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THE SOLUTION – ALTERNATIVES TO ANIMALS

There is a wide range of non-animal research techniques that, as well as being a humane approach to science can also be cheaper, quicker and more effective. These include cell, tissue and organ cultures; methods using chemistry, computers or imaging machines and studies using human volunteers. Here are just a few examples:

Cell cultures

Almost every type of human and animal cell can be grown in culture, although the cells behave more simplistically than in the living body. Cellular systems have been central to key research into cancers, sepsis, kidney disease and AIDS, and are routinely used in chemical safety testing, vaccine production and drug development.

Recently, scientists have managed to coax cells to grow in 3D structures, which can provide more realistic cell models on which to test potential therapies. This technology has already been used to grow pea-sized structures that closely resemble the human brain and 3D models of human tumours.

The Embryonic Stem Cell Test (EST) is a promising cell-based alternative that can be used to find out if a chemical or drug may harm the developing foetus. Instead of forcing pregnant rats and rabbits to consume the test substance in the cruel animal test, it is applied to mouse stem cell cultures. Substances are classed as toxic if they block the development of stem cells into berating heart cells, which can be seen through a microscope. In a validation study, the test was found to be 78% accurate, with 100% accuracy at detecting very toxic chemicals, while the animal test can only detect 60% of toxicants.

Human tissues

Both healthy and diseased tissues donated from human volunteers can provide a more relevant way of studying human biology and disease than animal testing. Human tissue can be donated from surgery (e.g. biopsies, cosmetic surgery and transplants) or after a person has died (e.g. post-mortems). These tissues can be used in many forms, including isolated perfused organs, precision cut slices, frozen tissue or in cell cultures. Post-mortem brain tissue has provided important leads to understanding brain regeneration and the effects of Multiple Sclerosis and Parkinson’s disease.

An important alternative made from human tissues is the Reconstituted Human Epidermis (RHE) skin model (Trade names, Episkin, Epiderm, EST-1000 and SkinEthic), which can be used to find out if a chemical or cosmetic is likely to be irritating to the skin. This fascinating model is made up of small discs of skin cells grown from human skin donated as a waste from cosmetic surgery. Instead of rubbing a substance onto the shaved skin of a rabbit in the cruel animal test, it is applied to discs of human skin and evaluated for signs of irritation. This model has been shown to be more effective than the rabbit test it replaces.

In chemico testing

The toxic potential of substances can sometimes be detected using relatively simple chemistry based methods and not requiring human cells. For example, the techniques that now test whether shellfish have dangerous toxins in them are based on chromatography methods – high performance liquid chromatography (HPLC). They replace extremely cruel tests in which the shellfish mixture was injected into the abdomens of mice. The number of mice who died within a few hours was the crude result used to decide if the shellfish were contaminated.

Another notable chemical test is the Direct Peptide Reactivity Assay (DPRA), which is used to assess whether a chemical or cosmetic will cause a skin allergy. The tests works by mimicking a key step in the development of allergies – the binding of proteins found in the skin to the substance. If proteins bind to the substance then it is very unlikely that it will cause an allergic reaction. It is hoped that this will soon replace cruel tests on mice and guinea pigs who have the substance painted onto their skin and are then examined for allergic reactions. These crude tests can only predict human reactions 72% of the time while the DPRA has been shown to be highly predictive and can alone correctly evaluate the skin sensitising potential of up to 91% of substances.

Organ on a chip

‘Organ-on-a-chip’ models have been developed which contain a series of tiny hollow chambers that are lined with real, living human cells from different parts of the body. These chambers are linked by channels through which a blood substitute flows, mimicking real processes in the body. Test drugs can be added to the blood substitute which then circulates around the device while sensors within the chip feedback information for computer analysis. These innovative devices can be used for studying biological and disease processes as well as drug metabolism. Devices have already been produced that accurately mimic the lung, heart, kidney and gut. The ultimate goal is to use these chips to create a whole ‘human-on-a-chip’.

