Team:TUDelft/HP/Gold Integrated
- Introduction
- Project Timeline
- Integration in our project
The key role of Integrated Human Practices in our project
Because our project was focused on tackling a problem extremely relevant to our society, it was essential that we looked at the impact our project would have and how we could adapt our design according to the acquired information from stakeholder dialogues. Only then would our project have the desired value to be able to contribute to the issue of antibiotic resistance. Developing a detection method in the lab is one challenge, but developing a detection method that could be used in the real world is another, more complex, challenge. The complexity of the challenge in the antibiotic field made it hard to find the niche in which we could apply and validate our detection method. By meeting with experts and stakeholders, we were able to shape our design to fit everyone's wishes as best possible, and make our design relevant and responsible. The timeline of our integrated human practices process is illustrated to give an impression on how our project evolved over time due to interviews with stakeholders, and those we collaborated with.
For example, we collaborated with farmer Paul Oosthoek and did experiments on his cow’s milk samples. Additionally, we performed experiments with the isolates gained from the experts Dik Mevius and Fimme van der Wal. Also, veterinarians gave us insights in their documents to gain more knowledge about the treatment procedures. Futhermore, multiple stakeholders participated in our project How can iGEM teams best include Relevance and Responsibility in their Design?
In the last section, we summarise the most crucial insights and how stakeholders interactions lead to impressive changes in our experiments and design.
Project Timeline
In this timeline, we take you on a journey through the evolution of our design. In this tree-like interactive element on this page, you can hover over different icons, that depict important developments in the project. Each icon will fold-out to show the insights and changes we gained together with further relevant information about people/institutions involved. Additionally, our timeline is featured in the second video of our video project!
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Our interactive timeline
Click on the icons in the timeline, and find out about all the insights we gained from our stakeholders and how the dialogues shaped our project.
Feedback Synergene/rathenau
Insights
- How to keep the GMO in a contained environment
- Think about worst case scenario, how to solve it
- Kill switch when fish swallow the GMO
- Way of how we sell our idea/ pitch presentation
- Other methods of how to tackle this problem without the use of GMO
- Talk with stakeholders to really understand what the problem is or where the problem is
- Ask them what kind of solution is required
- Relevance of using synthetic biology as a solution
Changes
- Change project while using the same elements
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Summary
We were invited to the Synenergene event organised by Rathenau Institute. This event was to make iGEM teams realise the importance of performing a responsible research in their project. During the event we came into contact with several stakeholders and experts.
iGEMMers guide to the future
Name
Zoe Robaey
Function
Researcher
Co-author iGEMer's Guide to the Future - SYNENERGENE/Rathenau InstituutInsights
- Many guidelines for Integrated Human practices
Changes
- Production of a video project explaining its value
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Summary
The iGEMmers guide to the future is a tool which helps iGEM teams to incorporate IHP in their project. On this website there are numerous methods on how to tackle several parts of the IHP, such as brainstorm mapping, stakeholder mapping and SWOT (risk analysis). Their goals is for us to do responsible innovation.
KNMvD
Name
Joost van Herten
Function
Senior Policy Advisor for Veterinary Affairs at the Royal Dutch Society for Veterinary Medicine (KNMvD). KNMvD is the professional organization for veterinary surgeons in the Netherlands. The KNMvD promotes the professional development considering veterinarians in the field of animal welfare, animal health, public health and food safety.
Insights
- The use of formularies by veterinarians considering the bacterial infections and the antibiotic treatment per animal specie.
- Contact with veterinarian experts
Changes
- Integration of detection method in current treatment protocols
- Narrowing the detection method to one disease
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Summary
The insights of the methods (formularies and guidelines) veterinarians use, gave us insights in how our detection method could add value to the current regulations concerning antibiotic treatment. We found out that the treatment per animal disease is very specific, and that we had narrow our scope to one animal disease to add value. In the future, the detections methods could be slightly adapted with regards to a specific animal disease.
RIVM
Name
Cécile van der Vlugt
Function
Risk Assessor GMO, National Institute for Public Health and the Environment
Insights
- Involved institutes in The Netherlands and Europe to tackle antibiotic resistance
- The political agenda on tackling antibiotic resistance
- The overview of current developments to tackle antibiotic resistance
- The need to decrease the overuse of current antibiotics
- The need to engage the public to implement our detection method not only in veterinary field, but also in society in the future
- The acceptance of the use of GMOs contained and in the environment
Changes
- The need to decrease inefficient antibiotic use to control resistance
- Development a new treatment strategy and frontline diagnostics
- A contained method detection method considering safety and public acceptance
- From a paper chip to a tube
- Include safety as a value
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Summary
Relevance
Korienke Smit and Cécile van der Vlugt gave insights on the political agenda concerning antibiotic resistance. This way, we were able to make an overview of the most important European and Dutch institutes and agencies. Besides new vaccines and new prevention strategies to tackle the infectious diseases, and besides the need for new antibiotics and new therapeutics, the increased use (including overuse and misuse) of the available antibiotics (ref. The Netherlands Center for One Health (NCOH)) should be stopped. The detection method could be used as frontline diagnostics and could be the key for new treatment strategies.
