EFFECT OF RADIATION ON HUMAN HEREDITY
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Wld Hlth Org. techn. Rep. Ser., 1959, 166
WORLD HEALTH ORGANIZATION
TECHNICAL REPORT SERIES
No. 166
EFFECT OF RADIATION ON
HUMAN HEREDITY:
INVESTIGATIONS OF AREAS OF
HIGH NATURAL RADIATION
i
First Report
of the Expert Committee on Radiation
This report contains the collective views of
an international group of experts and does
not necessarily represent the decisions or the
stated policy of the World Health Organization.
L I
RAR Y
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V.
if
WORLD HEALTH ORGANIZATION
GENEVA
1959
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This report contains the collective views of an international
group of experts and does not necessarily represent the deci
sions or the stated policy of the World Health Organization.
WORLD HEALTH ORGANIZATION
TECHNICAL REPORT SERIES
No. 166
EFFECT OF RADIATION ON
HUMAN HEREDITY:
INVESTIGATIONS OF AREAS OF
HIGH NATURAL RADIATION
First Report
of the Expert Committee on Radiation
Page
INTRODUCTION
1. The general problem
2. Survey of known areas of high-background radiation
3
4
PRINCIPLES OF PLANNING INVESTIGATIONS OF
HIGH-RADIATION AREAS
3. Type of information needed
4. Collection of specific information
5. Interrelationship of genetic studies with work which
might
be undertaken on the somatic effects of radiation
6. Statistical considerations
7. Side benefits from ad hoc studies
9
12
16
17
22
THE KERALA PROJECT
8.
9.
10.
11.
Statement of the general problem
Physical aspects
Radiobiological aspects of thorium and daughter products
Suggestions for information which should be collected in a
Kerala project
12. Suggested requirements in men and material
13. Summary and conclusions
WORLD HEALTH ORGANIZATION
PALAIS DES NATIONS
GENEVA
1959
f1
23
28
33
37
44
45
EXPERT COMMITTEE ON RADIATION
Geneva, 28 July - 2 August 1958
Members :
Professor J. A. Book, Director, State Institute for Human Genetics, Uppsala,
Sweden
Dr J. C. Bugher, Director for Medical Education and Public Health, The
Rockefeller Foundation, New York, USA
Professor L. Cavalli-Sforza, Istituto di Genetica, Universita di Pavia, Italy
Professeur A. Franceschetti, Directeur de la Clinique ophtalmologique,
Hopital cantonal, Geneva, Switzerland {Vice-Chairman)
Dr A. R. Gopal-Ayengar, Deputy Chief Scientific Officer and Head, Biology
Division, Atomic Energy Establishment, Trombay, Bombay, India
Professor J. V. Neel, Chairman, Department of Human Genetics, University
of Michigah Medical School, Ann Arbor, Michigan, USA (Chairman)
Dr W. J. Schull, Associate Professor of Human Genetics, Department of
Human Genetics, University of Michigan Medical School, Ann Arbor,
Michigan, USA (Rapporteur)
Dr A. C. Stevenson, Director, Medical Research Council Population Genetics
Research Unit, Warneford Hospital, Oxford, England
Representative of the United Nations Scientific Committee on the Effects of Atomic
Radiation :
Dr R. K. Appleyard, Secretary, UNSCEAR
Secretariat :
Dr I. S. Eve, Medical Officer in charge of questions concerning ionizing
radiation (Secretary)
Dr R. L. Dobson, Medical Officer dealing with questions concerning ionizing
radiation
Dr P. Dorolle, Deputy Director-General, WHO
Dr V. R. Khanolkar, Director, Indian Cancer Research Centre, Parel, Bombay,
India (Consultant)
Dr D. Klein, Charge! de Cours a la Clinique ophtalmologique, Institut de
Gendtique mddicale, Geneva, Switzerland (Consultant)
This report was originally issued as mimeographed document WHO/Rad/5.
PRINTED IN SWITZERLAND
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Wld Hlth Org. techn. Rep. Ser., 1959, 166
EFFECT OF RADIATION ON
HUMAN HEREDITY:
INVESTIGATIONS OF AREAS OF
HIGH NATURAL RADIATION
First Report*
of the Expert Committee on Radiation
INTRODUCTION
The first meeting of the WHO Expert Committee on Radiation (Effects
of Radiation on Human Heredity) was held in Geneva from 28 July to
2 August 1958. Dr M. G. Candau, Director-General, opened the meeting
and welcomed the participants. Professor J. V. Neel was elected Chairman,
Professeur A. Franceschetti, Vice-Chairman, and Dr W. J. Schull, Rap
porteur.
1. The General Problem
With the increasing use of ionizing radiation in medicine, science and
industry, there has been concern in many quarters about the genetic effects
which might be produced in man. From a public health point of view,
modern discoveries concerning radiation hazards are disquieting, but it is
difficult to set limits to, say, the medical use of radiation, or to determine
the risks of radioactive waste discharged into the environment, until a
clearer, quantitative conception emerges of the degree of genetic or somatic
harm that might result. The need for further information was pointedly
stated by the WHO Study Group on the Effect of Radiation on Human
* The Executive Board, at its twenty-third session, adopted the following resolution :
The Executive Board
1. notes the first report of the Expert Committee on Radiation (Effect of Radiation
on Human Heredity);
2. thanks the members of the Committee for their work ;
3. emphasizes the extreme importance of this type of study, and expresses the desire
that the Organization give all possible assistance in furthering such investigations ;
4. thanks the Government of India for its help in the studies carried out preliminary
to the work of the Committee; and
5. authorizes publication of the report.
(Resolution EB23.R15, Off. Rec. Wld Hlth Org., 1958, 91, 13)
— 3 —
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RADIATION
Heredity1 as follows : “ Only in the light of more knowledge can decisions
be taken to define more accurately the maximum amount of exposure
which may be accepted by individuals and populations without risk of
serious harm.” The Study Group recognized that the opportunities for
expanding our information on radiation-induced mutations and their fate
through studies, on human populations are few in number. One untapped
source of information suggested was the study of populations exposed to
relatively large amounts of background radiation, that is, radiation of the
order of one rem per year.
. There is no doubt that those concerned with radiation protection are
desirous of seeing an effort made to exploit the information potentially
available in the high-radiation areas if it is feasible to do so. It is patent,
however, that great difficulties are involved in designing and implementing
relevant studies. Furthermore, since it seems unlikely that any one area
of high natural radiation can provide sufficient data to permit firm
conclusions to be reached concerning the risks to human populations of
sustained exposure to low levels of radiation, it is clearly desirable that,
in so far as possible, studies on these special populations be conducted
with a view toward the ultimate synthesis of observations from several
areas. This and other considerations require the specification of certain
principles for the planning of investigations of high radiation areas. It
is the purpose of this report to consider the general principles of planning
investigations of high radiation areas which might apply to any part of
the world ; and to illustrate the application of these principles to a specific
situation, namely, in parts of Kerala State, and adjoining areas of
Madras State, India. The reasons for this choice will be apparent later.
i
2. Survey of Known Areas of High Background Radiation
A certain amount of information on natural levels of radiation in the
world is contained in the report of the United Nations Scientific Committee
on the Effects of Atomic Radiation.2 For the convenience of the reader,
and preparatory to a consideration of the feasibility of investigating the
areas of high-background radiation, certain tables are reproduced from
this and other pertinent documents.
Cosmic ray intensities (ionization in ion-pairs/cm3 sec) and the corres
ponding dose rates in air at NTP are given in Table 1 for certain loca
tions. The table shows that an increase in altitude from 0 m to 3000 m gives
1 World Health Organization (1957) Effect of radiation on human heredity, Geneva,
p. 11
2 United Nations, Scientific Committee on the Effects of Atomic Radiation (1958)
Report
Annex B: Radiation from natural sources, New York, p. 49 (document
A/3838)
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FIRST REPORT
TABLEI. COSMIC RAY INTENSITIES AND DOSE RATES
Altitude
Intensity
(ion-pairs/cm1 sec)
Dose rate
(mrad/year)
(metres)
At 50* latitude
Near equator
At 50* latitude
Near equator
0
2.8
2.4
41
35
1 500
4.5
3.0
66
44
3 050
8.8
6.1
128
89
4 580
18
12
263
175
6100
34
23
500
340
an approximately three-fold increase in intensity, while the latitude variation
even at 3000 m is only 50%. Nehcr’s data for sea-level intensity, on which
Table 1 is based, are 30% higher than those of other observers. Therefore,
the values given in this table may be considered as upper limits.
Other data relating to natural sources of radiation arc shown in
Tables 2 and 3.
TABLE 2. DOSE RATES OF EXTERNAL GAMMA IRRADIATION
FROM THE ELEMENTS Ra, U, Th AND K CONTAINED IN TYPICAL ROCKS
OF VARIOUS ORIGINS
Dose rate in mrad/year * from
Type of rock
Igneous rocks
Sedimentary rocks :
Sandstones
”‘Ra
”'U
’”Th
•°K
24
25.8
36.8
34.6
13
7.7
18.4
14.6
Shales
20
7.7
30.6
36
Limestones
7.7.
8.4
4
3.6
* Calculated from equations (1) and the data in Table VI of the report of the United Nations
Scientific Committee on the Effects of Atomic Radiation (see footnote on p. 4).
A factor which has to be taken into account in preparing figures such
as those in Table 3 is the shielding effect of the body tissues external to
the gonads. The values for this factor shown in Table 4 were calculated
by Spiers and are taken from a report by the Medical Research Council
of Great Britain.1
1 Great Britain, Medical Research Council (1956) The hazards to man of nuclear and
allied radiations, London
6
RADIATION
TABLE 3. DOSES OF EXTERNAL AND INTERNAL IRRADIATION FROM NATURAL
SOURCES UNDER USUAL CONDITIONS AT SEA LEVEL
Dose (mrem/year)
Irradiation
To gonads and
other soft tissues *
External irradiation :
Cosmic rays
28
47
Gamma rays out-of-doors
Internal irradiation :
«K
19
“C
1.6
»‘Ra
?
95
Total irradiation from all sources
• Including bone marrow, the contribution from radium in bone being only about 0.5 mrem
per year.
