (deep ocean vents, fresh water, cold to hot water, etc). Interestingly, most life consists primarily of water.

In addition to securing the abilities to form a plasma membrane and the machinery to perform essential functions, primitive cells needed to develop these abilities within the context of the physical and biophysical boundary conditions of Earth. These include background radiation and radiation from space that was not deflected by the geomagnetic field of the planet, the 1 g gravity of the planet, and the actual geomagnetic field plus any local magnetic influences. Thus, successful early life must have evolved mechanisms to negate such influences, or evolved adaptations to embrace their influences.

As life likely evolved initially in oceans, lakes or other water environments, perhaps initially boundary conditions such as the 1 g gravity were sensed but further adaptations were required when complex life emerged onto land and mobility and navigation were advantageous. However, the influence of the geomagnetic field would have been felt in early life forms, either with regard to incorporating elements such as iron ions into essential processes, or potentially in other as yet unknown defined manners. The commitment to an information containing molecule such as DNA to be central to reproduction fidelity is also an interesting choice as it can be sensitive to radiation damage and induction of mutations. However, early in evolution this sensitivity could have been used advantageously to use mutations to adapt to a changing biological and physical environment. Mutations could arise from lack of fidelity in copying the DNA and/or radiation-induced effects. As life became more complex and multicellular with differentiated functions, it is also likely that methods to minimize such influences would develop to decrease the likelihood of developing adverse situations that would compromise organism integrity. These latter could include tumor suppressor genes, DNA repair mechanisms, and controlled cell death.

While the 1g gravity of Earth would have been felt by organisms and resulted in settling to the bottom of a lake or near a vent in the ocean, organisms could have resisted this effect via the movement of the water or by attaching themselves to something in shallow water and nutrients could have come to them via water movement. The real impact of the 1 g gravity environment would likely have been felt when multi-cellular organisms emerged to live on land and the advantage of mobility and navigation against ground reaction forces required evolution of new adaptations. Thus, the development of legs for quadrupedal movement and legs and arms for bipedal mobility required evolution of effective adaptations and integration with visual or other sensors. Also, of interest in this regard are species that lived on land and developed legs, but then returned to the marine environment (i.e. whales and other marine mammals). The cardiovascular system of complex lifeforms living on land also required adaptations to function in the 1 g environment. As all tissues except perhaps articular cartilage are vascularized, these adaptations would affect all organ systems.

As evolution could not have predicted space flight and exposure to microgravity, it is interesting that atrophy of mechanically loaded tissues such as bone and muscles is rapidly evident after leaving Earth and living at LEO [discussed in 3]. In addition, cardiovascular effects are also very evident after exposure to microgravity. Interestingly, even prolonged bedrest on Earth leads to loss of bone and muscle and cardiovascular changes, so such tissues have evolved a “use it or lose it” paradigm even when still under the influence of a 1 g gravity environment on Earth [discussed in 3,4].

Another major boundary condition, the geomagnetic field of Earth, certainly “protects” life forms from the negative influence of solar radiation [discussed in 5]. Many forms of exogenous radiation originating from the sun, other cosmic sources (i.e. pulsars, black holes, supernovas] can be deflected by this magnetic field [discussed in 5; and others], and thus protecting the DNA from mutational events or resulting in cell death. For example, it has been reported to enhance radiation resistance by promoting DNA repair processes in cells [6]. From reading of the literature, this attribute is the main influence of the geomagnetic field on life. The real question then becomes “is it the only role” and if so, why and how did life forms develop systems that use electrical signaling with concomitant magnetic field generation within a powerful magnetic field? Such an environment may have led to development of a bioelectric code early in the evolution of simple and then more complex life forms [7], and such a code would also have an electromagnetic component. Thus, such a system may respond to exogenous magnetic fields as well [8] It would be intuitive to conclude that commitment to such systems, such as the brain and neural systems, as well as the heart and cardiovascular system could have evolved approaches to either negate the geomagnetic field or embrace it. Furthermore, as the distribution of elements on Earth that could lead to local magnetic fields is not uniform (i.e. large deposits of Fe containing hematite and taconite non-uniformly concentrated in various locals), the evolved adaptations to the geomagnetic field must account for the exposure to such local concentrations or suffer the consequences

