COST-BENEFIT RELATIONS IN AIR QUALITY STANDARDS:
BIOMEDICAL RESEARCH FOR ASSESSING
THE HEALTH COSTS OF AIR POLLUTION
Donald E. Watson, M.D.
Lawrence Livermore Laboratory
Community air-quality standards are set to reflect the costs
and benefits of air pollution control measures. The costs of air pollution
are both intrinsic (effects) and extrinsic (prices). Biomedical scientists
are concerned with evaluating the intrinsic costs of pollution, but the
standards are set by representatives of society, who evaluate the extrinsic
costs. Biomedical science is limited in meeting the expectations of the
lay public, since "causality" cannot be proven by epidemiological methods,
the range of human experimentation is highly restricted, and results of
animal experimentation may be misleading when applied to man. Furthermore,
not all the effects of air pollution have yet been discovered; consequently,
focusing onthe quantification of known effects alone will result in inadequate
assessment. Current methods for studying effects of pollutants include
biochemical, cellular, pathophysiological, pathogenetic, and epidemiological
techniques. Mechanisms are studied in the fundamental molecular and cellular
systems, whereas societal costs can be determined best by epidemiology
Community ambient air quality standards can be defined functionally
as the levels of air pollution that are acceptable to society. In the setting
of these standards, it is hoped that they represent a balance between the
costs and benefits of air pollution control measures. Evaluation and integration
of the health costs of air pollution tends to make the standards more stringent,
but consideration of the costs of abatement produces less stringent standards.
The minimum abatement costs—in dollars—are fairly easy to compute, but
evaluation of the health costs is not as easy. Health costs rank among
the most important costs of air pollution, but all of the possible health
effects have not yet been discovered, let alone quantified. Therefore,
accurate assessment of these costs for setting future air quality standards
depends on a major investment in biomedical research. This paper examines
current biomedical research capabilities in relation to the current strategy
for air pollution control. It also reveals some popular but unrealistic
expectations of biomedical science.
Cost-Benefit Analysis in Setting Standards
There are many independent facets to the cost-benefit analysis
leading to the setting of standards, involving many levels of activity—from
the basic scientific to the political. It is not easy to describe the standards-setting
process because some of these contributing factors are incongruous with
others. Nevertheless, the attempt must be made to synthesize them before
standards-setting can make any sense at all. This paper is one such attempt.
It seems logical to begin by describing the functional roles of both scientists
and the representatives of society who set standards, in terms of the cost-benefit
Intrinsic and Extrinsic Values
The distinction between "effects" and "costs," as the terms are
used herein, is fundamental. "Effects" are the "intrinsic" biological responses
to pollution, whereas "costs" are the "extrinsic" values that society ascribes
to those effects.1 As an illustration of these qualities of
value, consider a particular painting by Rembrandt; it may have an extrinsic
value (market price) of hundreds of thousands of dollars, whereas its intrinsic
biological value is virtually zero, since it is too indigestible to be
eaten, and too friable to serve as shelter or clothing. Esthetic appeal
accounts for only part of the great disparity between the intrinsic and
extrinsic values of the painting—a larger part arises from its uniqueness.
On the other hand, the market value of air is zero, despite its great intrinsic
This distinction between intrinsic and extrinsic values clearly
distinguishes the scientist's role in the standards-setting process from
that of society's representative; the scientist concerns himself with evaluating
the intrinsic effects, whereas society' s representative tries to put an
acceptable price tag on those effects. The former is concerned with "correctness"
and "incorrectness;" the latter with the moral questions of "rightness"
and tlwrongness." In short, the former develops knowledge, but the latter
It would be ideal, of course, if extrinsic values were established
based on knowledge of intrinsic effects. Similarly, it would be useful
if scientific research were to reflect society's values. Although these
two sets of values are not expressed in the same dimensional units, it
is still possible—and in my opinion, highly desirable—to create interfaces
for communication between the scientific and societal subcultures. In this
way, reconciliation between the intrinsic and the extrinsic values could
The Role of the "Standards-Setter"
The prime motivation for establishing air quality standards,
or for initiating any abatement procedure, is political. That is, the general
public, through its formal institutions, defines the goals and promulgates
the rules for air quality control. Society's political institutions give
the authority and responsibility for establishing acceptable standards
to the standards-setter. To carry out this responsibility, he must evaluate
the costs of air pollution and balance them against the costs of abatement.
