the impact of veterinary research...the royal college of veterinary surgeons’ vision for...

T H E I M P A C T O FVETERINARY RESEARCH

research_brochure_rev2.qxp:The Impact of Veterinary Research 5/9/07 16:51

Veterinary research is the study of animals, partic-ularly their health, disease and behaviour, andinforms and influences a far greater proportion ofour lives than many people realise.

Veterinary research contributes to quality and safety throughout the whole food chain. It plays acrucial role in human medicine through compara-tive studies, considers diseases that can cross fromanimals to humans, such as rabies and BSE, andis a key part of improving animal welfare andensuring environmental sustainability.

Veterinary research also contributes to the widereconomy, since exotic and endemic diseases ofanimals cost the UK hundreds of millions, evenbillions, of pounds each year in direct and indirectcosts.

Veterinary research is carried out by individualswith a range of scientific backgrounds, includingveterinarians. Research is undertaken at institutesand universities, by industry, including pharma-ceutical companies, and in veterinary practicesaround the country. It is funded by government,charities such as the Wellcome Trust, and bodiessuch as the Horserace Betting Levy Board.

There are numerous examples of veterinaryresearch leading the way in new developments in

biological sciences. For example, the first vaccineagainst a cancer-causing virus was against a chicken disease – Marek’s disease.

Other examples of comparative studies, extrapolat-ing work from animals to humans, include work onanimal retroviruses such as feline immunodeficiencyvirus and jaagsiekte sheep retrovirus that haveassisted in the search for a vaccine for humanimmunodeficiency virus (HIV). Investigations intoSalmonella enterica, a bacterium capable of caus-ing severe and potentially fatal food poisoning, haveallowed us to understand how the bacteria spreadfrom the initial site of infection to cause disease(page 4).

THE IMPACT OFVETERINARY RESEARCH

Veterinary research also contributes to the wider economy, since exotic and endemic diseases of animals cost the UK hundreds of millions of pounds...

Veterinary research is carried out by individuals with a range of scientific backgrounds, including veterinarians, atresearch institutes and universities, byindustry, including pharmaceutical companies, and in privately-owned veterinary practices.

Scientist preparing a sample in liquid nitrogen beforeexamining it on a transmission electron microscope.

Photo: Wellcome Trust

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The challenges we face in our society todaydemand a major reliance on science and it is likelythat this dependence will increase over the nextseveral decades.

New challenges to veterinary research include theintensification of animal production, greater globalmovement of humans and animals, and theextreme weather events associated with climatechange. All of these factors favour the emergenceof new diseases, such as Bovine SpongiformEncephalopathy (BSE) in the UK or Nipah virus inIndonesia; or alter the geographical range of exist-ing diseases, resulting in the monkeypox virus out-break in mid-western US in 2003 or the blue-tongue outbreak in sheep in northern Europe in thesummer of 2006 (page 6).

Veterinary research is a relatively small componentof the research sector, but it plays a crucial role inthe health of the UK human and animal populationand has saved the economy millions of pounds.However, this network of researchers and institutesdepends on secure and sufficient funding.

The Royal College of Veterinary Surgeons’ vision forveterinary research in the UK is of a vibrant, sus-tainable, well-connected research platform wherethe veterinary research community competes inter-nationally in attracting research income, produceshigh quality scientific outputs, ensures effectiveand efficient knowledge transfer and provides

excellent research training. The case studies onthe pages to follow illustrate the diversity of veterinary research ongoing today, and its rele-vance to the health and welfare of all animals,including man.

Veterinary research plays a critical role in ensuring the qualityand safety of the food chain.

Veterinary research is a relatively small component of the research sector, but plays a crucial role in the health of the UK human and animal population...

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Photo: Moredun Institute


Thirty years ago, the new electron microscope allowedminute structures inside cells to be visualised for the firsttime. Researchers examining a particular group of worms– the filarial nematodes – described how the cells of theworms were heavily populated by bacteria that seemed tobe ‘normal’ inhabitants. Their function wasn’t clear, but itwas noted that, should they be essential to the worm, theymight be a target for drug treatment. This was potentiallyimportant because there was no safe and effective drugto eliminate the filarial nematodes that cause severe diseases like river blindness (onchocerciasis), elephantia-sis in humans and heartworm infection in dogs.

Yet, inexplicably, this discovery was forgotten until the1990s. At that time, veterinary researchers at theUniversity of Liverpool, working with colleagues inGermany and Cameroon and funded by the World HealthOrganisation, were testing different potential drugs forthe control of river blindness. They were evaluatingdrugs in African cattle that were naturally infected with aclosely related parasite.

