During the design and course of our project, many foundational values were crucial to the decisions that we made. Most notably were social, ethical and scientific values as explained in detail below. The nature of our project in exploring a disease that is destructive to the livelihoods and wellbeing of many farmers meant that we had to handle external engagements sensitively and respectfully. In this way, social values as well as ethical and moral values were integral to these interactions. Furthermore, our project deals with a virulent disease which meant we had to handle our labatory work with sound scientific values in mind to not put any researchers at risk. In addition, this is an area of development that has been explored by many researchers before us. Therefore, being respectful of these developments made by others that we may be building upon and maintaining honesty was vital.
Social Values
Farming communities and their work is critical to the functioning of society. To put it simply, everyone has to eat and the stability of a society is underpinned by the success of farming communities. In 2024 alone, UK cattle farmers produced approximately 917 million kilograms of beef and nearly 15 billion liters of milk 1,2. The south-west (where Bovitect is based) contains 33% of England's cattle, producing £572 million and £1.6 billion worth of beef and milk respectively3. Our project aims to support the work of local, national, and international farmers by contributing to the management of an incredibly disruptive disease – Bovine Tuberculosis. In this way, our project works to preserve the livelihoods and wellbeing of cattle farmers, their families and their communities, supporting the farmers who support us.
Access to information is a key value we had in mind with designing our project. We realised integrating human practices would be a vital part given farmers are our target end-users. Because this demographic may not be familiar with complex scientific procedures nor have a controlled environment to run tests within, we had ensure we bridged the gap between the lab and the field by making the test as easily accessible and usable as possible. This consideration is ultimately what led us to pursue the Integrated Human Practices Award, as the success of our project is almost entirely dependent our team making a test that farmers can and want to use on the field. This sentiment was practiced primarily through interviews with local farmers but also extended into day-to-day work as we often had members of our iGEM team in non-traditional science degrees acting as sounding boards - ensuring that any information passed onto external non-expert participants was comprehendible to those less familiar with lab-work.
Furthermore, utilising the position of some members of the team who did not come into the project with scientific expertise and background was key to this. In this way they acted as a sounding board to ensure that any information we passed onto external non-expert participants was comprehendible.
Who did we consult?
Socially, engaging with external participants helped to ensure that our test was actually going to benefit farming communities and cattle. We soon became aware that the bTB testing regime and skin test effects many different actors throughout its chain of use. We therefore felt it was important to engage with stakeholder from each of these stages of use in order to accumulate not only all their different views and experiences, but how they might be affected by a new test that we develop. These participants included beef and dairy farmers, vets, the National Farmers Union and Members of Parliament.
Moral and Ethical Values
We also designed our project with moral values in mind. As our project aims to reduce unnecessary slaughter of cattle and prevent the spread of infection, the ethical values of preserving animal welfare were present throughout our project design. Additionally, moral values were critical in our engagement with external participants. This involved various ethical considerations including informed consent documents before any participation and being clear about how their information and input may be used. Furthermore, we always gave our external participants the option to withdraw their consent and not have their information published as well as always feeling able to decline answering any questions they were not comfortable with. Given the detrimental impact of Bovine Tuberculosis for the livelihoods of many farmers, it was crucial that we handled these conversations with the sensitivity and respect that they deserved. Additionally, by consulting experts in this area of research, we hope to be considerate to those researchers who have dedicated years to this research and not use any of their knowledge without permission. In this way we aimed to continuously practice honesty and transparency, this is similar to scientific values that were foundational to our project.
Who did we consult?
To ensure that our ethical and moral values were substantiated, we consulted the ethic department of our university in order to gain ethical approval. Furthermore, through consulting this department we developed sound regimes in order to receive properly informed consent for any external engagement. This included an information sheet about our project and how any information will be used as well as a clearly outside consent form that was signed by any participants prior to interview. This allowed any information collected and used by external participants to be responsibly and ethically implemented into our project.
Scientific Values
Honesty and transparency are key scientific values that were fundamental to our project. We know it can often be frustrating not having success in the lab, but we aimed to always report our failures as these are still signs of progress. Furthermore, amalgamating other research and collaborating is a natural part of scientific research, but accurately accrediting these sources is equally important. Therefore, we are always transparent throughout our project as to where we have built off of the work of other researchers.
A key value of scientific research is also safety. Given our project was based around a virulent disease, we made careful considerations to be able to conduct accurate research while also being safe. For example, no virulence factors were created or brought into the lab and no positive samples of bTB were used. Instead we were creative in identifying non-virulent factors to ensure our test was still sensitive while being safe for researchers.
Additionally, we worked to our best ability to conform to the 3Rs (Replacement, Reduction, Refinement) 4 to ensure responsible use of animal products in the lab. Beginning with replacement, we began by using synthetic blood to try and avoid using real animal products. However, we found that we needed to test compatibility with red blood cells so we worked to reduce the amount we used. We ordered the minimum amount of blood we could. Furthermore, in attempts to refine any impact on animals, we used blood from a local abattoir in which case this was an existing byproduct and no additional harm was done to animals.
Who did we consult?
In designing the content of our project, we sought the advice of our Principle Investigators (PIs) to ensure that our research in the Labatory was morally, ethically and scientifically sound and safe compounds were being used in the lab. This also included processes such as lab inductions for all the team and guidelines around working alone in the lab. Additionally, consulting our PIs regarding any substances used in the test so that nothing is harmful to end users.
The Impact of our Project
Through this thorough engagement with each stage of use of the current skin test for bTB, we gained an informed understanding of the shortfalls of the test and what areas our test would work to benefit. Using the specificity of the skin test as an example, by engaging with many different stages of use we can see the extensive impact that a more sensitive test (as we are working develop) would have.