TABLE 4. GONADAL SHIELDING FACTOR FOR GAMMA RAYS
IN THE HORIZONTAL, SITTING AND STANDING POSITIONS
Shielding factor
Position
Female
Horizontal
0.52
Sitting
0.58
Standing
0.59
Male
Average
Average
0.67
0.70
0.56
0.70
0.72
Mean factor for both sexes : 0.63
TABLE 5. MEAN DOSE OF IRRADIATION TO GONADS AND BONES
FROM NATURAL EXTERNAL SOURCES IN NORMAL AND MORE
ACTIVE REGIONS
Region
Population
in millions
Aggregate mean dose*
(mrem/year)
2 500
75
2. Granitic regions in France
7
190
3. Monazite region, Kerala in India
0.1
830
0.05
315
1. Normal regions
Monazite region, Brazil
* Using a shielding factor of 0.63 for y-rays and a dose rate of 28 mrem/year due to cosmic
rays.
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FIRST REPORT
Taking these factors into account, the figures given in Table 5 have
been advanced for different regions.
Inspection of Table 6 will afford an idea of the extent to which some
of the high-radiation areas now known differ with respect to the variables
which determine the feasibility of, and the weight to be attached to, an
investigation of a given radiation area. Not immediately evident from this
table are the difficulties within any given area of mounting and maintaining
a study of the scope necessary to detect the small differences which there
is reason to expect. It is not the purpose of this Committee to present
in detail the special problems posed by each of the areas given in Table 6;
it should be pointed out, however, that on the face of the data given in
this table the Kerala area of India would appear to be the only area now
known which might profitably be investigated. Although there are other
areas with larger populations, the levels of radiation obtaining there are
such that it is extremely doubtful whether an investigation would yield
significant data bearing on the radiation problem. At this juncture, it
might be well to state that the Committee is under no illusions regarding
the probability of any investigation of high background areas leading
TABLE 6.
SOME PARTICULARS OF AREAS OF HIGH NATURAL RADIATION
A. Areas with increased radioactivity from soil or rock
Area
Population
Demographic
information
available
Natural radiation
received (multiply
by 0.63 to get
gonad dose)
Possible
control
populations
Similar ethnic
group further
along coast
Part of Kerala State
and adjoining area in
Madras State
Approx.
80 000
Some information on
births and deaths:
could
probably be
developed
relatively
easily
Approx. 1300 milli
roentgen per annum
(plus about 200 mrad
beta rays)
ea in Bra
Monazite are;
zil (States of
il Espirito
Santo and Rio de
Janeiro)
Approx.
50 000
Specially prepared
statistics would be
required
Average
500 mrad/year
?
Mineralized volcanic
intrusives in Brazil
(States of Minas
Geraes and Goiaz) —
6 km1 in a dozen
scattered places
Pastureland,
scattered
farms, 1 vil
lage with 350
inhabitants
Very little
Average
1600 mrad/y<'ear
Peak value
12 000 mrad/year
?
Specialty prepared
statistics would be
I
required
180-350 mrem/year
Remainder of
France esti
mated at 4590 mrem/year
Primitive granitic, schistous and
le areas of France with slight
sandstom
elevation, of natural radiation said to
(out 1 /6th of French populacover ab<
lion (7 million)
There are also some areas of high natural radiation in the Belgian Congo, but these are said
to be uninhabited.
n
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RADIATION
TABLE 6 (continued)
B. Areas with high natural radiation in houses made of special materials
Area
Demographic
information
available
Population
Natural radiation
received (multiply
by 0.63 to get
gonad dose)
Possible
control
populations
Sweden — houses
made of light-weight
concrete containing
alum shale
Relatively
small
Special statistics
being obtained
158-202 mrad/year
(cosmic radiation
excluded)
Wooden
houses 4875 mrad/year
(cosmic radia
tion excluded)
United Kingdom
(Aberdeen) —
houses and build
ings made of granite
Population of
Aberdeen
approx.
186 000
Leukaemia statistics
being studied
Results from a few
buildings indicate
102 mrad/year
Approx.
78 mrad/year
in other cities
with brick
buildings,
e.g., Dundee
— population
178 000
Special statistics
necessary
Granite houses
85-128 mrad/year
Brick or concrete
houses
75-86 mrad/year
Wooden
houses 5464 mrad/year
Austria
houses
granite
?
C. High-altitude areas *
Area
La Paz, Bolivia (alti
tude about 11 909 ft
(3630 m) ; latitude
16*S)
Demographic
information
available
Population
Approx.
319 600
Some statistics
available but not
comprehensive
Natural radiation
received (multiply
by 0.63 to get
gonad dose)
Possible
control
populations
Approx. 3-fold in
crease in cosmic rays
near equator at 30004000 m above sea
level. Cosmic radia
tion tends to be about
a third of total
external natural radia
tion
This might
present diffi
culties as
lower oxygen
tension at
high altitude
is a compli
cating factor
Other high towns in South America —
Quito, Ecuador
—altitude
Bogota, Colombia
— altitude
Cerro de Pasco, Peru — altitude
9 350feet (2850 m) ; latitude
0°; population 212 873
8 660feet (2640 m) ; latitude 4-N ; population 325 658
13 973feet (4259 m) ; latitude 10°S ; population 19 187
Himalayan area — altitude 12087 feet (3684 m);.latitude 30°N ; population (Lhasa) about 20 000
* Populations and altitudes from the Columbia Lippincott Gazetteer of the World (1952)
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FIRST REPORT
9
to the demonstration of significant genetic changes. The Committee
is cognizant, however, of the desirability of obtaining meaningful data,
imperfect though they may be, on the consequences of prolonged exposure
to low doses of radiation. Such is the present status of knowledge of the
somatic and genetic effects of chronic low-level exposures that any proper
investigation of areas of high natural radiation is certain to contribute to
the fund of biological knowledge and the ultimate specification of the
genetic risks accruing from increasing exposure to ionizing radiations.
PRINCIPLES OF PLANNING INVESTIGATIONS
OF HIGH-RADIATION AREAS
3. Type of Information Needed
Before commenting on the kind of information to be sought in studies
of this nature, some general remarks should be made concerning the
factors which determine the significance or “ resolving power ” of such a
study, since they bear on the type of data to be collected.
These factors, as enumerated in Annex H of the report of the United
Nations Scientific Committee on the Effects of Atomic Radiation/3 are :
(^) the (cumulative) dose to the parents of the individuals under study ;
(b) the number of individuals whose parents have been so exposed ;
(c) the number of characteristics of genetic significance to be recorded ;
(^) the manner in which information on these characteristics is
collected ;
(e) the availability of a suitable control population.
In view of a recent finding2 that in the mouse fewer mutations occur
in response to chronic irradiation than are caused by acute irradiation
with the same dose, an added factor may be present in evaluating a
study in which the dose in question is accumulated over a long time.
It is difficult to consider these factors independently of one another
since, for instance, the decision as to the number (and type) of characteristics
to be recorded cannot but be influenced by the cumulative dose to the
parents of the individuals under study and the number of individuals
whose parents have been so exposed.
1 United Nations, Scientific Committee on the Effects of Atomic Radiation (1958)
Report ..., New York, p. 172 (document A/3838)
2 Russell, W. L. & Russell, L.B. (1958) Radiation-induced genetic damage in mice.
In : Proceedings of the Second United Nations International Cojtference on the Peaceful
Uses of Atomic Energy, Geneva, Vol. 22, p. 360
n
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RADIATION
3.1 Principles determining the type of information sought
Two seemingly different approaches to the study of genetic effects in
areas of high natural radiation exist. On the one hand, effort could be
directed toward the study of characters known to appear, or at least
thought to appear, as a result of single-gene mutations. This method of
study can be termed the “ specific phenotype ” approach, and it is assumed
that each of the phenotypes chosen for study arises as a consequence of
the mutation of one or a small number of genes. On the other hand, effort
could be directed toward the study of those genetic characteristics of the
population which it is assumed reflect the cumulative effect of mutation
at many loci, such as the sex ratio. This may be termed the “ population
characteristics” approach. These two approaches are not necessarily
mutually exclusive, and are so presented here largely for convenience.
In fact, the “ population characteristics ” approach would under most
circumstances lead to an accumulation of some information bearing on
the frequencies of specific phenotypes.
In general, the genetically more appealing “ specific phenotype ”
approach will not be feasible as it requires larger numbers of children
born to highly exposed people than will be available except under very
unusual circumstances. This assertion rests on two considerations. Firstly,
the number of characters with simple modes of heredity which are at
present known and which pose minimum diagnostic problems is limited,
perhaps in the neighbourhood of 100. Secondly, it may be anticipated
that the probability of a mutation per locus per unit dose will be of the
order of 1 X 10“7. Thus, the probability that any given individual will
possess one or more of the requisite phenotypes is extremely small. It
follows then that to obtain a sufficient number of individuals possessing
the requisite phenotypes for a statistically significant result to emerge,
a rather large number of observations must be made. It does not appear
that the prerequisites for this approach are met by any existing population,
and so in this presentation attention will be concentrated on the approach
which relies on less specific indicators for the demonstration of genetic
effects. Unfortunately, practically all of the less specific indicators of
genetic change which it is feasible to employ are influenced by a variety
of environmental factors, which makes the question of adequate controls
especially critical.
The indicators which may be utilized in the “ population characteristics ”
approach are of two types, depending on whether they emerge from the
essentially non-medical vital statistics of an area, or whether they depend
on medical and allied efforts in that same area.
From properly collected vital statistics, such items as birth-rates,
death-rates, life expectancies, fertilities and sex ratio can be extracted,
all of which may, with suitable reservations, be used as a basis for evaluating
genetic differences between populations.
f1
FIRST REPORT
11
On the medical side, population data of especial value for the evaluation
of genetic change include the frequency (and types) of congenital defects,
patterns of growth and development, and morbidity and mortality data.
In order that population comparisons with respect to any of these indicators
of genetic difference be valid, extensive information must be available
on the two or more populations concerned with respect to such mat
ters as :
(«) geography of the areas occupied by the populations ;
(6) origin of the groups in question ;
(c) inbreeding levels ;
(^) effective population size ;
(e) migration ;
(/) diet;
(g) cultural and religious practices affecting reproduction ;
(Ji) socio-economic conditions ;
(z) other factors influencing morbidity and mortality patterns.
Equally important, but generally less readily obtainable, is information
of a historical nature bearing upon several of the above.
An extension of the “ specific phenotype ” approach which appears to
merit exploration when comparing large populations, one of which is
subjected to a relatively small increase in radiation exposure, involves the
study of maternal and paternal “ age effects ” in the appearance of mutant
phenotypes. Such age effects, even in the male, are undoubtedly com
pounded of many factors, only one of which is an increasing probability
with the passage of time of induced mutation due to ionizing radiation.
However, a significantly increased age effect in the population exposed
to the greater amount of radiation could be construed as evidence for
the induction of mutation, and a quantitative treatment derived.
