The ethics of animal experiments
in 3 steps
Stijn Bruers
Bite Back
aug-2013
The 3 steps
• Step 1) Animal experiments are scientifically
unreliable: animal models lack predictability
for humans
• Step 2) Animal experiments are ethically
unjustifiable: too much loss of well-being
• Step 3) Animal experiments are ethically
unjustifiable : too much violations of basic
rights
Step 1: scientifically unreliable
• Imagine animals were not sentient. Do animal
experiments still have value?
– Applied biomedical research for human purposes: barely
– Fundamental research: yes
• Problem 1: too many false positive and false negative
test results
 Too low predictive value for humans
Effect humans
Effect Yes
animals No
Yes
No
True positive test
False positive test
Falss negative test
True negative test
Step 1: scientifically unreliable
• False positive tests
– Chocolate? Lethal for dogs!
– Safe medicines harmful for animals. E.g.: aspirin,…
– Many substances carcinogenic for mice but not for
humans
• Positive predictive value: if there is an observed
effect in animals, how big is the probability that
the effect will be observed in humans?
• Often < 50% probability!
• Delay of development of good products and
medicines
Step 1: scientifically unreliable
• False negative tests
– No observed effect in animals, but effect in humans
– E.g.: Softenon (thalidomide), Vioxx, cyclosporin,
TGN1412,… Tested safe in animal experiments,
dangerous/lethal for humans
– Smoking: lung cancer in humans, not in mice
– Epidemiological research instead of animal experiments
• Negative predictive value: if there is no observed effect
in animals, how big is the probability that the effect
will not be observed in humans?
• Often < 50% probability!
• Allows dangerous products on the market
Step 1: scientifically unreliable
• Problem 2: which species?
• Discovery of first antibiotic: penicillin (A.
Fleming, 1928)
– No effect in rabbits (false negative)
– Good result with dogs (true positive)
– Dangerous and lethal for rats, hamsters and
guinea pigs (false positive)
Step 1: scientifically unreliable
• How to predict the correct lottery number?
• Most of the time there is a winner, so look at
the collection of all lottery players?
No prediction possible
• Which player?
Step 1: scientifically unreliable
• Problem 3: how to cause a human disease in
healthy animals?
• E.g. MS, Parkinson,…
• Procedure is often merely harming animals
such that they acquire some symptoms (e.g.
shaking) instead of the disease
Step 1: scientifically unreliable
• No anecdotes! No “cherry picking” of examples
• But:
– Statistical analysis of collection of studies (metaanalysis)
– Blind peer reviewed
– Critical, impartial
 Reviews of systematic reviews
new (only last decade),
increasing recognition of importance
Step 1: scientifically unreliable
Reviews of systematic reviews (last decade)
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Anisimov V.N., Ukraintseva S.V., Yashin A.I. (2005). Cancer in rodents: does it tell us about cancer in humans? Nat
Rev Cancer 5:807-819.
Greek, R. and Menache, A. (2013). Systematic Reviews of Animal Models: Methodology versus Epistemology. Int J
Med Sci 10(3):206-221.
Hackam D. G., and D. A. Redelmeier. (2006). Translation of Research Evidence from Animals to Humans. JAMA 296:
1731-1732.
Knight A., Bailey J., Balcombe J. (2006) Animal carcinogenicity studies: 1. Poor human predictivity. Altern Lab Anim
34:19-27.
Knight, A. (2007). Systematic reviews of animal experiments demonstrate poor human clinical and toxicological
utility. ATLA 35:641-659.
Knight, A. (2008). Systematic reviews of animal experiments demonstrate poor contributions toward human
healthcare. Rev. Recent Clin. Trials 3:89-96.
Mestas, J and Hughes, CCW, (2004). Of mice and not men: differences between mouse and human immunology.
The Journal of Immunology, 172: 5.
Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, Macleod M, Mignini LE, Jayaram P & Khan KS (2007).
Comparison of treatment effects between animal experiments and clinical trials: systematic review. British Medical
Journal 334:197-203.
Pound P., Ebrahim S., Sandercock P., Bracken M.B., Roberts I. (2004). Where is the evidence that animal research
benefits humans? British Medical Journal 328:514-517.
Seok, J Shaw Warren, H et al, (2013). Genomic responses in mouse models poorly mimic human inflammatory
diseases. PNAS 110(9): 3507–3512.
