About the Use of Animals in Science - Blog by Dr Ray Greek
does the use of animals as predictive models persist in drug testing and
factors contribute to the continued use of animals as predictive models,
and little, if any have anything to do with science. The animal experimentation
industry is a multi-billion dollar business, with many vested interests
in both industry and academia that have much to gain by maintaining the
status quo—and much to lose by a dramatic change in how research is
conducted. Upton Sinclair in his 1935 classic I, Candidate for Governor:
And How I Got Licked wrote: “It is difficult to get a man to understand
something when his salary depends upon his not understanding it.”
would you describe the position of the scientific community relative to
the value of the animal model?
there is an awakening within the scientific community that animal experiments
are not accomplishing what they set out to do from the standpoint of prediction.
More and more scientists are beginning to question the validity of the animal
model but are reluctant to state that publicly for fear of committing career
suicide. With their livelihoods and professional stature at stake, as well
as those of their colleagues—not to mention the financial security
of the university that employs them—most scientists stick to the “party
line” that animals can predict human drug and disease response.
important to remember here that the biological sciences account for the
vast majority of grant money for most universities and hence even someone
from the chemistry or math department will hesitate to point out flaws in
the money machine for the university. Until a critical mass of scientists
is reached, do not expect to hear scientists, even scientists outside the
biological sciences, speaking out.
does the publish or perish system in academia fit into this?
universities in the United States, PhDs in science are promoted, and thus
more highly compensated and respected, on the basis of how many papers they
publish in the scientific literature. It is a system that remains deeply
entrenched in academia despite being widely criticized.
animal studies is the most efficient way to generate a large number of papers
in the shortest amount of time. It is far easier and faster to crank out
five papers using animals than to conduct human-based research. The five
papers may contribute nothing to ease human suffering, but that has never
been a requirement for promotion.
for animal experiments are also an excellent way for universities to obtain
lucrative research grants, which can provide substantial revenue for their
institutions. These grants generally come from the National Institutes of
Health (NIH), the federal agency in charge of allocating taxpayer-generated
funds for biomedical research, as well as from other government agencies
and private foundations. The public—and the policy makers who appropriate
taxpayer funds—are willing to fund this research because they have
been led to believe that results derived from animal experiments are directly
relevant for human health and well-being.
you implying that no one believes in the animal model—that it’s
all just a game?
There are many scientists who we would describe as true believers. They
really are convinced that animal models predict human biomedical outcomes.
it’s a matter of naiveté. PhDs start out using the animal models
because their professor tells them to and by the time they are ready to
perform research on their own, the animal model is all they know how to
use. Initially, some of these people really believed that the animal model
works, in part because they do not see the results of animal studies in
the clinics as physicians do. They really believe that they are helping
to cure disease. Eventually, many do figure out that the animal model fails—by
that time, though, they have a mortgage and three kids in college. (See
comments by Dr Hicks in Chapter 2.)
That doesn’t say
much for those in the scientific community. Don’t you think they’re
smarter than that?
very well educated and very smart people say very wrong things. Clever people
can make genuine mistakes. They may also voice their opinion because of
ego or because they have an ulterior motive. The bottom line is that while
people can make innocent mistakes, sometimes they just lie. There is a difference.
Susan Jacoby writing in The Age of American Unreason stated:
thought should not be confused with stupidity or sheer ignorance, because
it is often employed by highly intelligent people to mislead and confuse
a public deficient in its grasp of logic, the scientific method, and basic
arithmetic required to see through the pretensions of poorly designed studies.
