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188
THE LIFE SCIENCES
able to feed herself. A few hundred acres of new wheat were planted in
1964. By 1968, more than 20 million acres were under cultivation and
plans called for 40 million acres in 1970. Withal, this represents only a
fraction of India's farmland and is but a start.
The new wheats and rices emerged from painstaking crossbreeding with
available strains to provide seeds that carry the most advantageous char-
acteristics and with new mutants, each being examined for new useful
properties. These new grains demand careful nurture. Designed to resist
lodging, they also require and can make maximum use of fertilizers and
water. They must be planted at the optimum moment and carefully tended.
And, as in American agriculture, if the "revolution" is to be sustained, it
will be essential that in these regions there be a continuing program of
plant breeding to replace current strains as they fall victim to infection or
pests.
The revolution began 30 years ago, when the Rockefeller Foundation
sponsored a program to improve wheat and maize in Mexico. Through
these efforts, the average yield per acre of wheat had been increased more
than threefold by 1964. In 1959, the Rockefeller and Ford Foundations
decided on a similar effort with rice, the staple food in the Orient. To this
end, they established an International Rice Research Institute in the Philip-
pines. The successful new rice varieties were bred there, drawing on the
background of genetic information that had been accumulated in this coun-
try and Mexico. Success of the new varieties depends on packaging selected
seed, fertilizer, and pesticides so that the farmer has these essential inputs
at planting time. Perhaps the most significant aspect of this "green revolu-
tion" is that traditional farmers have been shown what can be done and are
thus receptive to the further changes necessary to extend and stabilize
these advances. There is no better illustration of the contribution of
biological science to human welfare.
MAN AND HIS ENVIRONMENT
Science is applied to human affairs through an increasingly complex net-
work of technologies. Each new technology finds acceptance if, for example,
it solves a problem, eases a burden, enriches life, assures the food supply,
or facilitates communication and transportation. But each such bene-
ficial technology must be examined for its potential social cost. In this
connection scientists must be particularly wary of threats to the public
health, to the fertility of the soil, to the quality of air and water, and to
the security of renewable resources.
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BIOLOGY IN THE SERVICE OF MAN 189
Perhaps 500,000 distinct chemical entities and mixtures are in current
use and hundreds more are added annually. Each must be considered for
its effects on the biosphere, particularly on man himself-effects that may
be acute, dramatic, and self-apparent or extremely slow, difficult to detect,
and even indirect. For these reasons an increasing force of trained scien-
tists is engaged in these activities. The level and pace of such activity are
patently insufficient to the national need. Such agencies as the Food and
Drug Administration and the Fish and Wildlife Service are seriously under-
staffed relative to national needs. Let us consider only a few pertinent
problems typical of this large and disparate field of concern.
Water Supplies
Although it may not long be true, most American communities may still
boast a supply of biologically safe water for domestic purposes. The char-
acter of the situation is such that potential hazards must be avoided from
the beginning rather than removed after their introduction. The life scientist
must be aware of these hazards, establish appropriate monitoring pro-
cedures, be aware of indications in the community of failure of controls,
and establish reasonable standards. Avoidance of improper metals is now
a long-established practice, as are a variety of procedures designed to
minimize the presence of pathogenic bacteria.
That human disease can be transmitted through the water supply has
been known in a qualitative way throughout history. Yet specific under-
standing of its role in disease transmission goes back only to the past cen-
tury, with investigations of the spread of cholera and typhoid fever. Co-
operative work by engineers, biologists, chemists, and physicians on the
organisms responsible for such diseases and on development of methods
for their control was so successful that these infectious diseases have been
virtually eradicated from developed countries in which adequate treatment
and sanitary control of water supplies are maintained.
Water can be freed of pathogenic microbial agents by (1 ) protection of
water sources against initial contamination; (2) removal of organisms by
filtration, adsorption, or similar physical means; and (3) chemical destruc-
tion of the organisms. All three approaches have been put under stress by
increasing population density and demand for water. Because of these
factors, coupled with a concurrent increase in sources of contamination
i.e., human and animal wastes completely uncontaminated primary sources
of water are becoming difficult to find.