3.2 The possible usefulness of studies on consanguinity effects
In populations long exposed to increased amounts of ionizing radiation,
there will presumably have occurred an accumulation of induced recessive
mutations. The magnitude of this accumulation will presumably depend
on many factors—severity of natural selection, degree of inbreeding, etc.
The possibility exists that this accumulation can be assessed by studies
comparing the magnitude of consanguinity effects in this population with
the magnitude of such effects in a suitable control group.
3.3 Approaches not depending on large population surveys
Several recent scientific developments, although still in need of technical
improvements, appear to offer alternative approaches to those just
12
RADIATION
enumerated. These approaches do not involve the surveying of large
populations but the study of somatic mutation in the individual, e.g.,
the frequency of erythrocytes altered in their serological behaviour,1 or
the appearance of chromosome changes or altered serological or biochemical
behaviour in somatic cells as studied in tissue cultures.
Whatever the contribution of these studies will be to the general problem
of the effects of radiation on man, it is clear that they can only complement
population studies but cannot replace them. In fact, while they will
contribute to the problem of the frequency with which mutations are
induced, whether they will contribute to the equally important question
of the fate of induced mutations in human populations is uncertain.
4. Collection of Specific Information
In offering the following general remarks concerning the specific
information to be sought, the Committee recognizes clearly the extent to
which the exact details will be shaped by the particular circumstances
surrounding any given study. If, however, studies in a variety of geographic
areas are to be comparable, then some measure of uniformity of approach
is obviously desirable. It seems reasonable to expect that such studies
will differ mainly in the intensiveness of the investigation. Accordingly,
the Committee urges that studies of areas of high natural radiation evolve
through certain specified stages, proceeding from data easily collected by
a minimum of medical personnel to a more elaborate programme where
success will involve rather substantial medical support.
4.1 The different levels at which information can be collected
The Committee suggests that it is appropriate to think in terms of
levels of information, the lowest level being that at which information is
most readily collected although, in some instances, it may be indispensable
to the acquisition of information at higher levels. At least six levels
can be recognized:
(1) Accurate demographic statistics, from which can be calculated
birth-rate, life expectancy, sex ratio, etc. This is essentially non-medical
data, an important consideration in countries whose medical personnel
are in short supply.
(2) Growth and development data. These can be collected at various
levels of complexity, according to techniques abundantly discussed in the
1 Atwood, K. C. & Scheinberg, S. (1958) Science, 127, 1058
FIRST REPORT
13
literature. Again, much of this information can be collected by non
medical personnel.
(3) Patterns of congenital defect. In the simplest form these are based
on observations by physicians on all new-born infants. A re-examination
at age nine months will approximately double the amount of defect obseived,
and a further examination at age 10 years should more than triple the
number of defects for evaluation.
(4) Morbidity and mortality patterns as based on clinical data. With
the addition of data of this type, the medical picture of the population
is brought near to completion. This, again, is not an all-or-none type
of observation—one can begin with certain key diseases and increase the
degree of reporting as facilities expand. Moreover, in contrast to many
developmental anomalies, progressive diseases such as malignant neoplasia
inevitably reach a stage where they impel recognition. Early recognition,
though perhaps most desirable for the welfare of the individual, may
imply a much greater expenditure of diagnostic effort than is requisite
for study purposes. In the studies of the type under consideration, some
compromises must be made to achieve a working balance between the
medical needs of the people and the available resources of the project.
(5) Laboratory studies. Laboratory studies are expensive, often
time-consuming, and require a high degree of technical skill which may,
in large population studies, confine their application to restricted samples.
They are, however, more objective in their nature, and can be made prac
tically free of any possible bias on the part of those carrying out the tests.
Suitable objects of study are blood groups, haemoglobins and other genetic
markers regarding the heritability of which information is being accu
mulated. Cytological studies on the chromosome complement of the
exposed populations may also prove fruitful. In addition, laboratory
services will be needed for the proper support of the studies essential for
the determination of individual health status.
(6) Necropsies. The final level, will consist of post-mortem studies on
a substantial fraction of the population.
The transition from one level to the next is of course not necessarily
on an all-or-none basis ; there may be a substantial degree of overlapping.
Thus, under most circumstances a necropsy programme will be introduced in
conjunction with efforts to obtain patterns of morbidity and mortality.
In collecting data such as that under discussion, it is necessary to bear
in mind from the beginning that the unit of study in genetics is generally
the family, and information should be collected with a view toward family
relationships.
Not enough is known concerning human genetics to permit accurate
statements concerning the relative value of the various types of observations
H
14
RADIATION
here enumerated. There are, however, increasing grounds for thinking
that the sex ratio and length of life may be relatively sensitive indicators
of radiation-induced mutations.1, 2 On the other hand, congenital defects
may, to a considerable degree, be the manifestation of complex genetic
systems whose expression is significantly influenced by environmental
variables and whose phenotypic response to increased mutation rates is
complicated and at present poorly understood.3 If this is correct, then
the type of data which is most easily collected under a wide variety of
circumstances may actually be that which is most pertinent to an evaluation
of radiation effects. Otherwise stated, if the amount of information of
genetic value which could be extracted from a population were to be
graded on a quantitative scale, it might well be that by the expenditure
of a certain effort 95% of the information could be extracted, whereas
the expenditure of only a quarter of that effort would yield 75% of the
information. Attention is again directed toward the critical role played
by the control population in the final analysis of data with reference to
any of these levels of information.
4.2 Classification and nomenclature of specific anomalies
If the various studies which are to be undertaken on this problem
are to be comparable, one requirement is for a uniform system of nomen
clature with which to record observations. For a variety of reasons, the
WHO Manual of the International Statistical Classification of Diseases,
Injuries and Causes of Death (1955 revision) has much to recommend it.
However, this classification is not sufficiently detailed with respect to
many entities of genetic interest; the possibility is raised that at the time
of the next revision of this manual some thought be devoted to expanding
certain sections to make them more useful for genetic purposes.
4.3 Standardization of anthropological measurements
The human body lends itself to a variety of measurements and ways
of measuring. It is suggested that in approaching the question of the
appropriate techniques to be employed, Martin’s handbook4 be used as
a reference manual. Attention is directed to the fact that these measurements
are overlapping rather than independent approaches to bodily proportions
and development. In comparing two populations, then, the comparison
1 Schull, W. J. & Neel, J. V. (1958) Science, 128, 343
2 Russell, W. L. (1957) Proc. nat. Acad. Sci. (Wash.), 43, 324
3 Neel, J. V. (1958) Amer. J. hum. Genet., 10, 398
4 Martin, R. (1928) Lehrbuch fiir Anthropologic in systematischer Darstellung, 2nd
ed., Fischer, Jena, 3 vols
n
FIRST REPORT
15
of individual measurements does not easily lend itself to a clear picture
of the significance of any differences which may be observed. It seems
inevitable that multivariate analysis of the anthropometric data will have
to be adopted. To a rather large degree, the scope of the multivariate
analysis will be dependent upon the computational facilities which are
available. In the absence of electronic computers, it would be inadvisable
to attempt to handle more than, say, six or eight variables. The variables
should be so selected as to represent both the linear and circumferential
components in growth, and, further, to minimize the correlations between
the measurements chosen.
4.4 Correlative studies on plant and animal material
At some point in the development of such studies, consideration must
be given to correlative observations on plant and animal material. For
instance, the frequency of chromosomal abnormalities in the dividing cells
of long-lived plant material might be a valuable observation. The possibility
of genetic studies on the local fauna, and especially on genetically wellinvestigated forms, such as Drosophila and mice, must be entertained.
The possibility that organisms living in high-background areas may
show an increased radiation resistance may deserve investigation.
4.5 Physical environment and dosimetry
Ultimately, the interpretation of any biological changes encountered
in these studies involves an adequate exploration of the environment.
Physical measurements and radiochemical analyses may be required to
describe fully the radiation field with respect to : (1) intensity and energy
levels of the various components ; (2) air transport of particulate material;
(3) concentration of specific radioisotopes in elements of the food chain ;
and (4) determination of the body burdens and distribution of the significant
radioactive substances.
Dosimetric computations made possible by precise characterization of
the radioactive environment may be supplemented by direct dose measure
ments, utilizing the most efficient instruments available at the time. Data
of the type indicated would permit later review and increasing refine
ment.
The dosimetric problems will vary from one area to another, depending
upon the nature of the radioactive deposits; however, it is important
that deposition of radioactive substances in tissues such as those of bone
or lung, which would appear to have little significance with reference to
gonadal dose, should not be overlooked, as it may be of significance in
the production of somatic effects.
n
16
RADIATION
5. Interrelationship of Genetic Studies with Work which might
be Undertaken on the Somatic Effects of Radiation
It is of paramount importance in studying the effects of radiation to be
able, if possible, to distinguish the purely somatic effects on the individual
who is born and who lives in a radioactive environment from the mani
festations of the genetic burden that may have been passed on to him
as a result of previous generations of exposure. The manifestations of
genetic changes are themselves, however, somatic, and it is important
to remember the degree to which the measure of seemingly “ pure ” somatic
• effect turns out to involve a genetic component. Despite this interplay
of genetic and somatic effects, observations on the several variables to
be enumerated in 5.1 and 5.2 seem justified, since they will bear on such
questions of basic interest as :.
(1) What are the forms of the dose-response curves in man at low
levels of radiation with reference to such varied phenomena as leukaemia,
bone sarcoma, etc. ?
(2) Are there threshold values below which somatic effects associated
with radiation exposure are not observed ?
(3) When a shortening of the life-span is encountered, to what extent
is it (a) a genetic effect; (b) a direct somatic effect of radiation, possibly
of greatest importance in intra-uterine life and early childhood ; and (c) a
combination of both?
5.1 Shortening of life-span
Shortening of the life-span following exposure to radiation is best
studied by an examination of age-specific death-rates. The interpretation
of such observations rests upon the general premise that the death-rates
in a population are a reflection of the biological state of the entire population
and not just something that pertains to those who die.
5.2 Other manifestations of somatic injury
The second class of somatic manifestation consists in the occurrence
of specific events, such as an increase in the frequency of various tumours
or of leukaemia, or the onset of some of the anaemias, which may be related
to radiation injury. There are lesions such as cataracts and other ocular
alterations where one can make observations which are pertinent to the
question of somatic injury. Special attention should be paid to such
phenomena in early childhood.
H
FIRST REPORT
17
6. Statistical Considerations
An attempt to state general statistical principles applicable to the
investigation of high-background areas is apt to lead either to the statement
of principles so broad that they contribute nothing, or to voicing what
would appear to be the obvious. At the risk of doing the latter, the Com
mittee affirms the general principle that the most important consideration
is the prior specification of the question or questions which the data can
hope to answer. Aside from this general consideration, there exists a
number of other statistical problems which may, to some degree, be antici
pated from the nature of investigations of chronic low level exposures.
