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With the creation of new animal protecting laws, the number of animals used in experiments has certainly decreased, however this total is still insignificant compared to the ratio of the immense increase in animals being brought in for experimentation. In an effort to further reduce experimental animal subjects, various alternatives have been constituted aimed at substituting animal models in drug, chemical and other forms of experimentation.
Over the past decade, the processing capacity and technology of computers have improved exponentially and are able to handle more intensive software and programming. Computers are considered to be an integral part in experimental laboratories to store large quantities of data and process them into an easily understandable form. Another great use of computers for researchers is the ability to generate various simulations to mimic and predict the effects of chemicals and drugs without the usage of animal models. The Structure Activity Relationship (SARs) computer programs have the ability to estimate the properties and biological activity of a selected chemical substance based on its molecular structure. The predicted activities include the carcinogenicity and mutagenicity of the tested chemical. Another popular computer software is the Computer Aided Drug Design (CADD) program which has the power to determine the receptor binding site for a selected drug molecule. The identification of the binding site enables researchers to establish which substances have no biological activity, hence avoiding using them which in turn saves a lot of time. Furthermore, using this program will enable the production of new drugs for specific binding sites, and finally animal testing is done to confirm the validity of the drugs. The two computer software (SARs and CADD) are cost-efficient, fast, and most importantly reduces the number of experimental animals being used, therefore the principals of the 3Rs by Russel and Burche are achieved.
Additionally, computers may be used to power intricate machinery like computed tomography (CT) scans and magnetic resonance imaging (MRI). These devices enable high imaging techniques which would give researchers information like the progression of a disease without any invasive surgery to the animals subjects. Normally, a few animals are required to be dissected or sacrificed in order to obtain the same results. Therefore, these modern machinery will decrease the animals used in experimentation dramatically as well as being able to uphold the Refinement principal by minimalizing the animal suffering while still obtaining the intended results.
The use of in vitro cell and tissue cultures provides an alternative to animal experimentation. Rather than using conventional in vivo studies which involves using the animal as a whole, this method takes advantage of the cells and tissues harvested from the skin, brain, kidney, and liver from an animal. The extracts would then be cultured and grown into fully functional test models which give similar cellular responses as animal models. An example of an application of this method would be in a Draize test where the irritancy and effects of chemicals were tested on the eyes of animals, commonly using rabbits as test subjects. This test is extremely painful and each animal only can be used once. Ke ping Xu and her colleagues cleverly cultured the bovine corneal organ and analyzed the toxicological effects of chemical irritancy in vitro, instead of using animal models. This culture method highlights the Reduction principal from the 3Rs as it manages to use an animal to its fullest potential in producing lots of experimental models. Therefore, wastage is prevented and less animals are used in the experimentation.
Instead of using animal cultures, the use of human cells gives a complementary alternative to animal experimentation, for disease and toxicology testing purposes. The genes of selected diseases are planted into embryonic stem cells which are later induced to transform into different human diseases tissues, and the tissues will be used for drug screening. The human tissues that are grown in the laboratory will provide a more accurate and similar impact profile to an actual human being during toxicological tests compared to the use of animals. Recently, scientists have managed to use the genes from a Parkinson’s patient to create an embryonic stem cell line which is used to study the degenerative symptoms of Parkinson’s disease. Animals are not the best model for reflecting a drug’s toxicity on the heart and liver. The human stem cell culture method not only provides more reliable results, but also eliminates the usage of any animals, as well as being cost-effective.
While humans can be used for their stem cells, they can also participate in a relatively new technique known as microdosing. Low doses of selected drugs are administered into a human subject and the metabolism data is obtained to study the effects of the drugs. The dose of the drugs is low enough to prevent any whole-body effects whilst high enough for the detection of cellular response. The ability of microdosing to screen out drugs that will likely fail is extremely accurate, fast and cheaper than conventional animal experimentation methods. It costs £0.25 million per drug tested and a period of 4-6 months for microdosing to take place.
The new legislations for animal experimentation have placed a tight restriction upon the methods used, in the best interest of the welfare of higher vertebrates like dogs, pigs, rats and cats. Many of these animals are known to exhibit a change in their behaviour and physiology like eating less food or the release of stress hormones in their bloodstream, when exposed to activities that are believed to cause pain. Also, the legislations in most countries only cater for live vertebrates and not for organisms from the lower phylogenetic orders. With all of this, it has been proposed that alternative organisms are to replace conventional experimental animals in experiments whenever possible.
Lower vertebrates are often considered to be an alternative as they share close genetic material to higher vertebrates like mammals. One example would be the use of the zebra fish. This fish is small, around 2-4cm in length so it can be stored easily. The main reason why this species is chosen from a whole range of fish is the transparent body is possess hence making it easier to observe the pheonotypc traits.
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