The ethics of animal experiments in 3 steps

Stijn BruersIARC

sept-2014

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

Effect humans

Yes No

Effect animals

Yes True positive test False positive test

No False negative test True negative test

• 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

Step 1: scientifically unreliable

• False positive tests– Chocolate? Lethal for dogs!– Safe medicines harmful for animals. E.g.: aspirin, tamoxifen,

Gleevec,…– Many substances carcinogenic for mice but not for humans.

E.g. soy isoflavones,…• 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)• Give me a substance, I give you a species for

which substance is harmful

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, HIV,…• 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 (meta-

analysis)– Blind peer reviewed– Critical, impartial

Reviews of systematic reviewsnew (only last decade), increasing recognition of importance

Step 1: scientifically unreliableReviews 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

5:807-819.• 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. Journal American

Medical Association 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. Proceedings of the National Academy of Sciences 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 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 (cfr. “painism” Richard Ryder)• 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– Right to bodily autonomy (no use of body against the will)

• 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 relevant1. 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