Although the worm in cattle is very similar to the parasitethat causes river blindness in people, cattle don’t goblind – indeed they are clinically unaffected – but theyprovide a means of assessing the effect of drugs onworms.

By chance, one cow was given an antibiotic to treat a bac-terial skin infection, and the researchers observed that itcured the cow’s onchocerciasis. Concurrently, scientistselsewhere reported bacterial proteins and DNA inhomogenates of filarial worm tissues. Suddenly the find-ings of the 1970s were ‘re-discovered’ and several teamsbegan systematic, controlled trials investigating the activityof antibiotics against filarial worms.

The Liverpool / German / Cameroon team were the first todescribe in a controlled experiment that antibiotic treat-ment could kill a filarial nematode, the implication beingthat the bacteria are essential for worm survival. Furtherwork has shown that the suppression of the bacteria overmany weeks is necessary to achieve worm death.

Meanwhile, medical researchers have been carrying out trials in Africa on humans affected by either onchocercia-sis or lymphatic filariasis and the promising results providethe greatest advance in the treatment and control of theseinfections for many years. Moreover, the Liverpool teamhas gone on to use the same cattle model to demonstratefor the first time that it is possible to vaccinate againstonchocerciasis.

Whilst the vaccine is not practical for large-scale humanuse, the results are crucial proof of principle that immuni-sation is possible against this infection and provide a valuable impetus in the development of a human vaccinefor onchocerciasis.

Taken together, the drug and vaccine research in cowsshows what a key contribution veterinary research canmake in the fight against human disease.

Langworthy and others (2000) Proceedings of the Royal Society, 267, 1063-1069Gilbert and others (2005) Journal of Infectious Diseases, 192, 1483-1493Tchakouté and others (2006) Proceedings of the National Academy of Sciences, 103,5971-5976

UNIVERSITY OF LIVERPOOL’S FACULTY OF VETERINARY SCIENCE

COWS ARE HELPING CURE RIVER BLINDNESS IN HUMANS

Cross-section of an onchocerciasis-causing worm. In the centre isCross-section of an onchocerciasis-causing worm. In the centre isthe uterus full of larvae. The brown colour in the tissues aroundthe uterus full of larvae. The brown colour in the tissues aroundthe margins of the worm ( ) and within the larvae of the uterus the margins of the worm ( ) and within the larvae of the uterus ( ) is specifically staining millions of bacteria. ( ) is specifically staining millions of bacteria.

ImageImage: University of Liverpool : University of Liverpool


The Bacterial Infection Group (BIG) at the University ofCambridge’s Department of Veterinary Medicine studiesseveral bacterial pathogens involved in human and animaldisease. One such pathogen is Salmonella enterica, a bac-terium that can infect humans and domestic animals causing severe, potentially lethal, infections such astyphoid fever and acute gastro-enteritis (food poisoning).

Tackling these diseases is becoming increasingly difficultbecause the bacteria are developing resistance to antibi-otics and the vaccines currently available are not alwayseffective. The BIG’s current research investigates severalaspects of the interaction of these bacteria with theimmune system to gain a clearer understanding of how thebacteria infect the host and how the immune system fightsthem.

Using advanced microscopy techniques to see bacteriapresent within individual host cells, researchers in the BIGhave found that, during its growth in the tissues, S. enteri-ca rapidly kills host cells at the site of infection andspreads to previously uninfected ones. This suggests thatthe bacteria are continuously escaping from establishedareas of infection to keep one step ahead of the escalatingimmune response.

The BIG is currently using mathematical models toimprove vaccine design so that it stops this spread ofthe infection more effectively. Complementary work isstudying the key mechanisms used by cells of theimmune system to restrain the growth of bacteria with-in host cells. This has led to identification of the toxicsubstances produced by immune cells that enablethem to achieve this.

However, the picture is complex. Several strategiescunningly devised by bacteria to prevent them beingkilled by these substances have also been identified.To counteract this, B cells and T cells (both subsets ofimmune cells called lymphocytes) continuously needto exchange signals for the activation of protectiveimmunity and the BIG is currently identifying the pre-cise nature of these activating signals.

A multi-fluorescence microscopy image of A multi-fluorescence microscopy image of Salmonella entericaSalmonella enterica (green-yellow)(green-yellow)within a CD18+ liver phagocyte (red). The cell nuclei are stained blue. within a CD18+ liver phagocyte (red). The cell nuclei are stained blue. Most phagocytes contain only one or few bacteria because Most phagocytes contain only one or few bacteria because S. entericaS. entericacontinuously escape from infected to non-infected phagocytes duringcontinuously escape from infected to non-infected phagocytes duringtheir growth in tissues. This is likely to be a mechanism that allows thetheir growth in tissues. This is likely to be a mechanism that allows thebacteria to remain one step ahead of the immune response.bacteria to remain one step ahead of the immune response.