Using sensitivity as an example, beginning with researchers and developers such as Prof Rees and Actiphage ® we understand the difficulties around increasing the sensitivity of the test. Then speaking with dairy and beef farmers we understood that the low sensitivity of the skin test is problematic as it can miss infected cattle and make it difficult to truly cleanse that farm of bTB. Furthermore, low sensitivity means that incolusive results are more likely and retesting needs to be carried out, (link to IHP interview). From vets, we then understood the implications for them that low sensitivity makes the results harder to read....(fill in when interview has been done). Then from unions (like the National Farmers Union) we understood on a larger scale the low sensitivity creates hostility between farmers and government testing regimes as well as greater difficulty in ridding the disease from endemic areas like the Southwest. This makes the culling that is occurring much less valuable if infected cattle remain in the herd. Then finally, the government implications mean that with low sensitivity, more testing needs to conducted for Inconclusive Reactors as well generally more testing as the disease is harder to get rid of if testing is not specific. This costs the government more money and requires more labour. Furthermore, hostility also builds between farming communities and members of parliament as complaints accumulate of inaccurate mandatory testing, as Ian Roome explained (link to IHP interview). In this case, it is clear that understanding the true extent to which shortfalls and consequent changes we hope to make to the testing regime affect all users of this testing and its results.
Ultimately, there are two main groups of actors that we hope our test will most positively impact:
cattle farmers
the government
For cattle farmers, it will do this by more accurately and effectively testing for and managing a destructive disease infiltrating their most precious asset – their cattle.
For the government, it will aid their mandated testing regime and hopefully save them money by helping to eradicate the disease sooner as well as ease any hostility between them and the farming communities. Ultimately, there is no corner of society untouched by farming communities as they fuel the people that make it up. Consequently, more effective management of the natural capital of farmers will undoubtedly have a widespread positive effect.
On a wider scale, our project has the potential to reduce badger culling. At the moment, badgers are thought to transmit TB to cattle (REFERENCE) and are culled as a result. If we could test badgers and declare them TB free, this could have a positive effect on their populations and help to preserve natural wildlife.
There is also evidence that our project is responsible and doing good for the world. Sustainable Development Goal 3 is 'Good Health and Wellbeing' 5. Within this, there is a sub goal (target 3.3) to 'End the epidemics of AIDS, tuberculosis, malaria, neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases'6. With eradicating TB as one of the UN's Sustainable Development Goals, we are hoping to contribute to this by aiding in the management of bTB. In this way, this supports the fact that our project is doing good for the world by conforming to the SDGs.
To ensure that our project is responsible, leaning into our social and ethical values will allows those who will be impacted by a change in the testing to voice any concerns that we may not have considered. We also have the guidelines outlined by iGEM that we have carefully conformed to. Furthermore, we have used a developed framework from UK Research and Innovation for responsible research 7 *link to framework below. This has allowed us maintain responsible research with external participants in relation to our project.
Use and Implementation of our Project
By engaging with stakeholders further down the user pipeline, like Ian Roome as a Member of Parliament (link to interview), we are able to get a more realistic image of how our test could be implemented in the real world. Here, Ian explained that engaging with the farming minister to try and arrange a pilot scheme would be an important way to try and implement our test. *add more after attomarker interview.
As previously mentioned, there is scope for our test to be applied to wildlife conservation to reduce badger culling. This would rely on safe capture and release of wild badgers to be able to test them, in the case that a blood sample is required. Otherwise, with further development perhaps a dung sample could be used. This would helpfully help to reduce tensions between conservationists and cattle farmers (REFERENCE?)
This project will hopefully also encourage the current testing scheme for bTB in the Southwest to be reviewed and improved by adding to this conversation and helping with momentum for change. Furthermore, this test and research has the potential to be used by other countries internationally that struggle with bTB.
Given the nature of our project as diagnostics research, future iGEM teams or researchers may be able to use our project to help inform theirs. For example, our contributions of contamination may be useful (link to bronze contribution).
Physically using the test, our end users will be veterinary practitioners. Or in the case that we can get approval for our test to be used privately, this could be cattle farmers themselves.
Integrated Human Practices
IHP Research Framework
We used a framework for responsible research and innovation to structure our engagement with external participants for integrated human practices. We took inspiration from the AREA framework developed by UK Research and Innovation (UKRI). These involved the stages Anticipate, Reflect, Engage, Act. We consulted as a team and slightly altered this framework to better suit the kind of external engagement we were undertaking, as seen in the second cycle. These stages include Intention, Contribution, Conclusion and Direction. These cycles ensured that we properly prepared, analysed and implemented any external feedback and information we recieved.
Human Practices Journey
Below is a chronological timeline of our interviews and feedback from external participants and how this effected and altered our project journey
Prof Rees Interview
26 July 2024 test
Prof Cath Rees, a Professor of Microbiology, and her team have been working to develop an alternative bTB detection system and consequently has experience working with Mycobacterium bovis specifically. She was therefore able to be an invaluable sounding board for our project as her expertise is extremely relevant to our project.
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Intentions
Prof Cath Rees is a Professor of Microbiology at the University of Nottingham with particular expertise in cattle pathogens including Mycobacterium bovis (bTB). Within this, Prof Rees and her team have been developing a bTB detection system using a bacteriophage, named Actiphage®. Consequently, she is an expert in the specific field that we were entering into, so it seemed vital to try and gain some advice and guidance and learn from her research process and contact with the farming community.
We contacted Prof Rees in hopes of gaining some advice and insight into this sector given her specific experience with Mycobacterium bovis. We were also aware that she had engaged with the communities effected by bTB and had a familiarity with the legislation surrounding bTB. These were all areas we felt we needed to break into but were unsure as to how and were hoping she could give us some guidance.
Contribution
This interview was largely our team sharing what our plans for the project were with Prof Rees, where she gave us some critical feedback. These were mostly surrounding the legislative barriers, feasibility of implementing our test and defining our market.
Most importantly, we learnt from Prof Rees about the laws around farmers privately carrying out tests in that they are not permitted to do so. She explained that technically, new tests can be approved but her personal experience with the rigidity around altering the current bTB testing regime was a useful insight for us.