He is the one who must make the final integration of much information including,
but not limited to, biological information. In short, he translates biological
"effects" into societal "costs."
A commentary on the inherent advantages and disadvantages of this
system is tangential to the theme of this paper. However, since the validity
of any cost-benefit analysis depends on the judgment of the analysts as
well as the scope of the analysis, it is appropriate to list those traits
that I believe characterize an "idealized" standardssetter:
First, he is concerned with the realistic goal of adopting "acceptable"
standards rather than visionary "perfect" standards. He recognizes that
"acceptable to society" does not mean "unanimous acceptability. He can
evaluate esthetic and intangible variables that have value to society but
may not have obvious prices. Finally, he is fully capable of making decisions
without insisting on guaranteed results; he lives by the admonition—paraphrased
from Harry Truman—"If you can't stand uncertainty, then stay out of the
kitchen." Briefly, he is the practitioner of an "art, which I have previously
defined as "a field in which it is more important to be right than to be
The Contribution of Biomedical Science
The role of the biomedical scientist in the process of setting
standards is discussed below, but the interaction between the scientist
and society's representative can be illustrated by an example: A scientist
might demonstrate that a given ambient level of sulfur dioxide is associated
with a measurable increase in mortality, and that most of the excess deaths
occur in persons who are either over 65 years or under 5 days of age. Furthermore,
he might calculate the increment in actual dollar costs that is caused
by those deaths. But, society puts its own value on those deaths; and that
extrinsic value—the price society is willing to pay—is the only one that
counts in the social assessment of air pollution damage.
Currently, it is believed that society places a fairly high value
on the protection of the most sensitive definable subpopulation within
the population. " Consequently, that criterion has been established as
the threshold "health effect" in setting ambient standards. This public
policy is reflected in the directions of traditional epidemiological and
medical health effects research. For example, patients with asthma and
acute myocardial infarction have been evaluated for response to ambient
air pollution levels.
Apparently, society also places a quite high value on the esthetic
consideration of "visibility." In fact, in the case of particulate pollution,
this "esthetic cost-factor" probably outweighs the intrinsic health effects
of aerosols; consequently, esthetic values and not health effects, are
the limiting factors in setting particulate standards.
The Air Pollution Control Strategy and Biomedical Science
Amelioration of health costs is an important benefit of air pollution
control programs, but the abatement costs are substantial, too. In addition,
costs of the abatement are much better known than its health benefits.
Consequently, standards-setting agencies such as the Environmental Protection
Agency and the California Air Resources Board have developed "shopping
lists" of questions they would like biomedical scientists to answer. Biologists
are asked to produce licritical data" and "definitive studies" in order
to provide defendable bases for air quality standards. Of course, "critical"
and "definitive" mean quite different things to different people, and those
words can have very expensive implications. Furthermore, in a world of
no absolutes, the defendability of standards depends largely on who is
being asked to judge them. Therefore, it is appropriate to examine thevalidity
of these requests to discover (a) whether they are scientifically realistic,
and (b) whether the "interested parties" are interested enough to pay for
the answers they are asking for. Only the former is discussed in this paper;
the latter issue is raised here only as a sobering thought.
The Limited Validity of the Strategy
The current strategy for air pollution research and control was
initiated by social pressures, and it is administered by social institutions.