As knowledge of the factors that affect the survival of waterborne patho-
gens and their sensitivity to various forms of water treatment increases, new
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190
THE LIFE SCIENCES
~. .,
methods of water management may well emerge. Research is needed to
provide sanitary engineers with a rational rather than empirical basis for
the design of facilities for collection, treatment, and distribution of water.
It has become apparent in recent years that traditional control measures
are inadequate to prevent the spread of certain viral diseases that may be
waterborne. Epidemics of infectious hepatitis have been known to be
caused by water contamination. A most dramatic example was the 1956
epidemic in Delhi, India, where nearly 30,000 cases of hepatitis resulted
from a temporarily contaminated water supply. There are now about 50
documented instances of similar, although much smaller, waterborne out-
breaks of this disease, several in the United States. Because the hepatitis
virus has only recently been identified and no animal other than man is
known to be sensitive to this virus, thus precluding an animal model of the
disease, there has until now been little opportunity to engage in the neces-
sary studies.
Other viruses are assumed to be waterborne but have not been shown
to transmit disease. With the possible exception of the polio virus, con-
firming epidemiological patterns have not yet been established. New tech-
niques are required to gain definitive information about the health hazard
these viruses present and the necessity for measures to remove them from
communal water supplies.
Increasingly, water authorities must be aware of chemical contamination
at the source, particularly by materials entering through groundwater or
washed from the air by rain. Such materials do not announce themselves;
one must be aware of the problem, perform appropriate analyses, establish
standards, and, when feasible, institute procedures for removal of offending
chemicals. Such actions may be taken on the general principle that no
contaminants are acceptable, but there is greater conviction and urgency
when the biological effects of a given contaminant are known. Most note-
worthy, perhaps, are the various agricultural chemicals insecticides, herbi-
cides, and fertilizers. The soil burden of nondegradable insecticides is
already such that they will be leached and present in communal waters for
years to come. Current levels are such that no general risk is known to
exist. Similar considerations apply to the herbicides. Although its tera
~,
togenic activity has resulted in a ban, 2,4~5-T concentrations in communal
water supplies are trivial. The problems presented by fertilizers and non-
degradable detergents are somewhat more serious. Nitrate from fertilizers,
leached from manure piles or from sewage-disposal plants, occasions
methemoglobinemia (the iron of hemoglobin is oxidized to the ferric state,
Fe:+, in which condition it is useless for internal oxygen transport). Sig-
nificant levels of methemoglobin caused by such contamination have been
detected in various populations. No known deaths have resulted, and, in
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BIOLOGY IN THE SERVICE OF MAN 191
almost all such cases, it has been possible to trace the contamination and
act accordingly. These incidents serve to point up the need for intelligent,
biologically sophisticated management of water supplies.
Air
The intensities of air pollutants in American cities today may be no greater
than they were 25 years ago, except for a few areas such as Los Angeles
or New York on bad days. But techniques for measuring the levels of
chemicals or particulate matter in the air, then as now, were less than ade-
quate. The most significant change in this quarter-century is that the
American people are beginning to demand a higher level of quality in the
environment. Levels of air pollution are difficult to measure, but new,
sophisticated instrumentation is being developed. The body of knowledge
concerning the biological effects of known pollutants is increasing but is
unconvincing. Experience has shown that, when meteorological conditions
heighten the concentration of atmospheric pollutants, individuals suffering
from chronic lung disease and perhaps those with cardiac disorders may
have serious reactions. Such episodes have no observable effect other than
discomfort in the average, healthy member of the population, the indi-
vidual of most concern to environmental biologists trying to evaluate the
potential for serious consequences of long-term low levels of exposure.
