What challenges does the UK face to eradicate Bovine TB?

Integration and Design

Risk Assessment

Our project had a number of important factors that had to be considered in terms of risk. Firstly we designed a test that is meant to be used in the field by vets on a day to day basis. Clearly this poses concern for the containment of any genetically modified organism in our test. However, as our test is planning to be cell free it removes the issue of organism containment. Phil Leighton explained to us the process of blood sampling a cow and also showed us a current standard blood tube. We decided to contain our test within the current blood collection tubes that are used universally in veterinary practice, removing the need for specialist training to use our test. Our RNA based test has a number of factors that also reduce risk.

Our test would use either a blood sample or dairy sample from each individual cow to test for bTB. Blood samples are taken from the base of a tail. Phil and Dick explained how cows are particularly anxious of people approaching and feeling their neck area, yet are much more comfortable with blood being taken from the tail. As most bTB tests are done in a crush (a safe way to contain the animal), they were unanimous in agreeing our test offers a safer alternative to the current Tuberculin skin test. Also, if our test could work with milk as a sample, risk of injury to the vet during sample collection is completely minimised due to the highly automated milking process that is seen across the UK Dairy Industry.

Feasibility Assessment

Due to the large scale use of our test, calculating a cost was important. Cell free kits are currently expensive to buy. Due to time constraints this is the method that our team used during our project, a method that would not be sustainable if our test was to be manufactured and used. To understand and try to combat this, we collaborated with Bielefeld iGEM 2015, a team who have been working on developing their own cell free kit. After multiple Skype meetings they sent us a spreadsheet with a cost breakdown for each cell free reaction using what they have developed. See the cost section of our wiki for more information.

End-User Assessment

One of the most interesting aspects of our project is how our test would be used. For vets it offers a faster and more accurate way to diagnose bTB infected cattle. Currently with the Tuberculin skin test there is a 72 hour period from injection to detection. This means bTB testing is highly time consuming and also limited. Phil explained how his practice can only bTB test from Monday to Wednesday in order to allow for sufficient time to pass before the second part of the test can be done during his practices working week. As our test would offer a result in a matter of hours, a whole farm could be completed within one day of bTB testing. Dick explained how his vets are able to test up to 1000 cows a day, yet these cows then have to be diagnosed three days later. The benefit of our test for his practice was the idea that our test would mean the whole testing routine could be completed within one day. Not only does this save his vet's time, it also saves a lot of hassle for the farmer as herding and bringing in cattle only once as opposed to multiple times is significantly easier.

Furthermore containing our test within the current blood sample collection tubes means there is no new technology being introduced to the primary end user, the vets. Blood collection is uniform across veterinary practice and our test does not require any additional training, due to the considerations we made when designing our prototype .

Away from the veterinary side, our test could have potential application for use by farmers as an animal health management tool. Michael Ross explained to us how the UK is in a situation with bTB where everyone has a reliance on everyone else. Farmers have to rely on the testing regime that is run by vets, and the testing regime is set centrally at a government level by the Department for Environmental, Food and Rural Affairs. In New Zealand the Animal Health Board (the body responsible for the mass progress in bTB eradication) had a heavy farming representation and testing was not carried out by vets. Farmers have a clear motive to be bTB free. Giving them the tools to manage the disease on their farm is one of Michael's primary aims, and our Ribonostics test could have an application for this.

Social Justice

Bovine TB is the UK's largest animal health problem and a truly challenging disease to try and combat. However the UK also manages the situation of Bovine TB in a way that is currently not working. When looked at simply, the main strategy the UK has to deal with Bovine TB is the use of the Tuberculin Skin Test to identify and immediately remove TB infected cattle. This test has an estimated sensitivity of around 80%. This means out of 10 infected animals 2 will not be detected and will therefore remain within the population, able to spread the disease. Dick made it clear that his practice has larger herds in high risk areas that are chronically infected with bTB because the current test is simply not sensitive enough to identify infected but not yet infectious animals. As vaccinating cattle with the BCG vaccine is banned under EU law, dealing with the disease in cattle is highly difficult. Identifying and removing infected animals is a strategy that deals with the symptoms of the disease as opposed to the root cause. This is where Michael Ross and his company Saved & Safe aim to make a change to the UK strategy to deal with bTB. Michael made it clear how our test could fit into his company's current strategy and helps allow development of a strategy that begins to deal with the infection (the root cause).

Click the image for the TB Strategy Document

The Department for Environmental, Food and Rural Affairs (DEFRA) has the development of a DIVA (Differentiation of Infected and Vaccinated Animals) test as a main priority for the strategy to eradicate bTB by 2038. A successful DIVA test would allow the use of the BCG vaccine and take steps forward towards establishing a bTB free UK. Our meeting with George Eustice helped us to understand how our RNA based diagnostic tool meets the criterion for a DEFRA DIVA test. DEFRA is responsible for all bTB testing across the UK meaning they are able to assess and implement the approach they see best. Developing a test that offers a new and unique approach to bTB testing was important for us but it was also important that our test could fit into the Strategy for Bovine TB Eradication document that they released in 2014.

In this document there are a number of key points relevant to the development of our test. The bTB research programme states how “Evidence [related to the development of new vaccination tools] needs to be multidisciplinary to provide a comprehensive understanding of the disease epidemic”. It also states the importance of “developing new diagnostics tests for surveillance”. We have approached solving the issue of bTB in the UK from a multidisciplinary approach due to the interdisciplinary members of our iGEM team. The fact our test offers a scientific solution that acts as a DIVA test, it paves the way for political change as a valid DIVA test would eventually allow for the reintroduction of the BCG vaccine.

Bovine TB clearly presents a number of important social issues also. Our public engagement was important to help us as a team understand the contentious issue of Badger-Cattle transmission of bTB. DEFRA has recently undertook a number of Randomised Badger Culling trials to assess the effect tackling the natural reservoir of M.bovis has on the cattle incidence of bTB. This trial was highly controversial. Our focus as a team was the detection of the bacterium in cattle that in a way that doesn’t interfere with the BCG vaccine, allowing the reintroduction of the BCG vaccine and therefore taking a step that is widely accepted to be necessary to eradicate bTB from the UK. In our public interview and surveys we deliberately avoided the topic of Badgers to avoid controversy. However a number of individuals, unprompted, made it clear that they are strongly against Badger culling. Similarly the farmers we visited had completely different views on Badger culling. The situation with bTB in the UK is highly controversial, however our test aims to identify infected animals with an extremely high degree of sensitivity, allowing the definitive identification of infected animals. With any disease it is important that healthy animals are protected and infected animals are identified. New Zealand, a country that saw a reduction of bTB incidence rate of 96% in 10 years had a clear strategy to deal with the natural reservoir, possums. Our test is a tool that offers a potential solution to a problem that currently costs the UK economy £1 billion every year, and finding this solution is what drove our Human Practices. Whether our test leads the way for social change is not for us as a team to decide due to the highly complex social aspect of our work.

Although each individual party of our Human Practices was unique, our Human Practices naturally overlapped for one main reason. Each party wants a solution to the problem that is bTB. Establishing this common ground and bringing together affected parties will eventually lead to an officially bTB status for the UK. It also allowed us to integrate the most important aspects of each party into the design and implementation of our Toehold test.