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Biomagnetic stressor effects in primates
Physiology and Behavior, Vol. 9, pp. 171-173, Brain Research Publications Inc., 1972. Printed in Great Britain.
Biomagnetic Stressor Effects in Primates H O W A R D F R I E D M A N A N D R O B E R T J. C A R E Y
Syracuse VA Hospital and State University of New York, Upstate Medical Center, Syracuse, N.Y. 13210, U.S.A. (Received 19 M a y 1972)
FRIEDMAN,H. AND R. CAREY. Biomagneticstressor effects in primates. PHYSIOL.BEHAV. 9 (2)171-173, 1972.--Squirrel monkeys were exposed to a steady state magnetic field of about 200 gauss. There were 10 exposure periods, 4 hr a day, for a total or 40 hr. Histological evaluation of the brains revealed no significant neuropathology. Urinary 17-hydroxycorticoids were significantly higher in the experimental animals than in the controls. This was the result of an initial transient elevation of the stress product early in the experimental period which subsided with continued magnetic field exposure. Magnetic fields
Biomagnetics
Stressors
Squirrel monkey neuropathology
A PREVIOUSstudy by the authors [1] attempted to replicate, with rabbits, an investigation [2, 3] which reported significant neuropathologic changes in rabbits and cats, the heads of which were exposed to steady state magnetic fields of 200-300 oe for 1, 10, and 60-70 hr periods. The type of neuropathologic changes found by the Russian investigators was not observed by Friedman and Carey. Rather, histologic findings in four experimental and two control animals, and in an electrode-implanted non-exposed animal, were consistent with the presence of the endemic encephalitozoonosis common to American rabbit colonies. There was the suggestion, however, of a possible stressor effect induced by the imposed magnetic field which had acted to unmask a subclinical, otherwise routinely undetectable, disease. This observation is consistent with that of other investigators: Barnothy [4] reported that 14 days of exposure to a static magnetic field of 5900 oe at the rate of 5 days per week could effect in mice a decrease in body weight and on occasion prove lethal to mares; and, more directly, a stressor effect was indicated in the observation made by Barnothy and Stimegi [5] that significant abnormalities occur in the adrenal cortex, liver, and spleen of mice subjected to steady state high-level magnetic fields. The current study attempts to determine whether a steady state magnetic field, similar in flux density to that used by the Russian investigators, can produce significant and objectively demonstrable stressor effects when imposed upon primates, and whether prolonged exposure to such a field can give rise to neuropathologic changes. Both considerations would have significant theoretical implications for understanding the relationship of external force fields to basic parameters of behavior as well as being critical for behavioral research in biomagnetics with human subjects.
experimental animal and a control as a pair. All animals had been previously subjected to a "Nutritional-Management Program" during a 30-day conditioning and quarantine period by the supplier who also furnished a certificate of negative T.B. test. APPARATUS AND PROCEDURE
Magnetic fields were produced by twin commercially fabricated water-cooled Helmholtz coils, 12.5 in. in diameter, fixed so as to provide a coil interspace of 11 in. The coils were powered by a d.c. power supply of 1 kW input and capable of 50 A, 22.5 V output. After an adaptation period of 14 days, urine collections were obtained for each of a pair of monkeys from six days prior to starting the experimental procedure until the day of sacrifice. Urine was collected daily at 8.00 a.m. from glass beakers below stainless steel metabolic pans attached to each cage. Feces, food, etc., were kept apart from the urine by the use of two fine-mesh wire screens, one of which was funnelshaped and placed in the base of the metabolic pan. The other screen was located above this and just out of reach of the monkey. Immediately upon collection the urine was transferred to plastic vials and frozen. The glass beakers, screens, and metabolic pans were washed daily. At the same time that urine collections started, mild tranquilization of the animals was begun through a daily i.m. injection (approximately 1.5 mg per kg of body weight) of Sernylan (pbencyclidine hydrochloride) in order to be