Scientific Purposes for WHich animals are used
Animals are used to understand human and animal biology, to mainain and improve human and/or animal health in welfare. THey are also used to improve animal management or production, for the achievement of educational ojectives and for environmental studies.
Some issues with these practices includehousing and management, procedures conducted on teh animals, and animals used by large companies to make drugs rom which the company can make large profits.
Animals Used in QUeensland for Scientific Purpose
Hundreds of thousands of animals are used or research and teaching purposes in thousands of separate scientific activities. In 2004, 36% of animals used were fish, 19% mice, 10% cattle, 4.7% sheep, 2.9% rats, rabbts or guinea pigs, 1.5% pigs and 8.2% others with no use of primates and a similar distribtion can be expected in other states.
Suppliers of Laboratory Animals
Institutions such as universities usually breed their own animals or sell to other institutions while veterinarians are employed to oversee health and welfare-usually with post-grad training in laboratory animal science. Major suppliers in AUstralia include Murdoch-Animal Resource Cenre, Mnoash University Animal services and University of Adelaide. Major (global) supliers include Carles River Laboratories, Harlan, The Jackson Laboratory (JAX) and B&K Universal Ltd.
Animal Prices
Prices vary depending on age, sex and geetic background. An 8 week old mous varies from $22 fo a standard strain o $80+ for a special strain while an 8 week old rate varies from $27 for a common strain to $140+ remembering to add cost of arifrieght and cost of specialised animal feed.
Other services provided include importations of a particular strain, serum or plasma from rats and mice, special requirements (such as aged, suckling, pregnant or conditioned), surgically modified animals or specially bred animals.
Species are chosen on a basi of convenience, availability, refinement and scientific suitability.
Congenic and Transgenic
congenic is a gnetic term that refers to specially bred strains of mice and rats that differ only in restrictedregions of the enome. Transgenic is an animal in which foreign gene(s) has been inserted ino thegenome. 'knockout' has specific modificatinos of a gene to obseve the physical manifestations of the genetic trait.
Animal Selection
- BALB/c mice: inbred albino mice that breed well, exhibit anxiety and male to male aggression, used in research for cancer, immunology, mammary gland tuumours dieth induced atherosclerosis and cardiovascular research.
- C57BL/6J: Black inbred mice and most widely used inbred strain throughout the wold and are used in immuniology, developmental biology, diabetes and obesity and cardiovascular biology.
- In group housed lab mic, barbering is a problem where they are frequently found with their whiskers and facial hair being removed.
- Mutant mice: these are mice that have natural, random or targeted mutations such as nude mic which have an autosomal recessive mutation on chromosome 11-only homozygous mutants exhibit nu phenotype.
- knockout mice: coat colour can be used to genotype the mice. knockout mie can be used to study the effects of the gene on physiology (mice with deletion of LDL receptors ave increased atherosclerosis)
- Sprague-Dawley Rat: most wildely used outbred ra in animal research, albino with docile disposition and good reproductive performance and meternal characteristic. Laboratory rats serve as important animal models for psychology an medicine reserach.
- Wistar rat: outbred white rat with redeyes, originated from the WIstar institue, docile and a good breeder. It is used in research requiring vigorous breding and economically piced animals. Often is useed in biological assays or preliminary studies prior to detailed studies using inbred strains.
- hooded wistar rat: outbred, white with black hood and black patches on teh body, good breeder.
- golden syrian hamsters: goo reproductive preformance, used for research in tozicology, carcinogenesis and behaviour studies.
- mongolian gerbils: docil, litter average 4.5, research use in cancer, nurition and toxicology.
- guinea pigs: originated in South America, used in experimentssince 1780, docile, mostlab strains descended from the dunkin Hartley Strain, long gestation period with average litter 4, require a large amount of vitamin C in diet and not used widely anymore.
- Rabbits: not used as widely as before, research uses include eye research (crneal damange) inflammation (ears) but mostly used for antibody production. Common strain is the New Zealand White.
- beagles: used mainly in teh USA and UK, research use includes canine nutrition, canine vaccine testing, canine pharmaceuticals and cardiovascular disease.
- Primates: primates used in research are mostly marmosets and macaques. THey enjoy rich social lives and complex mental abilities (which raises the question if they have greater potential for suffering in the laboratory) great Apes (gorila, chimps, baboon) have even greater mental abilities and the use of Great Apes has been banned in the UK in 1997 and now in the EU. Their use in AUstralia is only in very specialised lab with strict ethical health and physical requirements. Marmests are bred wel in captive colonies and rae relatively easy to handle an areused for reproductive and behavioural research. Macaques are usedforvaccine, HIV research and neurological research.
