< Professionalism

The use of animals in research is a widely controversial topic in today's scientific community. This topic raises an important professional issue - is it ethical to harm animals with the aim of saving human lives? The scope of this page is limited to cases and laws in the United States, though the professionalism is applicable everywhere.

Animal Research

Definition

Animal research is the use of living animals for research purposes that would be considered unethical to perform on humans first. Approximately 115 million animals are used annually around the world.[1] It typically involves the study of behavior, diseases, and safety of chemicals, cancer research, and psychological studies.

Toxicity Studies

Toxicity studies, which test the effects of toxins and poisons on organisms, are commonly used for drug, food, and pharmaceutical development.[2] The use of animals in these studies began in 1920 with the introduction of the LD50 test. The LD50 test is used to determine the single dose needed to kill 50% of the animals used in the research experiment.[3] Original animal-use involved testing eye and skin irritation in rabbits. Methods now include testing pharmaceuticals and carcinogenic chemicals via rats and mice. Common forms of testing include injection, skin application, and airway insertion.[3]

Cancer Studies

Animals are used to understand the growth and spread of tumors, develop new ways of diagnosis, and testing the efficacy of proposed treatments.[4] Research begins with either selecting animals with naturally occurring cancer, growing tumors from birth via genetic engineering or implanting cells in an animal’s specific organ.[4] The efficacy of new cancer treatments are determined based on its ability to shrink the tumor or slow its growth. 

Testing in General

The number of animals needed for testing ranges depending on the type of study. For example, evaluation of potential carcinogenic substances may require around 800 animals in total, while behavioral studies may require 80.[5] Of all animals, rats and mice are most commonly used. Other animals considered include: rabbits, guinea pigs dogs, and primates. The selection of animals depends on the cost, experimental time constraints, and assumptions on whether the reactions are representative of the human population.[5] In most cases, all animals used are euthanized after the research is completed.[6]

Laws and Regulations on Animal Research and Treatment

Most animal regulations are handled by executive agencies, state and local laws, or by scientific institutions.

Animal Welfare Act of 1966

Current regulations on animal research are primarily found in the Animal Welfare Act (AWA), which is a federal law that regulates the treatment of animals in research, exhibition, transport, and trading. Congress enacted AWA in 1966 and it serves as the minimum acceptable standard for animal care. While it claims to protect “millions of animals nationwide each year”, it excludes certain warm-blooded species such as rats, birds, mice, and livestock.[7] More inclusive protection policies may be found in other policies or guidelines outside the authority of the US Department of Agriculture.

The law is an illustrative example of a lack in professional integrity in animal treatment regulations, most notably for its exemption of rats, mice, birds, and livestock.[7] There is no justification on the grounds of emotional or cognitive complexity for these animals to be exempted when other animals of similar stature, such as dogs and cats, are not exempt. A justification could be made on the grounds of cost or convenience, but convenience is not a primary consideration in the execution of professional standards and ethics.

The Public Health Service Policy on Human Care and Use of Laboratory Animals

The Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) provides principles on vertebrate animal care in testing and research.[8] It includes the protection of more species than AWA. PHS requires that the institution doing research follows the Guide for Care and Use of Laboratory Animals as well as AWA’s regulations.[9] However, it is limited in that it is not a federal law and applies only to research funded by the PHS. More so, it is structured as a self-policing policy. 

Successful Research Outcomes in Animal Testing

Polio

Polio, a crippling and infectious disease infecting the brain and spinal cord, is almost nonexistent in the world today due to the vaccine.[10]  Many people, especially children, were falling victim to the disease throughout the 1900s. Medical professionals had speculations of what it could be/how it was transmitted, but had no evidence. It wasn't until 1908 when two doctors extracted a strand of polio from the spinal cord of a boy who died from polio and replicated it into monkeys.[11] They found that it was transmitted from monkey to monkey proving that polio is an infectious disease caused by a virus. The discovered model of transmission led to years of testing in mice and monkeys. While there is no cure for polio, the prior years of testing and discovery led to the eventual development of a vaccine as an effective means of prevention.[12]

Breast Cancer

In the early 1980s, researchers discovered a protein called HER2 that caused tumors in rats. They were able to create an antibody to target the protein. Later, medical researchers discovered the same tumor-inducing protein in women with breast cancer. High levels of HER2 indicate that the cancer is more likely to spread and less likely to respond to treatment.[13] In 1992, researchers developed Herceptin, an antibody, as a treatment therapy. After initial testing on monkeys, it was approved to use for non-pregnant women by the FDA in 1998.[14] Researchers continue to test the efficacy of it for women in breast cancer.[15] Currently, Herceptin claims to have helped change women’s prognosis of breast cancers, ranging from stage 1 to 3, from poor to good.[13]