Prof Rees also prompted us to define what our specific market would be. For example that we might want to focus on using the test to decide which cows to breed from. She explained that vertical transmission from undiagnosed infected dams to their calves is a large contributor to bTB re-entering a herd.
Given the government involvement with the management of TB, Prof Rees explained that it is important for us to fit our test within the current system to make its implementation more likely.
Prof Rees also suggested that we speak to a vet to understand more about the process of carrying out a bTB test so that we can better cater our novel test. She kindly gave us a contact of hers as a potential external participant to discuss this with.
Conclusions
The prohibitions around farmers carrying out private tests meant that we had to rethink where and how our test would be used. We explored the different options we had, either altering the target for our test so that it wasn’t testing directly for bTB or exploring routes to our test becoming additive to the current government testing regime.
This interview really pushed us to focus on the implementation and future pipeline of our test instead of just focusing on the scientific success of the test mechanism. As although this is vital, having a clear route to implementation in the market is also important. This meant that we felt it was very important we spoke to farmers who have personal experience with the effects of bTB on their herds and their livelihoods to ensure that we have support from stakeholders in the industry if we were to try and push our test through the legislation.
Direction
We decided to explore the route of introducing our test into the current government testing process instead of changing the target of our test. To do this, we reached out to MPs in our local constituencies to try and arrange an interview and explore the barriers to implementing our test.
We reached out the vet that Prof Rees gave us the contact of to arrange an interview as well as a local cattle farmer.
Warwick iGEM Meetup
26 July 2024
Collaboration and a multidisciplinary approach is what underpins modern scientific advancement. In recognition of this, iGEM encourages collaboration between teams alongside healthy competition. Our team attended the UK iGEM synbio meetup, and as a result had the opportunity to establish links with other UK teams alongside attending workshops and lectures on reproducibility, synthetic biology, presentation skills and ethics. As a result, we decided to more closely pursue collaborations both in the UK and abroad, as well as refine our outreach efforts.
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Intentions
Throughout the iGEM process, collaboration with other teams is heavily encouraged. By fostering a multidisciplinary environment across teams, each team can contribute its unique perspective to the project. Through attending this meetup we hoped to establish links to other teams, especially those with similar projects to us.
Several workshops and talks were also planned, including 'reproducibility and synthetic biology', 'synbioUK', and an ethics and science communication panel. From this, we hoped to develop a more thorough understanding of what responsible synthetic biological practices look like both at the bench and outside of the lab. We also intended to incorporate the methodology discussed in the reproducibility talk to ensure our experiments, particularly our contributions, were reproducible across teams.
We also had the opportunity to present a conference-style poster and receive feedback from other teams and academics alongside a workshop on presenting posters and judging sessions. From this, we hoped to gain valuable presenting advice and experience for the jamboree, as well as improve our skills communicating our research to those both inside and outside the biological sciences.
Contribution
Meeting other UK teams was an incredibly positive experience. We compared projects, approaches, methodology and team structures with other teams, and met several teams who had comparable aspects in their projects.
The 'reproducibility and synthetic biology' talk discussed methods and data processing techniques that underpin reproducibility across labs and experiments, and highlighted the reproducibility crisis in synthetic biology. This was particularly applicable to us due to the talk focusing on protein purification and measuring fluorescence, two key aspects of our project.
The ethics and synthetic biology panel allowed us to ask experts anonymous questions on a broad range of issues, including public communication in science, the ethical ramifications of gene editing humans and the long term implications of gene editing organisms released into the wild.
The poster presentation allowed us to present our research so far to both iGEM teams, scientists and researchers in other disciplines. This gave us invaluable presentation experience, and alongside the presentation workshop (which gave a host of useful tips on how to structure a presentation or a poster, as well as how to present these resources well) allowed us to finetune our approach to science communication to those both inside and outside the field. Spending time as a team creating the poster bought together many seemingly isolated aspects of the project, and also allowed us to develop a better idea of the shape and direction of our project.
Conclusions
Developing links with several teams allowed us to self-reflect on our own project and how we fit into a community of teams. In the immediate future, we decided to keep in contact with the teams we met at the UK meetup to continue to compare approaches.
We had had our own issues with consistently achieving the same results across different experiments in protein purification and probe measurements- we plan to go over our experimental methods with a fine tooth comb to ensure maximum reproducibility.
Discussing the ethical implications of gene editing gave us better insight into the risks and benefits of projects like ours that require and rely on the modification of natural organisms. However, even more impactful was the discussion around the ethics of science communication to the general public, and it ratified our decision as a team to disclose as much of the scientific background as possible to every stakeholder in the project, whether a scientist or layperson.
Direction
Given the success of the UK meetup, we decided to each out to teams outside of the UK that may be relevant or have shared aspects of the project for collaborative purposes.
The insight constructing the poster as a team gave us led to us deciding to implement more regular cross-team meetings, as well as use the structural tips we had been given to restructure the resources we use for outreach.
The presentation tips we were given will form the core basis of the development of our promotional and presentation videos as we approach the jamboree.
National Farmers Union (NFU) Interview
12 August 2024
We were lucky to speak with the Tuberculosis team at the National Farmers Union (NFU). By speaking to the union we were able to hear an accumulation of the opinions of cattle farmers from all over the country. From this, we received crucial information about issues with current skin tests, legislative issues and preferable samples. Consequently, we decided to cease looking into dung as a possible sample as well as focusing more on accuracy and identifying government stakeholders to interview.
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Intentions
We hoped that speaking to the National Farmers Union (NFU) would give us the opportunity to hear the consensus opinion of a large collection of farmers from across the country, with the union acting as their voice.
Consequently, we were hoping to learn similar things as to when we spoke to David Andrews (an individual farmer) but hear the perspective of the NFU on these topics. These included questions about the issues with the current test, what they would want our new test to look like, how would be best to carry out the test and how this might work with current legislation and government testing.
