Dutt and Jonathan Latham, PhD, Independent Science News
scientific research has cast grave doubt on the safety testing of hundreds
of thousands of consumer products, food additives and industrial chemicals
products, from soft drinks and baby foods, to paints, gardening products,
cosmetics and shampoos, contain numerous synthetic chemicals as preservatives,
dyes, active ingredients, or as contaminants. Official assurances of the
safety of these chemicals are based largely on animal experiments that use
rabbits, mice, rats and dogs. But new results from a consortium of researchers
and published in the Proceedings of the National Academy of Sciences suggest
such assurances may be worthless (Seok et al. 2013).
results of these experiments challenge the longstanding scientific presumption
holding that animal experiments are of direct relevance to humans. For that
reason they potentially invalidate the entire body of safety information
that has been built up to distinguish safe chemicals from unsafe ones. The
new results arise from basic medical research, which itself rests heavily
on the idea that treatments can be developed in animals and transferred
research originated when investigators noted that in their medical specialism
of inflammatory disease (which includes diabetes, asthma and arthritis),
drugs developed using mice have to date had a 100% failure rate in almost
150 clinical trials on humans.
to Kristie Sullivan, Director of Regulatory Testing Issues at the
Physicians Committee for Responsible Medicine (PCRM), this is not unusual
“about 90% of all pharmaceuticals tested for safety in animals fail
to reach the market, or are quickly pulled from the market”. Wanting
to understand why this might be so, the consortium decided to test the effects
of various treatments that lead to inflammation, and systematically compare
results between mice and humans. This postulated correlation across different
animal species is sometimes known as the concordance assumption.
a first set of experiments the researchers looked at acute inflammation
in mice brought on by various stimuli. These stimuli were bacterial toxins
(endotoxaemia), trauma, and burns. To measure responses the authors quantified
positive or negative changes in gene activity for thousands of individual
genes. The researchers found that changes in activity of a particular mouse
gene after treatment typically failed to predict changes in activity in
the closest related human gene. This was not the expected result. If humans
and mice are meaningfully similar (i.e. concordant) then gene activity changes
in mice should have closely resembled those in humans after a similar challenge.
But they did not.
further experiments, the researchers identified another difference. While
humans responded with similar patterns of gene changes to each of the three
different challenges (trauma, burns, and endotoxaemia), mice did not. The
three treatments in mice each resulted in a distinct set of gene activity
changes. This confirmed the initial results in the sense that mice and humans
responded differently. It also implied that the differences in gene response
between mice and humans are attributable not so much to a lot of detailed
‘noise’ but to fundamental differences in the physiology of
mice and humans in dealing with these challenges.
the researchers examined the activity of specific biological signaling pathways
after similar treatments. These too were highly divergent between mice and
humans. Surprised by the consistently poor correlations between the two
species, the authors then tested other human/mouse models of inflammatory
diseases. Again, the similarity between mice and humans was low.
summary, repeated experiments confirmed that, when it comes to inflammation,
mice and humans have little in common, a finding important enough in itself
given the prevalence of inflammation-related diseases in humans. These include
allergies, celiac disease, asthma, rheumatoid arthritis, and autoimmune
these results should not be a surprise. Concordance has been questioned
by numerous researchers, some of whom have noted that mice are separated
from humans by 120 million years of evolutionary change (Stoloff 1992; Greek
and Swingle Greek, 2003; Mestas and Hughes, 2004; Knight, 2007). And, unlike
humans, mice also suffer from different diseases, lack a gall bladder, have
no menstrual cycle, have multiple births, differ in immune systems, lifespan
and size, to name only a few dissimilarities.
the Seok study is not the first to conclude that mice are poor models for
human disease, but it is notable for being by far the most comprehensive.