Nevertheless, it is embodied in engineering diagrams and flow charts. In
the development of the strategy, it was assumed that a rational course
for controlling air quality would be to develop documents, "Air Quality
Criteria," detailing the available data about the health effects of each
of the pollutants. Then, by a process of interpretation, air quality standards
for each of the pollutants could be developed. Finally, by this plan, source
emission standards could be set for each pollutant to allow a technologically
feasible implementation of the standards.
Unfortunately, though, it has not been established that this strategy
conforms with Nature. On the contrary, in order for the grand strategy
to work, the biological effects of the individual pollutants must be superposable
when the pollutants are mixed; however, most biologists would expect nonlinear
interactive effects. In other words, based on their experience with biological
systems, their a priori prediction would be that the presence of any one
Pollutant would modify the biological response to any other pollutant.
In biological terms then, "smog" does not equal nitrogen dioxide plus oxidant
plus particulate plus carbon monoxide, and so forth.
Consequences of the Strategy—"Implied Research"
Whether or not it is valid, we must recognize the existence of
the grand strategy. Furthermore, since it does exist, certain other social
phenomena have become inevitable. Prominent among them is the belief among
politicians and other public officials that all they must do is to ask
questions in order to have their regulations and standards justified. That
fantasy is complemented—and in fact strengthened—by some scientific administrators
who are in search of funds. They get funds by promising that their people
will provide the answers to the questions—regardless of whether or not
the questions are answerable.
The experimental biologist must continuously be aware that his
chance of success depends entirely on whether he has asked the right question.
He must be able to exercise educated judgment to determine which questions
are within the limits of research capabilities. Inevitably, realistic research
will sometimes fail to conform with the expectations or hopes of the lay
public. When that happens, good sense dictates that the scientists should
provide answerable questions and testable hypotheses; otherwise, we can
expect to throw more and more money into the bottomless pit of "implied
research." This kind of research is usually justified by implying that
it will solve immediate problems by the application of scientific principles
and knowledge, even though those principles and that knowledge do not exist.
As a third consequence of the air pollution control strategy,
practically every layman has developed his own system for interpreting
and evaluating "health effects" data. Professional scientists and other
technical people are not immune from this disorder; they are sometimes
found promoting unsubstantiated speculation as fact, demanding "proof"
for untestable hypotheses, or in general, recklessly scattering invalid
criticisms of biomedical research—even though they may understand that
their own specialized training and supervised experience were designed
to help them avoid these pitfalls in their work.
Limitations of Experimental Methods in Biomedical Research
As indicated above, limits on experimental methodology determine
whether or not questions or hypotheses are realistic. Some of the very
broad limits are discussed here in general terms. Expectations and questions
commonly associated with biological research can be tested against reality
with these facts.
Nonlinear Interactive Effects
The problem of nonlinear interactions among the pollutants has
already been discussed. This phenomenon is the source of much discussion
in the process of setting standards, because even if the effects on a given
biological system were known for each pollutant, its behavior when mixed
with other pollutants would not be predictable. Thus, it appears unreasonableto
set a standard for each pollutant that is independent of all the others.
That is one reason deleterious effects are generally overestimated when
the evidence is inadequate, and standards are set conservatively.
"Proof of Causality"
A very common, but naive expectation of biological research involves
the "proof of causality." Some critics of air quality standards, citing
epidemiological studies, blithely assert that standards should not be set
until there is "proof" that air pollution causes mortality or morbidity.
In response, defenders of the standards often naively call upon scientists
to provide such proof. "Causality" is a red herring in these conflicts,
though; broadly speaking the experimental determination of causality would
not be directly applicable to setting standards, anyway. In fact, experimental
methods are in use that measure very fundamental physicochemical properties
of biological systems. As a rule though, results of these studies are only
remotely related to the kind of data needed to set standards based on integrated
biological effects. On the other hand, the "medical" and epidemiological
methods closest to the "practical" ideal, are removed by many levels of
complexity from questions of mechanism.
