Most scientists and governments say they agree that animal testing should cause as little suffering as possible, and that alternatives to animal testing need to be developed. The "three Rs",[1] first described by Russell and Burch in 1959, are guiding principles for the use of animals in research in many countries:
- 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.
- Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.
- Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
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.[2] 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.[3]
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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.” [4]
Types
Cell culture
Cell culture is currently the most successful, and promising, alternative to animal use. 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.[5]
- Skin corrosion
Human skin equivalent tests can be used to replace animal-based corrosive studies. Two products, EpiDerm[6] and EpiSkin[7] 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.[8] 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.[9]
- 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. [10] 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, irritants cause only reversible skin damage.
- 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.
Computer simulation
Examples of computer simulations available include models of diabetes,[11] asthma,[12] and drug absorption, 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.[13] Prior to this, live pigs were used as test subjects for crash testing.[14]
Other non-animal simulators have been developed for military use to mimic battlefield induced traumas. TraumaMan[15] 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.[16]
Several virtual humans have been constructed by creating a mathematical models of a human based on known human reactions. 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.[17]
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
In October 2006 the European Centre for the Validation of Alternative Methods (ECVAM) launched an online database of toxicology non-animal alternative test methods. Categories at present include in vitro methods, QSAR models and a bibliographic section.[18]
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
References
- ^ Russell, W.M.S. and Burch, R.L.. "The Removal of Inhumanity: The Three R's". http://altweb.jhsph.edu/publications/humane_exp/chap4d.htm. Retrieved on 2007-05-24.
- ^ Lipinski, Christopher (16 December 2004). "Navigating chemical space for biology and medicine". Nature 432 (7019): 855–61. doi:. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15602551&query_hl=1&itool=pubmed_docsum.
- ^ Malcolm Rowland (February 2006). "Microdosing and the 3Rs". National Center for the Replacement, Refinement, and Reduction of Animals in Research ( NC3Rs ). http://www.nc3rs.org.uk/downloaddoc.asp?id=339&page=193&skin=0. Retrieved on 2007-09-22.
- ^ [1] Center For Alternatives To Animal Testing.The Johns Hopkins University 1997-2009
- ^ "Special section: Monoclonal antibodies". Johns Hopkins Bloomberg School ofPublic Health. http://altweb.jhsph.edu/mabs/ascites.htm. Retrieved on 2007-09-20.
- ^ The Epiderm Skin Model – Manufacturer’s Web Site
- ^ Human skin to replace animal tests – New Scientist
- ^ EpiDerm Approved by EU, U.S. Regulators
- ^ Comparison of in vivo (draize method) and in vitro (corrositex assay) dermal corrosion values for selected industrial chemicals
- ^ The 3T3 Neutral Red Uptake (NRU) Phototoxicity Assay – MB Research Labs
- ^ "Diabetes". entelos.com. http://www.entelos.com/science/metabolic.html#diabetes. Retrieved on 2007-10-05. (from internet archive)
- ^ "Asthma". entelos.com. http://web.archive.org/web/20050415190556/www.entelos.com/science/respiratory.html. Retrieved on 2007-10-05. (from internet archive)
- ^ The History of Crash Test Dummies
- ^ I Was A Human Crash-Test Dummy
- ^ Home of the TraumaMan system – Simulab Corporation
- ^ TraumaMan Offers Lifelike Practice for Med Students
- ^ Using Computers to Assess the Heart
- ^ "Home page". Evcam Database Service on Alternative methods toAnimal Experimentation. http://ecvam-dbalm.jrc.cec.eu.int. Retrieved on 2007-10-05.
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External links
- 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
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