Team:UCopenhagen/Human Practices
Introduction
When science is done with the aim of making the world a better place, it should be done with the people it affects most in mind. Science is, and should be treated as, a social affair, where human practice takes the lead and ultimately decides the direction of the science. Reading through this page, we'll show you how human practices has shaped our project this year, and in these ways:
- ✧ We considered different aspects of the ethical ramifications of our project.
- ✧ We integrated expert feedback to develop a modular wet lab design.
- ✧ We decided against diagnostics based on expert and patient advice.
- ✧ We based the design of our patch on patient feedback.
- ✧ We integrated patient feedback into our dry and wet lab models by making sure that the time horizon of our patch (and thus amplification in our system) fit with patient needs.
- ✧ We developed an ethics guide to aid future iGEMers in their HP work.
The challenge
It is estimated that 60% of deaths are due to chronic inflammatory diseases like chronic respiratory diseases, heart disorders, cancer, obesity, and diabetes . Chronic inflammatory diseases are debilitating, often life-long illnesses. It increases mortality and implies high costs for therapy and care.Up to one-third of patients do not respond to biologics. Doctors assess the efficacy of drugs 14-16 weeks after prescribing them. Unfortunately, the way to determine the efficacy of drug treatments can be taxing for the patient. It often involves invasive methods of testing done on-site at the hospital. Some of these tests are expensive. For example, Rheumatoid patients can undergo drastic changes in their disease that go unnoticed between tests. When testing is done, effective treatment may be too late.
Our Solution
The CIDosis patch is a supplement to traditional forms of testing.
By providing a cheap, non-invasive test for inflammation that can
be used at home, we can create a clearer picture of the disease.
The core of our idea was to give patients more autonomy over their
medical treatment plans. Furthermore, we wanted to increase the patients' quality of life.
Our Motivating Values
We knew that we wanted to do something in the medical realm. The question was what? After sketching out two motivating values that we personally found important, namely increasing patient autonomy and reducing patient suffering, we set out to brainstorm how we could use the iGEM platform to achieve those goals.
Ethical considerations
Ethical considerations always arise when developing a scientific project. When we sat to brainstorm potential controversial aspects of our project or stages where ethical questions could be raised, we listed down the following:- 1) Colour of the patch: in order to avoid making the patch into a constant reminder for the patients that they have a CID, we thought it could be a good idea to camouflage the patch on the skin. This raised an important ethical question – how do you define “skin color”? We could make a palette of different colors but to avoid any discrimination, we settled for designing a transparent patch that served two purposes – it would be invisible on the skin and it would serve as a contrast to the color change produced by the patch.
- 2) False positives: If a person suffers from other sorts of acute inflammation, such as an infection or allergies, the patch could give a false positive. To amend this, we chose to focus on helping patients with chronic inflammatory diseases, whose inflammatory levels are sustained over time. Moreover, we decided to just check the variations on inflammatory biomarkers under treatment regimes, so the variations are monitored over time. An extra double-layer of caution is to add a healthcare professional to supervise the results.
- 3) Stress: Another ethical issue is potentially causing undue stress to patients if they see a color change that does not accurately reflect their inflammation levels. Not only could that cause mental distress, but it might also lead to unnecessary visits to the hospital. As you will see, this is an issue we grappled with for a long time.
- 4) GMO safety: we tried to ensure in the best way possible the containment of GMOs by creating a kill-switch or a life-switch.
- 5) Wrong use of the patch: The perspective of the user was also considered, and a user guide was developed to avoid any wrong use of the patch and to improve the efficiency of the patch.
You can check more of the considerations under proposed implementation.
Mental Distress relief
Having a chronic inflammatory disease not only causes physical stress but can also cause mental distress. The mental distress aspect of CIDs was a major concern for us. On the one hand, we like to believe that our product is ideally suited to alleviate some of the mental distress caused by having a CIDs. The CIDosis patch is ideally placed to feature in treatment plans that focus on patient empowerment. Increasingly, patients with CID’s wishes to take a more active part in their treatment. Feeling powerless in the face of a disease can undoubtedly cause mental distress, and CIDosis can help counter that. On the other hand, there is a potential danger in partly taking healthcare professionals out of the testing procedure. If the patient misreads the results or misuses the patch, it can plausibly cause mental distress or confusion in the patient.Some of our worries were addressed by talking with people who had experience in the area of self-testing, and by talking to patients who would potentially use it. Furthermore, our reflections around this topic materialized into an article that was facilitated by a collaboration suggestion from two teams from Taiwan – CSMU and NCKU (see certificate below). You can read more about how our product alleviates mental distress here
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The article itself was our take on how the CIDosis patch could help the target groups. However, our reflections would not be worth much if we were not able to validate them by getting expert input. This input came in the form of interviews with Johan Burisch and Anna Fryxelius. An important ethical takeaway from the interview was that while patients can feel stress through self-monitoring tools, the option of simply knowing if they are okay or not without too much technical jargon is enough for them to have faith in the product.
