Aging Studies in a Marshallese Population Exposed to Radioactive Fallout in 1954, Radiation and Aging

Page 2

AGEING STUDIES IN A MARSHALLESE population EXPOSED TO RADIOACTIVE FALL-OUT IN 1954 Robert A. Conard, Austin Lowrey, Maynard Either Keith Thompson and William A. Scott The Marshallese people who had been accidentally exposed to radioactive fall-out in 1954 have been examined annually sine e the accident for possible late effects of radiation, including the development of premature ageing. The accidental exposure of these people occurred on March 1, 1954 as a re suit of an unpredicted shift in winds following experimental detonation of a large thermonuclear device at Bikini in the Marshall Islands. A white, snow-like, highly radioactive material was deposited on the island and its 82 inhabitants. There were 64 people (55 now living) who received about 175 rads of whole-body gamma radiation , exposure of the skin from fall-out depo sited thereon, and also significant ‘internal absorption of radionuclides. Eighteen other Rongelape se (I 4 now living) were on a fishing expedition on a nearby island and received less than half the exposure of the other group. Evacuation of the islanders was accomplished two days after the accident. They were returned three years later (1 957 ) when radiation levels on the island were considered safe. Since the accident over 200 Rongelap people or their relatives who had not been exposed to fall-out returned to live with the exposed people and have formed the comparison population. Acute effects from exposure were noted in the Rongelap people during the first few months and consisted largely of early transient gastrointestinal and skin symptoms, followed by depression of lymphocytes, neutrophils, and platelets to one -half to one -third normal levels. The hematopoietic depression however did not result in any obvious infections or significant bleeding. “Beta burns” of the skin along with spotty epilation of the head were wide- spread during the first several months after exposure. No acute effects from the internal absorption of radionuclides were noted. No fatalities occurred, and the people had largely recovered from these acute effects of exposure by the end of the first year. Subsequent examinations have largely been concerned with the possible late effects of radiation. The most significant such finding has been the development of thyroid nodules and hypothyroidism during the past three years among the exposed people. This development is believed to be a late effect of radiation of the thyroid gland from internal absorption of radio iodines and from external gamma radiation at the time of the fall- out. During the two day period following the accident, before the evacuation of the people occurred,

Page 3

the inhabitants absorbed radio nuclides in the fall-out by inhalation and ingestion of contaminated food and drinking water. Based on radiochemical analyses of pooled urine samples taken several weeks after the accident, it was estimated that the adult thyroid gland received about 160 rads from the radioiodines, in addition to 175 rads from the external gamma radiation. In view of the smaller thyroid glands of the younger children, i t was estimated that they received in the range of 700-1400 rads in the more heavily dxpo sed group. As of March, 1966, a total of 16 cakes of nodules of the thyroid gland and two cases of hypothyroidism had been detected The largest incidence (79%) has occurred in the children exposed at less than 10 years of age. No such pathological change’ has been noted in unexposed children or children in the lesser exposed groups. Thyroid surgery has been performed on 11 cases with nodules. Ten of these cases, 9 children and one adult, were all found to have benign nodules. One 41 year old woman was found to have a cancer of the thyroid. Description of these thyroid lesions as well as the possible radiation etiology has been discussed in a recent paper (Conard, Rail and Sutow 1966). A general review of the findings in the Marshallese can be found in other references (Cronkite, Bond, Conard, Shulman, Farr, Cohn, Dunham and Browning 1955, Conard and Hicking 1965). There are few other so-called late kffects of radiation which can, with reasonable certainty, be ascribed to exposure in these people. Among these was an increased incidence of miscarriages and stillbirths noted among the exposed women during the fir st four years after exposure; lag in complete recovery of peripheral white blood cells and platelets to levels of the nonexposed comparison population; and slight retardation of growth and development of children, particularly boys exposed at less than five years of age. A hypothyroid etiology for growth retardation is strongly suggested by the recent findings of definite hypothyroidism in two of the most retarded boys in the Group (Conard et al. 1966; Sutow, Conard and Griffith 1965). General health and fertility have been about the same in the exposed as in the comparison population. The mortality rate has been somewhat higher in the exposed population but this population has a larger percentage of older people. Possible life - shortening effects of radiation can be best evaluated in the This report concerns an attempt to evaluate possible effects of radiation on the ageing process in the exposed population. During physical examinations ageing effects are usually referred to in a general qualitative sense. In order better to evaluate possible ageing effects, a more quantitative approach was indicated. There are a large number of criteria which have at one time or another been regarded as being age dependent. These studies represent an effort to select criteria which could be carried out under conditions of these examinations. The overall objective has been to combine the scores of the various criteria into one “average age score” for each

