The ethics of animal experiments in 3 steps

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

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: scientificallyunreliable Reviews of systematic reviews (last decade) • Anisimov V.N., Ukraintseva S.V., Yashin A.I. (2005). Cancer in rodents: does ittellusaboutcancer in humans? Nat RevCancer 5:807-819. • Greek, R. and Menache, A. (2013). SystematicReviews of Animal Models: Methodology versus Epistemology. Int J MedSci10(3):206-221. • Hackam D. G., and D. A. Redelmeier. (2006). Translation of Research EvidencefromAnimals to Humans. JAMA 296: 1731-1732. • Knight A., Bailey J., Balcombe J. (2006) Animalcarcinogenicity studies: 1. Poorhumanpredictivity. Altern Lab Anim 34:19-27. • Knight, A. (2007). Systematicreviews of animalexperimentsdemonstratepoorhumanclinical and toxicological utility. ATLA 35:641-659. • Knight, A. (2008). Systematicreviews of animalexperimentsdemonstratepoorcontributionstowardhumanhealthcare. Rev. Recent Clin. Trials 3:89-96. • Mestas, J and Hughes, CCW, (2004). Of mice and not men: differencesbetweenmouse and humanimmunology. 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 treatmenteffectsbetweenanimalexperiments and clinical trials: systematicreview. British Medical Journal 334:197-203. • Pound P., Ebrahim S., Sandercock P., Bracken M.B., Roberts I. (2004). Where is the evidencethatanimal research benefitshumans? British Medical Journal 328:514-517. • Seok, J Shaw Warren, H et al, (2013). Genomicresponses in mouse models poorlymimichumaninflammatorydiseases. PNAS 110(9): 3507–3512. • Shanks, N. Greek, R. Greek, J. (2009) Review: Are animal models predictiveforhumans? Philosophy, Ethics, and Humanities in Medicine, 4(2).

11. Step 1: scientificallyunreliable

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