Contribution
We were lucky enough to speak with multiple members of the NFU Tuberculosis team and have a wide range of inputs. We began with a discussion about the issues with the skin test, which confirmed our understandings. This was that accuracy, the stress of testing and time were the main issues.
We spoke about which samples would be most suitable for collecting and testing. Dung had been previously suggested by David Andrews, but this team did not seem to think this would be a viable sample to attribute the results to specific cattle. They also had concerns over how blood would be drawn if we were trying to reduce the need for using a crush. Sputum therefore seemed like a positive option as they explained that farmers often do not have much difficulty approaching and engaging with cattle in the field.
Their perspective on legislative issues were particularly interesting. They emphasised that laws around testing are particularly tight especially on who can test and collect samples. They suggested that to make our test more likely to get through government is perhaps to frame it as a development of vet testing so that it is quicker and more accurate. In this way there is less of a jump to suggesting that farmers administer their own test, and a new one at that.
The team also raised an interesting point that if we were to enable farmers to test themselves, would they be required to report positive results? In which case, many farmers may not want to test and admit that their herd has bTB. Many farmers often do their testing because they are mandatory, not out of choice. This would limit our demand for a privately administered test.
They also raised that there are doubts among the community about government testing in its accuracy.
We also passed David's idea about a separate test for meat and dairy farmers by the team. This was viewed very differently by the NFU TB team in that there should not be separate tests and one is not more important to test than the other.
Conclusions
The discussions about how some farmers do not want to test was an important alternative perspective to have. We were reminded that it is often easy to forget those who would not be interested in the test just because they have not come forward in opposition.
The doubts raised about current skin testing was positive for us as it will hopefully generate more demand and interest in a new test if the current one is dissatisfactory.
Direction
Echoed in some of our previous interviews, we were motivated to speak with a member of parliament to explore these legislative issues as this will likely change the user our product is directed at – be that farmers or vets.
The NFU's negative reaction to separate testing for meat and dairy farmers led us to decide to not pursue any developments of separate testing.
The emphasis on accuracy being a serious doubt among the cattle farming community has led us to really focus on that as one of our key selling points for this new test and to ensure that our test is as accurate as it can possible be.
We have also decided to reduce our research into using dung as a sample given that this group of experts did not think it would be viable for the type of test we are hoping to create.
Ian Roome (MP) Interview
22 August 2024
To explore the legislative barriers and solutions to implementing our test, we had the privilege of speaking with Ian Room, a member of parliment (MP) located in North Devon. His close involvement with local farming communities effected by bTB paired with a comprehensive understanding of the legislative framework made him a vital source of knowledge for our project. We were pleased to hear his positivity and support towards our concept and reiterated how beneficial it would be for farmers. His support in the case that we bring our product to government would be indispensable.
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Intentions
With all our previous interviews, the legislative barriers to implementing a new test came up multiple times. Consequently, we felt it was vital to get the perspective of a local member of parliament on this issue. After contacting many MPs, Ian Roome (North Devon MP) kindly agreed to speak with us. As County Councilor for the electoral division of Barnstaple North, Ian is familiar with the destructive impact of bTB and interacts closely with local farming communities. Going into this interview, we really wanted to get an understanding of how feasible it would be to implement our test into the current government mandated testing scheme. Additionally, we wanted to understand more about if the current support for cattle farmers is adequate in the eyes of parliament members as well as how MPs get involved in this issue.
Contribution
Ian was very supportive of our project and interested in its developments, condoning the widespread benefits it would have for farmers . His understanding of what support we might need for the government was very reassuring and exactly what we had hoped. He explained that government support and funding for the test would be very advantageous, especially to make it cheaper for farmers. He also was right in saying that government support would be very important for us to get our test from the labatory stage into the usability stage.
Ian emphasised that cattle farmers are rich in assets not cash, therefore maintaining the value of their cattle as their main assets through monitoring their contraction of bTB is vital.
Ian talked us through the process we would need to take in order to get this test on the government agenda and that keeping politicians informed during the development of such a test is definitely the right decision. He also agreed that, if successful, this could have a nationwide and international impact.
In relation to government support, Ian explained that DEFRA is underfunded and therefore inadequate in support that it offers to cattle farmers. For example, large delays in compensation for culling infected herds.
Ian also kindly gave us a contact of his that he thought would be helpful for us to speak to, Stuart Brocklehurst.
Conclusions
Ian's interest and support was very motivating for us, that a member of parliament could see the promise and importance of getting a test like this out to farmers and its benefit.
It was especially helpful to understand how we bring our test to the attention of the farming minister and that there is a pathway to get it there when we are ready for that.
It was also reassuring that to have the issues that we had extracted from our previous interviews and research reiterated by Ian. For example, the issues of DEFRA support, cost of testing and how vital it is for successful management of the disease.
Direction
We contacted Stuart Brocklehurst in hopes of being able to interview him.
We now have a pathway that we can follow in the case that we develop a successful test kit ready for market:
When we have a finished product, we would present this to APPG (All-Party Parliamentary Group) so that we would have many MPs together with a greater voice than one and this could get it onto the select committee agenda to discuss and then potentially be posed to the farming minister so the government can decide if they want to take this forward.
Attomarker Interview
3 September 2024
Attomarker are a rapid diagnostics development company within the field of medicine and personal health. Their diagnostics mechanisms are designed for use in many different settings from pharmacies to homes. Given their experience in the field of diagnostics, we hoped that by speaking to members of this company we could learn from their experiences and gain advice on our project. Shivali and Phillip who we spoke to provided us with some great points of development for our testing as well as some advice on scaling up in the future and public engagement.
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Intentions
In speaking with Shivali and Phillip from Attomarker we were hoping to gain advice from them on a few aspects of our project given that they are working at an industry scale of a similar style of project to us.
We were looking to hear about:
Advice on transitioning from biological parts in a lab to a publicly used product.
Their experience with government legislation
Advice on preparing a sample for transport and testing, specifically blood
We also wanted to hear how they engage with the public and get the message of their product out and heard.