UNIVERSITY OF CAMBRIDGE’S DEPARTMENT OF VETERINARY MEDICINE

AVOIDANCE TACTICS OF SALMONELLA ENTERICA

Tackling these diseases is becomingincreasingly difficult because the bacteria are developing resistance toantibiotics and the vaccines currentlyavailable are not always effective.

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ImageImage: University of Cambridge: University of Cambridge

Brown SP and others (2006) PLoS Biol. 4, 2091-2098 Ugrinovic S and others (2003) Infect. Immun, 71, 6808-6819Menager N and others (2007) Immunology 120, 424-432


ROYAL VETERINARY COLLEGECLUES FOR INJURY-FREE EXERCISE FROM HORSE FRACTURES

In the flat racing industry, lamenessremains the most important cause of dayslost from training.

Horses racing to the finish at Windsor. Studies have revealed that highHorses racing to the finish at Windsor. Studies have revealed that highimpact exercise produces a beneficial response from bone cells. impact exercise produces a beneficial response from bone cells.

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Success as an athlete depends upon training all the sys-tems of the body so that they contribute to performancebut avoid injury. Each system requires a different traininginput to achieve this balance. In the flat racing industry,lameness remains the most important cause of days lostfrom training. The most important injuries causing lame-ness are fractures. These do not always involve completebreaks in the bone but include ‘stress fractures’. These arepainful cracks in the bone that, if loading continues, mayprogress to a complete break but do not initially do so.Such fractures are not only common in horses but also inmilitary recruits, track and field athletes, ballet dancers,figure skaters and gymnasts.

Revealing the processes by which bones use the loadsapplied to them as stimuli to become strong enough toresist fracture has been a long-term pre-occupation at theRoyal Veterinary College (RVC), however, experiments canonly reveal so much. The acid test is to see which trainingregimens are the most successful in preventing fracture inthe field. To do this, the workers at the RVC accessed thedaily training details and veterinary records of 1,178 horses over two seasons. These data confirmed a relation-ship between the incidence of fracture and the exercise

distances trained at canter (<14m/s) and highspeed (>14m/s). This relationship suggests thatthe balance between the bones’ loading at high

and low speed may be more important to their pre-

disposition to injury than the absolute number ofloading cycles.

PhotoPhoto: RCVS: RCVS

In young horses at the start oftraining, the cumulative amount ofexercise at high speed is associat-ed with reduced risk of fracture.

“ “In addition, in young horses at the start of train-ing, the cumulative amount of exercise at highspeed is associated with reduced risk of fracture,whereas that at a canter is associated with anincrease. These findings are consistent with theresults from experiments in the laboratory whichshow that bones’ adaptive responses to loading arerelated to high strains, which would be caused byhigh loads, and high strain rates, which would beassociated with fast work.

This study is only the first of many needed toestablish the training programme that is optimumto produce strong bones resistant to fracture. Onceascertained it must be combined with the

optimum regimen for speed and endurance. These datashould make racing safer for the horses and reducewastage due to injury. They are unlikely to make it any easier to choose winners!

Verheyen KLP and others (2006) Bone, 39(6), 1322-30.


Bluetongue is a serious disease of ruminants, particularlysheep, and is caused by a bluetongue virus (BTV). Infectedsheep may lose condition, have muscle degeneration,develop respiratory distress and can die. Bluetongue wasonce a disease only found in Africa and Asia and parts ofthe Americas but in the last ten years has been encroach-ing northwards through southern and eastern Europe, coin-cident with increasing temperatures in Europe.

The first outbreaks in northern Europe originated directlyfrom a source outside Europe and were reported in thesummer of 2006 in the Netherlands, Germany, France,Luxembourg and Belgium.

New genetic techniques developed at the Institute forAnimal Health (IAH) to improve identification of the virustypes in Europe have made it possible to identify fromwhich regions of Africa and the Middle East these viruseshave come.

We also know that Culicoides imicola, an Afro-Asianspecies of midge that is a major vector of BTV, has spreadwidely throughout southern Europe in recent times. It hasbrought with it five different types of BTV, originating fromdifferent parts of Africa, the Middle East and Asia (seeright). For example, type 1 virus, similar to viruses presentin India, entered Europe via Anatolian Turkey. Type 2 virusentered Europe from the south, possibly from sub-SaharanAfrica, where it is endemic, or by moving across NorthAfrica via animal trade routes.

