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Microscope Figure 1 Figure 2

Images taken from the Wellcome Image awards, 2009-2012
Figure 1. 3D image of a developing embryonic mouse head at age 14.5 days. High-resolution episopic microscopy 3D reconstruction. Tim Mohun, National Institute for Medical Research, MRC. These images were created using high-resolution episcopic microscopy. Samples are embedded in plastic stained with a fluorescent dye. Each time a fine section of the sample is sliced away, an image of the remaining sample is captured. These images are then put together to create a 3D animation of the external and internal structure of the sample. from the point of view of developmental biology, this new tool can illustrate much more effectively the impact that certain mutations may have on the anatomy of the mouse embryo.
Figure 2 Confical microscopy image of Xenopus laevis oocytes, Vincent Pasque, University of Cambridge. Confocal and multiphoton microscopy are non-invasive fluorescent imaging techniques that use lasers of different wavelengths to excite the sample and produce the image. Samples can be detected simply from naturally occurring autofluorescence of the tissue or they can be labelled with fluorochromes to highlight specific tissues.

Fig 3 Fig 4 Fig 5
Cryogenically stored sperm

Liquid Dewar flasks (Fig.3): They are non-pressurized, vacuum –jacketed vessels similar to a "thermos bottle". They come with a loose fitting cap or plug that helps to prevent air or moisture entering and also allows excess pressure to vent.
Liquid cylinders (Fig.4): They are pressurized containers specifically designed for cryogenic liquids. This type of container has valves for filling and dispensing the cryogenic liquid, and a pressure-control valve with a frangible (bursting) disk as backup protection. Three major types of liquid cylinders have been designed for dispensing either liquid or gas, gas only or liquid only.
Dry shippers, (Fig.5) are dewar flask containers designed for transportation of frozen biological specimens (semen or embryos) in LN2 vapour at temperatures around -190°C. They are made of lightweight aluminium and work by absorbing LN2 into a thick layer of hydro-phobic material that surrounds the inner cavity of the container where the semen is stored. The dry shippers must be properly charged by filling with LN2 to the point of saturation of the absorbing material and then removing the excess LN2 to provide maximum holding time. The long holding time of dry shippers is obtained because there is superior insulation created by a double-wall aluminium shell that is filled with foil and also vacuum sealed.

The PCR machine
Polymerase chain reaction (PCR) technology, invented by Kary Mullis in the early 1980's is a quick and easy method for generating unlimited copies of a DNA fragment.  Initially the chain-building reaction was carried out in a step-wise process in test tubes exposed to the various temperatures and enzymes required but later it was automated, aided by the discovery and use of the Taq DNA enzyme that is resistant to high temperatures. PCR has become an essential technology for the detection of infectious organisms and the study and detection of variation and mutation of genes in laboratory and clinical science.  Within laboratory animal science it is vital for, the screening of infectious agents, health monitoring and the analysis and confirmation of genetically altered animals.

PCR process

The Animals (Scientific Procedures) Act 1986
Legislative changes during the past 50 years have had a major influence on the conduct of laboratory animal science.  Prior to the Animals (Scientific Procedures) Act 1986, research in the UK was carried out under the Cruelty to Animals Act 1876.  The 1986 Act (ASPA) introduced the concept of harm/benefit analysis, placed the 3Rs at the forefront of studies, introduced 'named' individuals with clearly defined roles and responsibilities toward the use of their animals, put a sharper focus on laboratory animals' housing and environmental control and coupled this with a robust inspection scheme.  This Act required scientists to justify the need for the use of animals in their research and the tight system of regulation gave the public greater confidence in this; this has been reinforced by the amendment of the Act in 2012 in line with the new European Directive. 
The ASPA is there to protect laboratory animals but the Serious and Organised Crime and Police Act in 2005 was important in protecting the animal research community from harassment and intimidation from animal rights extremists, providing for more effective policing and protection of UK research.

The training clicker and PRT
The last 50 years have seen growing efforts to understand and empathise with laboratory animals and use complementary techniques.  An example is Positive Reinforcement Training (PRT), which often uses aids such as the clicker, to avoid the restraint of an animal for the administration of substances or the collection of biological samples.  Restraint is now recognised as a significant stressor and one to be avoided if possible.  Giving animals the opportunity to cooperate voluntarily can result in less stress on the animal and, because the physiological responses to stress are reduced or eliminated, provides for better science for the investigator.
The clicker is used to facilitate PRT by providing a 'bridge' between the desired behaviour and the reward (usually food). Although PRT is predominantly used with larger animals, its use is expanding to laboratory rodents and other species. For more information on PRT training visit the NC3Rs website

Dolly the Sheep
Dolly was the first cloned animal to be created from an adult somatic cell.  She was born on 5th July 1996 at the Roslin Institute, Edinburgh, and became a global front page story.  The cell used as the donor for the cloning of Dolly was taken from a mammary gland and the production of a healthy clone showed that genes in the nucleus of such a mature differentiated somatic cell are still capable of reverting to an embryonic totipotent state, creating a cell that can then go on to develop into any part of an animal.  During her relatively short life, she had 6 offspring but was euthanised in 2003 because of progressive lung disease and arthritis, not uncommon in older animals of her breed.  

