Non-Animal Alternatives
More on research without animals
Research would not come to a standstill if experiments on animals were banned. Valuable research that is directly relevant to humans can be done in many ways that don't cause pain and death to animals.
Sadly, when they study normal physiology or the development of diseases, many researchers still automatically think in terms of "animal models". This is how they were trained, and they carry on the tradition. Animals are often used when the real aim is to find out about humans. For example, electrodes have been implanted in the brains of animals to learn more about processes taking place in the human brain. Diseases are produced in animals to mimic human diseases.
Even in disorders that don't normally affect animals, researchers cast about for an "animal model" rather than trying to develop non-harmful ways of studying the problem in affected humans. For example:
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Depression: rats are given repeated, inescapable electric shocks to the feet to produce "learned helplessness", a condition supposedly like human depression (1).
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Anxiety: a chemical injected into rats to produce escape behaviour has been used as a model for human panic attacks (2).
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Schizophrenia: the drugs methamphetamine, cocaine and phencyclidine have been injected into animals to produce symptoms of schizophrenia (3). The immobility caused by forced swimming in mice has been used as a model of depression in schizophrenia (4). Surgical damage caused to a particular area of the brain has been suggested as a model for learning problems in schizophrenia (5).
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Parkinson's disease: Monkeys are given a nerve poison to cause damage to neurons and to produce symptoms something like the human disease (6).
Alzheimer's disease: The damage caused by inserting a needle into part of the rat's brain has been used as a model for changes seen in human patients (7).
There is a "mouse model" of cystic fibrosis. However, this specially bred mouse doesn't get the airway disease which causes most of the sickness and death in human CF sufferers (9). A model that misses the most important aspect of a disease can't be a very good model!
There are more humane and more accurate ways of doing research.
Non-animal methods
Valuable research can be done without using animals. Methods include:
- body scans using new technology such as MIR or PET imaging;
- human tissues, either normal or diseased;
- studies with human volunteers;
- micro-organisms to test for dangerous chemicals;
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computers to store information on alternatives, or predict toxic effects.
Body scans
With new technology researchers can see inside human bodies without surgery. This opportunity allows them to study the activity of the brain and other organs in both healthy and diseased individuals.
PET (Positron emission tomography)
Small radioactive isotopes are tagged to molecules such as glucose, or a drug that is being studied. The molecules are then injected into a human. The isotopes are absorbed by the most active cells, where they produce high energy gamma rays. A computer records these emissions and constructs them into a coloured picture (10).The following are just a few examples of how PET has been used to gain knowledge about the human body.
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Brain function:
PET can be used to study which areas of the brain are involved in normal events such as vision or speech processing. It has also been used to investigate the areas of the brain involved in different anxiety disorders (11), and in the experience of pain (12). It can be used to study changes in the brain due to disorders such as schizophrenia (13), and it can monitor neuronal damage caused by strokes (14).
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Degenerative brain disorders:
PET can monitor changes in the brain of people with Parkinson's or Alzheimer's disease (15-16). It can also demonstrate the effect of treatment, such as electrical stimulation in the case of Parkinson's (17).
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Cardiovascular system:
PET can be used to study the function of the heart, for example, the blood flow and glucose uptake in heart muscle of people with diabetes (18). The effects of various chemicals, such as insulin, on blood flow through skeletal muscles can also be investigated (19).
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Other organs:
PET can be used to study normal physiology and diseases in organs such as the pancreas (20).
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Tumours:
PET can be used to monitor the development of tumours and their response to treatment. It can show how well drugs are absorbed into tumours (21).
- Drug research: PET can be used to show how a drug is distributed in the body, for example, to what extent it crosses from the blood vessels into the brain. It can also examine why some people respond better to some drugs than others (22).
MRI (Magnetic resonance imaging)
The human volunteer lies in a chamber with a huge magnet. The body is surrounded by a strong magnetic field and radio waves, which cause hydrogen molecules to spin. A computer records the energy released by the hydrogen molecules and constructs a picture.Since most of the hydrogen in the body is in water molecules, MRI distinguishes different body tissues on the basis of their water content. For example, it can distinguish between white and grey matter in the brain. It can effectively show nerve fibres in the spinal column, tumours, and changes due to degenerative diseases (10).
