Animals in Research ANSC 100 2024 PDF

Ethical Use of Animals in Research and Teaching Craig Wilkinson BSc, DVM University Veterinarian  Consider – Biomedical research Using the example of cancer, think about the research that might need to be done: What cellular changes or genes are involved in causing...

Ethical Use of Animals in Research and Teaching Craig Wilkinson BSc, DVM University Veterinarian  Consider – Biomedical research Using the example of cancer, think about the research that might need to be done: What cellular changes or genes are involved in causing it? How to diagnose it earlier, faster, more accurately? How to treat it and reduce adverse effects of drugs? Scientists need to use a lab animal species to do this work, since we can’t give people the disease so it can be studied. Much basic science may need to be done long before development of treatments or diagnostics Research will involve mice that have genes that cause them to develop cancer. The government will only approve testing in people of the diagnostic or treatment method after it is proven to be safe and effective in animals.  Consider – Agricultural and Veterinary Research We want to improve dairy production to help feed the growing world population, so we need to find out things like: What environments promote best health? How do we improve cow welfare? What happens to their immune system when you change their diet? If you feed them differently does their digestive efficiency change and do they require different feeds? What might a study of digestion and absorption of certain feed components involve? The research team may need to take blood samples, get digesta samples from the cow’s stomach (rumen) and collect fecal samples. Consider Wildlife Research: a Wolf/Caribou Population Study Consider a research project to study the interaction of endangered wolves and woodland caribou. They need to find out the home ranges and activities of several wolf packs and caribou herds. This will require them to: find individual animals (wolves, caribou) using a helicopter, and capture it either by darting it with a dart gun, or shooting a net over it with a net gun take samples such as pulling a tooth for aging and blood for DNA sequencing, weigh the animal put a radio collar on it so they can track the pack or herd Then they need to quickly get samples, put the collar on, and release the animal without injuring it or themselves! Ethics 5  The animal research behind the 2023 Nobel Prize in Physiology or Medicine Katalin Karikó and Drew Vaccines for COVID-19 Weissman Through their ground-breaking for their discoveries concerning findings, which fundamentally nucleoside base modifications changed our understanding of that enabled the development how mRNA interacts with our of effective mRNA vaccines immune system, the laureates against COVID-19 contributed to the development of effective mRNA vaccines against COVID-19 during the https://www.understandingani pandemic and the unprecedented malresearch.org.uk/news/the- rate of vaccine development animal-research-behind-the- during one of the greatest threats 2023-nobel-prize to human health in modern times. Over the last 40 + years, almost every Nobel Prize in Physiology or Medicine except one (1983 – to Barbara McClintock for her plant genetics research) has depended on data from animal studies. Most major medical discoveries and developments depend on animal research 2022 Nobel Prize in These chemical reactions Chemistry: to researchers are now used around the from California and world to explore cells, track Denmark (for work done biological processes and since 2000). target cancer drugs to Their development: “click specific tumor tissue. chemistry”, a process From this research, drugs where molecules snap are now in clinical trials on together like Lego, which people with advanced can be used to transport cancer. drugs to cancer tumors https://www.nobelprize.org while reducing side effects. /uploads/2022/10/popular- chemistryprize2022-2.pdf The 2020 Nobel Prize for Physiology or Medicine was awarded to Harvey Alter, Michael Houghton (now at University of Alberta) and Charles Rice for their discoveries that led to the identification of Hepatitis C Virus. They were recognized for their decisive contribution to the fight against blood-borne hepatitis, a major health problem that causes cirrhosis and liver cancer. This work involved working with animals at various stages. After initial work in mice, the final step involved demonstrating that the CBC News Report: Hepatitis RNA, when injected into the liver of https://youtu.be/S56qKthUxJI chimpanzees, resulted in the virus being detected in their blood, and caused Hepatitis research has saved pathological changes resembling those in millions of