Combined with results of previous experiments, its conclusions suggest researchers
should expect that mouse, and probably other animal testing, is of little
use in advancing the treatment of human illnesses, including heart disease
other words, the public is probably being badly served by much of the money
spent on medical research. According to PCRM’s Kristie Sullivan, “the
National Institutes of Health is giving researchers billions of dollars
every year for research on animals”. While missing out on potential
cures, the public is also likely being exposed to dangerous or ineffective
pharmaceuticals. Animal testing nearly prevented the approval of valuable
drugs such as penicillin and subsequent antibiotics, but it did not prevent
the thalidomide disaster of the 50s and 60s (Greek and Swingle Greek, 2003).
finding of non-concordance need not mean the end of medical research. It
could even herald a more promising and scientific era. Sullivan believes
that medical researchers “simply take for granted that animal models
are useful” even though other, and possibly better, techniques for
studying human disease are available. These include greater emphasis on
human clinical observation and making better use of cell cultures for research.
wasteful and unproductive medical research is arguably a sideshow besides
the misplaced confidence in the safety testing of environmental and household
chemicals. While medical failures affect the unwell, chemical toxins have
potential repercussions for everyone.
animals are not useful predictors of important disease responses in humans
it is unlikely they are useful as test subjects for toxicological safety.
In other words, lack of concordance means that the synthetic chemicals that
are found in industrial products, incorporated into food, and otherwise
spread throughout the environment, are essentially untested. The regulatory
process through which they passed was never a scientifically validated and
evidence-based system, but now the evidence shows it to have been functioning
as a system of random elimination. “We are not protecting humans”
says Kristie Sullivan, noting that “even a National
Academy study agrees that many toxicological tests are not human-relevant.”
are potential alternative toxicological tests, but despite multi-billion
dollar grants, and even a human
on a chip, the science is still incomplete. Michael Hansen, Senior Scientist
at the Consumers Union,
has been contributing to recent discussions over replacing animals for the
purposes of regulatory toxicology. He acknowledges that “we should
be moving towards in-vitro cell-based models” for chemical risk assessments.
But how this can be done is not yet clear. Hansen points out that not only
is “there a technical problem of how to incorporate them into an overall
risk assessment”, but also that “in-vitro alternatives have
yet to be validated”. Nevertheless, he still believes specific uses
for animal research remain: “for carcinogenicity, for example, mice
are appropriate models”.
interesting question, when an estimated 100 million mice are sacrificed
each year for medical research and in toxicology, is why it took so long
to test this fundamental assumption. The answer is that it has been tested
before, though not nearly as rigorously as it could have been. And the results
have, in the view of many, not supported the idea that animals reliably
model human physiology (Knight, 2007; Dressman, 2007).
kind of answer is that animal research is now big business. One genetically
engineered mouse can cost $100,000
while a mouse treadmill can set taxpayers back $9,600 (Greek and Swingle
Greek, 2003). For medical researchers, animal research offers
a steady income and a successful career pathway regardless of whether,
as in the field of inflammation, experiments deliver practical benefits
to patients. These are just some of the entrenched interests maintaining
the animal testing system. Other prominent beneficiaries include the food
and chemical industries which profit from the public perception of safety
derived from animal testing.
back to the time of ancient Greece, we have used animals to teach us about
the human body; however, it was not until 1937 — after 100 people
died from taking Elixir
Sulfanilamide — that Congress mandated drug safety testing on
animals. Since then, literally billions of mice and other mammals have been
sacrificed in a Faustian bargain—that their suffering was preventing
human experimentation. Seemingly, that calculation was misguided from the
failure of animal experiments to predict human responses and the inability
of alternatives to replace them leaves few options. Individuals can to a
limited extent protect themselves through avoiding packaged, processed and
non-organic food and buying goods made from traditional materials. But ultimately,
chemical exposure and chemical pollution are a collective responsibility.
HK et al, 2007. Gene
expression signatures that predict radiation exposure in mice and humans.
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Greek CR, Swingle Greek, J (2003). Specious science: Why Experiments on
Animals Harm Humans. The Continuum International Publishing Group, Ltd,
Knight A (2007) Systematic
reviews of animal experiments demonstrate poor human clinical and toxicological
utility. ATLA 35: 641-659.
Mestas, J and Hughes, CCW, (2004) Of mice and not men: differences between
mouse and human immunology, The Journal of Immunology, 172: 5.
Seok, J Shaw Warren, H et al, (2013) Genomic
responses in mouse models poorly mimic human inflammatory diseases.
PNAS February 11, 2013 online edition.
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