A staggering 17 billion chickens, almost 10 billion pigs, and nearly 2 billion each of cattle and sheep were produced as livestock worldwide in 2009. And, by 2050, demand for livestock is projected to double. With the added strain of increasing meat production on resources such as land, water, crops and energy, it’s vital to maximise the ‘output for input’, as Professor Duncan Maskell, Head of Cambridge’s Department of Veterinary Medicine, explained: “How you should apportion crops between food for animals and food and fuel for humans is a complex question, so it’s crucial to ensure that resource input counts in terms of output of meat, and one of the main moderators of this relationship is animal welfare, especially in terms of infectious disease.”

Viral epidemics can sweep through livestock, and endemic diseases such as respiratory infections can affect the rate at which animals grow. A further risk to food security is posed by bacterial infections of livestock that contaminate meat and cause food poisoning.

Research at the Department of Veterinary Medicine is tackling disease on all of these fronts in what Professor Maskell has described as “a perfect marriage between fundamental biological research and applied clinical outcomes.”

‘Flu-free’ chickens

A breakthrough was announced earlier this year that could prevent future bird flu outbreaks from spreading within poultry flocks. Dr Laurence Tiley, in collaboration with researchers in the Roslin Institute at the University of Edinburgh, produced the world’s first genetically modified chickens that prevent the spread of avian influenza.

One key aim of our research is to provide the fundamental knowledge and clinical tools to keep livestock healthy and our food safe

Since 2003, over 300 million poultry have been culled as a result of influenza outbreaks, and in some countries the virus is now endemic in wild bird populations. Preventing virus transmission in chickens would reduce both the economic impact of the disease and the risk for people who are exposed to the infected birds.

The scientists introduced a new gene that manufactures a ‘decoy’ molecule into the chicken genome. In a clever move to confuse the flu virus into ignoring its own replication needs, the decoy mimics an important control element of the virus and diverts the viral replication machinery away from its own genetic material.

“Because the control element is absolutely conserved across strains, we expect that the decoy will work against all strains of avian influenza and be difficult for the virus to evolve around,” said Dr Tiley, whose research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC). Although the birds become sick themselves, they don’t transmit the infection to other chickens, even those without the decoy molecule.

“At this stage, the chickens are not intended for consumption,” Dr Tiley added. “This genetic modification is a significant first step. Our objective now is to develop chickens that are completely resistant to avian flu.”

Threats from the wild

Viral epidemics are not just a concern in livestock, but also in relation to wildlife, as Professor James Wood explained: “Often, emerging infectious diseases originating from wildlife are a particular challenge because little might be known about the virus, how it’s transmitted to livestock and humans, or the potential for epidemics to spread.”

Nipah virus, for example, was first recognised in 1999 when an outbreak causing severe inflammation of the brain occurred in pigs and pig farmers in Malaysia. When the source of the virus was traced, it was found to be on fruit contaminated by infected fruit bats, the natural host of the virus.

“Bats epitomise the growing challenges associated with the spread of wildlife diseases,” added Professor Wood: “They are associated with a wide range of viruses, live in close proximity to animals and humans, and many important puzzles remain about the social, environmental and biological dynamics that shape pathogen transmission.”

The first steps to remedy this lack of information were taken last year when a unique network was created comprising experts from institutions worldwide including collaborators in Bangladesh, Ghana and Kenya. The consortium was funded by a Catalyst grant from the Medical Research Council and three other research councils.

“The network has a long-term aim of creating vitally needed interdisciplinary knowledge,” said Professor Wood, one of the leaders of the network, “as well as pioneering interventions geared to enabling bats, animals and people to co-exist with reduced disease risk.”

Super-vaccination at one sniff

Respiratory infections in pigs are a major animal welfare issue and cost the pig industry millions of pounds each year. An innovative project has begun the process of developing a ‘super-vaccine’ to guard against infection by the bacteria that are responsible for the most serious infections.

Funded with £5.6 million from the BBSRC, the consortium links experts from the University of Cambridge, Imperial College London (the project co-ordinator), the London School of Hygiene and Tropical Medicine, and the Royal Veterinary College.

Dr Dan Tucker, who together with Professor Maskell leads the Cambridge component of the five-year project, explained why these infections matter so much to food security: “When a pig gets sick it diverts its energy away from growth to fighting off the infection. This requires treatment with antibiotics and decreases the efficiency with which vegetable protein is converted into kilograms of meat.”

The goal is to create a single super-vaccine that can be administered by nasal spray and protect against Actinobacillus pleuropneumoniae, Haemophilus parasuis, Mycoplasma hyopneumonia/hyorhinis and Streptococcus suis. “Our gold standard would be to create a live vaccine based on a mutated version of one of these bacteria that no longer causes the disease, and then engineer it to display portions of the other three bacteria so that a strong immune response is made to all,” said Dr Tucker.

High-throughout sequencing in collaboration with the Wellcome Trust Sanger Institute is enabling the scientists to assemble the largest ever sequenced collection of these bacteria. The team has begun to identify which genes need to be ‘knocked out’ to provide a live vaccine – information that will also help in understanding why some strains cause more virulent disease than others.

Alongside vaccine development, a diagnostic kit will be developed to detect all four pathogens in less than six hours. The goal is to have a diagnostic test and potential vaccine ready for field trials at Huazhong Agricultural University in China within three years.

Safety first

Diseases can also be spread by meat. Although the global incidence of food-borne illness is difficult to estimate, up to 30% of the population in industrialised countries may be affected each year according to the World Health Organization.

Salmonella and Campylobacter – two of the most common sources of food-borne disease – are the basis of multiple research programmes at the Department of Veterinary Medicine, such as the research led by Professor Maskell. His team has particularly focused on understanding the dynamics of the interactions of bacteria with their animal hosts.

“Thanks to the completion of genome sequences for many of the chief culprits and the advent of high-throughput sequencing,” said Professor Maskell, “the door has been opened on many of the secrets of how pathogens such as salmonellae cause disease.”

“We are committed to maintaining strong basic research, but do this in the context of finding improved intervention strategies,” he added. “Health standards and life expectancy have gone up globally, and a large part of this is better nutrition. At many levels this means more meat and high-protein food. One key aim of our research is to provide the fundamental knowledge and clinical tools to keep livestock healthy and our food safe.”