lives: humans with the chronic disease. https://youtu.be/zfpFt2rYSuY https://www.understandinganimalresearch.org.uk/news/2020-nobel-prize- in-physiology-or-medicine-awarded-for-discovery-of-hepatitis-c-virus Ethics 9 The 2018 Nobel Prize for Physiology or Medicine was awarded to James P. Allison PBS Interview with James Allison describes discovery and Tasuku Honjo for their discovery of and its importance: cancer therapy by inhibition of negative https://youtu.be/witCJyEVt6E immune regulation. Their demonstration of different strategies for inhibiting the brakes on the immune system revolutionized cancer treatment and has fundamentally changed the way we view how cancer can be managed. Mice with cancer were cured by treatment with the antibodies that inhibit the brakes and unlock antitumor T-cell activity. This was developed into a therapy for human melanoma with results exceeding all previous treatments. Ethics 10 How are animals used in Science? Fundamental Research Studies of a fundamental nature in science relating to essential structure or function Examples: Studying the migration patterns or habitats of wild animals Investigating how certain hormones produced from the gut and brain regulate energy, balance, growth, and reproduction in fish How are animals used in Science? Medical and Clinical Studies Studies for medical purposes that relate to human or animal diseases and disorders Examples: Using rodents to study and better understand the genes involved in cancer Studying dogs to better understand and develop treatments for canine epilepsy How are animals used in Science? Regulatory Testing Testing the efficacy and safety of products and medications. Health Canada legally requires medical research be performed on animals before human trials can commence. Examples: Testing the safety of vaccines on rodents and non- human primates Testing the efficacy of a new medication for Multiple Sclerosis How are animals used in Science? Development of Products and Medical Devices Studies for the development of products or devices for human or veterinary medicine Examples: Development of new dietary products for farm animals Studies involving pigs to improve methods to preserve transplant organs or to develop artificial organs for humans How are animals used in Science? Teaching and Training Teaching and training to communicate scientific concepts, and develop practical skills and expertise in specific techniques Examples: Training veterinary students on disease prevention, diagnosis, and treatment Teaching biology students about how wild bird behaviour is studied Teaching agriculture and animal health students how to handle livestock (AN SC 101) Animal Research is necessary for Scientific Progress integral to ongoing medical research e.g. spinal cord and nerve repair; stem cell treatments (Parkinson’s and Alzheimer’s); gene therapy (muscular dystrophy, diabetes); molecularly targeted cancer medicines, etc.  Animal Research Saves Human Lives Theresa May (former PM of Animal research has led to: UK) – Type 1 Diabetes elimination of polio, smallpox, rabies and measles as public health threats in most of the developed world complete eradication of rinderpest in cattle and other livestock new diagnostic tests for early treatment (cancer, heart George Canyon – Type 1 Diabetes disease) effective treatments for serious illnesses (diabetes, leukemia, HIV/AIDS, hepatitis, cardiovascular disease, etc.)  Animal Research Saves Human Lives Surgical procedures evolve from animal models: new cardiac surgery techniques and organ transplants bioengineering advances (arterial stents, pacemakers, joint replacements) imaging technology (MRI, Selena Gomez – Kidney Transplant (Lupus) CT, PET, etc.) Animal Research benefits animals too Not only for the direct benefit of humans… It is necessary for us to better understand wildlife and basic biological principles. Improves the health, welfare, and productivity of farm animals. Vital to improving veterinary care, longevity and health of pets, both through application of discoveries in human medicine, as well as specific veterinary research. E.g. ‘Click’ chemistry may help treat dogs with bone cancer (news release Nov 2022) Research founded on the work that received 2022 Nobel Prize in Chemistry A researcher at U of PET scan images of Missouri College of Vet a dog show a Medicine has shown how cancerous tumor in the femur (thigh click chemistry can deliver bone). drugs to treat bone cancer tumors in large (>50 kg) dogs Was previously thought only to work in mice (much smaller bodies than dogs) https://showme.missouri.edu/2022/c lick-chemistry-may-help-treat-dogs- with-bone-cancer-mu-study-finds/  Animal research is not the only way It is used after, in addition to, and/or alongside computer modeling, tissue/cell cultures, epidemiological studies, and human (or veterinary) trials. Alternatives/Replacements are often used in teaching and training students These complementary approaches inform and direct what research in animals is essential vs. what might be of less use.  