To an experimentalist, the hoped-for panacea of "proven causality"
is never more than a temporarily useful working model that is a stepping
stone toward the development of more fundamental mechanistic hypotheses.
So, science can never be expected to provide a deterministic basis for
setting standards; human judgment cannot be circumvented by appealing to
a mythical scientific oracle.
Human vs Animal Experimentation
Some of the limitations that inevitably face experimental biologists
are social rather than scientific. These relate to the use of humans as
experimental subjects and to the problems resulting from interpretation
of experiments using experimental animals. Ethical considerations make
it highly risky—legally, as well as medically—to subject a person to experimental
situations that might be unduly hazardous. It would obviously be criminal,
for example, to conduct a gas chamber experiment to determine the lethal
dose of the pollutants to humans; consequently, these values will never
be known to a high degree of accuracy. Accordingly, when standards are
set, they are set in the absence of such information.
In contrast to the unacceptability of high-dose experiments, it
is apparently acceptable to "subject" persons to clean air; consequently,
some experiments have been designed in which clean air is the variable,
and smoggy ambient air the "normal" control. The rationale is that the
subjects can be put to no more arduous test than they would ordinarily
be exposed to. In a gentle stretch of that principle, it is apparently
also thought to be acceptable to use what might euphemistically be called
"partially clean blir"; that is, air having up to ambient levels of a single
pollutant, say CO, but none of the other components of smog. Nevertheless,
even with such ingenious experimental or semantic designs, the range of
information that can be achieved with such experiments is fairly restricted.
The use of experimental animals to determine physiological and
pathological effects of pollutants is the only available method for consistently
obtaining reproducible and reliable quantitative data. Yet, theoretically,
each extrapolation to man of results in lower animals must be justified
by analogous experiments in man. In actual practice though, the extrapolation
step can usually be circumvented satisfactorily by the experimenter's use
of good judgment based on his own experience and training.
Quantification vs Discovery of Effects
Finally, it is important to realize that, despite the often-repeated
calls for quantification of health effects, it is generally overlooked
that the known effects—the quantifiable ones—are undoubtedly far outnumbered
by the unrecognized effects. In other words, at this stage in history,
the ability to evaluate the total impact of pollution on biological or
human systems still depends much more on the process of discovery than
on the process of measurement. Unfortunately, though, since a proposal
to measure a known effect looks potentially more productive than a proposal
to look for unknown effects, funding agencies may give low priority to
the important research needed to discover effects—agencies anxious to produce
immediate results have probably not fully considered the necessity of funding
current basic research as an investment in future applications.
Systems for Studying Biological Effects
This paper is concluded by describing several research systems
that are being used for the evaluation of intrinsic pollution effects.
The examples below are not necessarily the most sensitive or the most widely
applicable; they have been chosen because they illustrate their respective
principles well, and because they represent current work. Examples are
given for systems at five levels of biological complexity and organization:
biochemical, cellular, pathophysiologic, pathogenetic, and epidemiological.
The study of biochemical reactions is a discipline very close
to the determination of mechanisms of action in living organisms. Conversely,
this discipline is also quite far from the study of integrated animal behavior
and function. Biochemistry, however, provides many predictive models for
the evaluation of toxicity in the whole animal. This is important because
carrying out long-term experiments on large populations of animals is very
expensive; to be efficient, experimenters would like to have a very good
idea of their expected results before they design their experiments.
An examination of the effect of ozone on protein function is provided
in a set of experiments with amino acids.3 Amino acids—the "building
blocks" of proteins—can conveniently be studied in vitro. Several distinct
patterns of damage have been described for individual amino acids exposed
to ozone. Tryptophan, an aromatic compound, is broken down stoichiometrically.
Methionine, a sulfurcontaining amino acid, is oxidized to methionine sulfoxide,
and histidine is degraded into several products, including ammonia. Glycine
and alanine are unaffected by ozone.