Uses of Laboratory Animals
The most common use is in fundamental researchin biology or medicine to study relationships between the processes that take place in the body or the causes of disease including physiology and animal behaviour. THe second largest area of animal use is applied research whic is the study of the processes of life, prevention/treetment of disease and factors related to health and disease and is used for bot veterinary and human medicine. Animals are also used for production and quality control of human and veterinary medicines (eg. testing polio vaccine on monkeys) as well as making medicines from living organisms or their products. Animals are also used for toxicology and cosmetics testing which is now banned in most countres-includnig Australia. As well as diagnosis of disease and education and raining.
Arguments for and Against Animal testing
- For: speciesism is morally right, utilitarianism (benefits to humans outweigh the costs to animals)
- against: animal suffering is not worth the benefits, role of animal research is exaggerated, role of clinical research, animal experiments can be misleading. adverse effects of animal testing on human health immoral and money can be better spent elsewhere.
• Viral disease that paralyses children, sometimes fatal
• Vaccine research used 1 million Rhesus monkeys, mostly from India
• Results from clinical research may have changed course of vaccine development
Welfare issues 1: Sources of animals
• Animals bred specifically for research – Adapted to laboratory conditions
• Wild-caught animals – Stressful – Endangered species
• Use of stray animals from pounds or animal shelters
Welfare issues 2: Housing of animals
• Animals spend much of their time in housing, so housing is important
• Often provided with physical needs – food, water and disease prevention – Five Freedoms?
Welfare issues 2: Housing of animals
• Barren environments – Boredom; stress
• ‘Environmental enrichment’ – Provision of a stimulating environment, which improves the animal’s welfare – Social stress? – Hygiene?
• Type of caging – Impervious surfaces with minimal angles/corners to:
• Reduce accumulation of dirt, debris and moisture
• Facilitate cleaning
• Number of animals per cage
– Enough space to turn around and express normal postural adjustment
– Unobstructed area to move around and rest
– Social animals should be housed in groups provided this is not contraindicated by the protocol in question and does not pose risk to the animals
Welfare issues 3: Procedures
• Pain in laboratory animals is historically poorly recognised and treated
• Different species show different behaviours – animals are not little humans
• Pain can produce undesirable changes
• Analgesia and anaesthesia can reduce pain – especially if given before pain starts
• Pain scores can help to measure pain
• Not all procedures are painful – For example, minor procedures or anaesthetisation
• However, some painful procedures may be seen as ‘minor’ as they are simple or common – Blood sampling by cutting off the tail tip – Routine I.D. by punching holes through ears
Welfare issues 4: Euthanasia
• Euthanasia happens as ‘humane endpoint’, end of trial, or integral to experiment •
Ideal: – Non-painful – Time to unconsciousness and death short – Reliable and non-reversible – Minimal psychological stress to animals – Safe for operator – Death must be confirmed
• Methods: injection, inhalation, physical
New frontiers: Genetic engineering
• Number of genetically engineered animals is growing fast in scientific research
• Includes manipulating genes within or between species to produce ‘transgenic’ animals
• Increasing number of possible commercial applications in animals
Animal applications of genetic engineering
• ‘Bio reactors’: Production of therapeutic proteins in milk
• Livestock/agriculture
• Transgenic animals as models of human diseases – ‘Oncomouse’ (patented)
• Xenotransplantation: Production of compatible organs for transplantation into humans – see later slide
- Two methods of producing transgenic mice
- Embryonic stem cell method
- The pronucleus method
Alternatives: the 3 Rs
• Experiments as ‘necessary evil’
• ‘The Principles of Humane Experimental Technique’ (Russell & Burch, 1959)
• 3Rs: Replacement, Reduction and Refinement
• Research without animals covers almost every scientific discipline
Research without animals
• Cell, tissue and organ cultures – Big advancements in in-vitro work
• Biotechnological research – Human genome project – Testing chemicals in-vitro
• Computer and mathematical models – Study mechanisms of drugs – Predicting effects
• Epidemiological studies – Studies disease in populations – patterns/causes
• Clinical research
• Human volunteers – Drugs – Psychology – MRI/PET scans
• Non-invasive
Replacement
• The replacement of sentient animals with non-living or non-sentient alternatives (Russell & Burch, 1992)
• Broadening definition to include ‘any approach in scientific research, product testing, and other technical procedures in which no animals are used’ has been proposed
Reduction
• The reduction in the numbers of animals used to the minimum necessary to achieve the desired objective – Pooling resources – Appropriate statistics – Avoid (unnecessary) repetition – Questions to ask before embarking on project using animals
Refinement
• Refinement of the care and techniques used to minimise the risks of harm and to welfare (i.e. to reduce suffering) – Suffering includes pain and other adverse experiences – Importance of housing conditions – Good welfare = Good science – Use of anaesthesia and analgesia – Humane endpoints
Animals used for scientific purposes in Australia
• In Australia, no person can use an animal for scientific purposes (includes teaching purposes) unless a written proposal has been submitted to and written approval received from an Animal Ethics Committee
• All institutions using animals for scientific purposes must have one or several Animal Ethics Committees
4th R of research?