Safety and public acceptance
Besides designing in a relevant for the field, the acceptance of our detection method was considered. We aimed to design a detection method that could be broadly implemented to detect resistance on the spot. The public should be comfortable to use our method. Our idea was based on detection with GMOs with a kill-switch on a paper-chip. However, considering safety and public acceptance, we have chosen not to use GMOs in the environment, but only the products of the GMO. Taking into account the public opinion on GMOs and bacterial resistance, we aimed to design a product that looks as safe as possible to make the public comfortable when using our detection method.
RIVM
Name
Korienke Smit
Function
Research assistant at National Institute for Public Health and the Environment (RIVM)
Insights
- Involved institutes in The Netherlands and Europe to tackle antibiotic resistance
- The political agenda on tackling antibiotic resistance
- The overview of current developments to tackle antibiotic resistance
- The need to decrease the overuse of current antibiotics
- The need to engage the public to implement our detection method not only in veterinary field, but also in society in the future
- The acceptance of the use of GMOs contained and in the environment
Changes
- The need to decrease inefficient antibiotic use to control resistance
- Development a new treatment strategy and frontline diagnostics
- A contained method detection method considering safety and public acceptance
- From a paper chip to a tube
- Include safety as a value
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Summary
Relevance
Korienke Smit and Cécile van der Vlugt gave insights on the political agenda concerning antibiotic resistance. This way, we were able to make an overview of the most important European and Dutch institutes and agencies. Besides new vaccines and new prevention strategies to tackle the infectious diseases, and besides the need for new antibiotics and new therapeutics, the increased use (including overuse and misuse) of the available antibiotics (ref. The Netherlands Center for One Health (NCOH)) should be stopped. The detection method could be used as frontline diagnostics and could be the key for new treatment strategies.
Safety and public acceptance
Besides designing in a relevant for the field, the acceptance of our detection method was considered. We aimed to design a detection method that could be broadly implemented to detect resistance on the spot. The public should be comfortable to use our method. Our idea was based on detection with GMOs with a kill-switch on a paper-chip. However, considering safety and public acceptance, we have chosen not to use GMOs in the environment, but only the products of the GMO. Taking into account the public opinion on GMOs and bacterial resistance, we aimed to design a product that looks as safe as possible to make the public comfortable when using our detection method.
Value Sensitive Design with modules
After mapping and interviewing different stakeholders, we were able to make a Value Sensitive Design of our project. In an extended report, we considered stakeholders values (including the values of iGEM) and translated these values to design requirements (figure hierarchical structure). We adapted our design and our project accordingly.
The reports of stakeholders mapping and the Value Sensitive Design can be found here:
Report sensitive design
Stakeholder analysis
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Summary
On different levels, policy-, competition-, and user level, we investigated the values that our design had to meet. How we translated the values of the stakeholders to design requirements can be found in the figure about the Hierarchical Nature of Values (figure 1). Even though some norms were contradictory (as can be seen figure 2, summary values and norms) , we aimed to meet all the norms and values as good as possible.
Figure. Hierarchical nature of values filled in for our home detection kit. Michelfelder et al. (2013).
Figure. Figure. Summary of values and norms (based on concerns and potentials different actors see) in the design process. Model inspired by Investigating Ethical Issues in Engineering Design (van de Poel, 2001).
AVINED
Name
Rik ter Loo
Function
Expert IKB Kip en Salmonella meat industry
Insights
- Forbidden to treat salmonella in chickens with antibiotics
- No high need to make big investments in treatment of chickens
Changes
- No focus on Salmonella and chickens
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Summary
Rik te Loo did not see any connection with the salmonella chicken challenges and the our detection method, because the treatment of Salmonella with antibiotics is currently forbidden. Antibiotic regulations considering chickens are currently.
