Using of Animals in Research:Ethics and Alternatives

By

Prof. Dr. Rabie Hassan FayedAnimal Behaviour & Management

Faculty of Vet. Medicine, Cairo UniversityGeneral Secretary of Egyptian Federation for Animal

Welfare (EFAW)rhfayed@cu.edu.eg

Uses of Animals

Animals are used in research or experimentation in place of human subjects for various reasons..

Animals are used most often in the following cases:• Disease Treatment• Prevention• Treatment of Injuries• Basic Medical Testing• Medical Diagnosis

Animals in Research

VaccinationsAnesthesiaAntibioticsNumerous medical treatments for various diseases

Today there exists a wide spectrum of views on this subject, ranging from those concerned with animal 'rights' to those who view animals only as a resource to be exploited.

All of these viewpoints have contributed to the development of ethical principles of animal use.

Ethics

is a term used to describe human-animal relationships and how animals ought to be managed and treated.

The subject matter includes  animal rights,  animal welfare,  animal law,   animal cognition,  wildlife conservation, the moral status of nonhuman animals, And the history of animal use

Animal ethics

Animal Rights

Right and Ethics Animal Suffering

The five freedoms were originally developed from a UK Government report on livestock husbandry in 1965 (Prof.Roger Brambell) then by Farm Animal Welfare Council (FAWC) In July 1979

Five Freedoms (Brambell's five freedoms)

Freedom from hunger or thirst by ready access to fresh water and a diet to maintain full health and vigour .

Freedom from discomfort by providing an appropriate environment including shelter and a comfortable resting area .

Freedom from pain, injury or disease by prevention or rapid diagnosis and treatment.

Five Freedoms

Freedom to express (most) normal behaviour by providing sufficient space, proper facilities and company of the animal's own kind.

Freedom from fear and distress by ensuring conditions and treatment which avoid mental suffering.

Five Freedoms

Five Freedoms

Animal experiments are widely used to develop new medicines and to test the safety of other products.

Many of these experiments cause pain to the animals reduce their quality of life in other ways.

If it is morally wrong to cause animals to suffer from experimenting on them.

Animal experimentation

Facts About Animal Research

85 % of the animals used in research are rodents - rats and mice that have been bred for laboratory useMost laboratory tests on animals are simple single type tests - change in diet, drawing a simple blood sample, administering a drugAnimals are given anesthetics if a procedure is going to be invasive in any way

Dogs, cats and non-human primates account for only 3 out of 1000 subjects in experimentation

Humans are still the largest group that is used for research and experimentation and beats out all other lab animals when it comes to testing.

Cont.

In favour of animal experiment Experimenting on animals is acceptable if

(and only if): suffering is minimized in all experiments

human benefits are gained which could not be obtained by using other methods

Two positions on animal experiments

Experimenting on animals is always unacceptable because: it causes suffering to animals.the benefits to human beings are not proven.

any benefits to human beings that animal testing does provide could be produced in other ways.

Against animal experiments

Alternatives

The three Rs

The three Rs are encouraged to follow in order to reduce the impact of research on animals The three Rs are:

Replacement. Reduction, Refinement,

means replacing 'higher' animals with 'lower' animals. Microorganisms, plants, eggs, reptiles, amphibians, and invertebrates may be used in some studies to replace warm-blooded animals.

Alternately, live animals may be replaced with non-animal models, such as ◦ dummies for an introduction to dissection for

teaching the structure of the animal or the human body,

◦ mechanical or computer models, audiovisual aids, or in vitro modeling.

Replacement

Replacing experiments on animals with alternative techniques such as: Experimenting on cell cultures instead of whole animals

Using computer modelsStudying human volunteersUsing epidemiological studies

1-Replacement

An alternative method should not require any animal-derived biological material. Examples of such methods or approaches include The use of predictions based on the physical and

chemical properties of molecules. Mathematical and computer studies of biological

processes (Simulation and Virtual Reality). Analysis of epidemiological data. research involving human participants . or research on isolated human cells and tissues in

culture .

complete replacement

However, many methods considered as Replacements also use some biological material obtained from living or humanely killed animals as research on cells and tissues derived from living or humanely killed animals for culture in vitro and animal-derived growth supplements such as serum derived from fetal or newborn calves. These methods can be called incomplete replacement

Incomplete replacement

Advantages of replacement

• Utilizing pre-existing knowledge for teaching.