Animal Research on Non-Human Primates

Valuing humans and monkeys in terms of dollars is frequently done. Insurance companies often use $50,000 when preparing a quote for a consumer.[16] Government agencies use higher values when considering the costs and savings of regulations, but this may be because the costs are absorbed by the businesses and industries affected, not by the organizations themselves.[17]. As of 2012, the FDA values a human life at $7.9 million, while the EPA estimates its worth at $9.1 million. On the other hand, monkeys are worth much less. Rhesus macaques may be purchased online for $2,000 to $5,000.[18][19] Valuing humans and animals is necessary economically, but the ethics are not so easy.

Isolation Experiments on Rhesus Monkeys

In the late 1950s, Harry Harlow performed psychological experiments on rhesus monkeys. To learn about infant-mother ties, he separated infant rhesus monkeys and placed them with surrogate mothers. These surrogates were either made of a bare wire mesh or covered in terry cloth. He found that those with a choice preferred the cloth-covered mother, which provided emotional attachments to the infants.[20] While the monkeys grew the same physically, their psychological development greatly differed. The monkeys preferred the cloth-covered surrogates far more than the wire frame alternatives.[21] Furthermore, those with the cloth surrogates were much more adaptable to frightening objects, quickly returning to their playful state. Contrastingly, the monkeys raised by the wire-frame surrogates often screamed in terror, showing their lack of psychological development.[20]

Later, in the 1960s, he isolated baby monkeys in an attempt to find out more about depression. Calling the isolation chambers the "Pit of Despair," Harlow's monkeys often went into emotional shock later in their lives. Many of these monkeys that went on to have offspring were negligent or abusive mothers.[22]

These experiments showed that babies look to their mothers for both basic needs and affection.[23] Those without the necessary contact developed serious psychological problems. While these conditions could be reversed initially, after a certain period, nothing could fix the emotional damage.[20]

Moreover, one of his students described his experiments as clearly insensible, and another attributed his experiments to the origins of the modern animal liberation movement.[22] Thus, Harlow's experiment is generally regarded as unethical. Despite this, Harlow remained unsympathetic and unapologetic, stating that the unethical treatment of a few monkeys is irrelevant when considering the potential benefits to humans.[24] While it is clear that this experiment was unethical, it still provided useful results in developmental psychology. In considering cases such as this, there is no clear, right answer. Whether the benefits of this research is worth the suffering of some monkeys is ultimately up to people to decide for themselves.

Polio Research on Rhesus Monkeys and Vaccine

Jonas Salk at the University of Pittsburgh where he developed the first polio vaccine.

When Thomas Francis, Jr. announced the success of Jonas Salk's polio vaccine on April 12, 1955, the world rejoiced. Often cited as one of the worst postwar fears in America,[25][26] polio afflicted countless victims including Donald Sutherland, Mia Farrow, J. Robert Oppenheimer, and possibly Franklin D. Roosevelt.

Discovering, testing, and curing polio involved monkeys at every step. In 1908 Landsteiner and Popper isolated the polio virus by injecting rhesus monkeys with spinal cord tissue from human patients.[27] At least one monkey became paralyzed in both legs. Later, three different types of polio strains were discovered after exhaustive testing on 17,000 monkeys.[28] Researchers infected monkeys which had immunity to a known type of polio with tissue samples of an unknown type to determine the unknown strain. Tested monkeys that became infected were killed.[28] Once Jonas Salk discovered the inactivated poliovirus vaccine (IPV), he needed to grow large amounts of the virus. Growing polio in a cell culture used monkey kidney cell cultures.[29] Finally, vaccines were tested by injecting them into monkeys, and again any infected monkeys were killed.[30]

When the use of monkeys saves as many lives and prevents as much paralysis as Salk's vaccine did, the ethics become unclear. Are the lives of tens of thousands of monkeys worth less than the lives of millions of people? If so, where do we draw the line? The International Association Against Painful Experiments on Animals (IAAPEA) believes that using monkeys gave a misrepresentation of the polio virus in humans and led to huge delays in formulating a vaccine.[27] Albert Sabin, who discovered the oral polio vaccine (OPV), argues that animal research was necessary. “My own experience of more than 60 years in biomedical research amply demonstrated that without the use of animals and of human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans but also among animals.”[31]