Overall, we hoped that this interview would act a sounding board for our project and provide us with issues to work out or reassurance that we are heading in the right direction.
Contribution
Phillip and Shivali gave us some suggestions of how to test our product to help with generating how it might look in a test kit and in relation to the stability of test.
This involved potentially using different buffers to stabilise our product
Set up different stability experiments within the lab of different conditions and see how our components react
These would help overcome issues with removing samples from the lab which is restricted.
Using DNA was easier as a more stable compound in their experience
They also have us some good advice about bringing a test to market. They explained about how there are different third party companies that they use for the expansion of successful research to bring it to market. These companies are for scaling up tests as well as designing how they will be transported and received by a user. They explained that often you can define the conditions you need, the time frames and the types of containers needed and a test kit can be designed for you.
In addition, they explained the different materials that are important when trying to bring on additional investors, as well as engaging public users. That there are different kinds of marketing materials needed for the different users you are trying to sell to.
They also explained that to help bridge the gap between the lab and public use, fitting into existing systems is important. This is similar to what David Andrews explained, that working within an existing farm system is the most effective way that a new test could be introduced (*link to interview). For Attomarker, this involved engaging with medical practitioners and they ways that they collect blood samples.
For veterinary practitioners, they suggested looking at monovettes as a hardware commonly used, as well as speaking to vets to hear about what their processes are so that we could try and fit into that.
When asking them about overcoming issues of opacity in blood samples, they explained that they often work with plasma or serum.
They also suggested looking at the requirements internationally where testing perhaps isn't involved in the government and mandated to test its functioning away from the government restrictions.
Conclusions
Phillip and Shivali were generally quite positive about our project, its potential and functioning which was reassuring to us to hear from people in a similar area but industry experts. Furthermore, they had experiences similar frustrations that we had in our lab work, but on a much greater scale which was equally reassuring.
Their explanation of using third party companies involved in scientific engineering was particularly interesting for us because we were struggling to see how we might bring our concept to a functioning kit, but hearing that this is a common difficulty and other experts are often employed for this was interesting for us.
As increased specificity is one of the key aims of our test, we wanted to explore how this idea of repeats suggested by Phillip could work in our test.
Given Attomarker's success with using plasma or serum from blood samples to conduct tests on as they have lower opacities, we wanted to explore how this might look in our test and how we could achieve this.
We could see how vital it was that we speak to vets about their process of testing and equipment that they would be comfortable using so that our test has the highest chance of implementation.
Direction
We decided to try and contact/research how a third party scientific engineering company and supplier could hypothetically produce our test into a functioning kit and inform our hardware. Using the example of a supplier that they provided us was a good start point for this.
Again, the idea of fitting into a system that already exists came up as a crucial way to aid implementation. Here, we wanted to work to identify some standard procedures on farms that we could work within.
We identified that using multiple targets in our test could work as a form of repeat to increase the specificity, we wanted to test this in the lab.
To increase the stability of our test, Cas12a might be preferable as it works with DNA and is therefore more stable.
Letting our blood sample settle and clot for some time before testing may help to separate out the plasma and make it easier to test on, as they had suggested. This is something we wanted to trial in the lab.
We worked to arrange an interview with a vet so that we could have some crucial additional input for the hardware of our project.
David Andrews Interview
26 July 2024
David Andrews (of Warson farm) is a carbon-negative beef farmer dedicated to creating high-quality and local beef, as well as breeding bulls with prime genetics. As our team strives to develop a test that gives farmers more agency over their own farms, David agreed to provide a beef farmers perspective on our plans for a novel bTB test. This resulted in us greatly further developing our perspectives on the needs of the farming community, and the avenues we can take to address them.
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Intentions
A key part of our strategy to maintain our project's adherence to ethical synthetic biology guidelines was ensuring our laboratory work wasn't divorced from our target users- farmers.
As a small-scale, local, and sustainability focused beef farmer, David Andrews was the perfect starting point to establish the current issues farmers face bTB testing, their attitudes around the current surveillance model, and what a beneficial novel bTB test would look like for their community.
In this interview, we aimed to begin establish a thorough picture of the current impact bTB and the associated surveillance has on local farmers. Using these perspectives alongside direct consultation on potential hardware, software and wet lab options, we hope to inform our engineering cycle and create a test 'by farmers, for farmers'.
Contribution
David Andrews provided us with a beef farmer's perspective on a variety of issues, specifically the burden current testing places on farmers and what a novel test could best offer farmers.
He illuminated many of the issues with the current tuberculin test, including those associated with the procedural administering of the test that we had not considered. Administering the test requires the cattle to be placed in a crush twice, which can be dangerous to both the cattle and the herdsman. The stress placed on the cattle also makes them unwilling to receive medical attention in the future, and can cause a loss of up to 1/8th of the muscle mass- this means a 1/8th loss on profit for cattle farmers.
He also thought that our proposed test held a great deal of promise compared to the current regime, especially in the areas of speed, sensitivity and affordability, as well as the potential for it to be integrated into the day-to-day operation of the farm.
However, he brought to our attention several issues with our current plan for testing development. Firstly, reiterating Dr. Rees's point on legislative issues, we were told that farmers cannot legally draw blood from their herd, impacting our plans for point-of use testing for farmers. As a member of the voluntary CHeCS regime, David was familiar with voluntary testing-integrating several diseases tests into one will be far more desirable for farmers, alongside some type of a grading system to distinguish farms that have a 'gold standard' of disease management.
Finally, as a beef farmer, he posed an interesting idea - as bTB does not affect the beef industry in the same way as dairy farmers (I.e., you cannot contract bTB from consuming the meat of infected cattle), there should be two separate testing regimes for beef and dairy farmers.
Conclusions
This interview made us significantly reconsider the direction we would take the novel test in terms of intended user and potential targets. It was disappointing to hear that we would have to either sacrifice developing a test that was accessible for farmers or using blood immune response markers (an approach better supported by the literature and experimental data). In response to this, we decided to continue to pursue both the RNA blood and bTB DNA pathways, with an increased focus on developing human practices that could still give agency to farmers in the absence of a test that could directly be used by them.