able to move the animal safely and keep it inactive during the hours of experimentation. Following the injection, the experimental monkey was placed in a plexiglass restraining chair which could be positioned so as to place the animal's head at the center of the field. The matching control animal was similarly tranquilized and confined in a chair at the same time and in the same unilluminated experimental room, but placed outside of the magnetic field. The 10 exposure periods were 4 hr in length at the same time each day, 5 days a week, for a 40-hr total. The upper limit of magnetic field exposure time was set by a preliminary investgtiaion which indicated the number of
METHOD
Animals Twenty-six 550-700 g female squirrel monkeys were used so that each of the 13 experimental sequences contained an 171
172
FRIEDMAN AND CAREY
times several squirrel monkeys could be safely and comfortably tranquilized on a daily basis. The magentic field imposed was the highest intensity of which the apparatus was capable, reading 200 gauss on the monitoring gaussmeter when the magnetic probe was placed at a point in the field corresponding to the position of the center of the animal's head. As with the previous study with rabbits [1], it should be cautioned that the recorded flux density does not reflect the absolute level to which the animal is exposed, but rather the level imposed experimentally over and above the ambient field intensity in the area. Within three days after exposure, each experimental animal, together with its control, was sacrificed by means of a lethal intravenous injection of Nembutal. lmmediatley after death each animal was perfused via an intracardiac catheter with 500 ml of normal saline followed by 500 ml of ammonium bromide formalin solution as described by Naoumenko and Feigin [6]. The whole brain was removed and placed in ammonium bromide formalin solution for 48 hr. At the end of this time a 5 mm thick frontal section was cut from the anterior forebrain and then embedded in paraffin. The block of tissue contains a large portion of the frontal cortex including sensorimotor cortex along with substantial parts of the caudate and septal nuclei. Sections, 6 t~ thick, were cut from this tissue block with a microtome and prepared for selective cell staining. Cresyl violet stain was used for nerve cells, hematoxylin and eosin stain for glial cells and nerve cells, silver carbonate impregnation for microglia, Cajal goldsublimate stain for astrocytes, Brown-Brenn stain for bacteria, and Giemsa stain for brain collagen. As the slides were obtained from each pair of animals, they were sent to a neuropathologist for independent evaluation. The physiological stress measure used was the amount of 17-hydroxycorticoids. An elevation in the production of these steroids is commonly considered, as Tepperman [7] indicates, to reflect a non-specific systemic body reaction to stress. Daily urine collections were combined into 72-hr period specimens in order to assure sufficient volume for convenient biochemical determination which was done as described by Glenn and Nelson [8]. This provided six determinations: two pre-experimental levels and four during the experimental period. RESULTS AND DISCUSSION
The typical neuropathologic findings consisted of occasional pyknotic neurons present indiscriminately in both experimental and control monkeys. However, a laminar necrosis appeared in the first experimental animal and in a later control animal. A slight but definite increase in astrocytes and microglia was observed in another control monkey, and evidence of an early granulomatous lesion appeared in yet another control. In terms of the histologic procedures used in this study, it is apparent that no significant neuropathologic changes can be attributed to the 40-hr exposure to a steady state magnetic field of flux density of approximately 200 gauss. Uncontaminated urine specimens collected consistently over the entire pre-experimental and experimental periods and which were not exposed to fortuitous artifacts either during collection or biochemical assay were available on 7 of the 13 pairs of monkeys. F o r convenience of statistical analysis the two pre-experimental period findings were averaged to provide a single base-line measure. Figure 1 presents, for each group, the mean milligrams of 17-hydroxycorticoids for each of the 72-hr experimental periods and for the mean pre-experimental base line.