BBC Radio 4 'The Reunion' September 2012

On Dolly's name, Ian Wilmut, who led the Roslin team, stated "Dolly is derived from a mammary gland cell and we couldn't think of a more impressive pair of glands than Dolly Parton's".

The Individually Ventilated Cage (IVC)
Good laboratory animal science dictates that animals should be disease-free and of high health status, since existing pathogens can alter an animal's response and affect the outcome of research, and that high standards of animal welfare are maintained.  Animals with altered immune status are particularly vulnerable to pathogens and are increasingly used in medical research.  The development of IVCs, in which each cage is effectively a separate barrier unit preventing the transmission of pathogens between cages, allowed susceptible strains to be maintained in higher health, resulting in fewer numbers bred and used and significant refinement in their condition and welfare.

IVC cage and rack

The MRI scanner   
Traditional methods of investigating human disease in animal models often involve invasive sampling and measurement of body fluids and tissues that require handling and restraint (which can be distressing for laboratory animals), after which the animals may be sacrificed for further analysis.  However, technological advances are making non-invasive imaging techniques increasingly available as practical alternatives to traditional procedures.  A variety of techniques can provide images of body systems (e.g. organs, tumours, molecular pathways) with varying degrees of accuracy and permit the refinement, reduction or replacement of the use of animals in experiments.  For example, imaging techniques allow serial studies on the same animal, so reducing inter-animal variation and thus the overall number of animals needed to achieve statistical significance.  Because diseases and responses to exogenous substances can be monitored in a temporal and spatial manner, a greater amount of data can be obtained from small numbers of animals and there is no need for invasive surgery and/or serial sacrifice.  Non-invasive imaging techniques can also enable more meaningful and humane endpoints to be used, e.g. by allowing early detection of cancerous cells and provide translational information between the animal model and the clinical manifestation of a disease.
Magnetic resonance imaging (MRI) technology is used to distinguish pathologic tissue (such as a brain tumor) from normal tissue. One advantage of an MRI scan is that it uses strong magnetic fields and non-ionizing electromagnetic fields in the radio frequency range, unlike CT scans and traditional X-rays, which both use ionizing radiation. The first patent for a MRI machine was submitted in 1972.

MRI scan of an anaesthetised rat
NC3Rs Information Portal

The camera and video
The ability to capture an image in the laboratory has allowed the recording of specimens, monitoring processes of change, measurements and analyses, and provided the means to transfer and share this information.  Within the laboratory animal science arena, video has enabled better animal monitoring, especially when coupled with behaviour analysis software, and the development of training materials to share good practice.  
An example of the latter is the material produced by Newcastle University on techniques  http://www.procedureswithcare.org.uk  and the recognition, assessment and alleviation of pain in laboratory animals http://www.digires.co.uk

Lab. diet
Fifty years ago, the National Research Council (NRC) published the first edition of 'Nutrient Requirements for Laboratory Animals', summarising the requirements for rats, mice, guinea pigs, hamsters, monkeys and cats.  It is now well understood that nutrition has an important effect on the performance, evaluation and reproducibility of experimental animal research, as well as on understanding requirements for breeding.
By the 1970's the desire for sourcing consistent and stable diets for research studies was growing and the NRC published revised requirements.  The American Institute of Nutrition (AIN) also recognised that experimental studies and the use of purified ingredients needed standardising and a committee formulated the first standard purified ingredient diet, 'AIN 76 Rodent Diet' in order to guide research.
In 1979, the American Food and Drug Administration (FDA) enforced regulations which demanded analysis and control of diet parameters - Good Laboratory Practice (GLP) was born.  This meant diets being regularly analysed to identify nutrients and possible contaminants.  In the 80's irradiated diets were introduced and the 90's saw the introduction of further regulations that increased standards beyond conventional diet manufacture legislation.

The knockout mouse
A knockout mouse is a genetically engineered mouse in which an existing gene has been inactivated, or "knocked out," by replacing it or disrupting it with an artificial piece of DNA.  Knockout mice are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined.  By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function.  The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans and Oliver Smithies in 1989, for which they were awarded the 2007 Nobel Prize in Physiology or Medicine.
Examples of research in which knockout mice have been useful include studying and modelling different kinds of cancer, obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease.  Knockout mice also offer a biological context in which drugs and other therapies can be developed and tested.
Many of these mouse models are named after the gene that has been inactivated.  For example, the p53 knockout mouse is named after the p53 gene, which codes for a protein that normally suppresses the growth of tumours by arresting cell division. Humans born with mutations that inactivate the p53 gene suffer from Li-Fraumeni syndrome, a condition that dramatically increases the risk of developing bone cancers, breast cancer and blood cancers at an early age.  Other mouse models are named, often with creative flair, according to their physical characteristics or behaviours.  For example, "Methuselah" is a knockout mouse model noted for longevity, while "Frantic" is a model useful for studying anxiety disorders.