Learning more about the variety of issues directly associated with not only the tuberculin test, but the operational and human issues that stem from it really made us consider how our test should work to ease these pressures. We wanted to therefore explore how we could try and reduce the need for using a crush to protect cattle and the herdsmen.
Direction
We decided to arrange a future visit to David Andrew's farm so we could better understand the conditions of farming, as well as talk to his staff. We believe this will give us valuable insight into how bTB impacts farms directly, and hear first-hand what bTB testing looks like.
We also decided to reach out to CHeCS, a non-profit that provides a voluntary test for a range of cattle diseases. This is typically used by farmers as a 'gold-standard' for cattle herd health.
Finally, to give us more insight into the complex legal issues surrounding bTB and bTB testing, we decided to reach out to the National Farmers Union- given they represent a large number of British farmers (including those in the local area), provide support throughout bTB outbreaks and campaign and lobby on the farmers behalf, we thought they would be well suited to give us a range of perspectives on bTB. We intend to ask their advice on further legislative challenges our test could face.
After hearing the stress and danger the current test places both farmers and cattle in, we decided to shift our hardware design to investigating potential avenues to avoid using cattle crushes.
David Andrews Farm Visit
8 August 2024
To gain a better idea of the operational framework that surrounds bTB testing and cattle health management, as well as the day-to-day operations of a beef farm, our team visited Warson farms in Devon. From this visit, we gained both a wide and narrow lens into the challenges bTB causes for local farmers, and the impact this has on both cattle and farming staff. From this, we decided to further investigate the relationships between different kinds of farmers, vets, governmental organisations and legislative bodies, and what impact bTB has on these relationships.
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Intentions
This visit to Warson beef farm was organised to gain a better idea of the needs of the group that forms the core motivation of the project- farmers. We believed that to develop a test that is feasible to use in the field, and that places the agency and needs of farmers at the forefront of its composition, it was necessary to conduct field research at a farm.
Leading on from our initial interview with David Andrews, in which he discussed blood as a flawed target and also the importance of a test being easily integrated into the day-to-day running of a farm, we decided to sample several different potential cattle byproducts. While at the farm, we decided to collect dung and sputum samples to later spike with our target DNA.
We also intended to learn more about the day-to-day running of a beef farm, and what health monitoring takes place alongside bTB surveillance.
Contribution
Warson farm is carbon negative on beef production, and utilizes a vast range of modern technology and strategy to maintain a healthy, premium beef cattle herd. The farm uses all recovered water, and rotates herds to maintain soil quality (which is closely monitored). The herd is fully naïve (meaning completely unvaccinated) and has achieved gold CHeCS standard (a voluntary cattle disease testing regimen). Genetics are closely monitored for several key characteristics, as the farm also sells premium breeding bulls as well as beef.
A high level of bTB monitoring and prevention is practiced at the farm. The farm is fully badger fenced to prevent cross-species infection, although a method to prevent infection from deer has not yet been produced. The farm is split into two separately registered enclosures to ensure at no point could the entire herd be exposed. Furthermore, the monitoring of soil acidity plays a role in bTB monitoring as well as environmental monitoring- bTB survives better in acidic soil.
Even with all of these precautions, the staff at Warson farms told us that bovine TB is by far the biggest threat to cattle health & business. Due to the farms presence in a high-risk area, the price they would get for a prime breeding bull is reduced by 8-10 thousand pounds, significantly impacting the farm's financial health. The stress of bTB testing can cause cattle to lose up to 1/8th of their bodyweight, significantly reducing the chance of cattle wintering well as long as the amount of beef produced.
The staff at Warson farm highlighted several distinct issues with the current TB testing and monitoring regime. Bovine TB overshadows other health management goals at the farm- Johnes disease (a chronic, infectious and usually fatal illness resulting from Mycobacterium avium subspecies paratuberculosis) testing cannot be done within 60 days of the test. Johnes disease affects 20-50% of all UK herds, and is incredibly contagious- testing and eliminating Johnes from cattle herds as quickly as possible is key[1,2]. Furthermore, the 6-month high-risk testing regime places a great amount of stress on cattle that are calving. Staff on the farm reported that the only inconclusive reactors they had had on the farm were pregnant cattle, making the involved and stressful task of birthing calves even more burdensome. Older cattle with thicker skin also display a similar anecdotal increase in reaction.
The government response to a reactor cattle, especially a pregnant one, can also put a large amount of strain on the mental health of farm staff. One staff member reported how 'If a pregnant cow is a reactor, APHA will come and slaughter it on the farm for danger of it giving birth while transporting, but if cow has just given birth, it's kept away from calf for 7 days then taken to slaughter'. As a result, the staff have to 'watch a cow cry for its calf for 7 days, or alternatively watching it be shot with its calf still alive at full term'. Furthermore, cattle that are resolved inconclusive reactors still cannot be sold- so they are often slaughtered anyway.
David reiterated his view that there should be a separate testing system for dairy and beef cattle, as if no lesions are found in the muscle (even if found in the lungs) muscle can still go into the food chain.
To the staff at Warson farm, an ideal test is accurate, sensitive test with a low rate of false positives, and is something that farmers can administer.
Conclusions
Despite the high level of investment Warson farm places into cattle health and bTB prevention, bTB is still the most significant threat to cattle, economic and staff wellbeing.
Even though a high level of preventative methods are practiced, by the simple fact of being in a high-risk area significantly impacts the farm's finances. The preventative methods themselves requires heavy and consistent investment, and the potential profit from cattle is reduced to a fraction of the potential earnings of the same cattle in a low-risk or bTB-free area.