2. Fe-Containing Molecules, Magnetic Fields and Evolution to Complex Lifeforms

As lifeforms became more complex, and within the boundary conditions of Earth, they likely had options for including specific elements into molecules performing a variety of functions. Bacteria depend on Fe for growth [reviewed in 9] and have complex interactions in this regard during infection [10] and in the host-gut microbiota relationship [11]. Therefore, prokaryotes evolved use of Fe ions for essential processes early, and this continued to evolve when they interacted with more complex eukaryotes. Thus, even in a strong geomagnetic field + background magnetic fields from Fe deposits, life forms incorporated Fe-containing processes into biological systems that grew in complexity.

2.1. Incorporation of Ferro-Magnetic Ions in Essential Systems and Molecules

It is interesting that Homo sapiens “inherited” a number of Fe-containing molecules via evolution [12], molecules that are essential for a number of important processes. These include hemoglobin reviewed in [13,14], cytochrome P450 enzymes [15,16,17], transferrin [18], ferritin [19], lactoferrin [20] and others [21,22,23,24].

The regulation of these Fe-containing molecules is tightly controlled as their dysregulation may be harmful to human health [12,25,26,27,28,29,30] as heme appears to have toxic properties [31]. Further evidence for the tight regulation of iron during pregnancy [32], exercise [33], and hypoxia [34] indicate that this ion is very important biologically. Thus, humans contain a considerable amount of Fe in their bodies normally, with an unequal distribution among organs. Therefore, processes involving such Fe-containing molecules could be influenced by both static and electromagnetic fields.

However, nearly all of the literature has been focused on the biochemistry of Fe ions and influences of static or electromagnetic fields on the function of Fe-containing molecules not the focus of much of the literature. Interestingly, exposure of mice [35] to static magnetic fields, or rabbits to electromagnetic fields [36] did lead to detectable alterations in iron metabolism. Given the extensive use of Fe-containing molecules and their associated processes, and the expansion of exposure to electromagnetic fields in everyday life, more extensive investigation of the relationship(s) between these aspects of Fe should be a research focus going forward, perhaps with a focus on neurodevelopment and maturation [37].

Finally, there can also be detectable alterations to iron metabolism in disease processes such as Alzheimer’s disease [38,39,40] and neurodegenerative conditions [41,42,43,44]. Whether these are cause or effect of the diseases is not well defined, but with such local alterations in Fe there may also be alterations to endogenous magnetic field patterns as detected by imaging modalities [45,46,47,48]. Whether the altered magnetic patterns are central to the manifestations of the neurodegenerative conditions or secondary and useful for diagnosis and assessment of disease progression is currently undefined.

2.2. Magnetic Fields and Navigation

Numerous reports using a variety of species, particularly those that migrate indicate that many of these species use specific brain centres to respond to magnetic fields to facilitate migration. These include birds [49,50,51], dolphins [52], fish [53], turtles [54], and some land animals [55]. Whether humans have a similar centre to facilitate navigation is still under investigation discussed in [56]. Thus, in this context, several species have evolved mechanisms to recognize and use the geomagnetic field to their advantage. Thus, the evolution of such migration/navigation facilitation centres must be integrated into other neural systems. How exactly this is accomplished remains to be determined for humans, but some genes have been implicated [58]. Furthermore, how such systems focus on the GMF and filter out background Fe concentrations or the influence of electromagnetic fields is not defined currently. However, the presence of such directional centres in the brain and the incorporation of their use to direction movement does indicate that evolutionarily, lifeforms recognized the GMF and used it for some purposes. Furthermore, some reports have speculated that magnetic fields (both natural and otherwise) could impact human health and disease, potentially at the level of circadian rhythms [59].