The following are just a few examples of how MRI has been used to gain knowledge about the human body.
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Brain function:
MRI can be used to study the normal functioning of the brain, for example, locating areas where visual stimuli are processed. It is also useful to discover how various abnormalities affect the brain, for example, epilepsy (23), schizophrenia (24), AIDS-dementia (25), and alcohol abuse (26).
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Cardiovascular system:
MRI can be used to examine artery walls for the development of atherosclerosis (27), or changes to the structure and function of the heart immediately after a heart attack (28).
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Drug research:
MIR can be used to assess the effect of different drugs or different doses of the same drug, for example the effect of different blood pressure drugs on the left ventricle of the heart (29), or the effect of different doses of a leukemia drug on damage to the bones (30).
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Tumours:
MRI can be used to monitor the growth rate of tumours, to decide when drugs should be given, and to assess their effectiveness (31).
- Arthritis: MRI can be used to detect early inflammatory disease in joints, and to assess the effectiveness of anti-rheumatic drugs (32-33).
Electroencephalography (EEG) and Magnetoencephalography (MEG)
Both these methods take measurements through up to 100 electrodes attached to the outside of the scalp. Both record brain activity, the EEG by measuring the electrical fields produced by brain neurons, the MEG by measuring magnetic fields generated by these neurons. These techniques detect changes in brain activity almost instantly. The equipment is relatively simple, and volunteers can walk around while measure-ments are being taken. However, the EEG and MEG recording don't show exactly where in the brain activity is going on, so they are best combined with MR images which link activity to very specific areas (34-35).EEG and MEG can be used to investigate brain activity during normal events like reading, looking at a picture or mental arithmetic (36). These methods can show the link between brain activity and muscle control (37), as well as the link between brain activity and painful stimulation (38). MEG has also been used to study differences in brain activity due to disorders such as epilepsy and schizophrenia (39-40).
Human tissues
Human tissues for research are available from:
- volunteers, for example blood samples;
- hospitals, for example operations for tumours in all organs, varicose veins, circumcisions and plastic surgery, epilepsy, as well as placentas after child birth;
- autopsies when people donate their body to medical science after death.
There are now a few organisations that make it easier for researchers to get human tissue. In the USA, the National Disease Research Interchange in Philadelphia collects tissues removed during operations and from donors, and distributes them to researchers (look at About Us and Our Mission and History in the NDRI web site).
In the UK, the University of Leicester is doing the same. They use organs that are not suitable for transplantation and would otherwise be destroyed.
The Cooperative Human Tissue Network within the National Cancer Institute in the USA has a human tissue network to distribute a wide range of cancer tissue for research. In their first 9 years they distributed 100,000 tissue samples to 600 researchers.
There are companies that market cell lines from normal tissues and from tumours. For example, the American Type Culture Collection has available over 2300 animal and human cell lines. The European Human Cell Bank has 500 cell lines from families with genetic and chromosome abnormalities.
Companies such as Clonetics market cell cultures derived from human skin, cardiovascular system, brain, respiratory system, kidneys and muscles.
Our document Toxicity testing shows how human cells from all the major tissues can be used to test toxic effects of chemicals.
Our document Drug Testing shows how human tumours are being used to test cancer drugs. Liver cells are used to investigate how drugs are broken down in the body. Liver cells and white blood cells are used to develop treatments for infections such as hepatitis and AIDS.
The following are just a few more examples of how human tissue can be used in research.
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Arteries and veins:
Veins can be obtained from autopsies, coronary artery by-pass grafts
or varicose veins. These veins are useful for investigating vascular
pharmacology (41), for example, to examine the effect of natural blood
vessel constricting substances (42).
Arteries from the brain are obtained from autopsies. They have been used to study spasms which narrow the artery and can cause strokes. Human arteries are a more accurate model than animals, not only because of species differences, but also because tissue can be taken from people with diseased arteries, the very people that treatment is aimed at (43).
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Heart tissue:
Hearts either from autopsies or removed during transplant operations
are very useful to compare healthy and diseases hearts. It is important
to test treatments on diseased hearts, because they do not respond in
the same way as healthy hearts (44-45). Human hearts have been used to
investigate why people who take drugs to lower blood sugar have more
heart problems (46).