The invasive nature of the current tuberculin skin test has a much wider health impact on cattle than the immediate ones the team identified. It prevents the monitoring of equally insidious and even more infective cattle diseases, and significantly impacts operational necessities like calving. Anecdotal evidence also suggests a potential link between cattle being immune impaired (from pregnancy and old age) and having a higher potential for being an inconclusive or positive reactor. This has the additional impact of placing farm staff under a severe seasonal stress.
The harsh, immediate and sometimes seemingly brutal response of DEFRA to inconclusive or positive reactor cattle can have a significant and long-lasting impact of farm staff. Some feel that, given meat from infected cattle can make its way into the food chain, this is disproportionate.
Direction
Continue to develop our non-invasive test, refocusing our efforts to look for a DNA target that doesn't require blood to be taken, while ensuring that the rate of false positives remains at an absolute minimum.
Evaluate how our test fits into the cattle health regulation farms already practice.
Contact more farmers, especially those in the dairy sector, to contrast and compare their experiences with bTB testing, monitoring and response.
Reach out to legislative and representative organisations to gain an idea of the bigger picture around bTB, and the relationship between farmers, vets, legislative and governmental regulatory bodies.
PSU iGEM Team Meetup
14 August 2024
In order to maintain our attempts to collaborate with other iGEM teams following our meetup in Warwick we arranged to meet (virtually) with Pennsylvania State University's (PSU) iGEM team. We were hoping to learn a bit about each other's projects and experiences doing iGEM. We were interested to hear about how bTB is prevalent in their area as well and how their team dynamic varies to ours.
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Intentions
In meeting with Pennsylvania State University's iGEM team we were hoping to make some connections for collaboration in the future and see if we could help each other at all. We were also hoping to just hear about how another team is doing, how they are structuring their work load, engaging with external participants, dealing with unsuccessful lab results, etc. We hoped that in this we could learn from each other's mistakes and successes.
Contribution
The PSU iGEM team gave us some interested information on how their team functions being much more separated between their team members working in the lab and members working on the wiki and human practices.
The members also shared their experiences of having repeated failures and frustrating experiences developing successful protocols in the lab.
We were only able to speak to the team involved in the lab work, so were unable to get much input from the members working on the wiki and human practices.
Given the rural location PSU, the team members suggested that they may have some contacts for us who work in the cattle industry in the USA.
The team members explained that TB in cattle is also a well-known issue there in their community.
Conclusions
It was reassuring to hear that another experience also had frustrating experiences with unsuccessful and slow results.
Talking with the PSU team made us grateful for the integration we have between all aspects of the competition where everyone on the team has some involvement in all aspects.
It was interesting to hear the TB is also a commonly known issue in area around PSU, which somewhat supports the idea that our test and project could be internationally applicable.
Direction
We want to maintain and support the integration of all team members being aware and partially involved in all aspects of the project as we felt that gave a strength that some teams like PSU may not have the privilege of having.
The mention of TB being prevalent in their area as well means we are still motivated that our test at some point in the future could have international implications.
David Cotton Interview
30 August 2024
David Cotton is a dairy farmer based in Sommerset who gave us a very useful alternative perspective on our project. Up to this point, our main input had been from beef cattle farmers but dairy farmers are still subject to the impacts of bTB and its effects. From David we learn about how bTB effects dairy cows differently, how he has dealt with repeated infections on his farm and his experience with badger transmission. As a result of this conversation, we are more confident that our test will be equally suitable for dairy farmers and gave slightly more preference to our Cas12 testing mechanism.
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Intentions
Going into this interview, we had similar questions to that of beef cattle farmers, but wanted to hear the perspective from a dairy farmer.
David also has had TB on his farm numerous times, so we were hoping to hear about how he has dealt with this as well as the support he received.
We wanted to hear about what he would want the test to look like and what his needs would be.
Contribution
David explained that he had tried using the gamma blood test and felt that collecting blood was just as easy as administering the skin test, but more advantageous because it only needed to be done once to get a result.
He reiterated that the skin testing process is stressful for cattle and can have negative impacts on the economic contribution of the dairy cow – this may not be as significant as the loss in weight of the beef cattle, but still notable. However, it was interesting to hear that in his opinion the impact is lower because the cattle are less stressed as they are more used to being handled as they are frequently brought in for milking.
David explained his experience of getting an inconclusive reactor (IR) where a cow is neither positive or negative for bTB. He thinks this is associated with when the cow is pregnant which may affect the immune response and therefore the skin test result. IRs are also problematic in the herd because isolation is recommended and retesting is needed.
David expressed some changes he would like to see in government testing regimes, for example less frequent testing in clear herds and more clear guidance on what test should be carried out when.
We also discussed the current support by DEFRA when a herd tests positive. David explained that although this compensation covers the cost of the cow, it does not cover the economic implication and cost.
We also learnt from David about his experience with badgers, that when the amount of badgers reduced, so did the presence of TB in herd. He also stated that a test that could be used on badgers could be very helpful in allowing there to be a more definitive idea if the badgers in the area are giving TB to the herds.
Conclusions
It was positive to hear that having had experience with blood samples, David felt it was a suitable sample to collect and test. Given that we are exploring this as a sample for our test, this was good to hear.
It was interesting to hear that although used for different products, the stress of the skin testing process negatively impacts the products from dairy cows. This reassured us that there would likely also be demand from dairy farmers for an alternative test.
David's issues with IR results suggested that the increased specificity would also be useful for him to reduce the likelihood of results like this.
From David's experience, the support from DEFRA is insufficient. Although this is not in our control, by providing more specific testing to try and reduce the amount of cattle being culled this could alleviate some of that loss.
The information we received about badgers made us think that if our test could also be used on badgers that would be very helpful, but this would only be the Cas12a test that would work.
Direction
Seemingly, Cas12a is better for dairy farmers because it would not as effected by the hormonal response to calving. Furthermore, it also has the potential to be used on badgers.
Given that David had success in using blood as a test sample, this supports our continued development of using this for our test.
Again, the increased specificity of our test compared to skin test has emerged as crucial and something we need to work to maintain to the highest standard in our test.
