Alternatives to animal testing
Encyclopedia
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:
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.
, 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.”
, 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.
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.
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.
cause only reversible skin damage.
Another approach has been the development of test methods that use cultured human cells. Human epidermal keratinocyte
s 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
.
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 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.
Animal testing
Animal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of millions to more than 100 million...
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
Moral obligation
The term moral obligation has a number of meanings in moral philosophy, in religion, and in layman's terms. Generally speaking, when someone says of an act that it is a "moral obligation," they refer to a belief that the act is one prescribed by their set of values.Moral philosophers differ as to...
for the use of animals in research in many countries:
- Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
- 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.
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
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
animal testing are in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
cell culture techniques and in silico
In silico
In silico is an expression used to mean "performed on computer or via computer simulation." The phrase was coined in 1989 as an analogy to the Latin phrases in vivo and in vitro which are commonly used in biology and refer to experiments done in living organisms and outside of living organisms,...
computer simulation
Computer simulation
A computer simulation, a computer model, or a computational model is a computer program, or network of computers, that attempts to simulate an abstract model of a particular system...
. 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
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. 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 MedawarPeter Medawar
Sir Peter Brian Medawar OM CBE FRS was a British biologist, whose work on graft rejection and the discovery of acquired immune tolerance was fundamental to the practice of tissue and organ transplants...
, the Nobel prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
-winning immunologist, along with Christine Stevens, founder of the Animal Welfare Institute
Animal Welfare Institute
The Animal Welfare Institute is a non-profit charitable organization founded in 1951 with the goal of reducing pain and fear inflicted on animals by humans...
(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.”
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 antibodiesMonoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
, 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
3T3 cells
3T3 cells come from a cell line established in 1962 by two scientists then at the Department of Pathology in the New York University School of Medicine, George Todaro and Howard Green. The 3T3 cell line has become the standard fibroblast cell line...
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.
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 irritantsIrritation
Irritation or exacerbation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant...
cause only reversible skin damage.
Another approach has been the development of test methods that use cultured human cells. Human epidermal keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s 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
Draize test
The Draize Test is an acute toxicity test devised in 1944 by Food and Drug Administration toxicologists John H. Draize and Jacob M. Spines...
.
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 constructMIMIC (immunology)
This article is about the vaccine development tool.MIMIC, or modular immune in vitro construct, is an artificial system imitating the human immune system...
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
Crash test dummy
Crash test dummies are full-scale anthropomorphic test devices that simulate the dimensions, weight proportions and articulation of the human body, and are usually instrumented to record data about the dynamic behavior of the ATD in simulated vehicle impacts...
, 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 MedicinePhysicians Committee for Responsible MedicineThe Physicians Committee for Responsible Medicine is a non-profit organization based in Washington, D.C., which promotes a vegan diet, preventive medicine, alternatives to animal research, and encourages what it describes as "higher standards of ethics and effectiveness in research." Its primary...
- Dr Hadwen TrustDr Hadwen TrustThe Dr Hadwen Trust is the UK's leading medical research charity that funds and promotes exclusively non-animal techniques to replace animal experiments...
- 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 CollegeJawaharlal Nehru Medical CollegeJawaharlal Nehru Medical College is a medical college located in Aligarh, Uttar Pradesh, India.The college is affiliated under the with Aligarh Muslim University.-History:...
, Aligarh Muslim UniversityAligarh Muslim UniversityAligarh Muslim University ,is a residential academic university, established in 1875 by Sir Syed Ahmed Khan as Mohammedan Angelo-Oriental College and later granted the status of Central University by an Act of the Indian Parliament in 1920...
, 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 CommissionEuropean CommissionThe European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
is funding (and will be funding) a significant number of large integrated research projects aiming to develop alternatives to animal testing.
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 LibraryUnited States National Agricultural LibraryThe United States National Agricultural Library is one of the world's largest agricultural research libraries, and serves as a National Library of the United States and as the library of the United States Department of Agriculture...
. 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