Modern AIDS Research on Non-Human Primates

One area that remains particularly contentious in both the scientific community and the realm of public opinion is the use of non-human primates (NHP) in AIDS research. Roughly 6 million people were infected with AIDS in 2007 and that number is projected to increase to 10 million by 2030 without further intervention.[32] Because the similarities of NHPs to humans both in anatomy and physiology, some groups contend that in specific cases, using NHPs is the only conceivable method for exploring possible vaccines and therapeutic treatments. For instance, the California Biomedical Research Association describes the use of NHPs as “an indispensable, and currently irreplaceable, bridge between basic laboratory studies and clinical use.”[33] Others however, like the Humane Society of the United States and People for the Ethical Treatment of Animals (PETA), have pointed out the dissimilarities between NHPs and humans in the progression of HIV/AIDS and Simian immunodeficiency virus (SIV).[34][35] For instance, chimpanzees infected with HIV-1 are unlikely to develop AIDS.[36] Because of the financial cost of maintaining chimpanzees and the increasing pressure from activists, researchers often substitute rhesus macaques for chimpanzees. Rhesus macaques can only be infected with SIV or SHIV, a chimeric HIV & SIV recombinant strain.[36]

Such differences between animal models and humans have been highlighted by the failures of many potential vaccines first tested in animal models. For instance, the AIDSVAX vaccine was effective in chimpanzees, but proved ineffective in a Stage III clinical trial involving 8,000 patients in 2003.[37]

Several advances in the treatment of AIDS/HIV have relied on testing with non-human primates. Notably, tenofovir (PMPA) demonstrated high effectiveness in treating SIV in macaques.[38][39] Zidovudine (AZT) also used macaques for testing.[40] Additionally, researchers laud NHP models for contributing to a greater understanding of toxicology, prophylaxis, and drug resistant HIV mutant strains.[38] A vaccine recently developed for SIV in macaques has demonstrated efficacy rates of at least 80% in preventing infection.[41] Researchers contend that generalizing such findings to humans will ultimately result in successful vaccines and therapies.[38]

The issue of NHP for AIDS research is increasingly an issue in the public domain. Researchers cite concerns about public outcry as one of the principle reasons for discontinuing the use of chimpanzees in AIDS research.[36] In 2005, AIDS patient groups formed the Patient Advocates Against PETA in response to PETA's rigid position on the use of animals in research. However, not all HIV positive patients agreed with this group's stance and have asserted their own concerns about the use of animals in drug and vaccine development.[40]

Rights: Humans vs. Animals

One main argument surrounding animal testing is on the basis of whether or not animals have rights. A right is "an entitlement considered to arise through natural justice and which is applicable to all members of a particular group."[42]

Equal Rights

Especially as the line between humans and animals blur, in criteria such as tool usage or language, the ethics of using animals in research is becoming more and more questionable.[43] As animals can be in pain and distress, humans should include them in their moral circle and recognize their need to reduce pain. Regardless of host, pain is pain, whether is come from a toxicity test or a physical trap.[44]

Moreover, giving only humans rights is a form of "species-ism." If we care about the suffering of other humans, we should also care about the suffering of non-humans. Furthermore, there are some animals that exhibit more brain function than some humans (e.g., infants, etc.). Just because humans are stronger than the animals does not give them free reign; with that logic, a stronger species could and enslave humans with no moral uncertainties.[44]

In place of animal testing, they may suggest these alternatives.

Unequal Rights

Animals are not equal to humans. Only humans can have rights, as rights also include duties to uphold these rights. However, the lack of rights does not equate to a lack of morality in treatment. This does not mean that humans are free to do what they want to animals - humans still may have obligations to animals, but that does not mean that the animals have rights. It is absurd to suggest that humans and animals would both have either no rights or the same rights.[45] Furthermore, because humans can act morally, often sacrificing the self for the greater concern of others, and animals cannot, humans should put human interests before those of animals.[46]

Many also argue that the benefits of animal testing do not outweigh its negative consequences. However, by summing the benefits over time, the results produced via animal testing (e.g., elimination of disease, lives saved, etc.) are so large that it would be unethical to not utilize animal testing. While researchers recognize the effects on the animals, they also see the importance of the research results.[45]

Animal Intelligence

A justification for why humans deserve higher moral consideration than animals is our uniquely complex cognitive capabilities. Throughout modern scientific research, more and more cognitive and behavioral traits previously thought to be only exhibited by humans have been found in animals. An argument can therefore be made for giving animals moral consideration in accordance with their mental and emotional complexity. To judge this, one must be aware of the current scientific understanding of animal intelligence. Because the brown rat is the most commonly used animal in research, and is exempt from protections in the Animal Welfare[47], the most relevant animal to discuss for contemporary animal research is the brown rat.