700
600
50(
Mq 400
300
20C
ooo , Pre - Expetimentol
i
~ Spec~rnert
~, Periods
FIG. 1. Mean milligrams of 17-hydroxycorticoids for specimen periods. The data were submitted to analysis of variance in accordance with designs for multifactor experiments with repeated measurements [9]. An F of 5.66 (df= I, 12) indicated a significant difference (p <0.05) between the two groups. A trend toward an interaction effect (F = 2.344, d f ~ 4, 48, p<0.07), pointing toward transience of response in the experimental group, encouraged further analysis of the data. Thus, a test to break down the interaction into its simple main effects indicated no significant group differences at the preexperimental base-line period, but at Period 1 the two groups were significantly different (F = 6.404, d f = 1, 60, p <0.05) as was the case at Period 2 (F = 9.515, dr= 1, 60, p <0.01). At Periods 3 and 4 there were no longer any significant differences. Inspection of the curves of Fig. 1, with the above analyses, indicates that the animals exposed to the experimental magnetic field respond significantly different than a control group in terms of production of 17-hydroxycorticoids. Further, there is the suggestion of a temporary sharp elevation of stressor response which lasts for about the first 6 days and then subsides despite continued exposure. (This is not unexpected in view of the pattern of Selye's [10] "general adaptation syndrome" which contains an early transient stage of resistance marked by an elevated response of stressor products.) It should be noted that inasmuch as urines were collected on a daily basis consecutively and then combined into 72-hr specimens, and that exposure to magnetic field occurred only during the five work-days of each week, the 72-hr urine specimens collected for Periods 1 and 4 followed 3 days of 4-hr exposure each, whereas the specimens for each of Periods 2 and 3 contained 2 days with radiation plus 1 day totally in the home cage without exposure. There is the possibility, then, that the mean values for the experimental group at Periods 2 and 3 may be somewhat depressed as a consequence of this artifact, and thus the differences between the groups are even larger than the foregoing analyses indicate. Lest the findings be a consequence of difference between the groups in urine volume output, a similar analysis of variance for output for all periods was performed. Neither between-groups nor interaction F's were significant (p > 0.10). In general, then, there was no evidence of any significant neuropathologic changes in the primate brains as a consequence of 40-hr exposure to steady state magnetic fields of approximately 200 gauss. Thus, as with the previous study
BIOMAGNETIC STRESSOR EFFECTS
173
with rabbits [1], the type of neuropathologic changes reported by the Russian investigators [2, 3] were not found in primates exposed to a field intensity level similar to that used with the Russian animals. The previous speculation by the authors [1] that a lowlevel magnetic field could act as a stressor gains support in view of the statistically significant difference in production of 17-hydroxycorticoids between the experimental and control animals. It is, however, important to note the strong trend in the data which suggests that the stressor effect is transient,
disappearing relatively rapidly probably as a consequence of adaptation. Since a study of the effects of magnetic fields upon human reaction time performance [11 ] indicated a significant change with modulated magnetic fields and none with low-level steady state fields, the implication would be that the former are more potent as stressors. A necessary next step, then, would be to undertake an evaluation of the effects of modulated fields upon primates and a comparison with the present findings based only on steady state fields.
REFERENCES
1. Friedman, H. and R. J. Carey. The effects of magnetic fields upon rabbit brains. Physiol. Behav. 4: 539-541, 1969. 2. Aleksandrivskaya, M. M. and Yu. A. Kholodov. Vozrnoznaya role neyroglyyi v voznyknovenyi bioelectricheskoy reactsiyi golovnogo mozga na pastoyannoyo magnitoye polie. Repts. Acad. Sci. USSR 170: 482-485, 1966. 3. Kholodov, Yu. A. Effect of electromagnetic and magnetic fields on the central nervous system. NASA "IT F-465, Transl. of "Vliyaniye elektromagnitnykh i magnitnykh poley no tsentral'nuyu nervnuyu sistemu." Academy of Sciences, USSR, Institute of Higher Nervous Activity and Neurophysiology, Moscow, 1966. 4. Barnothy, J. M. Development of young mice. In: Biological Effects of Magnetic Fields, Vol. 1, edited by Madeleine F. Barnothy. New York: Plenum Press, 1964, pp. 93-99. 5. Barnothy, Madeleine F. and I. Siimegi. Effects of the magnetic field on internal organs and the endocrine system of mice. In: Biological Effects of Magnetic Fields, Vol. 2, edited by Madeleine F. Barnothy. New York: Plenum Press, 1969, pp. 103-126.
6. Naoumenko, J. and I. Feigin. A modification for paraffin sections of the Cajal gold-sublimate stain for astrocytes. J. Neuropath. exp. Neurol. 20: 602-604, 1961. 7. Tepperman, J. Metabolic and Endocrine Physiology, 2nd ed. Chicago: Year Book Medical Publishers, Inc., 1968. 8. Glenn, E. M. and D. H. Nelson. Chemical method for the determination of 17-hydroxycorticosteroids and 17-ketosteroids in urine following hydrolysis with B-glucuronidase. J. Clin. Endo. Metabl. 13: 911-921, 1953. 9. Winer, B. J. Statistical Principles in Experimental Design. New York: McGraw-Hill, 1962. 10. Selye, H. The diseases of adaptation. Recent Progress in Hormone Research 8:117-142, 1953. 11. Friedman, H., R. O. Becker, and C. H. Bachman. Effect of magnetic fields on reaction time performance. Nature 213: 949-950, 1967.
Biomagnetic Stressor Effects in Primates H O W A R D F R I E D M A N A N D R O B E R T J. C A R E Y
Syracuse VA Hospital and State University of New York, Upstate Medical Center, Syracuse, N.Y. 13210, U.S.A. (Received 19 M a y 1972)
FRIEDMAN,H. AND R. CAREY. Biomagneticstressor effects in primates. PHYSIOL.BEHAV. 9 (2)171-173, 1972.--Squirrel monkeys were exposed to a steady state magnetic field of about 200 gauss. There were 10 exposure periods, 4 hr a day, for a total or 40 hr. Histological evaluation of the brains revealed no significant neuropathology. Urinary 17-hydroxycorticoids were significantly higher in the experimental animals than in the controls. This was the result of an initial transient elevation of the stress product early in the experimental period which subsided with continued magnetic field exposure. Magnetic fields
Biomagnetics
Stressors
Squirrel monkey neuropathology
A PREVIOUSstudy by the authors [1] attempted to replicate, with rabbits, an investigation [2, 3] which reported significant neuropathologic changes in rabbits and cats, the heads of which were exposed to steady state magnetic fields of 200-300 oe for 1, 10, and 60-70 hr periods. The type of neuropathologic changes found by the Russian investigators was not observed by Friedman and Carey. Rather, histologic findings in four experimental and two control animals, and in an electrode-implanted non-exposed animal, were consistent with the presence of the endemic encephalitozoonosis common to American rabbit colonies. There was the suggestion, however, of a possible stressor effect induced by the imposed magnetic field which had acted to unmask a subclinical, otherwise routinely undetectable, disease. This observation is consistent with that of other investigators: Barnothy [4] reported that 14 days of exposure to a static magnetic field of 5900 oe at the rate of 5 days per week could effect in mice a decrease in body weight and on occasion prove lethal to mares; and, more directly, a stressor effect was indicated in the observation made by Barnothy and Stimegi [5] that significant abnormalities occur in the adrenal cortex, liver, and spleen of mice subjected to steady state high-level magnetic fields. The current study attempts to determine whether a steady state magnetic field, similar in flux density to that used by the Russian investigators, can produce significant and objectively demonstrable stressor effects when imposed upon primates, and whether prolonged exposure to such a field can give rise to neuropathologic changes. Both considerations would have significant theoretical implications for understanding the relationship of external force fields to basic parameters of behavior as well as being critical for behavioral research in biomagnetics with human subjects.
experimental animal and a control as a pair. All animals had been previously subjected to a "Nutritional-Management Program" during a 30-day conditioning and quarantine period by the supplier who also furnished a certificate of negative T.B. test. APPARATUS AND PROCEDURE
Magnetic fields were produced by twin commercially fabricated water-cooled Helmholtz coils, 12.5 in. in diameter, fixed so as to provide a coil interspace of 11 in. The coils were powered by a d.c. power supply of 1 kW input and capable of 50 A, 22.5 V output. After an adaptation period of 14 days, urine collections were obtained for each of a pair of monkeys from six days prior to starting the experimental procedure until the day of sacrifice. Urine was collected daily at 8.00 a.m. from glass beakers below stainless steel metabolic pans attached to each cage. Feces, food, etc., were kept apart from the urine by the use of two fine-mesh wire screens, one of which was funnelshaped and placed in the base of the metabolic pan. The other screen was located above this and just out of reach of the monkey. Immediately upon collection the urine was transferred to plastic vials and frozen. The glass beakers, screens, and metabolic pans were washed daily. At the same time that urine collections started, mild tranquilization of the animals was begun through a daily i.m. injection (approximately 1.5 mg per kg of body weight) of Sernylan (pbencyclidine hydrochloride) in order to be able to move the animal safely and keep it inactive during the hours of experimentation. Following the injection, the experimental monkey was placed in a plexiglass restraining chair which could be positioned so as to place the animal's head at the center of the field. The matching control animal was similarly tranquilized and confined in a chair at the same time and in the same unilluminated experimental room, but placed outside of the magnetic field. The 10 exposure periods were 4 hr in length at the same time each day, 5 days a week, for a 40-hr total. The upper limit of magnetic field exposure time was set by a preliminary investgtiaion which indicated the number of