Logically, one would predict that if amino acids were capable
of being broken down by ozone, proteins containing them might also be susceptible
to damage. The experiment to test this prediction was carried out on pancreatic
ribonuclease. This protein was chosen, not because it is suspected as an
air pollution casualty, but for technical experimental reasons: its structure
and amino acid sequence are well known, it is an enzyme whose activity
depends on the integrity of histidine, it contains no reduced sulfhydryl
groups, and it contains no tryptophan. Experimentally, ozone reduces the
activity of this enzyme, thus supporting the mechanistic prediction.
Other biochemical systems that can be studied in the test tube
include the oxidation and peroxidation of lipids by ozone. These studies
may be related fairly closely to pollution effects, since it is believed
that the peroxidation of the unsaturated fatty acids is one contributing
factor to the overall aging process. In this regard, vitamin E, an antioxidant
agent, is becoming a popular research object—there is evidence that lipid
peroxidation of cell membranes in the lung can be retarded by antioxidants
such as vitamin E.
Pollution effects that depend on cellular integrity can be studied
in free-living protozoans, cell cultures, or organ cultures. Nucleic acid
synthesis, protein building, and reproduction are important processes that
can be evaluated by addition of small amounts of pollutants. In the case
of a one-celled animal called Tetrahymena, addition of methyl mercury
causes a linear increase in the time between generations.4 It
has been shown that protein metabolism is not affected in that system but
DNA synthesis is inhibited.5
The metabolism of the environmental carcinogen benzo(a)pyrene
(BaP) is being studied in organ culture, cell culture, and isolated enzyme
preparations.6 it is relevant to the question of species differences
that rodent, monkey, and human tissues metabolize BaP in the same way.
This is significant because BaP is carcinogenic only after it is metabolized.
Exposures to airborne BaP in city dwellers in this country are equivalent
to the doses received by light smokers.7
The effects of pollutants on individual organ systems such as
the pulmonary and cardiovascular systems can be evaluated by modified classical
physiological methods. Some of these methods have the advantage of being
adaptable for use with human subjects. Under well-controlled laboratory
conditions, physiological responses to stress, such as running on a treadmill
to exhaustion, can be evaluated before, during, and after exposure to controlled
concentrations of gaseous pollutants.
In studies more difficult to control—but more realistic—patients
with angina pectoris have been exposed to ambient air in Los Angeles.8
The time required to produce chest pain by mild exercise was reduced after
the exposure to ambient air containing high CO compared with low CO in
the controls. Also, electrocardiographic abnormalities were more pronounced
after such exposures.
A physiological response in animals that closely resembles asthma
in humans is the reaction to methacholine, a drug that causes respiratory
distress by constricting bronchioles. The threshold for the methacholine
effect can then be related to pollution concentration. In another asthma-like
condition in animals that is produced by inhalation of sensitizing antigens,
a high degree of susceptibility to ozone and nitrogen dioxide has been
Some effects of pollutants are severe enough to cause identifiable
structural damage. Controlled production of pulmonary lesions has been
accomplished consistently in mice exposed to ambient Los Angeles air.10
Major chronic pathologic changes are produced in the alveolar wall. This
effect is irreversible in older animals, whereas younger animals are more
resistant to the chronic changes. The pathogenetic sequence is very reproducible:
first, the endothelial cells forming the walls of capillaries undergo degeneration
and cell death. Following that, the epithelial cells that are the wall
of the alveolus itself undergo fragmentation. The most resistant structure
in the alveolar subunit is the basement membrane.
The resistance of animals to bacterial invasion is dependent on
several protective mechanisms in the lung. Important among these is the
macrophage system; a set of cells capable of ingesting foreign particles,
including bacteria. Ozone and nitrogen dioxide both reduce the efficiency
of the lung's protective mechanisms.11 It is interesting that
determination of the response to chronic exposures in these experiments
was limited by the fact that rats were unable to inhale enough of their
bacterial test burden after they had been exposed to ozone for a few hours.