Metacognition in Rats

Metacognition is the act of thinking about one's own thinking. It is a form of higher level thinking as it requires more complex mental effort than simple reaction to stimulus. A 2007 study called "Metacognition in the rat" suggested that rats are capable of metacognition. The researchers tested the subject rats' cognitive abilities by giving them a sound length discrimination test with an option to decline to take the test. The rats were played a sound, which would be classified as a long sound or a short sound. If the rats guessed correctly (by climbing through a tube they learned were associated with a certain length sound) they received a food reward, with no reward given for an incorrect guess. The researchers added a third tunnel, which would guarantee a food reward smaller than a correct guess. Showing an ability to judge their certainty of the correct answer, the rats reliably chose the third tunnel if the sounds were not clearly distinguishable.[48]

Altruism in Rats

Altruism is the act of doing something to the benefit of another without the expectation of any reciprocal benefit in return. It is not rare in animals, but is still arguably notable in mammals. In a study with rats, researchers taught rats how to open barriers. They then presented the subject rats with two barriers, one trapping the subject's cagemate and another holding chocolate chips. The finding was that rats would consistently free their cagemate before eating the chocolate chips, and share the chocolate in slightly over half of the trials.[49]

Deontological Ethics ("Duty-Based") vs. Consequentialism ("Outcome-Based" Ethics)

For a person that subscribes to deontological ethics, an action cannot necessarily be justified by its consequences. For a deontologist, the moral conformity of an action outweighs the possible good that an action's consequence can impart.[50]

In contrast, a consequentialist assesses an act based solely on its outcome or consequences. In this light, the good that an action creates can always outweigh the rightness or morality of the action and legitimize harmful behavior as long as the final outcome is beneficial. [51]

Limited Applicability to humans

Toxicity Test

After producing a new drug, the scientists need to make sure the drug is effective and safe for human use. Multiple species are required for a toxicity test. Limitations to humans are obvious. Some of the drugs that showed high levels of bioavailability in dogs [52] had very low levels in humans and vice-versa. Meanwhile, some chemicals like MPTP are extremely harmful to humans but neutral to rodents.[53] Second, only around 5% of drugs that show potential in animal studies ever get licensed for human use.[54] Third, since chemical reactions are different for humans and animals, some potential effective medicines could be missed at this stage.

Parkinson’s Disease

Rodents are often used to study Parkinson’s Disease. In the each trial, certain body functions of the rodents is disabled or blocked so that the symptom can be shown in the motor behavior test. Although the neuroanatomical components underlying motor control may be similar for humans and rodents, the manifestation of these motor deficits may be expressed differently between species. [55] Besides, the cause of the behavior failures cannot be determined for sure. The rodents need to learn most of the complex tasks so that scientists does not know if the failure to perform a task is from a motor deficit or from a learning deficit. At last, Parkinson’s Disease is slow and progressive. Since rodents have different reaction time to certain disabled body function from the humans, the symptom will also come out differently.

Conclusion

Not all ethical discussions are black and white. Professionalism involves knowing your own ethics perspective, especially when there is no easy answer. Animal research particularly illuminates inadequacies in codified ethics systems, that can often be unresponsive, vague, or self-contradictory. It also involves the inherent recognition that you hold power over others and that you always have a choice in how you use this power. Particularly, when determining when and if "the ends justify the means." The merits for using animals in research varies case by case, and it is essential that professionals consider their own motivations for performing the research as well as the ratio of animal suffering to long-term benefits for humans.

Furthermore, the changes in what's acceptable animal research provides a localized example of how professional standards change with society and new evidence. As new research on the effects of professionals' choices and actions, either on animals or humans, professional standards must change to fit the most accurate and current evidence.