These problems can be seen more clearly if one enumerates the types of
variates liable to be encountered. These variates may be grouped into
four classes, namely :
(1) the “ experimental” variables, the objects of the investigation ;
(2) controlled extraneous variables, the control being through selection
of the comparison population or estimation procedures ;
(3) uncontrolled extraneous variables which can be treated as randomized
errors ;
(4) confounded extraneous variables, these being uncontrolled variates
intimately interwoven into the fabric of the experimental variates, so
as to favour one group over another.
In a very real sense, the worth of a survey will be directly proportional
to the ability to recognize and delineate these variates. Clearly in an
“ ideal ” experiment confounded extraneous variables would not occur;
either by design or randomization these variates would be controlled or
become part of the randomized errors. In surveys, since it is frequently
impossible or not feasible to randomize the otherwise confounded
uncontrolled variates, one may attempt to select as experimental variates
those characteristics of the organism which, while subject to change by
the stimulus under investigation, are least influenced by other factors which
may be dissimilarly distributed in the groups under study. The alternative
is to attempt to separate the experimental and confounded variates through
selection of the comparison population and/or recourse to multiple ways
of classification, stratification, partial correlations, etc. It is unfortunate,
but true, that most of the measurements indicative of radiation-induced
genetic damage which are readily obtained are also influenced by a wide
variety of extraneous variables, among these being such things as maternal
age, size of family, and nutrition.
n
RADIATION
18
6.1 The value of general calculations, e.g. of the numerical criteria which
comparative surveys of an irradiated and a control population would
have to satisfy
From the introduction it will be evident that general calculations are
apt a priori to have only limited usefulness. This stems from the necessity
to make certain assumptions in the calculations which may or may not,
in fact, be satisfied. Moreover, since as a rule, the effect of confounded
variates cannot be specified in advance, the calculations are generally
with respect to an idealized situation, namely, one where it is assumed that
any difference which may exist between the two populations under compar
ison will be due to the “treatment” alone. Despite the uncertainties
which surround general calculations, they may serve as a guide to intelligent
planning, and afford some prior indication of the possibility of demon
strating effects of radiation or the worth of negative findings.
Perhaps the most meaningful general calculation which can be made
is to determine the approximate difference between a control and irradiated
population which may be demonstrable with the number of observations
to be expected in a given instance. This calculation does not require
assumptions regarding genetic mechanisms, selection, etc. For illustrative
purposes and to provide certain figures for planning, let us assume an
irradiated population of approximately 100 000 persons, that an adequate
control of equal size can be obtained, and, for the moment, that the observa
tions to be made will be based upon persons newly born. Clearly the
number of observations will be a function of the yearly birth-rate, and
the duration of the study (see Table 7).
TABLE 7. MAXIMUM NUMBER OF NEWBORNS IN AN INITIAL POPULATION
OF 100 000 FOR DIFFERENT BIRTH-RATES AT 5-YEAR INTERVALS
Population of new-borns in
Average yearly
birth-rate
5 years
10 years
15 years
20 years
25 per 1 000
12 500
25 000
37 500
50 000
30 per 1 000
15 000
30 000
45 000
60 000
35 per 1 000
17 500
35 000
52 500
70 000
20 000
40 000
60 000
80 000
22 500
45 000
67 500
90 000
40 per 1 000
45 per 1 000
To simplify subsequent calculations, let us assume that the study will
continue for either 10 or 20 years, and that during this interval the average
yearly birth-rate will be 35 per 1000. This implies, then, a total (in the
19
FIRST REPORT
combined populations) of 70 000 observations in- 10 years, or 140 000 in 20..
Now the difference which one may reasonably expect to detect is a function
of (1) the sample size ; (2) the confidence level (the frequency with which
one rejects the null hypothesis when it is true); and (3) the power of the
test (the frequency with which one rejects the null hypothesis when it is
false). Suppose one were interested in contrasting in these two populations
the frequency of some event such as the occurrence of a congenitally
malformed child, the frequency of stillbirths, etc. To illustrate the differences
which would be demonstrable, we shall assume (1) one-tailed tests of
significance, with a confidence level of 0.05; (2) a power of the test equal
to 0.90 ; and (3) that one will be contrasting a single exposed population
with its control. If two-tailed tests were used, the necessary difference
would be larger for a given proportion and sample size ; conversely, if
the power of the test were reduced, the necessary difference would be
smaller for a fixed proportion, sample size, and test hypothesis. It should
be noted that the efficiency of the study could be measurably improved if
exposures could be quantified so that regression techniques might be
employed in the analysis. Under the conditions previously given, the
minimum differences demonstrable are approximately as shown in Table 8.
TABLE 8. MINIMUM INCREASE IN FREQUENCY OF A GENETICALLY CONTROLLED
EVENT DEMONSTRABLE IN AN IRRADIATED POPULATION
Estimated frequency
in control population
Minimum frequency in irradiated population demonstrably
different from that in control group
for pop. of 35 000
for pop. of 70 000
0.001
0.00,18
0.0016
0.01
0.0123
0.0116
0.02
0.023
0.022
0.05
0.055
0.054
0.10
0.107
0.105
0.50
0.511
0.508
The demonstrable difference between means or standard deviations
can similarly be computed.
So far, one is on rather firm statistical footing, but as soon as one
turns to the obvious question “ Are these the differences we might expect
on genetic grounds?”, a very large element of speculation enters. From
the data compiled in Hiroshima and Nagasaki1 one would be tempted
1 Neel, J. V. & Schull, W. J. (1956) The effect of exposure to the atomic bombs on
pregnancy termination in Hiroshima and Nagasaki, National Academy of Sciences —
National Research Council, Washington, D.C.
n
22.
RADIATION
6.3 Sources of error and fallacies which could arise in field recording
The types of errors or fallacies which could arise in field studies can
arbitrarily be divided into two groups. Firstly, there will be errors which
are more or less unique to the area being studied. These could be specified
in advance only by someone thoroughly familiar with the region. Most
of these errors will have their roots in an imperfect understanding of the
culture of the people ; and presumably a number of them would be revealed
by a pilot study. Secondly, there exists a class of errors common to all
large-scale studies. Only three of these sources of error are singled out for
comment. The first of these is the problem of maintaining uniformity
of examination when a number of examiners are employed. There is no
simple solution to this, and only constant surveillance and careful indoc
trination of the examiners will minimize this source of error. The second
important source of error in studies on areas of high-background radiation
results from the examiner knowing to which population the examinee
belongs. With field recording and the differing geographical distributions
of the two populations, this type of error is inevitable, especially in view
of the emotionally charged atmosphere which surrounds the problems
of the effects of radiation. Some idea of the magnitude of this bias might
come from the inclusion in any programme of study of selected laboratory
procedures which could be conducted so that the technician was unaware
of the population from which the specimen was drawn. The third source
of error stems from the simple fact that intensive observations can hardly
be continued for any length of time without the population changing to
some degree. Perhaps the change is most apt to take the form of an increased
awareness on the part of the examined individual of the objectives of the
study, and, as a consequence, some loss of perspective. It is possible to
combat this only through a scrupulous attention to completeness of
examination from the inception of the project, and the selection of the
most objective, incontestable measurements possible, such as sex, anthropo
metric, or laboratory measurements.
7. Side Benefits from ad hoc Studies
It is apparent that properly organized studies of the type under discussion
cannot fail to result in many contributions to human biology other than
those concerned with human radiation genetics.
7.1 Opportunities for training young geneticists and other workers
The professional staff engaged in these studies will often consist of
five to ten highly-trained individuals—geneticists, statisticians, physicians,
etc. Opportunities will exist to provide students with a type of field
n
FIRST REPORT
I
23
experience which can be an integral part of their training for work in
human genetics.
7.2 Opportunities for developing techniques for the study of populations
The techniques for large-scale studies of various aspects of human
population genetics are still in their infancy. It is likely that for years
to come, each large-scale study undertaken will be encountering field
problems and statistical questions not previously solved. It is inevitable,
then, that studies of the type under discussion will make important
contributions to the developing methodology of human genetics.
7.3 Opportunities for the collection of information bearing on a variety
of topics in human biology
It is difficult to envisage a study on human radiation genetics which
would not yield information on a variety of other topics of interest to
human biologists. Thus, in the process of making allowance for the
extraneous variables mentioned in section 3, data will be collected concerning
the influence of diet, ethnic background, inbreeding levels, etc., on the
expression of the characteristics being utilized as indicators of radiation
effects. Information will also accumulate concerning the total impact
of hereditary disease on the populations under study, as well as data
concerning mutation rates and other specific items of general genetic
interest.
Attention is directed to the obvious problem of maintaining balance
between the various components of such studies. This applies not only
to the study of radiation genetics proper, but also to the side benefits to
which this section is devoted.
THE KERALA PROJECT
8. Statement of the General Problem
Although there exists a considerable body of knowledge on the sequelae
of effects produced by ionizing radiations on biological systems at different
levels of integration, the long-term consequences to human populations
exposed to continuous doses of relatively high radiation for very long
periods of time, and probably extending over many generations, have not
so far been studied. An ideal milieu for such studies would be a region
which is well populated and where, at the same time, the radiation field
is significantly higher than the normal background. A nearly unique
situation exists in parts of Kerala and Madras States in the southernmost
fl
24
RADIATION
region of the west coast of India. Here, along the coastal belt stretching
over a hundred miles in length and about a quarter of a mile in width from
near Kayankulam to Kanyakumari, interrupted deposits of ilmenite sands
containing radioactive material occur (Fig. 1). The radioactivity of the
sands is due to the monazite component which contains thorium and to
a limited extent uranium,
FIG. 1. POSITION OF THE KERALA AND
along with several other
MADRAS MONAZITE REGIONS
rare earth minerals, such
as rutile, sillimanite, zir
con and titanium-bearing
ores. The thorium con
tent ranges from 8% to
10.5% as against 5-6%
in the Brazilian monazite
deposits.1 Most of the
radioactivity (95%) arises
from thorium and its de
cay products.
Bomboy
The importance of
the Kerala and Madras
monazite regions stems
from the fact that the
population (estimated in
Madras
the region of 80 000,
living in a radioactive
Kayankulam
X
I
Chavara Noendakoro V
milieu, is subjected to
Quilon''zy
J
Trivandrum
I
low-level chronic irradia
Manavalakurichi /
|
\
tion and presumably has
Konya Kumori
Co^or
(Cape Comorin)
been so exposed for gene
rations. The two regions
to be studied are rather
well defined—the Chavara-Neendakara and Manavalakurichi—and com
parable control regions exist in nearby areas (see Fig. 1-3).
