Silent Spring to Scientific Revolution
John Peterson Myers, Ph.D.
essay first published in San
Francisco Medicine, November 2002)
Four decades ago in Silent Spring, Rachel Carson (1962)
wove together a fabric of evidence suggesting that parts of the
modern chemical revolution were having unintended consequences,
undermining human and wildlife health in unexpected ways. At the
time that fabric was more Chantilly lace than Afghan rug, with the
scientific pattern defined as much by the holes as by the threads
of connecting evidence.
thesis was compelling, nonetheless. It launched the modern environmental
movement. It stimulated a new branch of government focused on environmental
impacts. It led to bans of DDT and, since then, a host of other
chemicals. Most recently it spurred in 2001 a global treaty, the
Stockholm Convention, that requires phase-out and elimination of
twelve persistent organic pollutants. And it forced new scientific
questions to be asked about links between contamination and health.
four decades later, we are midstream in the scientific revolution
that her work helped foment. The revolution arises from scientific
discoveries which establish that many chemicals --both from the
natural world and synthesized in laboratories -- interfere with
the biochemical messaging systems that direct the biological development
of plants and animals, including humans (Cheek
et al. 1999; McLachlan 2001).
all biological development is under the control of various biochemical
messaging systems that are involved in the chain of events leading
to gene activation and expression. Hormones and growth factors,
among others, are key elements of these message systems. Normal
healthy development depends on the successful initiation of genetic
instructions by hormones and growth factors, among others, which
are key elements in these message systems. Disruption can cause
immediate effects, ranging from conspicuous teratological impacts
to subtle functional disabilities that may not be evident until
decades after exposure.
now demonstrates that a wide array of chemicals can disrupt these
messages without damaging the genes themselves. Much attention has
focused on disruption of hormonal signaling, which has become known
as endocrine disruption (Colborn et
of developmental disruption has burgeoned during the past decade
because of research funding by European, Japanese and North American
governments. New results are published virtually every week in journals
like Environmental Health Perspectives, Human Reproduction, Toxicology,
and Environmental Science and Technology.
example, a study published in September 2002 by a research group
in the Netherlands documented associations between variations in
background levels of in utero exposure to certain organochlorine
chemicals and gender-specific play behavior in children (Vreugdenhil
et al. 2002). Boys with relatively higher levels of
PCB exposure were less likely to engage in play behaviors typical
for boys; girls more likely to engage in play behavior typical for
boys. Boys with relatively higher levels of dioxin were more likely
to engage in more feminine play behaviors, as were girls.
findings are especially noteworthy because the levels of exposure
were not that high, but instead represented variations around background
levels common in European women. Moreover, these outcomes are consistent
with experiments carried out with laboratory animals examining exposure
impacts on sex-specific behaviors.
same research group had recently published studies demonstrating
impacts of in utero exposure on cognitive development and immune
system function (Huisman et al.
1996, Koopman-Esseboom et
al. 1996, Weisglas-Kuperus
et al. 2000). Their groundbreaking studies rest on detailed
tracking of the development of a cohort of individuals beginning
with measurements of the mothers’ serum contamination during
pregnancy, with careful attention paid to potential confounding
results like these are legion (Myers 2002).
They are forcing a series of conceptual shifts upon toxicology as
it integrates these new findings with long-standing assumptions.
These shifts are summarized in Table 1. The text below examines
several in greater detail.
1. Conceptual shifts
level contamination overwhelms detoxification and other defense
level contamination hijacks control of development
dose makes the poison”
dose response curves are common, in which low level exposures
cause effects that disappear at higher levels
high levels of exposure matter
caused at what had been assumed to be “background”
Focus on adults
of rapid growth and development (prenatal through puberty)
are most sensitive to exposure
small number of “bad actors”
chemicals thought safe are biological active and capable of
interfering with signaling systems
Immediate cause and effect
latencies are common; fetal programming can lead to disease
and disabilities decades later
chemicals one compound at a time
real life, mixtures are the rule. They can lead to effects
at much lower levels than indicated by simple experiments
with single chemicals.
on traditional toxicological endpoints like mutagenesis carcinogenesis,
range of health endpoints, including immune system dysfunction
(both hyper and hypo-active); neurological, cognitive and
behavioral effects; reproductive dysfunctions; chronic diseases
mapping of contaminant to disease or disability
contaminant can cause many different effects, depending upon
when exposure occurs during development and what signals it
disrupts. Multiple contaminants can cause same endpoint, if
they disrupt the same developmental process.
toxicology focuses on damage, such as cell death, mutations or genotoxicity
that occurs typically when cellular biochemical defense mechanisms
are overwhelmed. At high exposure levels many chemicals implicated
in message disruption are toxic in these traditional ways. At lower
levels of exposure, however, their impacts instead involve, in essence,
hijacking control of development, adding or subtracting to the body's
own control signals at remarkably low levels of exposure. A vivid
recent example is the discovery that a widely used herbicide, atrazine,
causes tadpoles to develop into hermaphroditic adults at a level
of exposure approximately 30,000 times lower than traditional toxicological
work had identified as toxic to frogs (Hayes
et al. 2002). The mechanism appears to involve enhancement
of aromatase conversion of testosterone to estrogen during development.
Elegant theoretical and empirical work suggests that for activated
signaling systems, there may be no threshold beneath which no effect
occurs (Sheehan et al. 1999).
key shift is the acknowledgement that the assumption that “the
dose makes the poison” can be misleadingly simplistic, if
it is used to imply that only high dose exposures induce effects.