Page 4

individual, comparing scores in the exposed with the unexposed comparable age groups. An earlier attempt to quantify these ageing criteria were presented in a previous publication (Conard 1960). In this report several new criteria have been added with further statistical treatment of the data. Materials and methods The study was hampered by the small number of people involved, lack of vital statistics on the Mar shalle se people, the language barrier, as well as uncertainty of exact ages in some of the older people. The ageing criteria to be presented were recorded only in adults (2o years of age and older). Data were recorded on 90 adults, 36 adults in the originally exposed group and 55 in the larger comparison population. The ages were reasonably well distributed except for a small number of people greater than 60 years of age. In selecting the criteria to be used the above menticned dtificulties Iimited the extent and usefulness of those tests which require motivation and co-operation on the part of the subject. Several tests were tried and discarded for these reasons, including vital capacity and cardiovascular response to two-step test. Also not included were several tests that were difficult to quantify such as baldness, retinal and peripheral arteriosclerosis. Several other tests were eliminated due to poor correlation with ageing such as serum folic acid and Vitamin B1 z levels. In this report 14 criteria of ageing are presenteih four involve the special sense organs (visual acuity, accommodation, arcus senilis, and hearing Ioss ); three involve neurological or neuromuscular function (vibratory sense, reaction time, and rapidity of movement); three involve the integument (skin looseness, skin elasticity, and hair greying); one test of strength; one cardiovascular test (systolic blood pressure); and two miscellaneous tests (serum cholesterol and body potassium). Two of the tests required subjective evaluation on the part of the examiner (hair grey - ness and arcus senilis); 7 required varying degrees of motivation and cooperation on the part of the subject (visual acuity, accommodation, hearing loss, vibratory sense, reaction time, neuromuscular function, and strength); 5 tests involved direct measurements ( skin loosene SS, skin elasticity, systolic blood pressure, body potassium, and serum cholesterol). Inte gumen~. A special c+er with constant spring tension was devised for skin examinations and the caliper and methods of skin examination have been previously described (Conard 1960; Hollingsworth, Goro and

Page 5

Conard 1961). (1) Skin looseness: The skin fold at the junction of the chin and neck was measured in millimeters as described previously. (2) Skin elasticim: Measured on the back of the hand by allowing the caliper to pinch a fold of skin for one minute and measuring the time for the skin fold to retract to the surrounding skin surface. The exact endpoint was sometimes difficult to measure in older people, and if the fold had not retracted completely in 90 seconds, this time measurement was used as maximum. (3) Grelin~ of the hair: The degree of greying of the hair was expressed on a zero to four plus scale as follows: 0, no Special Senses. (1) g~s: (a) Accommodation. Accommodation was measured in diopters by use of the Prince refracting rule. The aver - age reading of the two eyes was used. (b) Visual Acuity. Visual acuity was measured by Snellen’s test. It was found that by taking the square root of the average visual acuity (denominator) of the twa eyes the scale was more compressed and more linear. Thus the best vision of 20/10 was represented at 3.2 (the square root of 10), the worst reading of the 20/200 was represented as 14. 1 (the square root of 200), and intermediate readings similarly recorded. (c) Arcus Senilis. Estimated in the O-4+ scale. Only slight limbic clouding was considered 1+ with increasing clouding to marked clouding as 4+. (2) Ears: (a) Hearing. Audiometric examinations were carried out in a special cubicle lined with acoustic tile. A rugged screening type audiometer was used. Impairment of hearing was averaged for the two ears as follows: the decibel loss for each of the six frequencies (200, 500, 1000, 2000, 4000, 7000) for each ear was averaged and a mean frequency loss in decibels for the two ears was obtained. With regard to the reliability of determinations using the Print e refracting rule, Snellenls test and hearing acuity, it should be pointed out that these tests were carried out under standardized conditions, but in view of the necessity of using an interpreter under field conditions, it was not feasible to repeat the test by more than one examiner. It is believed, however, that the data from these tests were sufficiently reproducible to be of relative value, although not so accurate perhaps as might be obtained under more Cardiovascular Changes. (1) Systolic Blood Pressure. Obtained with the standard aeronoid cuff type sphygmomanometer. Two readings were obtained and the average of the two was used. There was no basic or adjusted level of physical activity such as resting for a standard period of time prior to the readings. Pressures were taken from the left arm with the subject supine during the course of the physical examination.