It has already been pointed out2 that, whereas most peoples receive
an average whole-body background radiation from all natural sources of
about 3 r per person per 30 years, these populations are estimated to
receive 10-15 times as much ionizing radiation. While further physical
monitoring is needed to establish more accurately the doses being received,
it seems clear that these estimates are likely to be reasonably accurate.
1 More recently, bigger deposits of monazite have been discovered in the Indian
State of Bihar. No measurements, however, have been carried out.
Gopal-Aycngar, A. R. (1957) Possible areas with sufficiently different background
radiation levels to permit detection of differences in mutation rates of “ marker ” genes.
In : World Health Organization, Effect of radiation on human heredity, Geneva, p. 115
25
FIRST REPORT
FIG. 2.
THE CHAVARA-NEEND AKAR A AREA
5
Aloppad
Pandora thuruthu\o
Ponmana
Karithura
CHAVARA
Parimonam
Neendakaro
ASHTAMUDI
\
LAKE
I
u
It should be noted that the excess amount of radiation being received
by these populations in Kerala and Madras States is, according to
present estimates, within the range of that necessary to double the
mutation rate.
Such excess radiation per generation is at least several times greater
than is likely to be received on the average by any substantial number of
n
I
1
RADIATION
26
FIG. 3. THE MANAVALAKURICH! AREA
0.5 km
0
.E
o
.E
i
o
Manavalakurichi
To Colachel
km
8.
(O
Kadiapatnam
Chinnaviloi
i'-’XJJ
ARABIAN
Rock Site
SEA
WHO 9Hj2 |
people elsewhere from the sum of natural background radiation, together
with the total of artificially-produced radiation on the present scale.112
8.1 The two areas where the sand beaches contain monazite, and the people
living there
8.1.1 The Chavara-Neendakara area
This beach is in Kerala State. It extends from the outlet of the Ashtamudi
Lake up to Kayankulam Lake, about two miles north of the village of
Azhyikkal. The strip is an island, as the two lakes are joined to the
landward side of the beach by a canalized lagoon. The area isolated
varies from a few hundred yards in width in the south to over a mile in
the north. It is convenient to call this the Chavara area, from the name
of a large village and district in the south of the strip. The form and
position of the area may be seen from Fig. 2. The ilmenite deposits have
a rather patchy distribution up and down the coast, partly by reason of
varying deposits by currents, and partly by reason of extensive removal
1 Great Britain, Medical Research Council (1956) The hazards to man of nuclear and
allied radiations, London
2 World Health Organization (1957) Effect of radiation on human heredity, Geneva
n
FIRST REPORT
27
of the richest ilmenite deposits over the past 30 years by three mining
companies. The distribution may also be affected by the violence of the
previous monsoon. Off the beach there is much sand lying in pockets and
the whole hard area has a surface covering of sand with very variable
monazite content.
This area is inhabited by not less than 60 000 people. The great majority
live by fishing. About half are Christians (Roman Catholics) and the
rest Hindu. There are a few Mohammedan fish traders but not all live
on the strip, most only come each day to bring fish.
The Christians and Hindus speak the same language (Malayalam) and
are obviously of the same stock. Superficially at least there is no difference
in their general environment, diet, or economic circumstances. Among
the Christians, consanguineous marriages may occur less frequently.
Among the Hindus, there is matriarchal exogamy so that a man seeks
a bride from another “ gotra ”.1 It is preferred that a man should marry
his full cousin who is his father’s sister’s daughter (and therefore would
probably be brought up in another village). Among Hindus, the full
cousin marriage rate is believed to be about 10-20 per cent. HinduChristian marriages are said never to occur.
Christians and Hindus alike are friendly and cheerful. The percentage
of literacy is very high. Accurate estimates of the live-birth rate are not
at present available for the area, but a number of indications suggest
that it is over 30 per 1000 of the population. Although stillbirths are
supposed to be registered, it is clear that there are many which are not,
and probably only those attended by the midwives or the few occurring
in the Indo-Norwegian Hospital at Neendakara are consistently recorded.
Prematurity is said to be very uncommon, but there are no data to support
such a contention. It would be reasonable to expect in such an area a
prematurity rate (on the weight standards of 2500 g) of 10-15% of total
births, a stillbirth rate of about 50-60 per 1000 live and stillbirths, and
an infant mortality of the order of rather more than 100 per 1000 live
births. Such scanty data as are at present available have suggested lower
figures than any of these, but they are almost certainly underestimates.
Selection of a control area having a population with the same religious
distribution and way of life, and following the same occupations (except
with regard to the sand-processing companies), should not be unduly
difficult. The same fisherfolk occupy the seashore villages north and south
of the area. To the south, however, the urban fringe of the town of Quilon
impinges, bringing an inevitable alteration in the population characteristics.
Consequently, a defined strip north of the Kayankulam Bar would probably
be most suitable as a control area. In the absence of a canal, the control
area could not be as conveniently defined as the monazite sand area, but
1 See section 8.1.2.
H
28
RADIATION
there should be no insuperable difficulties.. A small gap even of a mile
or two north of the monazite area might well be left out of the control
area so as to minimize the number of transfers between the area and of
marriages between people in villages in the study and control areas. Again,
only careful study would confirm the value of such a suggestion.
8.1.2 Manavalakurichi area
This area of monazite sand is located some 40 miles south of Trivan
drum. The area is not in Kerala but in Madras State. It is even more
densely populated than is the first area. It is about one mile long from
the mouth of the river Valliar to Chinnavilai village and has about 11 000
to 12 000 inhabitants in the beach villages. Again, some are Roman
Catholics and the others Hindus (roughly 50 : 50).
Most of the general remarks about the Chavara area arc applicable
here also and need not be repeated. All are of Tamil stock and speak
that language. The pattern of mating of the Tamil Hindus is different
from that of the Malayalam-speaking Hindus in the Chavara area. There
are a number of “ gotras ”, exogamous sections or sub-groups, each
bearing the name of a supposed ancestor in the community. A man can
only marry into a certain number of specified, exclusive sections, and his
sisters can only marry into a different group of sections.
The area is more difficult to define than Chavara but boundaries can
be set. North and south of the area there are Tamil-speaking people,
apparently of the same ethnic origin. A suitable control population for
study would not be unduly difficult to find.
9. Physical Aspects
By way of introduction to a presentation of the physical aspects of the
Kerala project, a summary is presented of the properties of thorium and
its daughter products.
Thorium, the element of atomic number 90, is widely distributed
throughout the earth’s crust, but appreciable concentrations occur less
frequently than in the case of uranium. It is the parent element of one
of the naturally radioactive series, decaying by alpha emission, the daughter
substances further decaying by beta and gamma emissions. The accom
panying chart (p. 29) shows the most important features of the chain
of transmutations, with the associated energies and the half-lives of the
products. As in the case of the other series, the end-product is a stable
isotope of lead, in this instance 208Pb.
From the biological standpoint, there are only two daughters that have
half-lives of sufficient length to give rise to problems. These are 228Ra
29
FIRST REPORT
THE THORIUM FAMILY
(Energies in Mev)
232'J'|1
1.39x 1010 years
I
a 4.0 ; y 0.055
I'
0
228Ra--------- ?----- - 223Ac—
(MsTh2)
(MsThi) 0.053
6.12 hours
6.7 years
0
1.55
2.18
T
0.09
—>
228Th
(RdTh)
1.90 years
a 5.4 ; t 0.08
224 R a
(Th X)
3.64 days ; y 0.25
5.7
a
220Th
(thoron)
54.5 seconds
a
6.3
0
216p0 -------
(Th A)
0.16 seconds
a
a
6.8
212pb .
(Th B)
10.6 hours
216At
3X10"4 seconds
0
0
0.59
7.8
212Bj -------
2.25
(Th C)
60.5 minutes
a
a
6.0
208T1 —
(Th C")
3.1 minutes
-> 2,2Po
(Th C')
3xl0-7 seconds
0
8.8
> 208Pb
1.8
' - ye;jars and 228Th (radiothorium) whose
(mesothorium 1) with half-life of* 6.7
Since
with the parent 232Th, it will
half-life is 1.9 years. £
----- 228Th is isotopic
,
exhibit the same chemical behaviour. This is in contrast to 2-8Ra which
behaves chemically as common 226Ra but has a much greater radioactivity
associated with its shorter half-life. 228Ra behaves in the body in a similar
manner to calcium.
The most commonly found thorium-containing minerals are silicates
and phosphates in combination with several rare earths. Some deposits
of the oxide are known, reflecting the insolubility of this compound.
Many of the salts of thorium, such as the chloride and nitrate are readily
soluble in water.
30
RADIATION
9.1 Probable gonad dose from gamma radiation
Three sample surveys of the monazite areas of Kerala and Manavalakurichi have been carried out, or are being carried out, by the Health
Physics and Air Monitoring Divisions of the Department of Atomic
Energy, Government of India, to estimate the internal and external radiation
exposures of the population in the coastal areas. The first of these studies
was carried out in 1956,1 the second in 1957,2 and a third is at present
being completed. Only a summary of the findings is given here.
Inspection of Table 9 reveals a twenty-fold variation in the average
gamma activity over the 10 villages in the surveys. The average gamma
field to which an individual residing in these areas is being subjected is
computed as follows :
rZPrXr
average =--------r^-^r
where Pr = the total population of village r
and Xr = the average gamma activity of village r in millirads per
year, as given in Table 10
The average so obtained is 1300 millirads per year.
In order to determine the total activity due to beta and gamma radiation,
use was made of the data obtained in the earlier survey (1956), in which
both the gamma and the (beta + gamma) counting rates were simulta
neously obtained. It has been calculated that the contribution from beta
rays to the total field was about 16% of the gamma contribution. Thus,
the average total field is about 1500 millirads per year.
Three observations are pertinent to the interpretation of the potential
biological significance of the above figure. Firstly, although in normal
circumstances the beta dose could be considered to have a negligible effect,
the fact that the decay products of thorium, mesothorium 2 (2.18 Mev),
and thorium C (2.25 Mev) are high-energy emitters should not be lost
sight of, especially when it is considered that the people come into close
contact with the surface of the soil every time they sit or sleep on it.
Secondly, it must be pointed out that the fishermen who largely inhabit
this area spend a major portion of their days out at sea where the radiation
level can be considered to approximate the normal background. The
average dose to which the population in this area is subjected can be
1 Gopal-Ayengar, A. R. (1957) Possible areas with sufficiently different background
radiation levels to permit detection of differences in mutation rates of “marker” genes.