Ethics Guide
When developing a project, it gradually becomes apparent that ethical issues permeate all aspects of it. Taking advantage of the Philosophy background of one of our team members, we decided to develop an ethics guide to help other future iGEM teams that might not have this knowledge within the team.
The guide is based on the philosophical method of casuistry. The method emphasizes mapping out the facts of your case, identifying its moral ambiguities, and comparing it to a paradigm case exhibiting a clear moral judgment. You can find the guide under our contribution page here!
A summary of the guide can be found below.
The guide is based on the philosophical method of casuistry. The method emphasizes mapping out the facts of your case, identifying its moral ambiguities, and comparing it to a paradigm case exhibiting a clear moral judgment. You can find the guide under our contribution page here!
A summary of the guide can be found below.
Considering Our Environmental Impact
Given that we are modifying nature, it is imperative for us to ensure that our product does not harm the environment and is safe to use. The entire process from manufacturing to transportation and eventually disposal has to be safe throughout and comply with national and international environmental laws. Therefore, we made an environmental analysis of our product as seen on our entrepreneurship page.Tailoring to Patient Needs
It was very important for us that this project was not developed in isolation. We knew from the beginning that our product would be of little use if we did not have input from relevant patient groups. In order to gain this input, we made some personal interviews with several patients, but we also needed a broader picture of the opinions of potential end-user’s. Therefore, we decided to send out several surveys. You can find a snippet of the results we obtained here:
Graph 1: We envision our patch as a supplement to current testing tools, and the survey results show that this approach is in line with the patients' needs and willingness to use CIDosis.
Graph 2: In accordance with our multitude of expert interviews, over half of the patients have switched medication more than 2 times.
Graph 3: Despite our concerns about a GMO product, a majority is comfortable with the GMO part of our patch.
Graph 2: In accordance with our multitude of expert interviews, over half of the patients have switched medication more than 2 times.
Graph 3: Despite our concerns about a GMO product, a majority is comfortable with the GMO part of our patch.
Our survey corroborates our conclusions from research and expert interviews (read more below in integrated HP) regarding the need for a monitoring tool like our CIDosis patch for CID patients.
When developing new medical devices it is essential to keep the patients in mind all the way. Our survey helped us confirm not only the need for new solutions, but also the willingness to try our monitoring patch. Our intention with a patch for supplementary disease tracking fits extremely well with the patient responses. In line with the iGEM goal of spreading awareness of SynBio, our survey results highlight the need for clear communication regarding the GMO to the patients. If it its explained clearly what the solution is, it can change people's perceptions drastically.
Introduction
In order to ensure that our science and project design were backed by a thorough understanding of the latest research and patient needs, we worked extensively with the following CIDosis stakeholders:• Doctor’s advice in choosing general inflammation rather than a specific illness
• Doctor’s advice in ensuring modularity of our scientific project
• Researchers advice in understanding the mechanism behind CIDs
• Patient feedback in the design of our patch
In this section, we will take you through our interviews with the relevant stakeholders. Our outreach not only helped us specify the target area of our project, but provided invaluable knowledge on how it should be executed.
Understanding Human Practice
When starting out our work, we were quite unsure about what exactly Human Practices entailed. Our understanding was that it would mean engaging with the end-users, healthcare professionals, and researchers. How we should go about doing so was somewhat unclear. In April 2020, the corona virus hit Denmark with force, and it became apparent that normal methods of outreach would be unavailable to us. Consequently, we had to restructure how we approach human practice work in general, and how we would approach potential target groups. We thought it would be a good idea to get some guidance from someone who is experienced from the past iGEM teams.
The Human Practices part of our project started in April 2020, and the first thing the team did was to approach a member of the HP Team from the 2019 UCopenhagen team – Signe Gybel.
Meeting with Signe – Ovulaid iGEM 2019
Signe Gybel helped us kickstart our human practice endeavor
She told us that two factors are
especially important for doing good work in human practices:
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1) One should investigate as many avenues as possible
2) One should be willing to improvise based on the responsiveness to our investigations.