2.3. Magnetic Fields and Cognition

One of the distinguishing features of Homo sapiens is their cognition, memory, reasoning and integration of significant aspects of the brain to formulate abstract thinking. How the current levels of these attributes developed during evolution is not known in any detail discussed in [60]. However, it is likely that it developed in discrete steps rather than in some linear process. Furthermore, it must have incorporated existing restrictions based on evolutionary choices made prior to and during the development of complex organisms. As the fossil record cannot assess cognition and brain functioning, some aspects of the evolutionary tree is dependent on interpretation of skull size and shape, as well as other activities of early hominids (artwork, burial practices, and other related activities). If indeed stepwise advances in cognition, memory ability and related brain activities did occur during evolutionary progression to Homo sapiens, then each step required effective integration into the existing paradigm. Interestingly, one is not apparently born with a fully developed set of cognition abilities and they may continue to develop during post-natal development and maturation as hypothesized by Piaget reviewed in [64]. As the fully functional brain of an adult Homo sapiens expresses a pattern of electromagnetic signals as detected by MEG reviewed in [65]; discussed in [66], there appears to be an intimate relationship between functional brain systems, brain biology (i.e. cell, biochemical and molecular) and magnetic fields.

While conventional thought would place emphasis on neural connectivity and biochemical/molecular interactions for such cognitive and memory abilities [62,67,68,69], some authors have advanced theories that consciousness is actually embedded in the electromagnetic field of the brain [69,70,71,72,73], while others have postulated that memory is also stored in magnetic fields [74]. In the theory by McFadden, called the Conscious Electomagnetic Information (CEMI) field theory, it postulates that information is stored in magnetic fields and used to regulate consciousness. For such a system to work, it would also depend on the integrity of the neuronal circuits to manifest some of the information stored in such fields. It would also have to account for the GMF of Earth and its variations, exogenous electromagnetic fields, and exposure of the brain to strong magnetic fields such as those associated with MRI, in order to maintain integrity. While potentially an interesting theory, and one that may fill in the gaps where existing neuronal theories are still lacking to some degree, it is clear that such a system would have to be integrated with the biological system during fetal development in order to accommodate subsequent maturation and have built in safeguards to resist influences of exogenous magnetic fields. A lack of effective integration during the developmental process could potentially lead to elaboration of conditions such as elements of the autism spectrum disorder. Furthermore, a decline in integration due to loss of specific neural cells or some other mechanism (i.e. loss of vascular integrity in specific areas of the brain) during the later stages of life could contribute to conditions such as dementia and specific conditions such as Alzheimer’s disease. Thus, many aspects of this theory and its consequences remain to be elucidated to further its rationale and potential feasibility. Clearly, the complexity of information storage, cognition and how information is processed is complex [75] and thus, the actual “system” for cognition and memory may rely on multiple components, some biological and some biophysical. An additional question is when in evolution did such a system, dependent on magnetic fields, arise and become functional? Likely it would have had to develop early in evolution as it is somewhat hard to imagine that it arose later since it would be such a unique configuration, particularly if it arose in a stepwise manner.

However, aside from the apparent limitations for a magnetic field as the information storage system related to consciousness and memory discussed above and elsewhere [76], several studies have attempted to investigate the effect of exogenous fields and hypomagnetic conditions on cognition. Regarding the former, 50-60 Hz fields [reviewed in 77], radiofrequency fields [78], and static fields [reviewed in 79] have been investigated and proposed. In such circumstances, results are somewhat inconclusive but it is clear that exposure to static fields such as during an MRI, have not been associated with any reported adverse effects. However, in the latter, the time of exposure is limited, while in the former situations with 50-60 HZ and radiofrequency fields, exposure can be more chronic but variable in intensity and exposure time.

The effects of hypomagnetic fields on a variety of species has been reviewed recently [2,3,80,81]. Interest in the effects of hypomagnetic fields has been stimulated both by the desire to better understand the relationship(s) between magnetic fields and life forms, but also since space flight presents the exposure of humans to life beyond the GMF of Earth [2,3,80]. Binhi & Sarimov [1] have reported that there is a zero magnetic field effect on human cognitive processes. However, the effects are modest but statistically significant but limited as the responses were assessed as an acute exposure. However, in actual space flight beyond the GMF of Earth, the lack of a GMF will be chronic but the astronauts will still be exposed to the electromagnetic fields of the equipment aboard the space craft or in the habitat such as on Mars. Of course, in deep space the astronauts will also be exposed to micro- or zero gravity, which also may contribute to cognitive changes discussed in [82]. Thus, long space flight associated alterations in brain activities [83] may be the result of multiple modalities (gravity, magnetic fields, stress, sleep depravation] including magnetic field alterations. However, as the magnetic field contributions are somewhat understudied [discussed in [3]], it may be prudent to better understand such magnetic field effects on astronaut cognition prior to sending them off on long-term deep space missions. Such studies would also benefit those on Earth as well.

