Lab Animal Welfare

Lab Animal Alternatives - The Three Rs

An increasing number of alternatives now offer 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 animals 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. In this edition of “Issues & Answers” from the Center for Laboratory Animal Welfare (CLAW), we will clarify these terms, describe our efforts to promote The Three Rs, and suggest good sources of further information.

 

Basic Uses of Laboratory Animals
Animals are used in many ways. They 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, in high school and college biology classes as well as for teaching anatomy and surgery in veterinary, medical, and nursing schools. They are also 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.

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 Center believes 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 towards ending the need for animal use in a scientifically sound way.

 

What is Meant by Alternatives?
The widely-applied concept of The Three Rs was originally introduced in the 1950s by William Russell and Rex Burch, British biologists who sought to lessen the suffering of laboratory animals.  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. Refinement means using modern medicine to minimize or eliminate pain and distress, and employing housing and husbandry techniques to enrich the captive environment to reduce boredom and promote natural behavior.

 

What Alternatives Are Currently in Use?

 

Replacements
The National Cancer Institute (NCI) has replaced nearly 6 million mice per year with human cells in an in vitro (test-tube) procedure used to detect anti-cancer compounds. NCI can now test 20,000 compounds annually, saving two-thirds of the cost of the animal test.

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 1993-94 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. The U.S. Department of Defense has developed computer models of dolphin echolocation (sonar) that will replace animals as underwater object detectors.

 

Reductions
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 by as much as 90 percent. 

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 not only enables experiments to end more humanely, without prolonged suffering, but also reduces the number of animals needed for certain types of research.

 

Refinements
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 into one eye of several rabbits, then checking the eyes at various intervals to assess any damage. 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. 

Animal use for eye irritancy tests has fallen by an estimated 85 to 90 percent as computer use for storing and exchanging information has increased, and as new in vitro tests have been developed that screen out potentially irritating substances before they are tested on animals.  New and more effective pain-relieving drugs are also being used at many research institutions to alleviate post-surgical distress.

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 now allow small monkeys to live in pairs or groups, reducing some of the stress experienced by these highly-social animals. Stones placed in frogs' tanks and stainless steel tubes large enough to hide in, are making laboratory life a little more interesting for some amphibians.

 

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 - where most lab animals are used in the US today - most scientists believe it is not feasible to replace whole animals in the near term.  They say we simply do not yet understand all the complexities of the human or animal body. 

In fact, recent advances in genetic engineering 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 created, whether intentionally or unintentionally, with genetic abnormalities.  Much work also needs to be done to increase the validation, acceptance, and use of alternatives in product safety testing by federal regulatory agencies. 

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

 

The Role of the Center for Lab Animal Welfare
The Center will continue to work with scientists and other animal protection advocates to promote the development, awareness, and implementation of The Three Rs, and to promote changes in regulatory procedures which hamper the use of non-animal product safety tests.  

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.

 

For More Information
To learn more about alternatives, contact: The Johns Hopkins Center for Alternatives to Animal Testing, 111 Market Place, Suite 840, Baltimore, MD 21202,  and the N.I.H. Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM).