Alternatives to animal testing

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Many scientists and governments say that animal testing should cause as little suffering as possible, and some argue that alternatives to animal testing need to be developed. The "three Rs", first described by Russell and Burch in 1959, are guiding principles for the use of animals in research in many countries:

1. Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
2. Reduction refers to methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
3. Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.

There is agreement on both sides of the debate that reduction and refinement of experiments on animals should be an important goal for the industries involved. Two major alternatives to in vivo animal testing are in vitro cell culture techniques and in silico computer simulation. However, some claim they are not true alternatives since simulations use data from prior animal experiments and cultured cells often require animal derived products, such as serum. Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems. Other alternatives, not subject to this criticism, involve the use of humans for skin irritancy tests and donated human blood for pyrogenicity studies. Another alternative is so-called microdosing, in which the basic behaviour of drugs is assessed using human volunteers receiving doses well below those expected to produce whole-body effects.

Origin

In 1954, Charles Hume, founder of the Universities Federation for Animal Welfare (UFAW) made an original proposal for the Three Rs to the UFAW to take in consideration alternatives for animal testing and change scientific study in laboratory animal experiments. Committee under the chairmanship of Sir Peter Medawar, the Nobel prize-winning immunologist, along with Christine Stevens, founder of the Animal Welfare Institute (AWI) in the U.S, and William Lane-Petter, the Secretary of the Research Defense Society of Great Britain provided financial support and managed the project to publish the concept of animal testing alternatives. The microbiologist R.L. Burch and the zoologist W.M.S. Russell were chosen to publish the work. "The Principles of Humane Experimental Technique" was published in London in 1959, and the book defined animal testing alternatives as “The Three R's: Refinement, Reduction, and Replacement.”

Types

Cell culture and tissue engineering

Cell culture can be an alternative to animal use in some cases. For example, cultured cells have been developed to create monoclonal antibodies, prior to this production required animals to undergo a procedure likely to cause pain and distress. However, even though cell or tissue culture methods may reduce the number of experiments performed on intact animals, the maintenance of cells in culture normally requires the use of animal-derived serum. Although exact figures are difficult to obtain, some have estimated that one million fetal cows are sacrificed each year to obtain the world's supply of fetal bovine serum, used to grow cultured cells.

Skin corrosion and skin irritation

Skin irritation and skin corrosion refer to localized toxic effects resulting from a topical exposure of the skin to a substance. Human skin equivalent tests can be used to replace animal-based corrosive and irritative studies. EpiDerm from Mattek and EpiSkin and SkinEthic RHE model two subsidiaries of L'Oréal, are derived from human skin cells which have been cultured to produce a model of human skin. These methods are currently accepted replacements in Canada and the European Union. In August 2010, OECD has published the Test Guideline 439 which describe the new procedure for in vitro hazard identification of irritant chemicals

Another synthetic replacement uses a protein membrane to simulate a skin barrier and is approved as a partial replacement by the US Department of Transportation and European Union.

Skin absorption

Several tissue culture methods which measure the rate of chemical absorption by the skin have been approved by the Organization for Economic Cooperation and Development (OECD), although they have not yet been approved as a replacement in the US.

Phototoxicity

Phototoxicity is a rash, swelling or inflammation, like a severe sunburn, caused by exposure to light following exposure to a chemical. The 3T3 Neutral Red Uptake (NRU) Phototoxicity Test, approved by the Organization for Economic Cooperation and Development (OECD), detects the viability of 3T3 cells after exposure to a chemical in the presence or absence of light. Although originally derived from a mouse embryo, the 3T3 cell line was developed in 1962.

Human-based

Skin irritation

A skinpatch test has been designed and is used in Canada to measure development of rashes, inflammation, swelling or abnormal tissue growth on human volunteers. Unlike corrosives, substances defined as irritants cause only reversible skin damage.

Another approach has been the development of test methods that use cultured human cells. Human epidermal keratinocytes have been cultured to mimic the human epidermis, and are used to measure skin irritation and dermal corrosion. This method has been accepted by the European Union, and is intended to replace the Draize rabbit skin irritation test.

Pyrogenicity

Pyrogens are most often pharmaceutical products or intravenous drugs that may cause inflammation or fever when they interact with immune system cells. This interaction can be quickly and accurately tested in vitro using donated human blood.

Modular immune in vitro construct

The MIMIC or modular immune in vitro construct uses human cells to create a model of the human immune system on which the efficacy of new vaccines and other compounds may be tested, replacing some steps of the vaccine development process that would otherwise be performed on animals. This process is faster and more flexible than previous methods but critics worry that it may be too simple to be useful on a large scale.

Computer simulation

Examples of computer simulations available include models of asthma, though potential new medicines identified using these techniques are currently still required to be verified in animal and human tests before licensing. Computer operated mannequins, also known as crash test dummies, complete with internal sensors and video, have replaced live animal trauma testing for automobile crash testing. The first of these was “Sierra Sam” built in 1949 by Alderson Research Labs (ARL) Sierra Engineering. These dummies continue to be refined. Prior to this, live pigs were used as test subjects for crash testing.

Other non-animal simulators have been developed for military use to mimic battlefield induced traumas. TraumaMan and the Combat Trauma Patient Simulator can be used to simulate hemorrhaging, fractures, amputations and burns. Previously, animals were intentionally subjected to various traumas to provide military training. TraumaMan is also now used for training medical students.

Computer models have been constructed to model human metabolism, to study plaque build-up and cardiovascular risk, and to evaluate toxicity of drugs, tasks for which animals are also used.

Institutes

Institutes researching (and organizations funding) alternatives to animal testing include:

• Center for Alternatives to Animal Testing
• UCDavis Center for Animal Alternatives
• Physicians Committee for Responsible Medicine
• Dr Hadwen Trust
• National Centre for the Replacement, Refinement and Reduction of Animals in Research
• Canadian Council on Animal Care Three Rs Microsite
• Alternatives to Animal Experimentation Laboratory, Department of Pharmacology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh. In the lab, response of drugs are demonstrated and taught by computer simulation exercises. This is the first such lab in India. In addition, a guide to alternatives to animal experiments in pharmacology is prescribed.
• Mahatma Gandhi-Doerenkamp Center for Alternatives to Use of Animals in Life Science Education, India.
• European Centre for the Validation of Alternative Methods (ECVAM), an online database of toxicology non-animal alternative test methods. Categories at present include in vitro methods, QSAR models and a bibliographic section. Under the Framework Programmes 6 and 7, the European Commission is funding (and will be funding) a significant number of large integrated research projects aiming to develop alternatives to animal testing.

See also

In vitro toxicology

External links

• International Network for Humane Education
• Go3R: semantic search to avoid animal experiments
• The Use of Databases, Information Centers and Guidelines When Planning Research that May Involve Animals, Animal Welfare Information Center Bulletin, National Agricultural Library. Provides an overview of databases, bibliographies and guidelines that provide useful information on alternative methods when planning research that may involve animals.
• CADASTER Seventh Framework Programme project aimed to develop computational methods to minimize number of experimental tests for REACH – Registration, Evaluation, Authorisation and Restriction of Chemicals