In fact, low exposure levels sometimes cause effects not seen at
higher levels (e.g., vom Saal et
al. 1997, National Toxicology Program
2001, Cavieres et al. 2002).
Researchers are now intensely pursuing these “non-monotonic
dose response curves” and the uncertainty about their underlying
mechanisms, which likely vary from case to case. One plausible hypothesis
is that at low, “physiological” levels, the contaminant
interferes with developmental signaling but does not activate biochemical
defenses against impacts that would be caused by higher exposures.
At somewhat higher levels, these defenses are activated and the
contaminant is successfully detoxified. At even higher levels, the
defense mechanisms are overwhelmed by the toxicant and more traditional
toxicological effects are induced.
scientific research has focused on mechanisms of message disruption,
it has implicated a wide array of chemicals. This expansion has
involved both ongoing identification of compounds capable of interfering
with estrogen, which was the initial focus, as well as research
broadening the range of message systems studied. Some of the most
troubling discoveries about “new actors” is that they
involve compounds in widespread use in consumer products, including
plastic additives like phthalates and plastic monomers like bisphenol
A, which leaches from polycarbonate products (e.g., Gray
et al. 2000, Masuno et
is not to say that we have complete understanding of even the best
known contaminants. This reality was highlighted by a study published
in 2001 about DDT, in which Longnecker et al. (2001)
report a highly significant association between DDT in maternal
serum and the likelihood of preterm birth. Their study used birth
records and stored serum from the mid 1950’s – ‘60s.
They concluded that the US had experienced a hitherto undetected
epidemic of preterm birth during this period because of DDT use.
Longnecker (pers. comm.) went further to estimate that because of
the close association between preterm birth and infant mortality,
up to 15% of infant mortality during that period may have been attributable
to DDT use.
chemicals have been identified that interfere with estrogen, androgen,
progesterone, thyroid, insulin and glucocorticoid signaling, among
others. The mechanism does not always involve mimicking (or inhibiting)
ligand-receptor binding. For example, as noted above, atrazine appears
to enhance aromatase conversion of testosterone to estrogen.
disruption may also intercede in steps leading to gene activation
after ligand-receptor binding. This was established by in vitro
experiments showing that arsenic selectively inhibits gene activation
by the glucocorticoid- receptor complex after normal ligand-receptor
binding and subsequent entry into the cell nucleus, at arsenic concentrations
far beneath cytotoxic levels (Kaltreider
et al. 2001). While human health impacts have yet to
be demonstrated via this mechanism, dysfunctions in glucocorticoid
action have been linked to weight gain/loss, protein wasting, immunosuppression,
insulin resistance, osteoporosis, growth retardation, and hypertension.
important issue raised by emerging science is the powerful interactions
that can occur within mixtures of chemicals, even though regulatory
toxicology is conducted virtually exclusively on pure single compounds.
Two results published in 2002 emphasize the importance of considering
mixtures: In the first, Rajapakse et al. (2002)
demonstrated that a mixture of estrogenic compounds, each present
at a level beneath that capable of producing a statistically detectable
estrogenic response in an in vitro system, combined to more than
double the response of the system to 17ß-estradiol. In the
second, Cavieres et al. (2002)
found that a common off-the-shelf dandelion herbicide mixture strongly
reduced fetal implantation rates in mice at one-seventh the concentration
considered safe for its principal herbicidal component, 2,4-D, by
the US Environmental Protection Agency.
issue of mixtures is complicated further by interactions now known
to occur between contaminants and infectious agents. Large increases
in disease risk can be associated with simultaneous exposure to
contaminants and infectious agents. For example, Rothman et
al. (1997) reported a >20-fold
increase in relative risk to non-Hodgkins Lymphoma with combined
exposure to elevated (but still background) PCBs and Epstein-Barr
virus. The mechanism underlying this result is unknown, but is possibly
due to well-established immune system impairment by PCBs. If this
mechanism is widespread, then current estimates of morbidity and
mortality due to contamination are likely to be unrealistically
low. Immune system interference by a variety of contaminants is
widely reported (e.g., Baccarelli
et al. 2002).
these conceptual shifts are also challenging the adequacy of current
epidemiology to guide regulatory standards. The patterns underlying
these conceptual shifts—including (i) non-monotonic dose response
curves; (ii) windows of vulnerability during development; (iii)
the ubiquity of mixtures; (iv) the likelihood that multiple chemicals
can induce similar impacts via disruption of developmental processes;
(v) the same chemical can cause different impacts depending upon
when exposure occurs; (vi) long latencies between exposure and manifestation
of impact in a mobile population, etc.—all increase the likelihood
of false negatives in epidemiology as it is currently practiced.
the revolution in science that Rachel Carson stimulated raises today
a series of troubling questions about whether current health standards
truly protect public health. Effects of low level, background exposures
are likely to be far more widespread than acknowledged, and involve
many more health endpoints than traditionally considered, yet these
new mechanisms of toxicity thwart the epidemiological tools now
available to establish human harm.
are confronting an enormous gap between what science now tells us
about the links between contamination and health, and the antiquated
approaches still used to safeguard public health. Health professionals
will be important contributors to narrowing that gap, first by informing
themselves about the underlying science, and then by helping to
advance public understanding of the emerging evidence. Carson’s
scientific revolution can drive a transformation in public health
that reinvigorates investments in prevention through exposure reduction.
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