METHOD
Animals Twenty-six 550-700 g female squirrel monkeys were used so that each of the 13 experimental sequences contained an 171
172
FRIEDMAN AND CAREY
times several squirrel monkeys could be safely and comfortably tranquilized on a daily basis. The magentic field imposed was the highest intensity of which the apparatus was capable, reading 200 gauss on the monitoring gaussmeter when the magnetic probe was placed at a point in the field corresponding to the position of the center of the animal's head. As with the previous study with rabbits [1], it should be cautioned that the recorded flux density does not reflect the absolute level to which the animal is exposed, but rather the level imposed experimentally over and above the ambient field intensity in the area. Within three days after exposure, each experimental animal, together with its control, was sacrificed by means of a lethal intravenous injection of Nembutal. lmmediatley after death each animal was perfused via an intracardiac catheter with 500 ml of normal saline followed by 500 ml of ammonium bromide formalin solution as described by Naoumenko and Feigin [6]. The whole brain was removed and placed in ammonium bromide formalin solution for 48 hr. At the end of this time a 5 mm thick frontal section was cut from the anterior forebrain and then embedded in paraffin. The block of tissue contains a large portion of the frontal cortex including sensorimotor cortex along with substantial parts of the caudate and septal nuclei. Sections, 6 t~ thick, were cut from this tissue block with a microtome and prepared for selective cell staining. Cresyl violet stain was used for nerve cells, hematoxylin and eosin stain for glial cells and nerve cells, silver carbonate impregnation for microglia, Cajal goldsublimate stain for astrocytes, Brown-Brenn stain for bacteria, and Giemsa stain for brain collagen. As the slides were obtained from each pair of animals, they were sent to a neuropathologist for independent evaluation. The physiological stress measure used was the amount of 17-hydroxycorticoids. An elevation in the production of these steroids is commonly considered, as Tepperman [7] indicates, to reflect a non-specific systemic body reaction to stress. Daily urine collections were combined into 72-hr period specimens in order to assure sufficient volume for convenient biochemical determination which was done as described by Glenn and Nelson [8]. This provided six determinations: two pre-experimental levels and four during the experimental period. RESULTS AND DISCUSSION
The typical neuropathologic findings consisted of occasional pyknotic neurons present indiscriminately in both experimental and control monkeys. However, a laminar necrosis appeared in the first experimental animal and in a later control animal. A slight but definite increase in astrocytes and microglia was observed in another control monkey, and evidence of an early granulomatous lesion appeared in yet another control. In terms of the histologic procedures used in this study, it is apparent that no significant neuropathologic changes can be attributed to the 40-hr exposure to a steady state magnetic field of flux density of approximately 200 gauss. Uncontaminated urine specimens collected consistently over the entire pre-experimental and experimental periods and which were not exposed to fortuitous artifacts either during collection or biochemical assay were available on 7 of the 13 pairs of monkeys. F o r convenience of statistical analysis the two pre-experimental period findings were averaged to provide a single base-line measure. Figure 1 presents, for each group, the mean milligrams of 17-hydroxycorticoids for each of the 72-hr experimental periods and for the mean pre-experimental base line.
