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==Ethics== Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament under pressure from British and Indian intellectuals enacted the first law for animal protection preventing cruelty to cattle.<ref>[https://web.archive.org/web/20061214034848/http://homepage.tinet.ie/~pnowlan/Chapter-77.htm British animal protection legislation].</ref> This was followed by the [[Cruelty to Animals Act 1835]] and the [[Cruelty to Animals Act 1849]], which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from the [[National Anti-Vivisection Society]], the Cruelty to Animals Act 1849 was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over. Today, these three principles are central to the laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see also [[Laboratory Animal Welfare Act]]) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program.<ref>[http://awic.nal.usda.gov/government-and-professional-resources/federal-laws/animal-welfare-act AWA policies].</ref> In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by a local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement.<ref>[http://grants.nih.gov/grants/olaw/investigatorsneed2know.pdf NIH need-to-know]</ref> "Replacement" refers to efforts to engage alternatives to animal use. This includes the use of computer models, non-living tissues and cells, and replacement of "higher-order" animals (primates and mammals) with "lower" order animals (e.g. cold-blooded animals, invertebrates) wherever possible.<ref>[https://web.archive.org/web/20000815070936/http://www.nih.gov/science/models/ list of common model organisms approved for use by the NIH])</ref> "Reduction" refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine the minimum number of animals that can be used to get a statistically significant experimental result.{{cn|date=March 2025}} "Refinement" refers to efforts to make experimental design as painless and efficient as possible in order to minimize the suffering of each animal subject.{{cn|date=March 2025}}
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