- Brain tissue: Tissue from the brain can be obtained from operations for intractable epilepsy or tumours. Such tissue can be used to study the normal function of neurotransmitters (47), the response of cells to oxygen deprivation (48), and biochemical differences in various parts of the brains of epileptics (49).
Human studies
Factors which have a positive or negative effect on health can be studied in living humans. In one kind of study, large groups of people are monitored over a period of time to answer questions such as:
- Do women who use hormone replacement after menopause have a higher rate of breast cancer?
- Do vegetarians have fewer heart attacks than meat eaters?
- Do children who live near the electromagnetic fields of large power lines have a higher rate of leukemia?
Human volunteers can be involved in a variety of experiments for which animals are still being used, such as learning and memory, or the effects of different diets on blood pressure and cholesterol.
People receiving treatment for diseases can be involved in experiments and information gathering. For example, patients receiving treatment for stroke were asked about their alcohol consumption. This information was linked to characteristics of their blood to understand more about risk factors in stroke (50).
People receiving treatment for mature-onset diabetes and high blood pressure have been involved in experiments to see if changes in diet could reverse their disease (51).
Some people have been in contact with the AIDS virus but have not become infected. Researchers have studied these individuals and found that they have a mutation in a particular gene, which prevents infection. The effect of this gene could provide a clue to protecting people who don't have the mutated gene (52).
Genetic research is important in trying to understand the causes of other diseases. For example, particular gene mutations have been found in families with hereditary Parkinson's and Alzheimer's disease (53-54). By looking at what these defective genes do, researchers can work on developing treatments to counteract their effects.
The study of humans after death provides invaluable information. In this way it is possible to understand the damage caused in the brain by diseases such as Alzheimer's, Parkinson's and Huntington's (55).
Many people affected by a disorder would be willing to help researchers understand their problem. A person affected by a birth defect, and arguing against animal experiments, has said:
" And while the cats and rats are not so happy to volunteer for these experiments, every person I know who is affected by birth defects, including me, is only too eager to help tease apart why something happens in some cases and not in others " (56).Micro-organisms
Our document Tests for chemicals that cause cancer or birth defects shows how useful Salmonella bacteria (Ames test) are for detecting cancer-causing chemicals. It also shows how the hydra, another minute organism, responds to chemicals like thalidomide that cause birth defects.
Bacteria called Photobacterium phosphoreum, emit light as part of their normal metabolism. When the bacteria come into contact with a toxic chemical, the amount of light emitted decreases in proportion to how toxic the chemical is. These organisms are commercially available under the trade names Biotox(TM) and Microtox(TM). They are particularly useful to test industrial effluents and waste water (57).
Bacteria have been genetically engineered to make products for which animals were previously used. By inserting a human gene into bacteria, they have been engineered to produce human insulin, growth hormone and monoclonal antibodies.
Computers
Computer databases are very useful to make information about alternative methods more easily available. For example:
- NORINA database lists over 3500 alternatives to animals in education. You can search NORINA on the internet.
- ZEBET Data Bank was set up in Germany to describe alternative methods of research. It now lists over 300 methods.
- INVITTOX database lists methods in toxicology, including technical information on in vitro techniques, their performance and applications (58). You can see 10 examples from this database at the Warsaw Medical School web site.
- GALILEO database lists results of toxicology tests on a wide range of chemicals, so that researchers can compare results from different in vitro tests (59).
Computers have also been used to predict the effects of new chemicals. Our documents Skin and Eye Irritancy and Cancer and Birth Defects show how systems such as COMPACT, Hazardexpert and DEREK have been used to predict the likely irritancy or cancer-causing potential of chemicals.
Computers are now being used to design new drugs in what is known as "rational drug design". The computer designs molecules to fit particular receptors in the body. (See our document Drug Testing for more details). I would like to see References for this document on research without animals.
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Brain function:
PET can be used to study which areas of the brain are involved in normal events such as vision or speech processing. It has also been used to investigate the areas of the brain involved in different anxiety disorders (11), and in the experience of pain (12). It can be used to study changes in the brain due to disorders such as schizophrenia (13), and it can monitor neuronal damage caused by strokes (14).