• Responsibility – To ensure the 3 R’s are taking place
Animal Ethics Committee membership in Australia
• Comprise at least four persons
• Category A – a person with qualifications in veterinary science, with experience relevant to the activities of the institution or in special circumstances, a person with qualifications and experience to provide comparable expertise
• Category B – a person with substantial recent experience in the use of animals in scientific or teaching activities
Animal Ethics Committee membership in Australia
• Category C – a person with demonstrable commitment to, and established experience in, furthering the welfare of animals, who is not employed by or otherwise associated with the institution and who is not involved in the care and use of animals for scientific purposes. The person should be nominated by an animal welfare organisation
• Category D – an independent person who does not currently and has not previously conducted scientific or teaching activities using animals and who is not employee of the institution
Terms of reference of the Animal Ethics Committee in Australia
• Enforced self-regulation
• Formally withdraw approval for any project or authorise the treatment or humane killing of any animal
• Examine and comment on all institutional plans and policies which may affect animal welfare
• Maintain a register of approved projects
• Perform all other duties required by the Code
Purposes of the Code
• Emphasise the responsibilities of investigators, teachers and institutions
• Ensure the welfare of animals is always considered
• Avoid pain or distress for each animal used in scientific and teaching activities (refinement )
• Minimise the number of animals used in projects (reduction )
• Promote the development and the use of techniques which replace animal use in scientific and teaching activities (replacement )
Definitions in the Code
• Animal – any live non-human vertebrate – Fish, amphibians, reptiles, birds and mammals – Encompassing domestic animals, purpose–bred animals, livestock and wildlife
• Scientific purposes – all those activities performed to acquire, develop or demonstrate knowledge or techniques in any scientific discipline – Activities for the purpose of teaching, field trials, environmental studies, research, diagnosis, product testing and the production of biological products
Justification & Responsibilities
• Scientific and teaching activities using animals may be performed only if essential to: – Obtain and establish significant information relevant to the understanding of humans or animals – The maintenance and improvement of human or animal health and welfare – The improvement of animal management or production – The achievement of educational objectives
Limiting pain and distress
• Considerations: – Choose the most humane method for the conduct of the study – Ensure the technical skills and competence of all persons involved in animal care and use – Ensure the animals are adequately monitored for evidence of pain and distress – Act promptly to alleviate pain or distress – Use anaesthetics, analgesics and tranquillising agents – Conduct studies over the shortest time practicable – Use appropriate methods of euthanasia
Key aspects of an Animal Ethics application
• Description of what happens to animals – experimental and other procedures; surgical and related procedures; conditions of handling and housing; arrangements for disposal of animals including methods of euthanasia
• Details of how the animals will be monitored throughout the experimental period
• Justification of number and species of animals and experimental design and statistical considerations
• Declaration that the applicant is aware of their responsibilities under the Code and other legislation and institution policies
Legal control of experimentation in UK
• Centralised inspection
• Scientific Procedures Act, which is administered by Home Office – Covers all vertebrates and octopuses – Licences for researchers, projects and institutions – Inspectors consider licence applications, inspect institutions to enforce act and give expert advice – Ethical review committees
Legal control of experimentation in USA
• Self-regulation
• Federal Animal Welfare Act – Excludes birds, rats, mice and farm animals
• Institutional Animal Care and Use Committees operate locally
• Big funders of animal research have own regulations
• Voluntary accreditation to private organisations
Questions
- Describe the 3 R's of research
- what are some arguments for and against using animals in research?
- what are the welfare issues involved in research?
- what animals are commonly used for research and why?
- what are the regulations on teh use of primates in research