Page 6

Neurological and Neuromuscular Function. (1) Vibratory Sense. Vibratory perception was measured over the head of the left tibia by an electric vibrometer, the instrument set at a standard frequency of 120/ sec at 20 volts. The endpoint was the voltage intensity required for perception of the vibration. (2) Neuromuscular Function. Measured by having the subject depress the key of a hand talley type of blood cell counter as many times as possible in the period of one minute. The total number of depressions represented the score. (3) Liqht Extinction Time. A battery of lights were connected in random series and the subject extinguished each light as i? appeared. The total time necessary to extinguish all of the lights was measured. This test involve d both manual dexterity and mental reaction time (Hollingsworth, Hashizume and Jablon 1965). (4) Hand Strength. Measured by a Smedly hand dynamometer (S. H. Stoelting Co. , Chicago, Illinois. ) The spring tension of the hand grip was measured in kilograms. The maximum squeeze strength in the dominant hand in three tries was Miscellaneous Tests. (1) Body Potassium Levels (40K). Since loss of muscle mass occurs with ageing and total-body potassium is closely related to muscle mass, it has been shown that body levels of potassium decrease ‘with age (Anderson and Langham 1959; Allen, Anderson and Langham 1960). Whole-body spectrographic analyses were carried out in the Marshallese using a lead- shielded structure. In this way 40K levels were obtained and presented as K/kg body weight. Accuracy of these data could have been improved by obtaining more precise determinations of lean body mass, such as by measurement of body water (Allen, &der son and Langham 1960). (2) Blood Serum Cholesterol Levels. These were obtained on sera which had been returned from the Islands. In order to place all of the data from each criteria on a common basis for comparison and combination, the data were converted to a percentage basis for each criteria. In the case of the measured data, values associated with least ageing were chosen as zero percent (sometimes the highest reading, as with hand strength; sometimes the lowest, as with hearing 10Ss ), and conversely the values showing most ageing were chosen as 100% The est50, 75 and 1007’o respectively. The data were examine d on an individual basis as well as on a population basis, comparisons were made largely by using means for each decade age group. & analysis of variance was used to determine differences among the factors of sex, age, and radiation levels. These data were programmed and analysed on a high speed digital computer (The Control Data Corporation 6600 at Brookhaven N’ational Laboratory). For each criterion, the combined score over sex and radiation level was cor~elated with age. A curve of

Page 7

second degree in age was used when there was a significant departure from linearity. The criteria vibratory sense, hand grip, light extinction time, hand tally count, and body potassium showed significant sex cliff - erences, and therefore were scaled for each sex (zero to 100’70). An attempt to correlate a combined “physiological’age score with chronological age was done by obtaining a weighted average score for combined criteria for each age group (see Table I). The absolute value of the correlation coefficients were used as the weighting factor. This has intuitive appeal, since the influence on the final combined score of any particular ageing criterion is prop~rtional to the absolute value of its correlation with age. The results of these tests are presented graphically in figs. 1-14 and in Table I. The mean values for each decade starting at age 20 are plotted at the midpoint of that decade for exposed and unexposed groups separately and combined, along with the standard errors of the means. The curve or straight line (whichever best represents the particular data) is drawn and its equation presented. The’ coefficient of correlation with age and significance is also presented. Most of the criteria show good correlation with ageing. It is apparent that most of the criteria show the least change with age in the younger age groups, from 20-40 years of age, particularly for systolic blood pressure, hearing, visual acuity, neuromuscular functions, and skin retraction. Above about 40 years of age the criteria show the greatest change. With a few criteria, …