The IKB Kip certification scheme is a global chain quality system for the entire poultry meat sector. IKB Kip is a dynamic system that is constantly developing. IKB Kip’s scheme management lies with the PLUIMNED foundation. This allows all links involved in the production of IKB Kip poultry meat (from breeding to processing) to ensure production methods guarantees, for instance regarding the quality and safeguarding of the quality
Gezondheidsdienst voor Dieren - Healthcare for animals
Insights
- Annual report on monitoring pathogen sensitivity for antibiotics
- Trend: rapid decrease of pathogen sensitivity for penicillins
- The roles of the farmers, veterinarians and diagnostic centers in this process
Changes
- Scope on penicillin resistance of Staphylococcus Aureus
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Summary
After an elaborate conversation with the Lotte Roos from GD, she sent us the annual report on monitoring pathogen sensitivity. This way, we gained insights in the trends considering resistance of mastitis pathogens. The sensitivity for penicillins is rapidly decreasing or there was no sensitivity.
Reflection with workshop
Insights
- Aspects that are still missing, like validation
- To do’s to achieve a responsible and relevant synthetic biology design
Changes
- Achieve relevance by validating the design at the farm
- Achieve responsibility by analyzing the risks when there is false positive or false negative
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Reflection of the workshop
Lists of responsible and relevant things in our project
Things that were considered as really responsible are listed below:
- Reliability (this is not yet know)
- GMO-free and safe
- Sensitive detection
- Contained
- The broad range of applications of TDPs
Things that were considered as relevant are listed below:
- Modules can be used separately and can be used for different purposes and broad applications: sustainable storability of TDPs
- Tackling a real societal/local threat (ABR)
- Costs (are unclear)
- User Friendliness
- Biobrick can be used for broad application and we contribute to an integrated synbio engineering system
Reflection. What is beyond the scope of iGEM and what is things we still can include?
Tackling a real problem
- Beyond the scope of the project:
- The need is to identify which AB is relevant to use when facing a disease. Our tool gives insights in which ABs not to use. Although we think that our strategy will help to reduce the abuse of antibiotics, the question in the market is slidely different. Prototype tests should give insights whether are device is relevant enough to tackle current challenges.
- Point out which AB to use
- Sensitivity and reliability
- Things we can do:
- What happens if there is a false positive or a false negative?
- Estimate the change to have a false positive or negative
- Make risks analysis: Contact TNO to talk about risks analysis
- What happens if there is a false positive or a false negative?
- Beyond the scope of our project:
- Being able to quantify detection
- Make Cas13a able to detect mutated genes
- Things we can do:
- User Friendliness:
- Things we can do:
- Contact farmer to check if we meet the friendliness requirements concerning farmers
- Contact industrial designer to think along with the final design
- Make a decision tree so the farmer knows exactly what to do after obtaining the test results
- Beyond the scope of the project:
- Develop an easier RNA extraction (specialist should look into this): Adjusting the detection protein to detect the DNA directly instead of the RNA. This would take a step of reverse transcription out of the protocol and make the assay more direct instead of indirect.
- Develop a service “a traveling lab in a bus” that does this kind of ABR tests (Front end runner)
- Things we can do:
- TDPs as sustainable storage solution:
- Beyond the scope of the project:
- Talk to TDP experts about the possibilities
- Talk to contextual experts to give insights on this sustainable solution
- Make a risk analysis concerning worldwide TDP storage
- Beyond the scope of the project:
- Costs savings:
- Beyond the scope of the project:
- Look into cheaper materials
- Beyond the scope of the project:
- What things need to be considered when bringing our prototype to the market:
- Next things to do: Brainstorm with TNO to gain insights and feedback
Conclusion
Concluding, we reflected our project with the different roles to make sure we did not miss anything. The workshop made us aware of the future challenge considering our project. Due to the reflection we gained insights in which things were beyond the scope of the project and we identified things we could still integrate in our project to make our project more relevant and responsible. Thinking from these four different perspectives was really effective. We were able to reflect the project on different levels, even though the team composition was balanced more towards the experts and system integrators.
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Summary
The goal of the workshop had two sides. For iGEM, this workshop will be a design evaluation/reflection exercise. For the CEE it is important to receive feedback on the Engineering Roles; possibly determining more engineering roles and match specific skills with the roles.
To conclude, we reflected on our project with the different roles to make sure we did not miss anything. The workshop made us aware of the future challenges considering our project. Due to the reflection we gained insights in which aspects were beyond the scope of the project and we identified aspects that we could still integrate in our project to make our project more relevant and responsible. Thinking from these four different perspectives was really effective. We were able to reflect on the project on different levels.
Integration in our project
There were several interactions with stakeholders that heavily impacted the direction of our design. Integrated Human Practices was extremely valuable in shaping our project. In response to dialogues with the public, risk assessors, and potential users, we changed our design from a GMO-based lab tool to a safe and reliable end product. Key points that we took from discussions with stakeholders were that the method needs to combine a simplified sample preparation, a fast, easy readout and the possibility for on-site use. We integrated all these in our project, by designing a cell-free method that can be stored for up to two weeks and produces a visible readout.