The most evident aspect of acute episodes of air pollution thus far is the
increase in airborne sulfur dioxide and other sulfur-containing products
from the combustion of coal and fuel oils. Normally less than 0.1 part per
million (ppm ), concentrations during prolonged inversions may rise to
0.5 ppm or more. Such concentrations are harmful to the most susceptible
individuals and discomforting, for the remainder. The fact that no evident
illness is occasioned in healthy members of the population should not lead
to a false sense of security. Effects not detectable by current procedures
are not necessarily absent. In a few cases, toxic effects of pollutants have
been documented. Beryllium, for example, is known to have produced
serious disease downwind of beryllium-processing plants. Pollutants of
well-established biological significance, e.g., carbon monoxide and dead,
are being added to the atmosphere in immense quantities, primarily from
automobile exhausts.
It is clear that all urban dwellers, because of the relatively high atmos-
pheric concentrations of carbon monoxide, carry significant amounts of
carboxyhemoglobin but not in sufficient quantity to limit physiological
function. In episodes of striking increase, the consequence is an additional
pumping burden on the heart, of no account in normal persons but perhaps
sufficient to lead to serious crisis in those with incipient cardiac failure.
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THE LIFE SCIENCES
From epidemiological studies, the connection between cigarettes and
lung cancer, heart disease, emphysema, and other diseases is now known.
The carcinogenic action of cigarette smoke has been confirmed experi-
mentally in animals, although specific chemical toxins have yet to be
identified. Inhalation of smoke by rodents does not cause neoplasia;
however, painting the tar of cigarette smoke on their skin is highly carcino-
genic. There is a possibility that smoke contains agents that are not in
themselves capable of producing cancer but that promote the growth of
tumors by somehow interacting with otherwise innocuous doses of car-
cinogens. The causal relationship to cardiac disease is not understood.
Nicotine does increase the oxygen requirement of the heart, while carbon
dioxide from the smoke reduces the available oxygen supply, but these
effects seem too small to account for known effects. Attempts to separate
the effects of cigarette smoke from those of more general air pollution
indicate a much higher correlation between smoking and disease than be-
tween community pollution and disease. It seems quite conceivable that
a combination of cigarette smoking and general air pollution accounts for
the higher statistical incidence of disease in the smoking population.
The necessity for monitoring the quality of air will not be lessened.
New technologies will pose new hazards, and existing technologies will be
used on larger scales. Thus, it is anticipated that combustion of fossil fuels
for generation of electricity will quadruple by the end of the century, while
that for transportation will double. Thus the potential gain from use of
more efficient, less polluting automobiles may be totally offset by the in-
creased level of use, a phenomenon demonstrated in the Los Angeles area.
Food and Drugs
Mounting concern with the effects of myriad chemicals in the environment
has brought under closer scrutiny the agents that are deliberately added
to food. Approximately 1,700 food additives are in use in the United
States, and an equal number of additional materials go into animal feed and
packaging materials. Each agent is subject to regulation by the Food and
Drug Administration, which issues specific requirements to define closely
the allowable concentrations of some agents and maintains a list of others
that are "Generally Regarded As Safe" (the GRAS list). The safety of many
of these materials that have enjoyed long tenure on the GRAS list is predi-
cated on limited examinations performed years ago and on their long and
seemingly innocuous usage by the public.
Safety is no longer easily assumed, nor is it a simple concept. When
cyclamates noncaloric sweeteners were first introduced in the early
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BIOLOGY IN THE SERVICE OF MAN
1950's, their use was limited to individuals who used them to sweeten
coffee or tea. A decade later, the diet-soft-drink era came into being, fol-
lowed by a mushrooming of the diet-food industry. The very fact that
cyclamates were then consumed by many people in substantial amounts
generated concern. Experiments voluntarily conducted by a pharmaceutical
house revealed bladder tumors in a group of mice that had been fed vast
doses of cyclamate over their entire life-spans (the equivalent of several
thousand sweetened cups of coffee per day for many. Although there was
no evidence of similar effects in human beings despite the huge scale of the
human "experiment," according to the Delaney amendment to the Pure
Food and Drug Act of 1958, any agent in food that causes cancer in any
species, regardless of dose, must be banned. Cyclamates, therefore, were
ordered removed from ordinary foods.