Piers Pepperell Interview
30 August 2024
Piers Pepperell is an experienced bTB vet whom was able to give us a fascinating insight into the practicalities of carrying out the testing regimes and offer a slightly different view from that we have received from farmers. He gave us a really insight into the areas of concern as well as ease for vets, which seemingly differ to that of farmers. For example, although crushes are perhaps more dangerous for herdsman and cattle, they are safer for vets. Furthermore, he expressed the importance in having an independent actor involved in the testing regime. Following this interview, we had more confidence in the equipment we were hoping could be used in the field as well as the demand amongst vets for a new binary result test but wanted to speak to more vets to get some second viewpoints on Piers' statements.
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Intentions
When we had spoken to Shivali and Phillip at Attomarker, they had urged us to speak to a vet to get clarification on certain things like equipment that they use, so one of our intentions was to learn about the use of equipment such as a centrifuge in field.
We really wanted to learn about the testing experience from a vets perspective. The shortfalls of the test, the subjectivity of establishing a result and the level specialist technicality involved in conducting the test.
We also wanted to acquire the view of a vet on if they think it would be feasible for farmers to test their own herds, as ultimately they would be one of the main parties affected if this shift were to occur.
Contribution
Piers explained that about 40% of the work at Mount Vets (the organisation he is a part of) is TB related and that one of the main issues with the skin test is that although the vets are thoroughly trained, the result is open to interpretation, it is not a binary result. This puts pressure on vets to read the results correctly because the whole future of the farm is in their hands.
He confirmed that the current skin test means that infected cattle will be missed – this becomes a problem if you are wanting to remove infection from the herd and take it longer to do this.
In terms of improving the skin test, he reassured us that there is a massive market for a test that is not a skin test and that it would definitely be better to not have to go out and test over two separate days.
Our test that would give a more binary answer would be something he would be interested in using.
Piers explained that there is some misunderstanding between vets and farmers; when there is a positive result but there are no visible lesions, the farmer is under the impression that their cattle were not infected, however infection is often asymptomatic to the eye.
Piers also expressed that he thinks sputum samples would be quite unlikely, which was different to some of the other input we had received. He explained that it would be difficult to put a swab into a cows mouth or nose would be difficult to get a proper sample and more likely for someone to get injured.
He stated that in his opinion a blood sample would be easier to take. Additionally, the good thing about a blood sample is that you can test for other things at the same time.
This is different for calves though, sputum would probably be easier for them but you would want the same samples universally.
One of the good things about the current test is it can be done on any type of cow – beef, dairy, calf.
For a vet, Piers explained that a crush is actually much safer.
Piers brought up using dung as a sample again, that it would be an easy sample to obtain and there would likely be a higher concentration of bTB there.
When asking Piers about his view of a future where farmers could test their own herd, his perspective was that the difference in vested interest between farmers and vets is important.
It is the farmers interest that their herd does not have bTB, whereas vets have their name attributed to the testing and their professional/medical honor to keep in mind so are more neutral actors to be reporting results of infection.
It is not the skill level of carrying out the test that is the issue, it is more that farmers are not sworn in to behave in a professional manner. Although they might, they do not have the same responsibility to do so. Furthermore, farmers have many other responsibilities and adding another one to their plate might not be a good idea.
Piers did not see a situation where getting farmers to test themselves being successful – it is positive to have an independent actor involved.
In regards to equipment, Piers seemed confident that a centrifuge could be set up on site and could be used for testing. However, not all farms have electricity by the crushes but usually something could be arranged.
Conclusions
Slightly different perspectives from Piers as a vet and David Cotton as a farmer where David felt the guidance was unclear on how to proceed when there is a positive test and found a lot of the regiments confusing whereas Piers explained that it is straightforward and not confusing. This leads us to think there might be some barriers to the communication of knowledge from scientific experts and government to farmers.
It seems that there is a market and interest among vets for a test for a more binary result, which ours would hopefully give. This was reassuring for us to know that this demand spreads in the medical field, not just for farmers. Especially since it will likely be used by vets first, this confirmation of interest was very useful.
It was exiting to hear that a centrifuge can often be set up during testing, this gives us more options for separating our red blood cells from the sample and reducing the opacity for a more clear fluorescence reading.
Piers' perspective on farmers conducting tests was really interesting, as previously we had been focusing on the technical difficulty being the issue, however it seems that the role that vets play in bTB testing is less about ability but more about where their interest lies. Actually, having an independent actor involved in the testing regime is important.
Direction
Piers' view on the importance of having an independent party conducting the testing gave us a renewed perspective on perhaps going down the route of a new test for vets rather than farmers. It would still be quicker and more sensitive, but whilst it is still government mandated testing, it seemed important to pay attention to where the interest of the person conducting the test lies.
We had more confidence in exploring options of testing using a centrifuge which should open more doors for us.
We were also more motivated to speak to more vets and further establish if there is demand in this market (rather than just farmers) for a new test.
Click for References
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[2] The UK Dairy industry [Internet]. Dairy UK. Available from:https://www.dairyuk.org/the-uk-dairy-industry/#:~:text=The%20figures%20speak%20for%20themselves
[3] Department for environment, food and rural affairs (2022). Total Income from Farming in the South West of England. [online] GOV.UK. Available at: https://www.gov.uk/government/statistics/total-income-from-farming-for-the-regions-of-england/total-income-from-farming-in-the-south-west-of-england#:~:text=Figure%202.5:%20Breakdown%20of%20livestock [Accessed 3 Sep. 2024].
[4] The 3Rs | NC3Rs [Internet]. Nc3rs.org.uk. The 3Rs | NC3Rs; 2017 [cited 2024 Sep 4]. Available from: https://nc3rs.org.uk/who-we-are/3rs
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[7] Framework for responsible research and innovation [Internet]. Ukri.org. 2023 [cited 2024 Sep 9]. Available from: https://www.ukri.org/who-we-are/epsrc/our-policies-and-standards/framework-for-responsible-innovation/