3. Exogenous Electromagnetic Field Effects on Biological Systems

3.1. Power Lines and Cancer

For several decades living near high voltage power lines and associated electromagnetic fields has been raised as a risk for human health [84,85], particularly cancers [86,87,88]. While several clinical trials have determined that the incidence of certain types of cancers are not more frequent in such environments, many people fear that some cancer clusters, particularly of leukemias are associated with living near high power lines [89,90], but thus far the data is inconclusive [91,92,93,94]. As the incidence of cases in such “clusters” is still a small percentage of people living close to such power lines, if there is an effect of EMF on cell transformation, it is not a general effect, and the impact may be due to an underlying defect in some metabolic control mechanism in a susceptible subpopulation.

3.2. Cell Phone Use

Similar to fears about living close to high voltage power lines, in recent years a potential risk of excessive cell phone use and tumors has also emerged [95] or been implicated in cancer development [96], but again the results are somewhat inconclusive [97]. However, some reports [98,99,100] indicate that the effects of such fields may go beyond cancers. Of particular interest is the potential link between electromagnetic field exposure and autism [100], a spectrum of conditions localized to the brain arising during development, and the possible association between cell phone use and headaches [99] as both involve the brain.

This latter point regarding non-cancer related issues is likely relevant to both the power line issue and cell phones as a large number of widely used appliances in the home emit electromagnetic fields when active. The question then arises as to why there has not been more conditions/diseases linked to exposure to electromagnetic fields? The answer is not known but clearly humans are very heterogeneous genetically, they are exposed to a variety of environmental insults (air pollutants, artificial chemicals, food additives), some consume alcohol or smoke, and other variables that could confound any potential associations with electromagnetic fields. Also, one would potentially expect that the most obvious effects would be on systems that generate EMF such as the cardiovascular and brain/neural systems. Furthermore, if human systems had inherited via evolution intrinsic mechanisms which allow adaptation or incorporation of endogenous magnetic fields into regulatory systems, one might expect the most overt influences of exogenous EMF would be early in life during development and maturation, or during senescence/aging when systems start to fail.

In addition, variation in the background static magnetic fields would have differentially affected populations living in different parts of the Earth [discussed in 3]. Exposure to such variation preceded the advent of extensive EMF exposures, most of which is a recent development over the past few hundred years. Some reports [101] have implicated such variation in childhood morbidity, but this is currently conjecture and not proven to have cause and effect. However, the concept does then arise that potentially, where you were conceived, developed and matured could impact how you would respond to subsequent EMF.

4. Uses of Magnetic Fields for Health applications

Humans, and other animals, plants and microorganisms have been exposed to a variety of magnetic fields other than the geomagnetic field of Earth and deposits of ferro materials [discussed in 102]. In addition, magnetic fields, static or electromagnetic, have been used for decades in attempts to improve outcomes for repair of a variety of tissues [reviewed in 103–108]. The studies used magnetic fields of varying frequencies and intensities and employed both patients and preclinical models. However, the magnetic fields used in the studies were often variable and it is sometimes difficult to compare studies. Magnetic fields have also been used to study cells [109] and processes such as development [110].

4.1. The Musculoskeletal System (MSK)

Magnetic fields have been used to influence the healing of a variety of tissues of the MSK system. These include soft tissues such as ligaments, tendons, cartilage and menisci, as well as bone, and the studies have spanned several decades [111].

Ligament and Tendon Healing: Using a solid core electromagnet, Frank et al [112] reported that exposure to the field following injury to the rabbit medial collateral ligament led to improved mechanical and biological healing parameters over 6 weeks. Subsequently, Lin et al [113] reported that 2. 10, 50 gauss (G) pulsing electromagnetic fields (PEMFs) during early healing of surgically induced defects in the rabbit patellar ligament/tendon led to improved outcomes, with 50 G yielding the best outcomes. More recently, Xu et al. [114] used exposure to a combination of static and electromagnetic fields (combined magnetic fields, CMF) to assess patella-patella tendon healing in a rabbit model. The authors assessed a variety of biomechanical and biological parameters and found that exposure to CMF led to significantly enhanced healing properties of the tissue at 16 weeks but less so at 8 weeks post-injury. Also in a rabbit model, Hu et al., [115] demonstrated that exposure to a CMF led to enhanced healing of the bone-tendon interface, potentially bey enhancing osteogenesis. Thus, for these soft tissues, and in rabbits, exposure to magnetic fields led to enhanced healing outcomes.