In : World Health Organization, Effect of Radiation on Human Heredity, p. 115
2 Bharatwal, D. S. & Vaze, G. H. (1958) Radiation dose measurements in the monazite
areas of Kerala State in India. In : Proceedings of the Second United Nations International
Conference on the Peaceful Uses of Atomic Energy, Geneva, Vol. 23, p. 156
[1
31
FIRST REPORT
TABLE 9. SUMMARY OF THE RESULTS OF SURVEYS OF THE MONAZITE AREAS
OF MANAVALAKURICHI AND NEARBY REGIONS
I
Population
Type of
house •
Number of
houses
scanned
Average gamma
activity in
millirads per year f
Kadiapatnam
6 000
B
C
7
12
2814
Manavalakurichi
11 000
A
B
C
15
18
3
2164
Muttam
6 000
A
B
C
6
5
13
736
Midalam
10 000
A
C
20
20
Villingem
10 000
A
B
C
10
9
3
131
Karamanal
2 000
A
B
C
6
7
6
1283
Kovalam
1 000
C
1
814
370
Name of
village
1573
Kullatoor
2 000
A
B
4
6
Vettoor
3 000
B
10
527
Varkala
1 000
A
12
138
t Mean of all readings taken in the village
* See below
construed, then, at a level which is lower than the measured 1500 millirads
per year. Finally, rather wide variation in exposure exists in any given
locality ; this is,’ in part, a function of the extent to which the monazite
sands are incorporated into house construction. The effect of an individual’s
type of house upon the exposure he may experience will be treated in
some detail in the next section.
9.2
Variation in exposure from house to house
The people of the coastal regions usually live in small and more or
less closed huts. These are mainly of three types, a brief description of
which is given below :
Type A
This type of house usually has two to three rooms with a courtyard.
It is fenced on all sides by a low mud wall. The single-storeyed structure
has walls and floor of brick and cement. The roof is of either tile or bricks
\ oo
32
RADIATION
located on a wooden structure. The rooms are provided with windows
and have good ventilation. The living habits of the inhabitants of this
type of house are generally hygienic. The people sweep and clean the
floor often, but make liberal use of the sand for flooring and for piling
about the roots of coconut trees in the compounds. This type of house
constitutes about 15% of the residential structures. .(The average floor
space may not exceed 150 sq. ft.)
Type B
The type B house consists of one or two small rooms, with an occasional
courtyard attached. The walls and floors are of mud and the ceiling
of tiles. These houses do not usually have windows and are therefore
poorly ventilated. Most of the houses which are built on the outskirts
of a village or town have coconut trees growing in the compound, and
monazite sand is used liberally around their roots. 60% of the houses
belong to this category.
TABLE 10.
MAXIMUM AND
MINIMUM GAMMA LEVELS IN THE THREE TYPES
OF HOUSES
Type
Maximum gamma level
A
3000 mrad/year
53 mrad/year
B
3200 mrad/year
105 mrad/year
C
4000 mrad/year
145 mrad/year
TABLE 11.
Number
Minimum gamma level
NUMBER OF SURVEYED HOUSES OF EACH TYPE SHOWING DIFFERENT
ACTIVITY LEVELS INSIDE
Gamma activity
in millirad per year
Number of A
type houses
Number of B
type houses
Number of C
type houses
Above 3000
0
1
7
2
Between 2500 and 3000
2
8
3
3
Between 2000 and 2500
8
13
4
4
Between 1500 and 2000
18
5
15
5
Between 1000 and 1500
11
1
9
6
Between
6
11
17
7
Below 500
28
23
3
73
62
58
500 and 1000
Totals
4
FIRST REPORT
33
Type C
These are shack-like structures, about 10 ft in height, built out of
bamboo and palm leaves, the floor being covered with sand or thick coats
of mud.
Table 10 shows the maximum and minimum gamma levels encountered
in the three types of huts described above.
In Table 11 is given the distribution of the surveyed houses of the three
types in different activity zones.
The weight to be given to the structural differences between these three
types of houses in appraising individual exposure is a perplexing problem.
It will be the aim of future surveys to provide additional information
pertinent to this point.
10. Radiobiological Aspects of Thorium and Daughter Products :
Possibility of Gonad Dose being Produced from Internal Deposition
of Radioactive Elements
While precise figures with respect to the body burdens and distribution
of the significant radioactive substances are not at present available for
individuals within the Kerala and Manavalakurichi areas, observations
do exist regarding the possibility of a significant gonad dose being produced
from the internal deposition of radioactive elements. Since certain of these
observations have not yet been published, the evidence for concluding
that a significant gonad dose from the internal deposition of radioactive
elements is improbable is presented here in some detail.
10.1 Considerations of chemical toxicity
Thorium is an element of generally low toxicity. Under ordinary
circumstances there is little transport to the tissues from the external
environment. Salts of thorium as well as the oxide, when ingested, remain
in the content of the gastro-intestinal tract and are excreted in the faeces
with almost no absorption. Dusts, when inhaled, are for the most part
passed through the intestinal tract without absorption. Following prolonged
inhalation of thorium-containing dusts formed from the nitrate, fluoride,
oxide, and oxalate, a variety of laboratory animals (rats, guinea-pigs,
rabbits, dogs) failed to show any pathological changes save for minor
changes in the white blood-cell count and in the bone-marrow.
A study of the employees in a thorium refinery1 which had been in
operation for over 30 years, and where exposures were considerably in
1 Albert, R. et al. (1957) A.M.A. Arch, industr. Hilh, 11, 234
34
RADIATION
excess of the acceptable standards for uranium, disclosed no evidence of
overt industrial disease attributable to thorium.
When thorium salts are injected, acute toxicity is usually determined
by the anion rather than by the thorium. The oxide is so inert that an
LD50 cannot easily be determined ; it has been widely used in colloidal
form for roentgenography, especially of the liver and spleen. Thorotrast,
injected intravenously, is promptly phagocytized by the reticuloendothelial
cells, especially of the two organs mentioned. The material remains
relatively fixed in these tissues, but over a long span of time there is a
slow movement of the material with secondary deposition in more distant
organs, especially the bone-marrow.
In patients who had received thorotrast many years previously, diffuse
fibrosis of the liver, spleen, lymph nodes, and bone-marrow has been
found. In one case, a carcinoma of the liver developed 15 years after
the patient received thorotrast. The tumour showed a massive accumulation
of thorotrast.
Following the injection of salts of thorium into muscles or connective
tissue, the thorium is generally retained at the site of injection and only
slowly released into the circulation. This movement is much slower than
in the case of radium.
Once thorium compounds have been absorbed, they are excreted very
slowly ; for practical purposes it can be said that once within the body
proper, thorium is retained indefinitely.
Following injection of the chloride in the rat, the greatest amounts
are to be found in the skeleton. The preferential movement of thorium
to the bone continues throughout the periods of observation reported.
In a study by Lanz et al.,1 47% of the total was in the bone 64 days after
injection of the chloride in the rat. The next greatest site of concentration,
on a gram basis, is the kidney.
10.2 Considerations of radiological toxicity
The radiological aspect is of far greater significance than the purely
chemical consideration of toxicity. As indicated before, the first disinte
gration step from 232Th is the formation of mesothorium or 228Ra. As
a radium isotope, this is stored more avidly in bone than is thorium.
Studies in a laboratory worker accidentally injected with 227Th freshly
extracted from an equilibrium mixture with 227Ac have been illuminating
with reference to the behaviour of the daughter 223Ra. Using the whole
body counter and taking advantage of the fact that all of the gamma
photons over 300 kev are derived from the 223Ra, it was possible to make
1 Lanz, H. et al. (1946) The metabolism of thorium, protactinium and neptunium
in the rat (US Atomic Energy Commission, document MDDC-648)
FIRST REPORT
35
good estimates of both 227Th and 223Ra in the body and to obtain excretion
data up to 221 days.1
There was a marked preferential excretion of radium over thorium,
so that from 33 days onward the activity ratio of Ra to Th was approxi
mately 15% of the value expected upon purely physical grounds. Most
of the excretion of both radium and thorium was by way of the faeces.
In this and other studies, radium retention was found to be described
by the expression :
Retention = 0.3 t-0-7
where t is expressed in days. The retention is clearly the resultant of both
radioactive decay and metabolic elimination.
Similar studies in dogs, using 228Th by injection and following the
behaviour of the 224Ra daughter, showed that the latter behaved as though
it were being continuously injected intravenously, yielding constants for
the retention somewhat at variance with those in the human case.
Further theoretical studies by the Argonne National Laboratory Group 2
have been based upon the following assumptions :
(1) thorium is administered only once in the complete absence of
its daughters ;
(2) no thorium is eliminated by the mammalian body ;
(3) the radium daughter produced by the thorium parent behaves as
though it were injected into the blood-stream.
The third assumption leads to the adoption of the following equation
for radium retention R(t) at time t in days :
R(t) = At-b
for t=il, where A and b are constants and, to a first approximation,
A = 1 —b. The validity of the general form of this equation has been
amply verified for radium injected intravenously in several species.
The second assumption is based upon the negligible excretion found
in many different experiments. A single factor would seem to represent
the thorium retention satisfactorily.
Since the calculations appear to fit the data in the cases of the pairs of
gamma-emitting isotopes studied, it seems reasonable to extend the calcu
lation to 232Th — 228Ra and to 228Th — 224Ra. The calculated activity
ratios for selected times for these two pairs are shown in Tables 12 and 13.