700
600
50(
Mq 400
300
20C
ooo , Pre - Expetimentol
i
~ Spec~rnert
~, Periods
FIG. 1. Mean milligrams of 17-hydroxycorticoids for specimen periods. The data were submitted to analysis of variance in accordance with designs for multifactor experiments with repeated measurements [9]. An F of 5.66 (df= I, 12) indicated a significant difference (p <0.05) between the two groups. A trend toward an interaction effect (F = 2.344, d f ~ 4, 48, p<0.07), pointing toward transience of response in the experimental group, encouraged further analysis of the data. Thus, a test to break down the interaction into its simple main effects indicated no significant group differences at the preexperimental base-line period, but at Period 1 the two groups were significantly different (F = 6.404, d f = 1, 60, p <0.05) as was the case at Period 2 (F = 9.515, dr= 1, 60, p <0.01). At Periods 3 and 4 there were no longer any significant differences. Inspection of the curves of Fig. 1, with the above analyses, indicates that the animals exposed to the experimental magnetic field respond significantly different than a control group in terms of production of 17-hydroxycorticoids. Further, there is the suggestion of a temporary sharp elevation of stressor response which lasts for about the first 6 days and then subsides despite continued exposure. (This is not unexpected in view of the pattern of Selye's [10] "general adaptation syndrome" which contains an early transient stage of resistance marked by an elevated response of stressor products.) It should be noted that inasmuch as urines were collected on a daily basis consecutively and then combined into 72-hr specimens, and that exposure to magnetic field occurred only during the five work-days of each week, the 72-hr urine specimens collected for Periods 1 and 4 followed 3 days of 4-hr exposure each, whereas the specimens for each of Periods 2 and 3 contained 2 days with radiation plus 1 day totally in the home cage without exposure. There is the possibility, then, that the mean values for the experimental group at Periods 2 and 3 may be somewhat depressed as a consequence of this artifact, and thus the differences between the groups are even larger than the foregoing analyses indicate. Lest the findings be a consequence of difference between the groups in urine volume output, a similar analysis of variance for output for all periods was performed. Neither between-groups nor interaction F's were significant (p > 0.10). In general, then, there was no evidence of any significant neuropathologic changes in the primate brains as a consequence of 40-hr exposure to steady state magnetic fields of approximately 200 gauss. Thus, as with the previous study
BIOMAGNETIC STRESSOR EFFECTS
173
with rabbits [1], the type of neuropathologic changes reported by the Russian investigators [2, 3] were not found in primates exposed to a field intensity level similar to that used with the Russian animals. The previous speculation by the authors [1] that a lowlevel magnetic field could act as a stressor gains support in view of the statistically significant difference in production of 17-hydroxycorticoids between the experimental and control animals. It is, however, important to note the strong trend in the data which suggests that the stressor effect is transient,
disappearing relatively rapidly probably as a consequence of adaptation. Since a study of the effects of magnetic fields upon human reaction time performance [11 ] indicated a significant change with modulated magnetic fields and none with low-level steady state fields, the implication would be that the former are more potent as stressors. A necessary next step, then, would be to undertake an evaluation of the effects of modulated fields upon primates and a comparison with the present findings based only on steady state fields.
REFERENCES
1. Friedman, H. and R. J. Carey. The effects of magnetic fields upon rabbit brains. Physiol. Behav. 4: 539-541, 1969. 2. Aleksandrivskaya, M. M. and Yu. A. Kholodov. Vozrnoznaya role neyroglyyi v voznyknovenyi bioelectricheskoy reactsiyi golovnogo mozga na pastoyannoyo magnitoye polie. Repts. Acad. Sci. USSR 170: 482-485, 1966. 3. Kholodov, Yu. A. Effect of electromagnetic and magnetic fields on the central nervous system. NASA "IT F-465, Transl. of "Vliyaniye elektromagnitnykh i magnitnykh poley no tsentral'nuyu nervnuyu sistemu." Academy of Sciences, USSR, Institute of Higher Nervous Activity and Neurophysiology, Moscow, 1966. 4. Barnothy, J. M. Development of young mice. In: Biological Effects of Magnetic Fields, Vol. 1, edited by Madeleine F. Barnothy. New York: Plenum Press, 1964, pp. 93-99. 5. Barnothy, Madeleine F. and I. Siimegi. Effects of the magnetic field on internal organs and the endocrine system of mice. In: Biological Effects of Magnetic Fields, Vol. 2, edited by Madeleine F. Barnothy. New York: Plenum Press, 1969, pp. 103-126.
6. Naoumenko, J. and I. Feigin. A modification for paraffin sections of the Cajal gold-sublimate stain for astrocytes. J. Neuropath. exp. Neurol. 20: 602-604, 1961. 7. Tepperman, J. Metabolic and Endocrine Physiology, 2nd ed. Chicago: Year Book Medical Publishers, Inc., 1968. 8. Glenn, E. M. and D. H. Nelson. Chemical method for the determination of 17-hydroxycorticosteroids and 17-ketosteroids in urine following hydrolysis with B-glucuronidase. J. Clin. Endo. Metabl. 13: 911-921, 1953. 9. Winer, B. J. Statistical Principles in Experimental Design. New York: McGraw-Hill, 1962. 10. Selye, H. The diseases of adaptation. Recent Progress in Hormone Research 8:117-142, 1953. 11. Friedman, H., R. O. Becker, and C. H. Bachman. Effect of magnetic fields on reaction time performance. Nature 213: 949-950, 1967.