Meniscal and Cartilage Healing: Recently, Wang et al [116] reported that healing of injuries to the avascular region of the menisici of male rats could be enhanced by exposure to pulsed electromagnetic fields over an 8-week study period. In addition, exposure to the PEMF also prevented the progression of the injury and development of osteoarthritis in the affected joints. The authors concluded that exposure to the PEMF led to enhanced fibrocartilage production and decreased inflammation. Interestingly, studies of electromagnetic fields with patients with established osteoarthritis (OA) do not appear to have regenerative effects on tissues but may reduce pain for some patients [117,118]. Whether this effect on pain is due to an effect on inflammatory processes in OA or some other mechanism remains to be determined.

Bone Healing: The study of exogenous magnetic fields on bone healing has had a long history [reviewed in 103,119–121]. Such studies have been performed on a variety of species, and investigators have used both in vivo studies and in vitro studies using bone cells. In vitro studies have been used in attempts to better understand the genes influenced by PEMFs on bone cells or osteogenic precursor differentiation [122]. In guinea pigs, exposure to both static and PEMFs enhanced bone repair of mandibular osteotomies based on histology [123].

Of particular emphasis in the use of magnetic fields on bone healing has been applications to promote compromised healing such as non-unions where natural healing either is protracted or fails. In a recent study of PEMFs in the healing of carpal scaphoid non-unions, the PEMF did not off any benefit [124]. Similarly, EMF exposure exhibited inconclusive effects on delayed or non-union fractures of long bone in adult patients [125]. In contrast, in a small study of 29 patients, the use of a CMF protocol led to enhanced healing of a variety of non-union fractures in both male and female adults [126]. In other reviews of the literature regarding magnetic field effects on non-unions, the consensus appears to be that exposure to magnetic fields (i.e. biophysical stimulation) is an effective modality [127,128,129], and an approach that avoids some of the complications associated with surgical interventions. Whether this variation in outcomes and conclusions is due to the type of magnetic fields that are applied, when and how they are applied, or to host factors is not clear at the present time. Furthermore, it is also not clear at this time how such biophysical interventions impact cells at the biochemical or molecular levels. Some reports indicate it may involve effects on iron metabolism [130], while others indicate it may be at the level of immune and inflammatory process regulation [131]. The influence could be a combination of those elements as an emerging them is an effect of the magnetic fields on inflammation and inflammatory processes. This conclusion would also be supported by reports indicating static magnetic fields can also influence inflammation in the liver of mice [132].

In surrogate models of bone loss in space or immobilization, namely prolonged hindlimb elevation in rodents to remove loading of the bones, it has been reported that PEMF exposure can prevent bone loss due to hindlimb elevation in rats [133], and that exposure to a static magnetic field in addition to loading in the 1 g environment can enhance recovery of bone in mice [134]. In the rat study, the activation of the sAC/cAMP/PKA/CREB signaling pathway was involved in the prevention of the bone loss [133]. In this circumstance, the rat tissues were not overtly injured but were undergoing atrophy, and thus the results may indicate that there is an interaction between magnetism-based mechanisms and loading via the ground reaction forces.

4.2. The Brain and Neurological Integrity

As discussed earlier, functioning of the brain leads to the generation of electromagnetic fields that can be measured by techniques such as SQUID or magnetoencephalogram (MEG) [reviewed in 65,135]. Such techniques can be used for both fetal [136] and adult [137] brain assessment. As such, these techniques can be used to detect neurological issues during development and during aging when loss of neurological integrity can occur with some frequency. However, a limitation of techniques such as MEG is that the detection system does not penetrate deep into the brain.