We started by finding a relevant case in which our device could make a contribution. Through a conversation with a veterinarian, we were advised to narrow our scope to mastitis, an udder infection affecting dairy cows.
Every milk farmer faces mastitis, a challenging udder disease affecting dairy cows.Bouwe Gall Frank (veterinarian)
This infection is not easy to get rid of; udders are exposed to the open environment, making the infection a common re-occurrence. All dairy farmers we spoke to in the Netherlands have had to deal with mastitis. Farmers want to have fast administration of antibiotics when treating this disease, as time is of the essence. Our tool makes sure that fast treatment of mastitis can be done in a responsible way, without misusing antibiotics, thereby helping to prevent the evolution of antibiotic resistant bacteria. Looking to mastitis, we adapted our tool to detect relevant resistance genes in the common pathogen, Staphylococcus Aureus (SAU), causing this disease.
It is relevant to be able to detect SAU pathogens. As there is a huge difference in sensitivity for antibiotics considering MRSA, it would be added value to have a conclusive result on the sensitivity.Maaike van den Berg (veterinarian)
After talking to experts with expertise in mastitis from the Wageningen Bioveterinary Research Center in Lelystad, we found that detecting the mecA and blaZ genes was the way to go.
MecA can be used to detect resistance against all β-lactam antibiotics.Fimme van der Wal (agricultural researcher)
Detection of blaZ is a conclusive result to exclude commonly used penicillin treatment.Dik Mevius (agricultural researcher)
For further information about these genes check out our applied design and demonstrate page.
After defining our end-users and detection goal, we looked at how we could make our device as user-friendly as possible. From the start of our project, we wanted to integrate the use of tardigrade intrinsically disordered proteins (TDPs) which are able to maintain the functionality of other proteins upon desiccation. This fitted perfectly in our design with respect to our end-users, as our TDPs enable the transportation and storage of our detection tool at room temperature. Normally, protein function can be maintained when stored at -80 degrees celsius, something that is not always available at your local dairy farm! We also envisioned that this improved storage method will be advantageous for shipping our versatile RNA-detection tool for broader applications. For further information on our TDPs, check out our TDP design page.
Adding to the storability, we realised that our tool needed to give a readout visible to the naked eye. At a farm, there are no fancy lasers or microscopes, so we had to get creative! We started by designing a microfluidics paper chip with GMOs with a kill switch to detect resistance genes, but gained crucial feedback on this.
Even if GMO kill switches were reliable, there is no public acceptance to use GMOs in the environment. If it will be accepted in the future, it will take years from now to legislate this principle. Innovation based on this gets stuck.Cecile van der Vlugt (Risk Assessor GMO)
This led us to come up with a new application: CINDY-Seq. This method allows for a simple yes or no answer to the question: is the pathogen causing mastitis in my cow resistant to penicillins, or even all β-lactamases depending on the design of Cas13a, in a matter of hours, without the use of GMOs in the environment. For more information on how CINDY-Seq works, please visit our coacervation design page.
Now that we completed the design of our detection tool, we needed to look at how we could make the sample preparation as simple as possible for a farmer, as farmers like to do most things themselves.
We try to do most things by ourselves to prevent high bills from the veterinarian.Tjerkje Poppinga (dairy farmer)
In the case of mastitis, the pathogen is present in the milk of the infected cow. By hitting the books and optimising existing protocols, we came up with an easy method to prepare a fresh milk sample for the detection tool. To know more about which methods we came up with, look at our sample prep design page where we describe this extensively.
Finally, our integrated human practices strategy helped us to think a step further about our design, regarding, for example, the costs involved in our device and what it should actually look like; what kind of ‘kit’ will it be and what will it contain? We also looked at the feasibility of our device in the context of whether or not farmers would actually be allowed to use such a device and what needs to be done considering legislation to make this possible.
Only veterinarians can prescribe or change antibiotic treatments.Engeline van Duijkeren (veterinarian)
Stakeholder interactions shaped our final design and made it feasible to transform our detection method into an application, resulting in a toolbox with which the farmers can perform the resistance test themselves on-site, instead of being dependent on slow lab processes. Simple, cheap and safe methods - for example the hand-powered centrifuge and boiling method during sample preparation, together with an optimized readout - make our device applicable for rapid frontline diagnostics. We developed our toolbox to detect the most relevant multiple antibiotic resistance genes, expanding the impact of our product to achieve better animal and human treatment strategies, see our applied design page for more info!
