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Alternatives to the Use of Animals in Research

An increasing number of alternatives now offers new hope for the welfare of millions of animals used in biomedical research, product safety testing, and education.

While the use of alternatives doesn’t always mean eliminating animal testing altogether, the number of animals being used has been dramatically reduced in recent years, and the lives of many others have been significantly improved. The words now used almost universally by the research community and by animal protection advocates to describe alternatives are “The Three Rs” — Replacement, Reduction, and Refinement. This page clarifies these terms, describes efforts to promote “The Three Rs,” and suggests good sources of further information.

Basic Uses of Laboratory Animals
Animals in laboratories are used in many ways. Each year, an estimated 11-23 million animals worldwide serve as models for testing the safety of a wide range of consumer products, including cosmetics, drugs and vaccines, household cleaning products, pesticides, industrial chemicals, automobiles, and toys. Animals are also used in education: they are used in high school and college biology classes, as well as for teaching anatomy and surgery in veterinary and nursing schools. In addition, they are used for biomedical research on the workings of the human body and mind and for studying disease. Whether or not it is necessary to continue to use laboratory animals is a matter of opinion. However, when testing alternatives are available, the most humane stance is to forgo animal testing and use other methods.

Some believe animals are suffering needlessly since alternatives exist, and because tests on animals rarely predict human response. Others say alternatives can never replace the value of live animals in research, and public health and safety and the future of biomedical research would be seriously jeopardized without animal testing. The MSPCA’s position is that the truth lies somewhere between these two extremes and that support for the development of alternatives offers scientists and animal activists an excellent way to work together toward ending the need for animal use in a scientifically sound way.

What is Meant by Alternatives?
The widely-applied concept of “The Three Rs” — Replacement, Reduction, and Refinement — was originally introduced in the 1950s by William Russell and Rex Burch, British biologists who sought to lessen the suffering of laboratory animals. Though many may assume Russell and Burch’s concept specifically seeks to eliminate animal testing in favor of alternatives, the Three Rs are much broader and seek to alleviate animal suffering in a variety of ways.

“Replacement” means substituting other systems for whole animal use. Examples include human and animal cell, tissue, and organ cultures; chemical systems; blood products; computer simulations; and plastic organ models. “Reduction” means decreasing the number of animals to the minimum needed to yield accurate data and is often achieved through more strategic study planning. “Refinement” means using modern medicine to minimize or eliminate pain and distress; it also includes employing housing and husbandry techniques to enrich the captive environment to reduce boredom and promote natural behavior.

What Alternatives Are Currently in Use?

In 2010, in vitro (test-tube) testing became more popularized as an animal substitute for studying diseases. In vitro procedures are now commonly used in cancer research to successfully reduce animal testing, save money, and receive results faster than with animal models.

At some veterinary schools, plastic soft-tissue organ models are replacing the dogs traditionally used to teach beginning surgery. A study conducted at the University of Illinois in the 90s showed that students who learned to cut and suture using these and other alternative models performed just as well in surgery on animal patients as did those trained on dogs. A company called SynDaver produces a line of synthetic canine models that mimic all of a dog’s body systems and can even be programmed to simulate various diseases or medical complications. Such technology allows for live animals to be replaced with realistic substitutes in veterinary teaching programs throughout the world.

The Department of Defense currently uses more than 8,500 live animals every year for training. During combat trauma training, animals are subjected to shooting, stabbing, burning, amputations, and death.

In May 2017, the U.S. Coast Guard announced they will use human simulators instead of live animals in their combat trauma training, however, there have been no shown attempts to slow the marine program. The simulators have artificial blood, breakable bones, and internal organs, which closely replicate those of an actual human. This allows trainees to perform life-like surgery on simulators without hurting animals in the process. Additionally, EPA committed in 2019 to reduce reliance on mammalian animal testing by 30% by 2025 and to end it entirely by 2035. Also, in February 2020, the EPA issued final guidance that reduces unnecessary testing on birds in the pesticide registration review process, which is expected to save 720 test animals annually. And in July 2020, EPA released guidance that reduces unnecessary testing on fish in the pesticide registration process, expected to save 240 test animals annually.

The classical LD50 test, used to determine toxicity, measures the dosage needed to kill 50 percent of the treated animals. Formerly used to satisfy national and international requirements for product safety testing, the LD50 required as many as 200 animals per test. One widely accepted alternative is the “limit” test, which requires only 6-10 animals. This test uses a small number of animals to determine minimum and maximum toxicity, and a limit is set on the number of doses to be tested. As a result of this and other alternatives, the number of animals used in LD50 testing has recently fallen significantly, and the LD50 test no longer represents an international testing standard.