1 Gustafson, P. F. et al. (1955) Thorium-227 Accident. In : Argonne National Labo
ratory, Quarterly Report, October 1955 (document ANL-5486)
2 Reynolds, J.C., Gustafson, P. F., Marinelli, L. D. (1957) Retention and elimi
nation of radium isotopes produced by the decay of thorium parents within the body —
calculations and comparison with experimental findings (Argonne National Laboratory,
document ANL-5689)
36
RADIATION
TABLE 12. ACTIVITY RATIO [A(t)I OF
“‘Th TO ,2,Ra AS A FUNCTION OF TIME
A(t)
t(days)
b = 0.7
b -= 0.5
b = 0.3
A(t)
t(days)
A(t)
t(days)
0.000692
5.80
0.000358
24.9
0.00133
19.3
0.000558
0.00643
74.8
0.00235
58.0
0.000832
295
0.0146
249
0.00429
193
0.00124
590
0.0230
499
0.00596
386
0.00153
1 480
0.0397
1 250
0.00886
966
0.00198
2 950
0.0556
2 490
0.0113
1 930
0.00232
4 430
0.0644
3 740
0.0127
2 900
0.00250
4 990
0.0135
3 860
0.00261
0.0762
8 730
0.0144
6 760
0.00275
14 800
0.0778
12 500
0.0147
9 660
0.00280
30 000
0.0783
30 000
0.0148
30 000
0.00283
0.00126
8.86
0.00297
29.5
88.6
0.0697
5 900
10 300
7.48
TABLE 13. ACTIVITY RATIO [A(t)J OF
“'Th TO “*Ra AS A FUNCTION OF TIME
b = 0.7
b = 0.5
b = 0.3
t(days)
A(t)
t(days)
A(t)
0.251
1.87
0.178
1.45
0.118
0.363
3.73
0.242
2.89
0.151
0.426
5.50
0.277
4.34
0.169
0.463
7.47
0.297
5.78
0.179
15.5
0.508
13.1
0.323
10.1
0.193
22.1
0.520
18.7
0.330
14.5
0.197
30 000
0.524
t(days)
A(t)
2.21
4.42
6.63
8.83
30 000
0.333
30 000
0.200
10.3 Considerations from thorotrast injections
When thorotrast is injected, it is largely held in the reticuloendothelial
system of the liver and spleen. It is found that approximately 2/3 of the
228Ra produced is retained with the phagocytized thorotrast and only
about Vs enters the blood stream and is available for translocation. The
FIRST REPORT
37
228Ra which is released from the thorotrast deposits is redeposited in the
skeleton.
On the basis of the quantitative information at present available, a person
who has carried a body burden of 4 g of 232Th as thorotrast for several
years should have the following range of activities (in curies) in the skeleton :
Minimum :
1.8 x IO-9 228Ra + 1.8 x IO"9 228Th + 1.9 x IO"8 224Ra + 1.7 x 10-8 Em
Maximum :
1.8 X IO"9 228Ra + 5.5 x IO'8 228Th + 3.7x IO"8 224Ra + 3.3 X IO"8 Em
Considering the energy delivered to the bone by these activities in
comparison with the 11 Mev per 226Ra disintegration, these limits are
approximately equivalent to 40% and 100% respectively of the dose from
the presently accepted maximum permissible level of 0.1 microgram of
226Ra.
Where the thorium has been acquired in soluble form permitting
dispersion through the tissues, it may be anticipated that the above range
of bone activity will be achieved by a little over 1 g of 232Th total body
burden.
10.4 Gonadal exposure from internally-deposited thorium
From all the foregoing, certain conclusions may be drawn concerning
the gonadal exposure resulting from internally-deposited thorium. By
any route of acquisition other than direct injection into the gonads,
secondary deposition of thorium compounds in the testis and ovary is
negligible, even following thorotrast injections. Gonadal exposure can
therefore occur only from the gamma emission of the daughter products
held in the skeleton. Since the partition of energy between gamma and
alpha plus beta emissions is similar in the thorium series to that of radium
plus its daughters, it appears to be approximately true that for a gonadal
exposure equivalent to that resulting from the maximal permissible body
burden of radium for occupational purposes, the huge amount of 4 g
of thorium as thorotrast, or 1 g of the element as a soluble compound,
would be required. Even in this extreme case, we would be considering
a lifetime dose of a few roentgens, certainly less than 10.
11. Suggestions for Information Which Should Be Collected
in a Kerala Project
To provide the appropriate perspective for the suggestions of the
Committee, it should be stated that the Committee was primarily concerned
with the first stage of collection of information, namely, the ad hoc
38
RADIATION
census, and to a less extent with the procedures to follow this census.
The Committee wishes to emphasize the tentative nature of the sugges
tions which follow.
11.1 The ad hoc census
There was general agreement that the first step in the Kerala study
should be to select control populations as nearly comparable to the exposed
populations as possible, and, as soon as reasonably convenient, to define
certain essential characteristics of these populations by a census procedure.
Clearly, to a considerable extent the suitability of a population chosen
as a control will only be known after an ad hoc census. However, it may
well be necessary to make a rather arbitrary choice of control areas (bearing
in mind the principles set out in sections 4 and 6 of this report), rather
than delay the selection until the characteristics of the exposed population
are more completqjy revealed by a census. The advantages derived from
conducting the census of the control and exposed populations as nearly
concurrently as possible offset to some extent the disadvantages of having
to select the control population before adequate characterization of the
exposed population is available. Such is the nature of the present problem,
however, that modifications may have to be subsequently made in the
composition of the control population, irrespective of when it is selected
—a point of importance not only in terms of effort and finance but in
further underlining the need for census-taking at a relatively early stage.
Attention should be paid to the matters of size and geographic distri
bution of the control populations. In particular, there may be merit
to distributing, if possible, the control population for a given exposed
population over several geographic areas. The extremely high population
density existing in the study area could be troublesome if the control
population does not have the same density. This might be offset to some
degree by obtaining, as control, observations at a variety of population
densities. In practice, of course, due regard would have to be paid to the
practical difficulties associated with suggestions of this type.
11.1.1
The timing of an ad hoc census
As regards the timing of an ad hoc census, it was fully realized by the
Committee that local circumstances and local knowledge of the response
of such communities to questioning must determine what preparations
are essential. At present, the major preliminary work would seem to be
(a) accurate mapping of the geographical areas involved ; (Z?) training of
the census-takers ; (c) publicity efforts designed to enlist the maximum
support of the populations ; and (J) the study of the social and cultural
pattern of these populations with special reference to factors pertinent to
FIRST REPORT
39
this investigation. It was stressed, however, that there were many factors
which favoured as early a census-taking as feasible. Thus, it seemed
important to have basic population information before any steps were
taken to increase medical care in the study areas. Moreover, to a consid
erable extent the planning and execution of subsequent stages of the
investigation will be dependent upon the information collected by the
ad hoc census concerning individuals, families, and the population as a
whole.
11 J. 2 The form of the ad hoc census
With reference to the form of the census, there seem to be many
advantages in keeping to the conventional pattern of census-taking which
has two essential features : («) a census of those living in each house and
the specification of a “ head of household ” ; (Z>) a census of individuals,
giving the information basic to the needs of demography, and a specification
of the relationship of the individuals within a household to the head of
the household.
An important disadvantage of following this plan too closely is that
the basic unit in genetics is the family, and even on the narrowest definition
of the family the members do not necessarily live in the same house. This
difficulty can be surmounted, in part, by designing the census procedure
in such a way that the children of a given parent can be identified. The
exact method by which this is to be done and the extent to which sibships,
half-sibships and other degrees of relationship may then be constructed,
will depend on local considerations regarding name frequency, and also
on the information required for the precise identification of each individual
within the populations.
11.1.3 The information to be collected at the ad hoc census
If a conventional census procedure is adopted, the next questions which
must be dealt with arc (a) how much information additional to normal
census requirements would it be desirable to have at this stage, and (6)
how much of this is it practicable to collect, bearing in mind considerations
of time and the state of general and special education of the actual census
staff ?
It was the consensus of the Committee that the following list represented
the minimum information to be obtained on each individual and each
household.
Individual
(1) Reference serial number
(2) Name of individual and names of father and mother
n
40
RADIATION
(3) Sex
(4) Language
(5) Religion
(6) Date of birth
(7) Places of birth of individual and his or her parents
(8) Age
(9) Marital status
(10) Gotra
(11) Occupation
(12) Educational attainments
(13) Consanguinity of parents (give details)
(14) Whether one of twins, triplets, etc.
If married, then:
(15) Relationship to spouse (give details)
(16) Age at marriage
(17) Living male children
(18) Living female children
(19) Age of spouse at marriage
If a woman, then:
(20) A complete roster of all pregnancies, including age of mother at
the termination of each pregnancy, anomaly in offspring, death of
offspring, stillborn infants, and those pregnancies terminating in a
miscarriage or abortion.
Household
(1) Area number (from previous governmental censuses)
(2) House number (from previous governmental censuses)
(3) Village
(4) House map reference
(5) Type of house by construction (A, B or C)
(6) Some measure or measures of social and hygienic status
(7) Date of visit
(8) Name of visitor
(9) A roster of persons normally living in the house beginning with
the eldest male (unless he is not related to the family). This roster
is to include, for each individual, personal serial number, sex, year
of birth, age, name, seen or not seen, and a family tree showing relation
ship to the head of the household.
n
FIRST REPORT
41
It was agreed that certain items in the above list would have to be
subsequently checked and expanded ; notable in this respect is the infor
mation on consanguinity, reproductive performance of the mother, and
migration.
11.2 The collection of demographic data following the completion of the
ad hoc census
It was recognized that a system would have to be devised to maintain
the accuracy of the demographic and reproductive performance statistics
of these areas at a high level over a considerable number of years. This
would involve constant combing of the population to detect failures or
inaccuracies in the reporting of births, deaths and marriages : in this con
nexion, the principles involved in organizing “census tract areas” are
relevant. The possibility was discussed of utilizing Catholic church records
as a source of information and as a means of detecting breakdowns in
the registration system.
11.3 Other steps to follow the ad hoc census
As here envisaged, the ad hoc census is primarily a device by which
to characterize the study populations and to afford a basis for the efficient
planning of subsequent stages in the investigation. Obviously then, the
ad hoc census must be supplemented by certain other steps. Among these
are the following:
11.3.1
The checking and elaboration of certain information collected at
the ad hoc census
In the ad hoc census, practical considerations will prevent the collection
of such further information regarding individuals and their relationships
as would require “ follow-up ” visits to their houses. However, since, as
presently envisaged, every individual in the population will ultimately be
interviewed and examined, the census information could be checked and
supplemented at the time of this interview. At this stage, family relation
ships should be checked and recorded in some pedigree or equivalent
form so that not only degrees of consanguinity but the specific relationships
which have contributed to these degrees are recorded as exactly as possible.
This interview could also serve to provide a medical or family history
with respect to certain items of interest.
11.3.2 Examination of individuals and recording of variables
Any consideration of the type of physical examination is immediately
beset by questions regarding (a) the objectives of such an examination
42
RADIATION
and (Z>) how these objectives can be reached with the personnel likely
to be available. As already noted, the objectives are to record (a) segre
gating characters—morphological, physiological, or biochemical—and
(b) continuously distributed characteristics. Recording of the former
requires, in general, a level of training not required in the latter.
An enormous number of physician hours would be consumed by
physical examinations sufficiently complete to record the bulk of segregating
characters. It is virtually certain that sufficient physicians would not be
available for a programme so based. However, there are the so-called
screening procedures that have been designed to reject people unsuitable
for certain tasks, e.g., entrance into the Armed Forces or industry, or to
pick out, for treatment or for more elaborate investigation, individuals
with certain diseases and disorders. Similar procedures might well be
developed for use in the Kerala project to screen out segregating characters.