See Also

References

  1. ↑ Humane Society International. (n.d.) "About Animal Testing" http://www.hsi.org/campaigns/end_animal_testing/qa/about.html?referrer=https://www.google.com/
  2. ↑ Parasuraman, S. (2011). Toxicological screening. Journal of Pharmacology & Pharmacotherapeutics, 2(2), 74–79. http://doi.org/10.4103/0976-500X.81895
  3. 1 2 Shanks, N., Greek, R., & Greek, J. (2009). Are animal models predictive for humans? Philosophy, Ethics, and Humanities in Medicine : PEHM, 4, 2. http://doi.org/10.1186/1747-5341-4-2
  4. 1 2 The Institute of Cancer Research. (n.d.). "Animal Research at the ICR" http://www.icr.ac.uk/our-research/about-our-research/animal-research/animal-research-at-the-icr
  5. 1 2 Nuffield Council of Bioethics. (n.d.). "Animal Use in Toxicity Studies" https://nuffieldbioethics.org/wp-content/uploads/Animals-Chapter-9-Animal-Use-in-Toxicity-Studies.pdf
  6. ↑ UC Irvine. (2013). "Euthanasia of Research Animals" http://research.uci.edu/compliance/animalcare-use/research-policies-and-guidance/euthanasia.html
  7. 1 2 Animal Welfare Act. https://www.nal.usda.gov/awic/animal-welfare-act. Section 2132 g.
  8. ↑ U.S. Department of Health and Human Services. (2015). "Public Health Service Policy on Humane Care and Use of Laboratory Animals" https://grants.nih.gov/grants/olaw/references/phspolicylabanimals.pdf
  9. ↑ National Association for Biomedical Research. (2015). "THE PUBLIC HEALTH SERVICE POLICY OVERSIGHT"http://www.nabr.org/biomedical-research/oversight/the-public-health-service-policy/
  10. ↑ Centers for Disease Control and Prevention. (2014). "What is Polio?" https://www.cdc.gov/polio/about/
  11. ↑ Understanding Animal Research. (2014). "Polio Vaccine" http://www.understandinganimalresearch.org.uk/why/human-health/polio-vaccine
  12. ↑ The History of Vaccines.(2017). "History of Polio ( Poliomyelitis )" https://www.historyofvaccines.org/content/articles/history-polio-poliomyelitis
  13. 1 2 National Cancer Institute. (n.d.). "A Story of Discovery: HER2’s Genetic Link to Breast Cancer Spurs Development of New Treatments"https://www.cancer.gov/research/progress/discovery/HER2
  14. ↑ Animal Research Info. (n.d.). "Breast Cancer" http://www.animalresearch.info/en/medical-advances/diseases-research/breast-cancer/
  15. ↑ UC Los Angeles. (2008). "Animal research generates new treatments, benefits society" http://newsroom.ucla.edu/stories/animal-generates-new-treatments-45057
  16. ↑ Kingsbury, K. (2008). "The value of a human life: $129,000." In Time Health. http://www.time.com/time/health/article/0,8599,1808049,00.html
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  18. ↑ Wild Animal World. http://wildanimalworld.com/gpage.html
  19. ↑ Primatestore.com. http://www.primatestore.com/forsale.asp
  20. 1 2 3 Herman, E. (2012). "Harry F. Harlow, Monkey Love Experiments." The Adoption History Project. http://darkwing.uoregon.edu/~adoption/studies/HarlowMLE.htm
  21. ↑ Herman, E. (2012). "Harry F. Harlow, 'Love in Infant Monkeys,' 1959." The Adoption History Project. http://darkwing.uoregon.edu/~adoption/archive/HarlowLIM.htm
  22. 1 2 Battuello, P. (2011). "Harry Harlow’s Pit of Despair." In Behalf of Animals. http://inbehalfofanimals.com/2011/05/30/harry-harlows-pit-of-despair/
  23. ↑ Schultheis, E. (1999). Harry F. Harlow. http://muskingum.edu/~psych/psycweb/history/harlow.htm
  24. ↑ Hansen, S. (2002). “Love at Goon Park” by Deborah Blum. http://www.salon.com/2002/11/13/blum/
  25. ↑ O'Neill, W. (1989). American high: The years of confidence, 1945-1960. New York: Simon and Schuster.
  26. ↑ (2009, Feb. 2). "American Experience: The Polio Crusade." In Los Angeles Times. Television Review
  27. 1 2 IAAPEA. "Monkey experiments delay polio breakthrough." http://www.iaapea.com/101_page.php?id=87