Toys for dogs
In July 1997, Lord Williams, a Home Office Minister, indicated in a written reply to a Parliamentary Question that, 'The Inspectorate will audit all commercial dog facilities to identify best practice and innovations with respect to the housing and care of animals (dogs), and that this information will be used to inform national standards.' The survey encompassed 27 Designated Establishments and commercial breeders in the UK and its recommendations were published in 1998.
These included the necessity to house dogs in pairs or groups, unless there were persuasive scientific or welfare reasons against; the requirement for staff to be educated and trained in all aspects of dog welfare; staffing levels to be sufficient to provide significant human-animal interaction and socialisation programmes; and the need for the animals' environment to have complexity and choice, including the use of treats and toys, as well as high standards of cleanliness.

Research Animals Department, RSPCA (10/2005), Supplementary resources for lay members of local ethical review processes: The dog: Good practice for housing and care, Horsham, RSPCA, pp 1-5  (155KB)

Image joint © Understanding Animal Research/Wellcome Images.

The RSPCA Science Group
The RSPCA Science Group, established in 1976, is a centre of expertise which provides the scientific basis that helps enable the Society to advance animal welfare effectively.  The research animals team is formed of specialist scientific staff who work with those involved in the regulation, care and use of animals in experiments, both nationally and internationally, to develop and promote practical measures that will help to: ensure critical assessment, on a case by case basis, of the necessity and justification for animal use; replace, or avoid, the use of animals; reduce the numbers used; refine experimental procedures, housing and care to improve welfare and to minimise and preferably avoid suffering.
There has been a long and effective collaboration between the RSPCA team and LASA throughout their existence.
http://www.rspca.org.uk/sciencegroup/researchanimals.

The whole-body plethysmograph
Whole-body plethysmography is used to measure respiratory parameters in conscious unrestrained subjects, including quantification of bronchoconstriction and bronchodilation.  The plethysmograph has two chambers, each fitted with a pneumotachograph.  The subject is placed in one of them (subject chamber) and the other remains empty (reference chamber).  The pressure change is measured by a differential pressure transducer with one port exposed to the subject chamber and the other to the reference chamber.
A plethysmograph (such as the Buxco chamber shown) allows the measurement of respiratory function in conscious and unrestrained rodents, free from the effects of anaesthesia.  It also enables the same animals to be studied on repeated occasions over long periods of time.  This system has been widely used to develop novel therapies and the potential effects of substances on the respiratory system.  Previously, such studies would have involved significant restraint or terminal anaesthesia and larger numbers of laboratory animals.

The 96-well plate ...
... then the 384 and 1536, and now the 3456 and 9600, microtitre  plates.  Microtitre plates are flat plates that support multiple 'wells' (small test tubes), arranged in a rectangular matrix that allow assays to be conducted with much smaller volumes than before and by automated processes.  The earliest plate was developed in 1951 but, by the 1990's, numerous companies were producing these for multiple applications involving filtration, separation, optical detection, storage, reactions or cell culture.  Their use has significantly reduced the volumes of biological samples required to be collected from laboratory animals for analysis or routine microbiological monitoring.  Furthermore, commercially available plates for serology have permitted on-site health monitoring of research colonies, providing for more rapid identification of pathogens and resolution of problems.

The whirling hygrometer
Before the introduction of electronic sensors in computerised building management and monitoring systems, the humidity of animal holding rooms was measured with a whirling hygrometer, in which the instrument is fitted into a ratchet or  'football rattle' device that is whirled around in the air.
The correct environmental conditions for housing laboratory animal species are critical to their health and welfare and the outcome of the science for which they are used. In the UK, these conditions are prescribed in Animals (Scientific Procedures) Act Code of Practice for the care and accommodation of animals.  Humidity is a key factor, recommended to be between 40 and 70 per cent for rodents.  In rats, low humidity can result in ringtail, an epidermal disease in which the tail swells as a consequence of annular constrictions along its length (hence the name "ringtail") and subsequently dehydrates and sloughs; in the most severe cases, the process may end up in the tail becoming gangrenous and dropping off.  Feet may also swell and redden.

A jellyfish and its GFP
Green fluorescent protein (GFP) is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range.  Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the jellyfish, Aequorea victoria in the 1960's. GFP was not utilised as a tool for molecular biology until 1992 but its importance was recognised in 2008 when Martin Chalfie, Osamu Shimomura, and Roger Y. Tsien were awarded the Nobel Prize in Chemistry for its discovery and development.  The GFP gene is used as a reporter of expression; it can be introduced into an organism and maintained in their genome to tag a protein, thus cells in which the tagged protein is expressed will fluoresce.  Transgenic GFP mice and other species are increasingly used in gene therapy and regenerative medicine research.