Genetic analysis also revealed that the type 16 BTV inEurope had probably originated from a vaccine strain ofvirus, that is the vaccine had mutated back to a disease-causing form. Novel vaccines are being developed to avoidthis reversion. Recent research at the IAH has revealedthat the strain of BTV that caused northern Europe’s firstever outbreaks in 2006 was not closely related to thosepresent in southern Europe, but wasserotype 8, which is found in sub-SaharanAfrica. Details of its route to northernEurope remain a mystery.

IAH research has also shown that themidge Culicoides imicola is not the onlyspecies of midge capable of transmittingBTV. Rather, two other species complexesthat are already widely established, espe-cially in northern Europe (including theUK), are also capable of spreading thevirus, highlighting the potential for its fur-ther spread.

Climate change is likely to exacerbate thelevels of risk. Current research at IAH isconcentrating on developing new genera-tions of safer vaccine, and assessing thethreats posed to UK livestock by theseviruses under existing and future climatescenarios.

This work was supported by the Biotechnology andBiological Sciences Research Council, the Department forEnvironment, Food and Rural Affairs, the EuropeanCommission and the Wellcome Trust.

Mertens PP and others (2007) Journal of General Virology, in pressPurse BV and others (2005) Nature Reviews, Microbiology, 3, 171-181

INSTITUTE FOR ANIMAL HEALTH, PIRBIRGHT LABORATORY

BLUETONGUE SPREADS CLOSER TO UK SHEEP POPULATION

Genetic analysis of bluetongue viruses isolated in Europe has revealed not only thatGenetic analysis of bluetongue viruses isolated in Europe has revealed not only thatfive types of the virus (1, 2, 4, 9 and 16) have entered the region since 1998, butfive types of the virus (1, 2, 4, 9 and 16) have entered the region since 1998, butalso the routes by which they came. Serotype 8 has been isolated from the 2006also the routes by which they came. Serotype 8 has been isolated from the 2006outbreak in northern Europe; its provenance is currently unclear. outbreak in northern Europe; its provenance is currently unclear.

ImageImage: Institute for Animal Health: Institute for Animal Health


DID YOU KNOW THAT IN...

RCVS Belgravia House 62-64 Horseferry Road London SW1P 2AF T 020 7222 2001 F 020 7222 2004 E [email protected] W www.rcvs.org.uk

1880Griffith Evans, who studied at the Royal Veterinary College(RVC), discovered the first disease-causing trypanosome

(Trypanosoma evansi) in horses in India.

1892John McFadyean developed the first laboratory in Britaindevoted exclusively to veterinary diagnosis and research,and in 1900 he proved that African horse sickness, a seri-ous and fatal disease of horses, mules and donkeys, was

caused by a virus.

1897Bernhard Bang, a Danish veterinarian, was the first scien-tist to use tuberculin on cattle, and realised its importancein identifying infected animals. He went on to develop con-trol measures for bovine tuberculosis that led to a dramaticdecrease in the incidence of the disease. In 1897, Bangalso discovered the bacterium Brucella abortus to be thecause of “undulant fever” in cattle. This organism caninfect and cause chronic disease in humans.

1923Gaston Ramon, a French veterinarian working at thePasteur Institute, manipulated the deadly diphtheria and

tetanus toxins into effective vaccines.

1945Robert (“Robin”) Coombs, graduate of the EdinburghVeterinary School, published a method to detect the agglu-tination of red blood cells in the presence of antibodies.This became known as the Coombs Test and is used forcross-matching blood types prior to transfusions and thediagnosis of a number of autoimmune diseases. For exam-ple, it is used in diagnosing haemolytic disease of the newborn associated with a rhesus negative mother.

1950sWalter Plowright, Fellow of the Royal College of VeterinarySurgeons, developed a vaccine against the cattle plaguerinderpest. Due to the success of the vaccine, rinderpest ispredicted to be the first animal disease to be eliminatedworldwide by 2010.

1970Vaccination against Marek’s disease was introduced usinga vaccine developed by Peter Biggs, a Fellow of the RoyalCollege of Veterinary Surgeons and a graduate of the RVC.This was the first example of an effective vaccine against anaturally occuring cancer in any species.

1996Peter Doherty, an Honorary Fellow of the Royal College ofVeterinary Surgeons, was awarded the Nobel Prize forPhysiology or Medicine for his work on immune recognition.

Cover photo: Moredun Institute

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