[ (Jacoby 2008) p229]
there is a difference between what the scientific evidence supports and
what scientists say. The motto of the Royal Society for the Advancement
of Science in London, England (the world’s oldest scientific society)
is Nullius in Verba, which translated loosely as Don’t take anyone’s
word for it. In the present context, this is good advice.
however, is replete with examples of very smart people simply making mistakes:
Martin Blaser, director of the Division of Infectious Medicine at Vanderbilt
University, called Barry Marshall’s claim that the bacteria Helicobacter
pylori caused ulcers, “the most preposterous thing I have ever heard
(Mohnmaney 1993).” (Dr. Marshall received the Nobel Prize in Physiology
or Medicine in 2005 for his role in the discovery of the connection between
H. pylori and gastric disease, reversing decades of medical doctrine which
held that stress, spicy foods, and too much acid in the stomach causes all
Agassiz, the famed paleontologist, glaciologist, and geologist who first
proposed that the earth had been subject to a past ice age, denied Darwin’s
theory of evolution and said in 1867: “I trust to outlive this mania
[(Pigliucci 2002) p13].” He wasn’t the only one. The great geologist
Charles Lyell also denied evolution, believing instead that there were many
centers of creation where new species appeared as needed [Ibid.].
Kelvin, the great mathematician and physicist who developed the Kelvin scale
of absolute temperature measurement, thought the sun had not been around
long enough for evolution to be the modus operandi of the forms we have
today [Ibid p21]. Lord Kelvin (truly one of the brightest people ever to
have lived) also thought that the study of physics had almost yielded essentially
all truths as of 1900. Even today, there are many smart people who doubt
evolution and others who underestimate the amount of truth science has yet
otherwise sophisticated people in England rejected the Germ Theory of Disease,
vaccines, and science as a thought process for decades in the 1800s.
Simon Newcomb published a paper explaining why airplanes would never fly.
His analysis was perfect except for the lift effect of airfoil (the reason
airplanes fly)—and perhaps his timing as well. He published his analysis
two months before the Wright brothers flew.
the brightest, most disciplined, and ambitious among us are resistant to
change. If we’ve always done something the same way, we’re unlikely
to change unless forced to do so. So when scientists who’ve been experimenting
on animals for years, and who have published the results in hundreds of
articles in professional journals, are confronted with solid evidence of
the futility of the animal model, it is no wonder that they either balk
or dig their heels in. In that respect, they allow themselves to become
victims of the system by blindly following in the footsteps of previous
too, it’s a question of differentiating how animals are actually being
used. If you confuse using animals as predictive models with using them
as a modality for the generation of ideas, then clearly you are going to
be using faulty reasoning. We often see this in what animal modelers themselves
claim about animals predicting human response. It can actually be a very
contentious issue because many animal modelers and their supporters claim
that no one seriously believes or claims that animal models are predictive—rather,
they are used merely as heuristic devices. Yet their statements in the scientific
literature (some of which appear below) would seem to indicate otherwise,
not to mention the fact that they use the predictive value of the animal
model to justify its use to the taxpaying public and their policy makers.
For example, Gad wrote
in Animal Models in Toxicology 2007:
sciences' use of animals as models to help understand and predict responses
in humans, in toxicology and pharmacology in particular, remains both the
major tool for biomedical advances and a source of significant controversy
. . . by and large animals have worked exceptionally well as predictive
models for humans-when properly used . . . Animals have been used as models
for centuries to predict what chemicals and environmental factors would
do to humans . . . This work [in 1792] consisted of dosing test animals
with known quantities of agents (poisons or drugs), and included the careful
recording of the resulting clinical signs and gross necropsy observations.
The use of animals as predictors of potential ill effects has grown since
that time . . . Very few are familiar enough with some of the history of
toxicity testing to be able to counter with examples where it has not only
accurately predicted a potential hazard to humans, but where research has
directly benefited both people and animals. There are, however, many such
examples. Demonstrating the actual benefit of toxicology testing and research
with examples that directly relate to the everyday lives of most people
and not esoteric, basic research findings (which are the most exciting and
interesting products to most scientists) is not an easy task . . . If we
correctly identify toxic agents (using animals and other predictive model
systems) in advance of a product or agent being introduced into the marketplace
or environment, generally it will not be introduced (or it will be removed)
and society will not see death, rashes, renal and hepatic diseases, cancer,
or birth defects, for example. (Gad 2007) (Emphasis added.)
the author of a well-known handbook on animal experimentation, has observed:
“A third important group of animal models is employed as predictive
models. These models are used with the aim of discovering and quantifying
the impact of a treatment, whether this is to cure a disease or to assess
toxicity of a chemical compound(Hau 2003).” Akkina is saying the same:
“A major advantage with this in vivo system [genetically modified
SCID mice] is that any data you get from SCID-hu mice is directly applicable
to a human situation(Anonymous 2008).”