Shanks, N. Greek, R. Greek, J. (2009) Review: Are animal models predictive for humans? Philosophy, Ethics, and
Humanities in Medicine, 4(2).
Step 1: scientifically unreliable
Step 1: scientifically unreliable
• Why lack of predictive value? Why that many
false positive and false negative results?
1. Theory of complexity: small differences can
generate big effects
– Gene regulation, complex interactions
– E.g. chimpanzees: 98% of genes in common with
humans, yet not susceptible for HIV, hepatitis and
malaria (false negative tests)
2. Theory of evolution: small and large differences
between individuals, populations and species
Step 1: scientifically unreliable
• Current biomedical research (medicins and toxic
substances): very specific, strongly dependent on
complex interactions of genes,…
• At this specific level: differences between species
(and populations, sexes, ages, individuals…)
become important
• No longer at a rough (less specific) level (such as
e.g. the overall functioning of blood vessels
• Additional confounding factors: breeding
procedure, stress in animals, sickening (infecting)
animals
Step 1: scientifically unreliable
• Alternatives of animal experiments become
more and more reliable, because more
human-specific and more technological
developments
– Epidemiological research
– Clinical research
– Autopsies
– Human (stem) cells and tissue cultures
Step 1: scientifically unreliable
• New technologies
– Computer simulations and mathematical models
– Microdosing
– MRI-scanners
Step 1: scientifically unreliable
• New technologies
– Gene chips (DNA microarrays)
– Human-on-a-chip
Step 1: scientifically unreliable
• Animal testing can be harmful to people:
1. Misleading
– False positive and negative results:
• Preventing development of good products
• Allowing harmful products
– Alternatives are more reliable, so fewer false
positive and false negative results
– Animal studies are wasting scarce resources
(money, time)
Step 1: scientifically unreliable
• Why are there still animal experiments?
• Psychological mechanisms of animal
researchers
– Habit
– Belief
– Peer pressure
– Money
• Step 1: what if animals were not sentient?
Science
• Step 2: what if animals are sentient?
Ethic of well-being
Step 2) ethically irresponsible: welfare
loss in animals
• Animals are too different from humans for
contemporary biomedical research
• But animals are equal to humans in terms of
global functions: circulatory, respiratory,…
and consciousness (feelings)!
• So:
– Concerning what is ethically relevant: strong similarity
between humans and animals
– Concerning what is scientifically important: strong
differences between humans and animals
• According to animal researchers: the opposite!
Step 2) ethically irresponsible: welfare
loss in animals
• Well-being of animals should be taken into
account
• Place yourself in the position of an animal used in
experiments, and measure the loss of well-being
• Increase well-being of everyone, giving priority to
the worst-off
• Loss of well-being due to breeding, confining,
testing and premature killing of animals
• Lab animals are often in the worst-off positions
Step 2) ethically irresponsible: welfare
loss in animals
Three R’s
• Refine
• Reduce
• Replace
Credibility of animal researchers?
• Regularly violating 3R’s in earlier experiments
• What do researchers eat?
– No vegan: researchers violate 3R’s 3 times a day!
– Animal products are not necessary for healthy diets
Step 3) ethically irresponsible: animal
rights violations
• Humans not only have a right to live and to flourish
• Also the basic right not to be used as merely a means to
someone else’s ends
• Humans are not tools
– E.g. slavery
– No use as property
• No coerced human experimentation
– Not even according to 3R’s
– Not even if well-being of other people would increase
more (if human experiments would be beneficial for a vast
majority)
– Not even if seriously mentally disabled orphans would be
used
Step 3) ethically irresponsible: animal
rights violations
• Species is not morally relevant
1. Arbitrary: why species instead of population,
subspecies, genus, family, order, class,…?
2. Artificial and far-fetsched: how to define a
species? Relevance of fertility of potential
offspring?
Step 3) ethically irresponsible: animal
rights violations
3. Fuzzy boundaries:
human-animal hybrids,
chimeras, ancestors,
genetically modified
humans?
4. No merit: we did not
choose to be born as
humans
5. Comparison with racism:
genes not morally
relevant
Conclusion
• Step 1: many experiments should stop
• Step 2: more experiments should be
prohibited (not only for cosmetics)
• Step 3: nearly all animal experiments should
be prohibited