The CID Framework
It immediately became apparent that doing human practice is a daunting task. In order to make sure our work was structured and presented in a meaningful way, we looked towards different frameworks we could work within. We found the AREA framework inspiring. The AREA framework is a cyclical method for incorporating relevant community and expert opinion into the work you are doing. The AREA framework is a European commission endorsed guide to responsible research and innovation. The framework weighs Anticipating the impact your work will have; Reflecting on the ethical, societal, and economic importance of that impact; Engaging with the people who can help to develop and design our project; and, lastly, Acting on the input we have received. In order to make each of the steps more actionable, intuitive and easy to remember for the entire group, we made our own framework inspired by AREA. We call this framework CID, reflecting the patient group we want to help. CID stands for Considerations, Interview and Decision.
- Considerations: Combining the “Anticipate” and “Reflect” steps of the AREA framework, in this step we map out the potential impact areas of our project and reflect on the ethical and societal impacts it can have. This includes mapping out the relevant stakeholder, such as patient groups, business experts and health care professionals.
- Interview: In this step we engage with the relevant community. This includes scheduling interviews with patients, getting expert opinion on our trouble areas, and sending out surveys. This is done for us to get outside input into what path we should follow, and to let the relevant stakeholders influence the design of the project.
- Decision: In this step we attempt to summarize what we have learned from the two previous steps and based on the provided information we decide what the best course of action is. Furthermore, based on the information gathered in the previous step we might encounter new areas and aspects that we need to consider. Thus, the last step leads directly back to the first step and a new iteration of the cycle begins.
How HP affected the project direction
We knew we wanted to make a non-invasive sweat based test kit for inflammation, we needed to know where such a device would be most useful. We were also uncertain about whether such a device could function as a diagnostic device, or whether it was best to focus on monitoring. In order to find out more, we set out to talk with some experts to see where a CIDosis patch would fit best. Head of Department, Tuberculosis and Mycobacteria, SSI - 7th May
Meeting with Troels Lillebæk
In tuberculosis (TB), inflammation is part of the pathogenesis. We thought it could be a good starting point for our research. In order to find out more, we contacted Troels who specializes in the subject. The key takeaways from the meeting were:
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We should combine several biomarkers for optimal precision
• We should focus on supplementing tests, instead of substituting them
To read more about the interview click here
Chief Physician, Department of Gastroenterology – 24th April 2020
Benedicte Wilson
According to Benedicte, clinical symptoms might not reflect the level of underlying inflammation, so continuous monitoring is important. Our key takeaways from this meeting were:
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IBD and EoE are diseases that can require frequent testing
• Certain CIDs can have sudden inflammation spikes without co-occurring symptoms.
• Techniques for testing inflammation by sampling feces are widely used. A patch could be a good replacement.
To read more about the interview click here
Meeting with Dr. Dinithi Iddawela - 26th April 2020
MD, Internal Medicine, UCSF Fresno
As mentioned, in the initial stages of our idea development, our focus was directed towards diagnostics. Tuberculosis was just one of our potential target groups. The possibility of diagnosing specific CIDs was also on the table. In order to know more about this topic, we interviewed Dr. Dinithi Iddawela.
The main takeaways from the meeting was:
The main takeaways from the meeting was:
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It would be more realistic for us to focus on monitroing CIDs, rather than making a diagnostic tool
• A precise monitoring tool is important for knowing whether a specific treatment plan is working.
• A precise monitoring tool would make personalizing medicine easier.
• A monitoring patch could help patients be more self-aware of their disease
To read more about the interview click here
Lector at Biomedical Institute, University of Copenhagen – 4th May
Meeting with Henrik Hasseldam
Henrik echoed the insights offered by Dr. Iddawela. The main takeaways from this meeting was:
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We should focus on making a general inflammation monitoring tool, as tailoring it to specific disease can be difficult.
• A monitoring tool could provide a solid foundation for dosage- and treatment personalization of medicine. It could also be useful in predicting attacks.
• Making a modular platform would be a good idea, as it opens for the possibility of monitoring levels of multiple inflammation markers.
To read more about the interview click here
Center for Rheumatology and Spine Diseases – 27th April
Meeting with Claus Henrik Nielson
Claus validated our idea to make a monitoring tool. The main takeaways from this meeting was:
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Interleukin 6 would be a good biomarker for us to focus on. Present tests mostly focus on CRP levels, and IL-6 correlates well with CRP levels.
• Patient compliance can be low when it comes to monitoring, due to the invasive nature of the monitoring procedures. As such, CIDosis might be a good supplement.
To read more about the interview click here
These sets of interviews were instrumental for the development of our project. We started out with an idea for a non-invasive at home test for inflammation. Part of the development phase of any project is narrowing down what exactly the project is. By interviewing different experts, we managed to exclude specific inflammatory diseases and diagnostics as potential paths for us to go down. Furthermore, we started to get a clear idea about the scientific feasibility of developing a monitoring tool for general inflammation. At the same time, we started talking to our wet lab team about the possibility of making a modular design, so we could expand to different biomarkers depending on the patient's illness and needs.