Some scientists are using state-of-the-art medical technologies such as the MRI (magnetic resonance imaging), the MRS (magnetic resonance spectroscopy), and CAT (computer-aided tomography) scans to detect tumor growth and organ deterioration at early stages. This non-invasive imaging not only enables experiments to end more humanely, without prolonged suffering, but also reduces the number of animals needed for certain types of research.

The Draize test is used to determine the irritancy of substances such as shampoos or household cleaners that could accidentally drip or be sprayed into human eyes. It involves placing a test substance, such as a household cleaner chemical, into one eye of several rabbits, then checking the eyes at various intervals to assess any damage. An alternative to the Draize test, called the low-volume eye test (LVET) uses one-tenth of the amount of the substance. It reduces the potential for pain and discomfort, and is more predictive of possible human eye irritation, because it more closely simulates human experience than the standard Draize test. Although still legally allowed in the U.S., the National Institutes of Health recommend using alternatives when available.

Animal use for eye irritancy tests has fallen significantly as new in vitro tests have been developed that screen out potentially irritating substances before they are tested on animals. For example, in 2018, a reconstructed human cornea epithelium (RCE) model was created using tissue so closely related to the human cornea that it allows the test to distinguish between all irritant categories. New and more effective pain-relieving drugs are also being used at many research institutions to alleviate post-surgical distress.

Steps are also being taken to minimize the stress of mice, the most commonly used animals used in research. When mice undergo routine procedures (such as blood pressure measurement, injections, and blood collection), they are often held in cylindrical or cone-shaped restrainers that are inherently uncomfortable and offer no easy-to-grip surfaces for the mice. This causes them to have a continuous loss of balance, and their panic to get out of the container can result in trauma as they fight to wriggle out. In 2015, a veterinary technician at the University of Michigan developed the LACube, a square restrainer with a textured floor that is comfortable and safe for mice, eliminating any unnecessary stress to the animal during routine procedures. More recently, the University of Chester ran a study to determine the best handling strategies to result in the least stress in mice. The researchers found tail restraint to result in negative behaviors from the mice, where tunneling or hand cupping pick-up methods result in more positive behaviors from the mice.

Some research facilities have developed new ways to enrich the laboratory environment. This enables animals to express more of their normal behavior and alleviates two of the biggest problems facing laboratory animals: isolation and boredom. New caging systems, for example, now allow small monkeys to live in pairs or groups, reducing some of the stress experienced by these highly social animals. Stones and stainless steel tubes placed in frogs’ tanks provide a little bit more enrichment for these animals. Yet these small measures also underscore the limits to which animal lives in laboratories can be improved, and the urgency that remains to find non-animal alternatives.

One of the newest advancements in animal-alternative technology is the development of the Organ-on-a-chip (OOAC). Identified as a “Top Ten Emerging Technology” by the World Economic Forum, OOAC works using four components — microfluidics, living cell tissues, stimulation/drug delivery, and sensing — to mimic the physiological response of an organ. Response measures include the fluid shear force, concentration gradient, dynamic mechanical stress, and cell patterning as a drug passes through the organ. OOAC is currently being used to reduce animal models in testing drug effects on human organ systems. The overall goal of OOAC is to create a multi-organ-chip to study how drugs cycle through an entire organ system. Currently, successful OOACs are liver, lung, kidney, heart, and intestine-on-a-chip all being used to make major scientific advancements in medicine.

Can Alternatives Replace All Animal Tests?
The simple answer is: not yet. While the number of animals used in teaching and in product safety testing has fallen dramatically in recent years, in biomedical research, which is where most laboratory animals are used in the U.S. today, most scientists believe it is not feasible to replace all animals in the near term. Biomedical scientists say we simply do not yet understand all the complexities of the human or animal body.

In fact, recent advances in genetic engineering (see our Genetic Engineering webpage) research now threaten to dramatically increase the number of animals used in biomedical research, as scientists race to put new technology to use. New refinement techniques — the third, often forgotten “R” — need to be developed to improve laboratory animal veterinarians’ ability to assess pain and relieve the discomfort of animals who have been genetically modified. Much work also needs to be done to increase the validation, acceptance, and use of alternatives in product safety testing by federal regulatory agencies (see our Product Safety Testing webpage).

Meanwhile, momentum for alternatives development continues to build. Pressure from animal-protection groups and consumers — as well as growing scientific awareness that non-animal alternatives often produce cheaper, faster, and more accurate results — will ensure the continued expansion of alternatives to laboratory animal procedures.

We believe a well-informed public is essential to improving the welfare of animals. We encourage concerned individuals to learn more about alternatives and to communicate with elected officials, federal and state regulatory agencies, educational institutions, and industry representatives about increasing the use of alternatives in research, testing, and education.


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