4.2.1. Detection of Brain Injury or Diseases

Detection of mild brain injury (i.e. post-concussive syndrome) using electromagnetic approaches has been proposed [138]. MEG can also be used for localizing and characterizing epileptic events [139] and potentially, post-traumatic stress disorders [140]. While not an “overt injury” to the brain, space flight has led to the detection of cognition-associated changes [82,141,142,143]. The basis for such changes is likely not due to leaving the GMF of Earth completely since life in LEO on the ISS thus far, so may be related mainly to gravity changes, stresses, and living in confined environments. Some reports have questioned whether head-down tilt bedrest, a surrogate for spaceflight, captures the true nature of spaceflight induced cognitive changes [144]. This surrogate is performed on Earth so the 1 g and GMF environments are still functional, but the subjects are not exposed to the ground reaction forces associated with the 1 g environment. It does however, mimic aspects of cardiovascular changes associated with space flight discussed in 3. To effectively capture space flight related cognitive changes may require new technology for real time assessments [146].

Detection of disruptions of functional networks using MEG, and fMRI have been reported in patients with dementia [147], with some characteristics associated with specific types. MEG analysis in Alzheimer’s Disease [148,149,150] has revealed abnormalities, even in early disease [151,152]. In addition, some reports have discussed the potential role of magnetic fields as risk factors for development of neurological and neurodegenerative diseases [153,154,155].

4.2.2. Health Benefits of Magnetic Fields on the Brain

Pulsed electromagnetic fields have been reported to positively effect microvascular perfusion and tissue oxygenation of the healthy rat brain [156]. Furthermore, the concept that electromagnetic fields could facilitate brain repair via neural stem cells has also been proposed [157], but not yet proven.

Interestingly, transcranial stimulation with PEMFs has been reported to positively influence depression [158,159] and potentially, transcranial magnetic stimulation may exert positive effects on post-traumatic stress disorder [160]. Furthermore, transcranial magnetic stimulation may also alleviate aspects of Alzheimer’s Disease (AD) [161]. Further studies in a mouse model of AD reported that exposure to a specific frequency of electromagnetic stimulation led to improved symptoms [162]. It should be noted that these studies were performed against a background of the GMF of Earth. Thus, improvements via exposure to a specific magnetic field appeared to “correct” disease-associated defects in the functionality of the brain. While the molecular mechanisms responsible for the improvements in patients is not known, in the mouse model, exposure to the 900 MHZ fields led to decreased amyloid plaque deposition in specific areas of the brain of the mice.

While many aspects of studies focused on “correcting” loss of brain integrity using exposure to magnetic fields are not well described, this is an emerging field of study. It is clear that there may be significant variation in outcomes depending on the frequency or intensity of the magnetic fields used for the studies. What the implications are in this regard for psychological, cognitive or neurodegenerative conditions remains to be determined.

4.3. Magnetic Field Effects on Wound Healing

Enhancing wound healing using magnetic fields has had a long history, with cells in vitro, preclinical models and some patient-based studies reported [163], but most studies have used rodent models of cutaneous healing or cells in vitro [164]. In some studies, authors have used diabetic animals as wound healing in such animals is often compromised.

Using cells in vitro, exposure to a variety of static magnetic fields led to changes in cell migration via the membrane and cytoskeleton [165]. Other studies have implicated low frequency electromagnetic fields in enhancing wound healing via anti-inflammatory mechanisms [166].

Using in vivo models, Ekici et al [167] reported that exposure to static magnetic fields led to increased mechanical strength of dermal wounds on the backs of male rats. However, other healing parameters did not appear to be affected. As strength of the scar tissue likely relates to the organization of the extracellular matrix, this effect of the magnetic fields may represent an effect on how well the scar tissue becomes organized. Other reports have used rats with chemically-induced diabetes. Cheing et al [168] reported that PEMFs promoted early wound healing and myofibroblast proliferation in such rats, and thus enhance wound closure. Similarly, Zhao et al [169] reported that exposure to static magnetic fields enhanced wound closure in diabetic rats with elevated wound strength. As compromised angiogenesis in diabetic rats is one variable that may lead to impaired wound healing in diabetic rats [170,171], the magnetic fields may have improved healing via alleviating such vascular issues [106] or other factors. Also in a rat model, exposure to PEMFs enhanced the repair following induction of a frostbite injury [172]. Exposure to the PEMFs led to improved wound strength and accelerated growth of the deep layers following injury.