A pilot study on the lines suggested below should reveal the worth of this
suggestion (it will be noted that the screening efficiency would be susceptible
to test in various ways).
The dominating factor is a shortage of medical manpower. It seems
likely that there are available qualified nurses with further training in
midwifery and public health. Experience has shown that in school
health examinations the efficiency of suitably trained nurses in recog
nizing defects is high, e.g., in New York City and in New Zealand. Some
such scheme as follows might therefore be used. First, groups of nurses
would be trained in the exact procedures required and tested for their
efficiency. Each individual in the population would then be interviewed
by such a trained nurse ; she would have with her the census record
and would check and complete it along the lines previously suggested.
She would then :
(1) Record certain characteristics, probably (a) specified anthropo
metric measures, (b) colour vision, and (c) visual acuity.
(2) Make a standard examination directed toward revealing any
general abnormality or peculiarity. This examination would include a
systematic inspection of each part of the body ; all negative findings
would be recorded and all anomalies, diseases or disorders would be
described. There would be a standard record sheet.
(3) Place a suitable mark on the record sheet of any person exhibiting
an anomaly or other positive finding or use some other device to ensure
that he was referred for more detailed examination by a physician.
It should be noted here that even diseases obviously caused by
environmental factors, such as trachoma or scabies, should be
recorded, but in view of their frequency, patients need not necessarily
be referred to a physician for assessment, but only to a dispensary
for treatment.
FIRST REPORT
43
With reference to item (2) above, it is suggested that observations
might be recorded with respect to :
(a) any obvious abnormality of physique or bodily conformation;
(Z>) any obvious general syndrome;
(c) abnormalities of skeleton and extremities, mouth, ears, skin, hair,
nails, eyes, or central nervous system (palsies or ataxias).
There remain many procedures by which important variables could
be detected but which require special skills or which would be too time
consuming to apply to every individual in the population. It would seem
that the most likely approach would be by ad hoc sampling procedures.
Attention is drawn to the following :
(a) skilled ophthalmological, neurological, dermatological, and other
special examinations ;
(b) urine studies (e.g., for sugars, porphyrins, phenylketones, etc.)
using chromatography techniques ;
(c) blood studies using haematological, serological and electro
phoretic techniques.
The Committee was of the opinion that it would greatly increase the
co-operation of the population with respect to the procedures just outlined
if clinical facilities for the diagnosis and treatment of certain common
diseases prevalent in the area, such as helminthic infestations, scabies,
and especially trachoma, could be set up as early as is consistent with
the objectives of the ad hoc census.
11.4 General remarks
Certain particulars of the methodology of census-taking have been
considered above ; it seems appropriate, by way of concluding this section,
to consider briefly the somewhat broader methodological problems raised
by the Kerala study. This report has repeatedly stressed the desirability
of conducting investigations of high-radiation areas in a manner whereby
data from a number of these studies may be compared. For this to be
meaningful requires a measure of uniformity. The Committee would urge,
therefore, that where available, internationally accepted procedures of
measurement be employed. Thus, the ad hoc census should, to the limit
feasible, be conducted along the lines suggested in the United Nations
handbook of population census methods.1
The Committee would also call attention to the fact that the Kerala
study may well establish a precedent for subsequent studies in other areas
1 United Nations (1954) Handbook of population census methods. New York
n
44
RADIATION
and that due consideration should therefore be given to the adoption
of measurements and methods potentially applicable elsewhere.
12. Suggested Requirements in Men and Material
As presently envisaged, the Kerala study would proceed through a
series of well-defined steps, from the initiation of a programme of collecting
demographic statistics to, ultimately, a medically supported effort to
characterize the patterns of morbidity and mortality obtaining in this
area. It is convenient, therefore, to view the resources in men and material
required in terms of the successive stages in the evolution of the study.
12.1 The ad hoc census
This should be completed, if at all possible, within a period of one
month : an adequate staff should be available with at least five inspectors.
The exact number of staff might be determined by a pilot survey.
The census workers must have a good education and considerable
coaching in census methods. It would be advantageous to be able to
employ them on subsequent work in maintaining the accuracy of the vital
statistics, and, possibly, in some of the screening procedures such as simple
anthropometry and checking of census information.
12.2 The on-going registration of births and deaths
It seems reasonable to expect that some 8000-9000 registerable events
will occur within the study populations in any given year. The staff
necessary to record these events (births, deaths, and possibly marriages)
will depend largely upon the number of registration centres. If a single
centre is maintained in each study area, three clerks should be able to
handle the work load anticipated for any given area.
12.3 Processing of the vital statistics
Possibly 10 clerks or stenographers would be needed for coding, code
checking, and mechanical analysis procedures. The precise number will
depend, however, upon whether these operations occur within the study
areas, or in some more centrally located area such as Trivandrum.
12.4 Screening examinations and medical support
The problem of medical manpower is clearly going to result in a
compromise, there being no likelihood of the availability of more than
a limited number of men and women. Much could be done, however,
(I
FIRST REPORT
45
by planning the screening procedures well, so that the doctor’s special
skills were not employed on work which could be satisfactorily done by
clerks or para-medical workers. In this connexion, it would seem desirable
to employ, whenever possible, health visitors in the screening procedures.
It may also be possible to utilize medical students from Trivandrum.
There is need for as high a rate of acceptance of autopsy as possible,
particularly in the case of stillborn infants and children dying at an early
age.
12.5 Laboratory facilities required
It is difficult at this stage of the planning to foresee the demands for
laboratory facilities; however, the possibility that laboratory space and
personnel will be required at some time in the evolution of the programme
should not be overlooked. The availability of air transportation may
suggest sending blood and other samples for examination to laboratories
out of the area, at least for more complicated or extensive types of
investigation.
12.6 Other requirements
The most obvious requirements of a non-personnel nature will be (1)
adequate, independent land and water transport; (2) office accommoda
tion ; and (3) access to data-handling machinery of a variety of types.
12.7 Institutional relationships
The Committee hoped that the active participation of the interested
educational institutions would not only greatly add to the scientific resources
available to the study, but at the same time substantially advance the
educational interests of the institutions themselves.
13. Summary and Conclusions
1. There is an increasing interest in many parts of the world in the
effects of radiation on man and his environment, but opportunities to
study the genetic effects of the irradiation of human populations are limited.
One such opportunity arises through the existence, at widely scattered
points on the earth’s surface, of areas with significantly increased amounts
of background radiation. This report has attempted to review the general
considerations which enter into the study of such areas, and to apply
these general considerations to the steps that might be taken in organizing
studies in one of the better known of these areas, namely, the Kerala
area of India.
n
46
RADIATION
2. After a brief survey of the known areas of high-background
radiation, the kind of information to be collected in such studies has been
discussed. The decision as to what types of information are most appro
priate depends upon many factors which will vary widely from population
to population. Only rarely will it be feasible to base a study on a com
parison of the frequency of appearance of specific mutant phenotypes
in the irradiated and control populations. Much more frequently, reliance
must be placed on a comparison of populations with respect to those
characteristics which we assume reflect the cumulative effect of mutation
at many loci, characteristics such as sex-ratio, life-span, fertility, etc.
3. It is suggested that it is convenient to consider such studies in
terms of “ levels ” of information, the lowest levels being not only most
readily collected and making the fewest demands on the time of specialized
personnel, but also, in some instances, being indispensable to the acquisition
of higher levels.
These levels are:
(«)
(b)
(c)
(^/)
(e)
(/)
accurate vital statistics ;
growth and development data ;
patterns of congenital defects ;
clinical morbidity and mortality patterns ;
laboratory studies;
necropsies.
4. The general statistical considerations which must enter into any
such study as this have been reviewed. These are of two types : (a) consid
erations which enable conclusions to be reached concerning the possible
biological significance of the study, and (Z?) considerations which will guide
the analysis of the data.
5. The Committee wishes to emphasize the fact that properly designed
and conducted studies on radiation genetics in such areas cannot fail to
make significant contributions to many aspects of genetics and human
biology. The Committee also draws attention to the role properly designed
genetic studies may play in extending existing information concerning the
somatic effects of continuous exposure to relatively high levels of back
ground radiation.
6. With respect to a specific study in Kerala and the adjacent areas,
the following points should be mentioned :
(«) There is a relatively stable population of approximately 80 000
persons living in well-defined areas in which the background radiation is,
on the average, 10-15 times that normally encountered. The available
evidence suggests continuous occupation of these areas by at least some
of the ancestors of the present population for relatively many generations.
(I
FIRST REPORT
47
’
44
■ J to investigate not only the occurrence of
There is thus
an opportunity
induced mutations, but the fate of these mutations as regards visible effects
on the populations in which they are being introduced.
(b) What appears to be a suitable control population is readily
available.
(c) The first step towards the actual conduct of studies in these areas
would appear to be a carefully conducted ad hoc census. The items to
be included in such a census are outlined in section 11.1.3. This census
would serve the dual purpose of defining accurately the area under study
and of answering certain important questions concerning the comparability
of the control populations.
(J) Although a considerable amount of information on the important
question of dosimetry is available, more extended measurements aimed
at producing the best estimate of the mean individual accumulated gonad
dose at various ages arc essential.
(e) Following the completion of the ad hoc census, a continuing
effort at the collection of accurate demographic and vital statistics would
appear to be the next step in the evolution of the programme.
(/) In the interests of better planning and to ensure maximum co
operation from the population, it is desirable to initiate pilot medical
studies and services at the onset of the investigation. These pilot studies
must be conducted in such a fashion as not to disturb the objectives of
the ad hoc census.
(g) As soon as feasible, it would appear appropriate to perform some
type of systematic, standardized medical examination on all, or an appro
priately selected sample of, the inhabitants of the high-level and control
areas.
(//) It seems unwise to specify further the details of an elaborate study
when many of the factors necessary to intelligent decisions are still lacking.
7. The Committee regards it as rather improbable that the investigation
of any of the high-background areas known today will, by itself, lead to
the demonstration of significant genetic changes. The Committee is
cognizant, however, of the desirability of obtaining meaningful data,
imperfect though they may be, on the consequences of prolonged exposure
to low doses of radiation. Such is the present status of our knowledge
of the somatic and genetic effects of chronic low-level exposures that any
proper investigation of areas of high natural radiation is certain to contribute
to the fund of biological knowledge and the ultimate specification of the
genetic risks accruing from increasing exposure to ionizing radiations.
u
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