But this points up major difficulties. Where is the rational limit? How
shall one balance the beneficial effects of voluntary caloric restrictions and
avoidance of obesity bv millions of Americans against the very remote
chance of tumors in a few? By any seemingly reasonable standard, cycla-
mates had been adequately screened for toxicity until an almost absurd
experiment was undertaken. It is noteworthy that, among the group of
animals at half the tumor-producing level in the diet, absolutely no lesions
were encountered! Quite conceivably, an equivalently rigorous and exten-
sive review of the GRAS list will yield some similar experiences. When
there is available a substitute that, by the same yardsticks, is innocuous,
the course is clear. But when there is no substitute? This dilemma risk
versus benefit, and not necessarily to the same individuals characterizes
most major decisions concerning the environment. The difficulty cannot
readily be mitigated, but certainly each such decision should rest on thor-
ough understanding of the biological implications.
It cannot be assumed that toxicological data are adequate for many of
the familiar chemical entities in the environment, let alone the scores of
new ones. It was only 25 years ago that investigators learned of the effect
of nitrate on hemoglobin. Recognition that cadmium in low concentrations
in water may have adverse physiological effects and that some water sup-
plies occasionally carry appreciable quantities of this element is even more
recent. A Public Health Service standard for an allowable limit of cadmium
was not set until 1962.
The task of the toxicologist is complicated by the fact that what is usually
required is an analysis not of the acute effects of large doses but of the
effects of very small doses accumulated gradually, of variability of response
within a large population, and of the effects of other environmental variables
and of disease. If there is evidence that a toxic compound accumulates
in the body and that no tolerance develops to it or that its effects are
~. ~, ,
193
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THE LIFE SCIENCES
irreversible, that agent is more menacing than one that can be detoxified
or readily excreted or whose effects are reversed when it is removed from
the environment.
The interaction of chemicals is often difficult to determine. The inter-
action of trace amounts, difficult enough in themselves to detect, compounds
the difficulty, but can be of critical importance. A few years ago, it was
found that when malathion and EPN (ethyl nitrophenyl benzytriphospho-
nate), both organophosphate insecticides, are fed together to experimental
animals, the toxic effects are considerably greater than the sum of the
toxicities of both chemicals. In consequence, the Food and Drug Ad-
ministration issued a regulation requiring that each new organophosphate
be tested jointly with every organophosphate already approved before the
new insecticide is cleared for sale. The pyramiding of tests that this would
engender is apparent. Relief came when the basis of this hazardous inter-
action was elucidated, thus permitting use of simpler means for predictin
dangerous combinations.
Both of these insecticides are toxic because they inhibit cholinesterase,
an enzyme essential to normal functioning of the neuromuscular system.
Alone, malathion is only mildly toxic to mammals because it is itself de-
stroyed by another group of enzymes, the aliesterases, before it can render
extensive damage to cholinesterase. The aliesterases, however, are inhibited
by EPN, thus opening the way for the total toxic effect of the malathion
that accumulates. Understanding of the underlying mechanisms in this
situation has permitted direct measurement of the effects of new pesticides
by testing them against appropriate enzyme systems, offering a rational
approach to the design of new pesticides.
The need to overcome similar problems in testing procedures and to
acquire the ability to predict adequately what will occur in given situations
is evident. Toxicologists, aware of their own limitations and responsible
for protecting the public health, would have to lean on crude and cumber-
some procedures to avoid any uncertainty about the safety of products they
stamp with approval. But even excessive caution cannot guarantee safety
if the substance of fundamental biological knowledge is inadequate. Re-
sults of extensive testing on animals may not be applicable to man. Thalid-
omide only rarely deforms unborn rats though it consistently deforms
human beings. Relatively early identification of the effects of this com-
pound in man must be attributed to the fact that it results in a deformity
that is so rarely seen ordinarily that the problem was readily evident.
Phocomelia, an anomaly in which the limbs fail to develop, is so rare a
congenital abnormality that it immediately aroused suspicions of some
environmental agent when the deformity began to appear in a relatively
Representative terms from entire chapter:
cigarette smoke
