1. The ethics of animal experiments in 3 steps
Stijn Bruers
Bite Back
aug-2013

2. 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

3. 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
Yes No
Effect animals
True positive test
False positive test
Falss negative test
True negative test

4. 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

5. 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

6. 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)

7. 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?

8. 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

9. Step 1: scientifically unreliable
No anecdotes! No “cherry picking” of examples
But:
Statistical analysis of collection of studies (meta-analysis)
Blind peer reviewed
Critical, impartial
Reviews of systematic reviews
new (only last decade),
increasing recognition of importance

10. Step 1: scientifically unreliable
Reviews of systematic reviews (last decade)
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:
Greek, R. and Menache, A. (2013). Systematic Reviews of Animal Models: Methodology versus Epistemology. Int J Med Sci 10(3):
Hackam D. G., and D. A. Redelmeier. (2006). Translation of Research Evidence from Animals to Humans. JAMA 296:
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:
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:
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:
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).

11. Step 1: scientifically unreliable
Human vs animal bioavailability 1. Graph generously provided by James Harris PhD, who presented it at the Center for
Business Intelligence conference titled 6th Forum on Predictive ADME/Tox held in Washington, DC September 27–29, 2006 and is
adapted from data that appeared in Grass GM, Sinko PJ. Physiologically-based pharmacokinetic simulation modelling. Adv Drug
Deliv Rev Mar 31;54(3):433–5.

12. Step 1: scientifically unreliable
Why lack of predictive value? Why that many false positive and false negative results?
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)
Theory of evolution: small and large differences between individuals, populations and species

13. 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

14. 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

15. Step 1: scientifically unreliable
New technologies
Computer simulations and mathematical models
Microdosing
MRI-scanners

16. Step 1: scientifically unreliable
New technologies
Gene chips (DNA microarrays)
Human-on-a-chip

17. Step 1: scientifically unreliable
Animal testing can be harmful to people:
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)

18. Step 1: scientifically unreliable
Why are there still animal experiments?
Psychological mechanisms of animal researchers
Habit
Belief
Peer pressure
Money

19. Step 1: what if animals were not sentient?
Science
Step 2: what if animals are sentient?
Ethic of well-being

20. 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!

21. 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

22. 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

23. 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

24. Step 3) ethically irresponsible: animal rights violations
Species is not morally relevant
Arbitrary: why species instead of population, subspecies, genus, family, order, class,…?
Artificial and far-fetsched: how to define a species? Relevance of fertility of potential offspring?

25. Step 3) ethically irresponsible: animal rights violations
Fuzzy boundaries: human-animal hybrids, chimeras, ancestors, genetically modified humans?
No merit: we did not choose to be born as humans
Comparison with racism: genes not morally relevant

26. 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