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Animal research: In search of options
Dr Waman V Lawate | Thursday, November 27, 2008, 08:00 Hrs  [IST]

The use of animals for research purposes has a long history and has been a subject of many articles and books, both in defence and in opposition, over the past 150 years or so.

Different animals are continued to be used on a large scale for medical research and training. Animal studies generally come under three categories. They are:
● Biomedical and behavioural research
● Education
● Drug and product testing

Animals as research objects
To a certain extent, animals are like children and dependant upon our husbandry for welfare. As such, animals occupy a special relationship with humans. This is primarily the position with pet animals. An experimental animal under use is not a volunteer. Also, animals do not have any option of consent as their human counterparts do. Hence, they are basically helpless victims.

Most critical breakthroughs in research are based on multiple, fundamental studies carried out on experimental animals for which there are no appropriate alternatives.

How does one determine if animal experimentation has been productive and justified? One criterion often quoted is the relationship between animal research and the Nobel Prize, which is generally considered to be an index of scientific significance. Since 1901, approximately 75 per cent of Nobel Prize awarded in physiology or medicine has been for discoveries and progress made through the use of experimental animals.
Alternate methodologies

In recent years, alternative methods of biomedical research and safety evaluation of chemical and compounds have come under increasing scrutiny. The development represents the convergence of several factors such as:
● Accelerating development in basic biologic methodology and understanding, especially in vitro
● Increasing realisation of the wastefulness of such tests as the classic LD50
● Increasing insistence from the public and animal rights groups that new understandings and methodologies be pressed into service of reducing animal use and alleviating animal suffering

The US FDA is no more asking results of conventional animal toxicity for new drug approval. Instead, Environmental Protection Agency (EPA) has developed a test which depends on the 'limit' test using fewer animals (4 to 10 vs. 30 to 100) to screen toxicity.

Animal rights organisations are successfully changing the product testing protocols in some industries. Of particular note has been their effectiveness in the cosmetic industry.

Three 'R's
Most research organisations and scientist follow a practice known as the "three Rs" - which stand for replacement, reduction and refinement in alternatives. A book has been published in 1959 entitled "The principles of Human Experimental Techniques" by Russel and Burch. They wrote that scientific excellence and humane use of laboratory animals are inextricably linked. The scientific basis for the three Rs has been endorsed and reaffirmed in the 1980s and 1990s by numerous national and international agencies and scientific societies.

Replacement
Replacement alternatives are methods that use organisms with certain sensitivity or that which do not use whole animals. They include improved information exchange to avoid unnecessary repetition of animal experiments. Some of the replacement alternatives are physicochemical techniques and structure-activity relations, mathematical and computer models, use of invertebrates, plants and micro organisms, in vitro methods and human studies, including the use of human volunteers, post marketing surveys and epidemiology. In the biomedical sciences, in vitro methods are being used increasingly not only because they provide precisely the some information as do animal studies, but also they offer the most scientific approach. Unfortunately for most basic researchers, replacement is problematic. Alternative methods such as tissue culture systems simply cannot approximate the complexity of whole animals, especially in areas of neuroscience and behaviour. Neuroscientist point out that one cannot study learning and memory, or the effects of stress, except in a fully functional animal.

Reduction
This refers to areas where the number of animals used can be reduced. For example, the number of animals used in acute toxicity testing is being reduced as scientists have discovered ways to obtain accurate toxicity data using fewer animals. In addition, scientists can now screen for the binding of some potential drugs by using isolated receptor preparations rather than using hundreds of animals.

Refinement
Refinement alternatives are methods that eliminate or minimise pain and enhance animal well being. Assessment of animal pain and distress are currently based on subjective evaluators of abnormal behaviour or appearance. Because proper evaluation of pain relies largely on the ability to understand the behaviour and needs of each species of laboratory animal, it is presumed by investigators that a procedure that inflicts pain and distress in humans will do the same in animals. Much pain and distress can be diminished or eliminated with the proper use of anaesthetics and analgesics. Researchers can enhance animal wellbeing by using environmental enrichment techniques such as proper handling, appropriately sized cages and group housing of social species

Other alternatives
Other alternatives most commonly employed in biomedicine include cell, tissue and organ cultures, computing modelling and the use of minimally invasive procedure that produce less stress while more toxicological research is being carried out in vitro, the hazard assessment is only in the early stages of development. Because of the improved cell culture techniques, experimental models have been developed to assess the important biological characteristics such as:
● Membrane permeability
● Active and passive transport of ions and other compounds through the membrane
● Cellular respiration and energy metabolism
● Integrity of the cytoskeleton
● Growth inhibition and cell viability
● Inhibition of cell-cycle controlling factors
● Measurement of macromolecular synthesis (DNA, RNA and proteins)
● Changes in cell morphology
● Release of mediators
● Release of specific proteins
● Release or uptake of dyes or radioactive markers
● ATP levels

Scientists have been, and are searching continuously for alternative methods to animal use in biomedical and behavioural research for a variety of reasons, including an interest in the welfare of animals and a concern for the increasing costs of purchasing and caring for animals. Further, alternative methods, when developed may be more efficient and effective research tools. While search continues, the chances that alternative method would completely replace animals in the foreseeable further are very little. Nevertheless, some industries, such as cosmetic industry are making significant strides. Similarly, in medical schools, the availability of new technological tools such as videos, computer and models and patient simulators are very useful. A significant development is that in cancer research, they now use 60 human tumour cell lines, from seven main areas - colon, lung, melanoma, kidney, ovary, brain and blood. This technique is working well and gives good results.

The magnitude of human experimentation worldwide is quiet substantial. Thousands of trials are being carried out. Each trial involves many volunteers who are the first to take experimental therapies facing certain risks. Yet, without human experiments, we would not know with any degree of certainty, whether potential new preventives such as vaccines, drugs and surgery, are safe. Even then, these therapies can prove toxic in many ways. In a long and continuing tradition some physicians have often chosen to become the first volunteers.

(The author is a technical consultant based in Mumbai.)

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