Health effects inferred from epidemiological studies have been
predominant in evaluating air quality standards up to the present. While
this type of experiment theoretically could indicate the actual health
costs to a population exposed to pollution, the results are measures of
the degrees of association among variables, and do not directly address
questions of mechanism. Nevertheless, in human studies, the "experiment
in nature" is a noncontroversial form of human experimentation. Also, by
carefully selecting target populations in advance, fairly high levels of
control can be achieved. Such studies are being initiated among school
children in three areas of the Los Angeles basin, and among asthmatics
in urban areas.12
Community air quality standards are set to reflect a balance
between the costs and benefits of abatement measures. The costs of air
pollution are evaluated in terms of both the "intrinsic" biological responses
and the "extrinsic" value that society places on the effects. These qualities
of value clearly distinguish the separate roles of "science" and "society"
in the standards-setting process: Scientists are responsible for investigating
and measuring intrinsic costs, whereas representatives of society evaluate
extrinsic costs. The skills and knowledge required for these roles are
distinct; nevertheless, there is an increasing tendency for the lay public
to judge scientific merit according to the needs of technology or society.
Poor understanding of the capabilities of biomedical science by
funding agencies leads to unnecessary expenditures of funds for "implied
research." This wasteful practice of pursuing unrealistic goals inevitably
results from aiming at desirable applications without regard to the need
for developing knowledge to apply.
Maximal productivity in research depends on asking realistic questions
and designing realistic experiments. Therefore, research can be expected
to be much more productive when it is directed from the field by working
scientists, rather than from the "top" by a funding bureaucracy.
The systems and methods developed by scientists for determining
the intrinsic effects of pollutants represent several levels of biological
organization and complexity. They include biochemical, cellular, pathophysiological,
pathogenetic and epidemiological techniques. The epidemiological methods
are closely related to the evaluation of total human health costs of pollution,
but these studies cannot provide "proof of causality." On the other hand,
the basic physicochl-mical studies of mechanism are not useful for estimating
the overall costs'. The entire spectrum of research is needed for an adequate
assessment of the intrinsic biological costs of pollution.
This report was prepared under the auspices of the U.S. Atomic
Energy Commission. The author thanks the many people—scientists and laymen,
public officials and private citizens—who have contributed to this project.
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2. D.E. Watson, "Comparative Environmental Costs of Various Energy
Sources; a Perspective," in Proc. Health Phys. Soc. Sixth Ann. Topical
Symp., Radiation Protection Standards: Quo Vadis, Vol. 2, pp. 366-376
3. J.B. Mudd, R. Leavitt, A. Ongun, and T. T. McManus, "Reaction
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Mucosa in Organ Culture," unpublished document. (1972).
7. D.E. Watson, The Risk of Carcinogenesis from Long-Term Low-Dose
Exposure to Pollution Emitted by Fossil-Fueled Power Plants, University
of California, Lawrence Livermore Laboratory, Rept. UCRL-50937 (1970).
8. W. Aronow, C. Harris, and S. Rokaw, "The Effect of Freeway
Travel on Angina," Ann. Intern. Med. in press (1972).
9. Y. Matsumura, "The Effects of Ozone, Nitrogen Dioxide and Sulfur
Dioxide on the Experimentally Induced Allergic Respiratory Disorder in
Guinea Pigs: III. The Effect on the Occurrence of Dyspneic Attacks," Am.
Rev. Resp. Dis. 102, 444-447 (1970).
10. R.F. Bils, "Ultrastructural Effect of Air Pollution on Lung
Cells," J. Air Pollut. Contr. Ass. 18, 313-314 (1968).
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and the Antibacterial Defense Mechanisms of the Murine Lung," Arch.
Intern. Med. 127, 1099-1102 (1971).
12. S. Rokaw, Tuberculosis and Respiratory Disease Association of Los
Angeles. California, personal communication (April 1972).