Again, these effects of magnetic fields were observed on Earth in the presence of the GMF of the planet, any local EMFs from other equipment, and any input from local deposits of Fe-containing compounds.

5. Conclusions and Suggestions for Going Forward

Life, from simple single celled organisms to Homo sapiens have been shaped by the boundary conditions of Earth. Via evolutionary processes, commitments to specific metabolic and reproductive processes have led to the integrated functioning in the context of 1 g gravity, the temperature range, the nutrient availability, the geomagnetic field, and variation in such parameters as a result of choices made millions of years ago. Thus, magnetic field parameters do not exert their influence in isolation, but in the more complex context. Until recent advances have led to the generation of significant electromagnetic fields, and space flight the opportunity to go beyond the boundary conditions, both gravity and magnetic fields, but particularly magnetic fields potentially may have overlapping effects on some biological systems (integration of biology and biophysics).

Regarding magnetic fields, during evolution simple cells could have either used magnetic fields in their progression to independent growth and preproduction, developed methods to negate the impact of magnetic fields, or a combination of both, depending on the systems involved. As microorganisms, as well as birds and mammals can use magnetic fields for navigation purposes, obviously biological systems evolved to use magnetic fields to enhance survival. While not used for navigation purposes, it is of interest that many biological systems use the magnetic Fe ion as an essential component of proteins (i.e. transferrin, ferritin, lactoferrin) and cell function (i.e. hemoglobin in red blood cells for oxygen transport). Certainly, the biochemical and biological role(s) of Fe-containing molecules has been extensively studied, but whether there is also an influence of magnetic fields on function studied much less. This could be an area of focus going forward.

While the effects of exogenous magnetic fields on human biology and cognition have been extensively studied within the boundary conditions of Earth, long-term space flight is presenting the opportunity and challenge of understanding the role and influence of magnetic fields on human functionality, and in particular cognition, memory and function. As space flight beyond the boundary conditions of Earth could not have been anticipated by evolutionary pressures, this excursion beyond the magnetic fields of Earth and exposure to electromagnetic fields presents a unique opportunity. It is not just the deep space travel, but also the opportunity to live on a planet such as Mars which has a 1/3 g gravity but little to no geomagnetic field, and living in habitats that require equipment generating EMFs. While it may be possible to optimally generate Faraday cages [173] to eliminate exogenous EMFs, one would be left with no EMF and little to no GMF, such as those used in preclinical model studies [174,175,176]. If feasible for humans, this may also require further adaptation of living quarters and workstations to generate artificial static magnetic fields. However, much of this discussion is hypothetical at this point, but certainly studies to date either on Earth or from astronauts who have lived on the International Space Station for some time, magnetic fields may influence cognition and brain functions, so deep-space flights can be viewed as a set of experiments, or a new set of conditions that one should be prepared for as once on a deep-space mission, there is no readily turning back.

The implications of this set of “experiments” in space could have implications for those remaining on Earth. First, if there is heterogeneity in astronaut responses to such altered magnetic conditions, it would likely mean all Homo sapiens are heterogenous in this regard. Depending on the response patterns, the “outcomes” of the study of astronauts could have implications for diseases or conditions arising during fetal development that may require effective integration of biology and biophysics, particularly for the brain and cognition, behavior and memory development and maturation. Failure to integrate could lead to or contribute to conditions such as autism. On the other end of the life spectrum, during aging a failure of the integration system could lead to dementia and other brain conditions. Thus, deep-space flight and moving beyond the boundary conditions of Earth for an extended time could provide new information for how Homo sapiens function in a magnetic world, as well have consequences for astronauts attempting to survive and function at long distances from the boundary conditions of Earth that shaped their evolution. Thus, magnetic influences on human health and disease may exist and have been mainly a silent partner throughout most of evolution. However, the advent of exposure to new and chronic electromagnetic fields and the opportunities provided by space flight may elaborate some of their previously undetected influences. Such further investigations may reveal commonalities of magnetic influences in all humans based on evolutionary choices made long ago, but also some individual response patterns to gain or loss of magnetic fields given the heterogeneity of humans [177] and previously documented variation in response to microgravity conditions reviewed in [3,178].