Alternatives – “Before the bar of human justice, vivisection stands condemned on three main counts: cruelty to animals, uselessness to Man, and obstruction on the path of true knowledge.”
Dr. M. Beddow Baily, M.D., IRCP, Member, Royal College of Surgeons.1
In 1959 two British scientists, Russell and Burch, developed the concept of the three Rs: Reduction (scientists should reduce the number of animals used in experiments);
Refinement (scientists should minimise pain and distress to animals by modifying their experiments) and Replacement (there should be the replacement of all experiments on animals through the use of suitable non-animal methods).
Even though it has been many years since Russell and Burch developed this concept, it has only been in recent years that major progress has been made in the field of alternatives research.
Their development is particularly important as alternative methods are not only more humane but can in fact be more reliable than animal tests.
In 1986 two forms of legislation were passed that in theory promoted the concept of the 3 Rs, the Animals (Scientific Procedures) Act 1986 and the 86/609/EEC Directive (binding in all E.U countries).
However, despite it being a legal requirement under these laws for scientists to find non-animal alternatives, in practice they are reluctant to do so.
The research establishment views animal based tests as ‘traditional’ and prefers to maintain the status quo, despite its obvious flaws, rather than embrace the more humane and scientifically credible technology of non-animal science.
At the time of the 1986 Act, the then government claimed that “the reduction in the number of animals used and the reduction of suffering is at the heart of the Bill”,
and yet over a decade passed and a change in Government before the UK banned animal testing for cosmetics, arguably the most trivial and indefensible use of research animals.
Resistance to change amongst the majority of researchers and a lack of serious commitment from government, means that the development and implementation of alternatives is an extremely low priority.
The amount of money the government dedicates to alternatives is miniscule when compared with that invested in animal research.
Whilst millions of pounds is pumped into animal testing, the UK government set aside a mere £259,000 during 1998-1999 for research into the 3 Rs.
Yet even where refinements and alternatives already exist, ineffective monitoring and implementation frequently mean that researchers continue to ignore them without fear of reprimand.
In 1999 the BUAV threatened to legally challenge the UK government on a point of principle for continuing to issue licences for the infamous LD50 test when three other validated methods of determining the acute toxicity of a substance (using less animals) were already available.
Although the BUAV does not accept refinements as alternatives to animal research, the fact that the Home Office continued to allow scientists to ignore these refinement methods was a clear breach of both UK and E.U law, and made a mockery of provisions under the 1986 Act.
In November 1999 the government finally admitted that the BUAV’s interpretation of the law was correct, leading to the end of issuing licences for the LD50 (toxicity) test.
However, this example clearly demonstrates the level of resistance within industry and government to alternative methods of research.
Another major obstacle is presented by the regulatory authorities.
Before a non-animal method can be used as a full replacement to an animal experiment, it must go through a ‘validation’ process.
(This is despite the fact that, in their development, animal experiments were never subjected to such a rigorous validation procedure.)
Validation requires that the non-animal method must be tested against the equivalent animal test it is intended to replace.
However, as one of the main scientific arguments against animal testing is that it is inaccurate, how can a potentially useful and scientifically accurate alternative be accepted if it must compare to a test that is experimentally flawed?
Data from animal experiments are simply not sufficiently scientifically robust to be used as a benchmark for the development of alternative methods. Instead, for real progress to be made the scientific community urgently needs to adopt a total change of attitude.
Rather than remaining stuck in the science of the past it must refocus its efforts on the technology of the future.
Following are a few examples of the range of non-animal methods that could end the use of dogs and other animals in experiments.
This particular range concentrates on the areas of research where dogs are more commonly used such as toxicity and cardiovascular experiments.
The use of human cell and tissue cultures has produced a range of alternatives for toxicity testing and biomedical research.
Human cells or tissues are taken from cadavers or following surgery via biopsies or excisions, and are kept in nutrient fluid to help them grow in vitro (in the test tube).
Only one cell can produce numerous cultures and therefore provides a more economical as well as biologically relevant and humane alternative.
Scientists can use a battery of 5 integrated cell culture techniques to test the toxicity of a substance.
By combining the information they can assess how that substance would affect the whole body.
This system, called the EDIT Program, is currently being developed in Sweden using human cultures.
In vitro tests can also be used to investigate target organ toxicity.
A human corneal epithelial cell line has been developed to produce a model of the human cornea (the front of the eye).
Primary cultures of human corneal epithelial cells are transferred to produce the HCE-T cell line.
The HCE-T cells are cultured on membrane inserts to produce a 4-6 layer epithelium.
This can be used to assess the toxic effects of chemicals on barrier function.
In vitro methods are also already available to study the toxicity of the lens and retina.
A combination of two other in vitro methods, the FRAME fluorascein leakage test (FL test) and the Alamar BlueTM assay can be used to establish the potential ability of chemicals to cause toxicity.
In vitro methods can also be used to study the effects of chemicals on electrical and mechanical activity of the heart, coronary perfusion, potassium channels & myocardium.
Artificial organs and systems
Artificial systems are a major breakthrough. A group of scientists in the Netherlands has developed the ‘Techno-tum’ or artificial gut to mimic the action of the gut to study absorption of chemicals.
Another example is the ‘POP Trainer’ consisting of artificial organs with a simulated blood supply.
The development of these systems could play a major part in replacing the use of animals, particularly dogs, in experiments.
Computer and mathematical models
Predicting toxicity from the molecular structure of drugs is now possible with sophisticated computer software that analyses structure-activity relationships (SARs).
This works on the understanding that chemical activities, for example unwanted toxic effects or desirable therapeutic effects, are dependent on molecular structure.
In fact, the chemicals involved in the triple AIDS therapy were developed through the use of computers which analysed the viral enzyme and predicted the kinds of chemicals that would block its action.
Furthermore, such chemicals (which have now been proved safe in humans and beneficial treatment for AIDS patients) were initially delayed by the pharmaceutical industry, as they were harmful to dogs.2
Physiologically based pharmacokinetic models (PBPK models) are already used to predict absorption, distribution, metabolism & excretion (ADME) of compounds per species / per route of exposure, and mathematical models are also currently being developed to simulate heart function.
Oxford scientists are currently using computer models capable of reconstructing heart rhythms to explore how heart attacks might be prevented.
3 Running on Europe’s largest supercomputer, the models comprise 30 million equations and over one million virtual cells and behave almost exactly like a living human heart.…