• Applying known principles to new systems to look for similarities.

• Using less expensive animals or models to screen large numbers of agents for toxicity or mutagenicity.

chiefly stem from the fact that any models are dependent on pre-existing information.

In a system as complex as a live organism, all of the variables in physiology and pathology are not known.

Thus, any research on new biological processes must utilize a living organism at some point.

Disadvantages of replacement

means minimizing the number of animals needed to perform an experiment or teach a concept. By examining these parameters, the IACUC can determine if thoughtful experimental design was employed to minimize overall animal use.

2-Reduction

Cont.

Reducing the number of animals used in experiments by: • Improving experimental techniques• Improving techniques of data

analysis• Sharing information with other

researchers

Consulting with a statistician to use only the numbers of animals required to achieve significance.

Minimizing variables such as disease, stress, diet, genetics, etc., that may affect experimental results.

Cont.

Cont.

• Performing appropriate literature searches and consulting with colleagues to ensure that experiments are not duplicated.

• Using the appropriate species of animal so that useful data is collected.

• Replacement whenever possible.

means refining experimental protocols to minimize pain or distress Using a Protocol Form. Examples of refinement include: Identifying pain and distress and making

plans for preventing or relieving it.Receiving adequate training prior to performing a procedure.

Using proper handling techniques for animals.

3-Refinement

Refining the experiment or the way the animals are cared for so as to reduce their suffering by: Using less invasive techniquesBetter medical careBetter living conditions

Refinement

Causes of Pain or distress 

Repeated use of, large volumes of, or intradermal injections of Freunds complete adjuvant.

Intra-peritoneal implantation of ascites-producing hybridomas for monoclonal antibody production.

Prolonged (greater than 1 hour) physical restraint.

Malignant neoplasms. Prolonged food or water restriction. Distal tail biopsy in animals over 3 weeks of age (tail snipping).

Electrical shock or other adverse stimuli that are not immediately escapable.

Paralysis or immobility in a conscious animal.

Cont.

Inflammatory disease.Organ failure resulting in clinical signs.

Non-healing skin lesions.Whole body irradiation at high doses.

Withdrawal of more than 10% of an animal's blood volume.

Cont.

Studies that require the animal to reach a moribund state or die spontaneously as the endpoint of the study.  The earliest endpoint possible should be used to prevent pain or distress.

Prevention of pain

Cont.

Ensuring that drug doses are correct and that the drugs used are not expired.Ensuring that procedures to be performed on the animal are reasonable for that species.Using appropriate anesthetics and analgesics for potentially painful procedures.

Performing surgeries and procedures aseptically to prevent infection.

Performing only a single major survival surgery on any one animal, whenever possible.

Performing appropriate post-surgical care, including thermoregulation and fluid balance.

Cont.

The majority of animals are killed at the end of the experiment, either because their tissues are required as part of the experiment, or because the scientific objectives have been achieved and the animal can no longer be used. If the experiment leads to an increasing amount of suffering during its course then it is best for the animals to be killed as early as possible. This approach is described as operating ‘humane endpoints’

Refining endpoints

Cont.

Setting the earliest possible endpoint for the experiment. That is, if the necessary information can be gathered before the animal experiences any ill effects from the experiment, this should be defined as the endpoint and the animal subsequently euthanized.

If measuring toxicity of a compound or survival following implantation of a neoplasm, a pilot study may determine that once certain clinical signs are seen, or a tumor achieves a certain size, the time course until debilitation or death are predictable. Subsequent experiments may then utilize the earlier endpoint of tumor size or clinical signs of toxicity, rather than death as the endpoint.

Example 1

If it is known that particular clinical signs such as decreased body temperature lead to a specific outcome such as death, then animals can be killed as soon as these signs appear. Other markers that can be used to define humane endpoints include flank twitching and chemical and haematological changes in the blood

Example 2

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