Computer models

With the growing sophistication of computers, the ability to ‘model’ aspects of the human body is ever more possible. The first model of how the heart works was developed decades ago but thanks to advances in technology, models have become much more sophisticated and other virtual organ models, including the lung, musculoskeletal system, digestive system, kidney, skin and brain now exist. Human metabolism models can predict the effects of new drugs in humans and are regularly used by pharmaceuticals. Computer models of whole biological systems based on existing information and mathematical data are currently being developed on which ‘virtual’ experiments can be conducted in minutes, instead of experiments which can take months or even years.

QSARs (quantitative structure-activity relationship models) are computer programs which can predict the toxicity of new chemicals or drugs based on their similarity to more established compounds. They are based on the principle that similar chemicals should have similar biological properties. Greater computer power and the ability to generate large databases have facilitated the development of these methods and a wide range of models now exist that cover a variety of toxicities.

Microdosing

Microdosing is an innovative technique that measures how very small doses of potential new medicines are absorbed, distributed, metabolised and excreted by the human body (in so called ADME studies). These microdoses are radio-labelled, injected into human volunteers and measured (usually in blood samples) using a very sensitive measuring device called an accelerator mass spectrometer. Currently, it is estimated that 40% of drugs fail in human trials because the traditional ADME studies conducted in animals do not accurately predict how the drug would behave in humans. In 2009, international drug regulators (ICH) endorsed the use of microdosing in early clinical trials to improve the speed and safety of drug development.

Imaging studies

Rapid advances in technology have allowed for the development of sophisticated scanning machines that can ‘see’ inside the brain and provide detailed information about its structure and function in both healthy volunteers and those with brain diseases and other neurological disorders. Imaging machines can be used to monitor the progression and treatment of brain disease as well as help researchers understand the causes by comparison with healthy volunteers and those with disease. For example, one recent study used PET scans to show that ecstasy abuse causes long-lasting effects on glucose metabolism in the brain and that the effects are more severe in cases of early drug abuse.

Volunteer studies

Microdosing and imaging studies allow human volunteers to be used safely because they utilise special equipment. However, less technical studies in research areas such as nutrition, drug addiction and pain can still be performed by exploiting the ability of humans to consent to unpleasant, but not harmful, procedures. For example, one recent study asked patients with heart disease and diabetes to eat chocolate bars and consent to small muscle biopsies being taken to see if the chocolate improves the condition of their muscles. Another study was able to identify the role of special sweat glands (not found in other animals) in repairing the skin by asking volunteers to consent to small biopsies being made on their skin so the researchers could monitor the healing.

Population research

Studying and comparing illnesses in human populations can help scientists to identify the risk factors and causes of human diseases so that the necessary steps to prevent or reduce the occurrence of disease can be taken. Understanding the roles of genes, lifestyle, diet and occupation, has had a tremendous impact on saving lives. For example, these types of studies have led to the discovery that smoking causes cancer and that high cholesterol and poor lifestyle choices increase the risk of developing heart disease.

ALTERNATIVES AND THE LAW

European law (EU Directive 2010/63/EC) clearly states that “wherever possible, a scientifically satisfactory method or testing strategy, not entailing the use of live animals, shall be used instead of a procedure.” It also states that EU governments should promote non-animal alternatives.

The legal obligation to use non-animal alternatives relies on those alternatives being officially seen to be available, and that in itself is a long and complex process. Once a non-animal method has been developed, it is then required to go through a formal validation process to demonstrate that the method is reliable and works. This validation usually includes further development, trials and assessment, all of which can take many years, particularly if funding is tight (which it invariably is for non-animal research).

In addition, even though EU legislation dictates that animals must not be used when alternative methods are available, in practice enforcement of this is very weak and punishments for researchers who disobey the law are usually minimal. The BUAV has had to take the UK Government to court, and threaten to do so on other occasions, because it was misapplying the law relating to alternatives. The BUAV also regularly comes across published research papers where animal experiments have been performed in areas such as fundamental (curiosity driven) research, despite the fact that there were very obvious and more appropriate non-animal methods of research that could have been used instead.

Unfortunately, in many other countries, such as Japan or the USA, there is no legislative requirement obliging researchers to use alternatives. So in those countries there is absolutely nothing stopping researchers from continuing to conduct cruel animal experiments even if a non-animal replacement is widely available.