Alternatives are important… but No complete Replacements to animal research exist – Computer models and cell cultures can’t give vital information about the intricacies of living cells and tissues, or the safety and efficacy of a substance in a living system. In agriculture and wildlife biology the animal is the subject of the study, not a stand-in for humans. Researchers try hard to avoid causing significant pain or distress. Care is taken to protect animals from undue stress (or pain) which can distort study results. Refinement of methods  Animal research is carefully regulated and supervised The Canadian Council on Animal Care www.ccac.ca Oversees and ensures (certifies) exemplary care for laboratory animals at all institutions in Canada Produces guidelines and policies Conducts regular mandatory reviews and assessments (inspections) of animal research facilities and programs (ACC function, policies & procedures) Requires adherence to “3R’s” Accreditation is required for academic institutions using animals  At Every Institution Researchers must apply to Veterinarians and trained an Animal Care Committee animal technicians must and describe and justify care for and oversee all everything they plan to do, animal use before animal use is permitted to start Facilities are regularly visited and reviewed for ACCs review carefully and upkeep require changes to improve care and welfare ACCs and vets may stop experiments if necessary, Post-Approval Monitoring or intervene in other ensures research is ways if needed. conducted as described  Did You Know? The majority (>72%) of research animals used in Canada are mice and fish. (CCAC 2022 Data) Some odd numbers appear (cattle – 13%, occasionally others year/year) Dogs, cats, rabbits and non-human primates account together for less than 0.7 percent of total animals used in Canada. Many of the dogs/cats reported as “used” (and many farm animals) are not used for invasive research, but in clinical trials or in teaching/training vet students and RVTs. 1,340,916 1,198,299 2022 CCAC Animal Data Report https://www.ccac.ca/en/facts-and-legislation/animal-data/ 462,025 161,669 138,329 2022 CCAC Animal Data Report Animal Research follows “the 3Rs” “The 3Rs” Reduce the number of animals used; Refine studies to ensure humane conditions; Replace animals with other models whenever possible (alternatives). All projects must address how these are considered and applied Reduction Refers to any strategy that will result in fewer animals being used Number of Animals must be statistically significant (enough) without being excessive (too many) Careful study design Excellent animal care and health management Use of: Pilot Studies Efficient Data Collection Reduction is often a result of the other 2 R’s  Replacement Refers to methods which avoid or replace the use of animals in an area where animals would otherwise have been used Use of animals of lower sentience (think/feel/perceive) where possible mice instead of dogs; fish instead of mice; invertebrates instead of fish = “relative replacement” Computer simulations for some research Videos or computer simulations for teaching Substitution of a simulator, mannequin or dummy for teaching Use of tissue culture or abbatoir (processing plant) sources for research or teaching  Refinement Refinement refers to the modification of husbandry or experimental procedures to minimize pain and distress More comfortable, stress-free housing Better training of personnel Use of improved, less invasive techniques Better equipment Better anesthesia/analgesia Better post-procedural care Improved monitoring and “endpoint” determination Humane euthanasia techniques The “4th R” – Respect! Quality Animal Care = Quality Science Austin Matthews, Toronto Maple Leafs Quality Animal Care = Quality Science  Interested in learning more about Biomedical Research involving animals? How are animals cared for and why is animal research necessary? https://youtu.be/2NCNEC53ZRs How does animal research change our lives? (A video series that thanks animal care staff who work in research facilities) https://www.loveletterseries.com Liviya’s Story (A girl with a rare, potentially fatal aplastic anemia that was successfully treated with horse antibodies) Brick in the Wall (A story about how dogs with a rare genetic disorder have helped develop a cure for an uncommon human disease) What does an animal facility look like? Animal Facility Tour: https://youtu.be/5RC2HhRCQ3s?si=ZfBAIndDF1NfETV4