  28. 1 2 Spice, B. (2005). "Developing a medical milestone: The Salk polio vaccine." In Pittsburgh Post-Gazette. http://old.post-gazette.com/pg/05093/481117.stm
  29. ↑ National Research Council. (1988). Use of laboratory animals in biomedical and behavioral research. Washington, DC: The National Academies Press, p. 28.
  30. ↑ Spice, B. (2005). "Tireless polio research effort bears fruit and indignation." In Pittsburgh Post-Gazette. http://old.post-gazette.com/pg/05094/482468.stm
  31. ↑ Blue Sky Science. (2011). "Albert Sabin and the monkeys who gave summer back to the children." http://speakingofresearch.com/2011/02/01/the-monkeys-who-gave-summer-back-to-the-children/
  32. ↑ Tonks, A. (2007). The quest for the AIDS Vaccine. BMJ, 334(7608), 1346-8.
  33. ↑ California Biomedical Research Association. (n.d.) Fact sheet: Primates in biomedical research. Retrieved from http://ca-biomed.org/pdf/media-kit/fact-sheets/FS-Primate.pdf
  34. ↑ Humane Society of the United States.(2009)."Questions and Answers About Monkeys used in Research" http://www.humanesociety.org/animals/monkeys/qa/questions_answers.html
  35. ↑ PETA.(n.d.). "AIDS: Contagion and Confusion." http://www.peta.org/issues/animals-used-for-experimentation/aids-contagion-and-confusion.aspx
  36. 1 2 3 Nath, B.M., Schumann, K.E., & Boyer, J. D.(2000). The chimpanzee and other non-human-primate models in HIV-1 vaccine research. Trends in microbiology. 8(9), 426-431. Retrieved from http://www.sciencedirect.com/science/article/pii/S0966842X00018163
  37. ↑ Bailey, J. (2005). Non-human primates in medical research and drug development: a critical review. Biogenic Amines, 19(4-6), 235-255. Retrieved from http://www.safermedicines.org/pdfs/reportbiogenic.pdf
  38. 1 2 3 Van Rompay, K. K. A. (2010). Evaluation of antiretrovirals in animal models of HIV infection. Antiviral research, 85(1), 159-75. doi:10.1016/j.antiviral.2009.07.008
  39. ↑ http://www.thebody.com/content/art17228.html
  40. 1 2 AVERT.(2011). "HIV Drugs Vaccines and Animal Testing." http://www.avert.org/hiv-animal-testing.htm#ref2
  41. ↑ Barouch, D. et al. (2012). Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature DOI: 10.1038/nature10766
  42. ↑ "Right," Definition 9a. Oxford English Dictionary. http://www.oed.com/view/entry/165853
  43. ↑ Bowd, A. (February 1980). "Ethics and Animal Experimentation." American Psychologist, 224-225.
  44. 1 2 Ryder, R. (2005). "All beings that feel pain deserve human rights." The Guardian. http://www.guardian.co.uk/uk/2005/aug/06/animalwelfare
  45. 1 2 Cohen, C. (1986). "The Case for the Use of Animals in Biomedical Research." New England Journal of Medicine, 315(14), 865-870.
  46. ↑ Wilson, S. (2010). "Animals and Ethics." Internet Encyclopedia of Philosophy. http://www.iep.utm.edu/anim-eth/
  47. ↑ Animal Welfare Act. https://www.nal.usda.gov/awic/animal-welfare-act. Section 2132 g.
  48. ↑ Foote, Allison and Crystal, Jonathon. (2007). "Metacognition in the rat." Curr Biol, 17(6), 551-555.
  49. ↑ Bartal et al. (2011). "Helping a cagemate in need: empathy and pro-social behavior in rats." Science, 334(6061), 1427-1430.
  50. ↑ http://plato.stanford.edu/entries/ethics-deontological/
  51. ↑ http://plato.stanford.edu/entries/consequentialism/
  52. ↑ N.Shanks,R.Greek, J.Greek, (2009), Are animal models predictive for humans, Philos Ethics Humanit Med, 04-02, doi: 10.1186/1747-5341-4-2
  53. ↑ G.Siegel, B.Agranoff, R.Albers, S.Fisher and M.Uhler, (1999), Basic Neurochemistry, 6th edition, Basic Neurochemistry, 0-397-51820-X
  54. ↑ Waters, H. (2011, March 8). Q&A: Improving preclinical trials, The Scientist. http://www.the-scientist.com/?articles.view/articleNo/29581/title/Q-A--Improving-preclinical-trials/
  55. ↑ J. A. Potashkin, S. R. Blume and N. K. Runkle. (2011), "Limitations of Animal Models of Parkinson's Disease." Parkinson’s Disease, 658083, pp.4.
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