Animal Testing and the “3Rs”

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PostPosted: Tue Apr 21, 2009 9:29 am    Post subject: Animal Testing and the “3Rs” Reply with quote

Globally, scientific research uses millions of animals in experiments every year and despite being a contentious issue, the number of animals used in scientific procedures is still very high. Undeniably, it is a costly, time-consuming practice and it is questionable whether animal research results can be always be accurately extrapolated to the human situation.

Scientists and governments clearly state that animal testing should cause as little suffering to animals as possible, and that animal tests should only be performed where necessary. As far back as 1954, the British Universities Federation for Animal Welfare commissioned a study on humane techniques in experiments with laboratory animals. The scientists Russell and Burch carried out the work and published their ideas in 1959 in their book 'The Principles of Humane Experimental Technique'. Among their ideas was the concept of the so-called “three Rs” and the principle that the best criterion for choosing experiments to perform is the criterion of humanity.

The "three Rs" are now guiding principles for the use of animals in research in most 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.
Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals still used.
Since the start of the 21st Century, there has been a rapidly increasing emphasis on non-animal techniques to avoid the problem of extrapolating results from one species to another in medical research and toxicology.

State of the art techniques at the micro- and nano-scale can provide the means whereby animal experiments are improved or replaced by a range of alternative methods that could prove cheaper, quicker, more reliable and meaningful, and more effective.

Fish and chips
Writing in the journal ‘Science', the NIH and EPA noted that between 10 and 100 tests can be run in a year using live rodents such as rats and mice. Some tests can be done more quickly using alternative animals such as fish and fruitflies. But more than 10,000 tests can be run every day using specialized cell or tissue-based test systems or lab chips.

An example of a highly-advanced approach to non-animal testing is the ‘MetaChip' - actually a glass slide dotted with 20-nanolitre droplets—each 20 billionths of a litre—of a solution containing human liver enzymes. Researchers can test toxicity of compounds by introducing these chemicals into the solution droplets and seeing how they react. The H µ REL Microchip is an example of a ‘Human-Relevant Toxicity Testing Method': a microfluidic device that allows toxicity and targeting of a nanomaterial to be tested in a multi-chambered microchip connected by microfluidic channels. This design efficiently allows more than one cell type to be tested during each experiment and also illustrates whether the nanomaterial of interest is targeted to a specific cell type. The precision with which the cell's cyclic changes over a time course can be monitored is much improved over animal-based toxicological methods of past decades.

Cell culture
It is possible to obtain human cells and tissues from biopsies, post-mortems, placentas, or as waste from surgery, and grow them in the laboratory. Cell cultures are used in many medical fields, and have contributed enormously to our understanding of the underlying mechanisms of cancer, Parkinson's disease, and AIDS . Cell and tissue cultures are routinely used in vaccine production, toxicity testing, drug development and to diagnose disease.

Analytical technology
Technological advances are resulting in improved molecular methods for analysing and identifying new compounds and medicines. Researchers are now selecting new anti-cancer and anti-malaria drugs, based on their molecular interaction with DNA , as an alternative to selecting drugs by animal tests.

New methods of rapidly analysing DNA samples from humans have been developed and are currently being used to understand the biochemistry and genetics underlying various illnesses, leading to better treatments. As an example, genes that predispose individuals to fibrosing lung disease are being researched as an alternative to modelling the illness in animals such as genetically modified mice. A recent laser technology ( MALD-TOF-MS ) combined with genetic analysis has been applied to identify infectious microbes without animal testing, as an alternative to older tests that relied on rabbits and guinea pigs.

Tests with simple microorganisms, such as bacteria, fungi, yeasts and algae are being used as early indicators of chemicals that are likely to be harmful, and are frequently faster and cheaper than animal tests. Bacteria can be genetically manipulated to manufacture useful products previously obtained from animals, such as human insulin and monoclonal antibodies.

Computer models
Computers are increasingly being used to model the structure and actions of new drugs, and to predict their safety. Computer models of whole biological systems are now being developed with which ‘virtual' experiments can be conducted as alternatives to animals. Such simulations employ models such as that of the human placenta and foetus which can assist the identification of novel treatments for problems affecting unborn babies; and a model of the human jaw and teeth for dental research. These replicas are based on relevant human data and can be used to carry simulated experiments. Further research is being carried out using mathematical modelling to predict how cells behave and differentiate, to improve cancer treatments, and to explore illnesses of ageing.

Population research
Studying diseases in human populations, and the effects of lifestyle, diet and occupation has already revealed a great deal about cancer, heart disease, osteoporosis, and birth defects. Such information is vital to improving human health and providing clues to the causes of illnesses. A large population study into how foetal and infant growth influences the development of heart disease in later life has recently provided an alternative to experiments on pregnant animals.

Volunteer studies
While the merit of studying the whole human being for medical research has long been recognised, ethical restraints have limited this. New scanning and imaging techniques are making it increasingly possible to conduct safe and ethical studies on human volunteers, where previously animals had been used. A variety of sophisticated imaging techniques to non-invasively investigate the intact human body are available. These include using a MEG scanner to study epileptic patients; investigating pain in patients with functional MRI; and developing a novel technique, TMS , to study the function of the human brain in healthy volunteers.

To date, a number of non-animal test methods have been formally validated and have been accepted by some countries as replacements for existing animal tests.

• An embryonic stem cell test, using mouse-derived cells to assess potential toxicity to developing embryos, has been validated as a partial replacement for birth-defect testing in rats and rabbits.
• The 3T3 Neutral Red Uptake Phototoxicity Test, which uses cells grown in culture to assess the potential for sunlight-induced (“photo”) irritation to the skin.
• Human skin model tests such as the validated EpiDerm™ test, which has been accepted almost universally as a total replacement for skin corrosion studies in rabbits.
• The use of human skin left over from surgical procedures or donated cadavers can be used to measure the rate at which a chemical is able to penetrate the skin.
• The use of a clinical patch test in human volunteers, which can confirm that a chemical will not cause irritation or allergic skin reactions.

Conference: Towards Reducing Animal Testing: 28-29 May 2008, The Royal Society, London

This two-day conference, the first of its kind in Europe , examined the role nanotechnology could play in improving or refining the development of alternatives to animal testing whilst maintaining safety.

Themes included:

• a review of some of the most promising human cell-based in vitro models
• novel lab-on-a-chip and bioreactor systems for screening, toxicology and targeting studies
• surface modification at the nanoscale to improve biosensors and in vitro test systems
• potential new strategies for applying nanotechnology to alternatives
• the role of the European Centre for the Validation of Alternative Methods (ECVAM)

Conference speakers included:

Dr Sandra Coecke, ( IHCP-ECVAM , Italy ); Dr Fanqin Frank Chen (Lawrence Berkeley National Laboratory, USA ); Dr Antonio Garcia ( Arizona State University , USA ); Dr Béatrice Schaack (CEA Grenoble, France); Dr Andy Bennett ( FRAME , UK ); Dr Peter Ertl, (Austrian Research Centers (ARC) GmbH).
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