Fomchenko and Holland
express a similar sentiment in 2006:
[genetically engineered mice] closely recapitulate the human disease and
are used to predict human response to a therapy, treatment or radiation
schedule . . . Using in vitro systems and in vivo xenograft brain tumor
modeling provides a quick and efficient way of testing novel therapeutic
agents and targets, knowledge from which can be translated and tested in
more sophisticated GEMs that faithfully recapitulate human brain tumors
and will likely result in high-quality clinical trials with satisfactory
treatment outcomes and reduced drug toxicities. Additional use of GEMs to
establish causal links between the presence of various genetic alterations
and brain tumor initiation or determining their necessity for tumor maintenance
and/or progression provide us with a glimpse into other important aspects
of brain tumor biology. (Fomchenko and Holland 2006)
Krewski et al. of the
Committee on Toxicity Testing and Assessment of Environmental Agents imply
the predictability of animal models when they state:
the foreseeable future, some targeted testing in animals will need to continue,
as it is not currently possible to sufficiently understand how chemicals
are broken down in the body using tests in cells alone. These targeted tests
will complement the new rapid assays and ensure the adequate evaluation
of chemicals. (Committee on Toxicity Testing and Assessment of Environmental
Andrew Rowan, now of
the Humane Society of the United States, stated in a book review of Brute
Science in 1997:
differences in xenobiotic metabolism . . . are well known to toxicologists
and are taken into consideration when trying to predict potential effects
in humans. Such differences are not insuperable problems nor do they render
all animal toxicology useless. (Rowan 1997)
use of prediction is not confined to the scientific literature. If anything,
it is even more widespread when scientists are speaking to the public. Chris
Smith, a doctor and a clinical lecturer in virology at Cambridge University
who hosts The Naked Scientist podcast, stated in the October 21, 2008 podcast:
week scientists have made a giant step forward really in a bit of work which
might help people who are paralyzed because they have had a spinal cord
injury to get moving again. They’ve shown this just using monkeys
to start with but monkeys are very good models for how humans work so we
think the same technique should work in humans (Smith October, 19 2008).
science as a whole is self-correcting and the scientific method is the best
way we have of understanding the material world, scientists are still human,
with all the frailties associated with being human. Many scientists have
not questioned the basis of their belief in the utility of animal-based
studies because it is so traditional and so deeply ingrained that it seems
like a fundamental fact of life.
2008. Of Mice...and Humans. Drug Discovery and Development 11 (6):16-20.
on Toxicity Testing and Assessment of Environmental Agents, National Research
Council. 2006. Toxicity Testing for Assessment Agents: Interim Report: National
E. I., and E. C. Holland. 2006. Mouse models of brain tumors and their applications
in preclinical trials. Clin Cancer Res 12 (18):5288-97.
SC. 2007. Preface. In Animal Models in Toxicology, edited by S. Gad: CRC
Jann. 2003. Animal Models. In Handbook of Laboratory Animal Science. Second
Edition. Animal Models, edited by J. Hau and G. K. van Hoosier Jr: CRC Press.
Susan. 2008. The Age of American Unreason: Pantheon.
T. 1993. Marshall’s Hunch. New Yorker, 64-72.
Massimo. 2002. Denying Evolution: Sinauer.
Andrew. 1997. Book Review. Brute Science. Animal Welfare 6:378-81.
Chris. October, 19 2008. The Naked Scientist Podcast. In Fusion: The Power
of the Sun.