However, we needed to know whether this was something people needed or wanted. As such, we set out to interview potential target groups for such a device
How HP affected the proposed implementation
Talking to doctors and healthcare professionals gave us a more scientific perspective on how to design the patch and what the potential uses for it could be. However, patients are arguably the most important stakeholders in the product. As such, getting their perspective would give us more clarity on how the patch could look, what ethical considerations we needed to keep in mind, how long they would be willing to wear the patch, the preferred colour and designs and their feelings about having a GMO product on their skin. Furthermore, we needed to know if there were any CID patient groups that would especially benefit from our product. We are making a general inflammation monitoring device, but each CID is somewhat specific and has specific treatment needs. Our previous interviews had indicated that there was a need for our product, but we needed the perspective of patient groups. In order to gain such insight, we spoke to patients with different chronic inflammatory diseases and sent out surveys to get a broader perspective.
Eosinophilic Esophagitis (EoE) – 24th April
Meeting with Jessica Chzarn
Our first meeting with a person who could potentially use a product like ours was Jessica Chzarn. Jessica suffers from a chronic inflammatory condition called Eosinophilic Esophagitis (EoE). The key take aways from the meeting were:
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There is not known cure for Eoe. Diet restrictions is the most common way to control the disease
• The disease is often asymptomatic, making monitoring the disease important.
• testing for internal inflammation is usually done by endoscpoy. An invasive procedure that relies on potentially dangerous anesthetics.
To read more about the interview click here
Survey for Crohn's and Colitis Association – 26th May
Teitur Vagadal
Teitur Vagadal was so kind to distribute a survey we had made within the Danish Association for Crohn’s and Colitis. The feedback was very encouraging. We received responses from 14 patients aged between 22 and 58 years. The results from this survey were very comparable to the results of our general survey, snippets of which can be found at the top of this page. Some key points were:
- ✧ On average patients get blood tests every 2-3 months
- ✧ Most people said that the reason for changing medication was that it was not efficacious
- ✧ All of the survey takers were willing to wear a patch that contained GMOs (if properly walked through what that entails)
Some patient questions and concerns were also raised. Some of them were:
- ✧ What would the patch look like?
- ✧ Where would I wear it?
- ✧ How do I report the results to the hospital?
The survey partly resolved some of the concerned we had regarding patient compliance and GMO perception. It did also made clear that we needed to specify our product more. We realized that we should specify where the patch should preferable be worn, and that we should make the tracking app a more integral part of the product.
Chronic Obstructive Pulmonary Disease (COPD) – 31st August
Maria Martin and Justo Herraiz
Maria and Justo suffer from COPD, which could be a target group for us. The main takeaways from the meeting was:
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Changes in medication for COPD patient are often routine-based, and not based on any type of testing.
• Their trust in the healthcare system was big, due to their dependence on it. This translates into a willingness to use GMO products.
To read more about the interview click here
Inflammatory bowel disease (IBD) specialist, Herlev Hospital – 7th October
Meeting with Jakob Seidelin
Our meeting with Jakob served us as a confirmation that our patch would be needed. The most important takeaways from this meeting was:
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1/3 of treated IBS patients are non-respondents.
• 1/3 of those who responds to treatment lose the desired effect after one year
• The CIDosis patch could ideally replace endoscopy
To read more about the interview click here
We realized that there is a need for a non-invasive method of monitoring internal inflammation. Some patients, like Jessica, are asymptomatic and do not show any external signs of pain or discomfort. However, inflammation does not need to cause pain or discomfort to be harmful. As such, it is still necessary to detect and monitor general inflammation in order to control and treat it. Furthermore, the surveys gave us an indication of how useful such a patch would be for patients, and whether they would be willing to use it.
How HP Affected the Scientific Approach
As a team of students from varying fields, we realized that we needed outside help to guide our scientific endeavors. As such, we reached out to people with fields of expertise different from our own. The help we got was invaluable, and played an integral part in defining the execution of our project.
Marcus Medom Ryding – 28th June 2020
BSc in Quantitative Biology and Disease Modelling, MSc in Bioinformatics and Systems Biology
For this project, we needed to know how to do the science and use ordinary differential equations (ODEs) to model our work. We also needed to know how to make our research useful for future teams and synthetic biologists. Our team member, Aje, thankfully has a friend who was part of the DTU iGEM Team in 2019, LEAP, and knows a thing or two about quantitative biological data and standards. The key takeaways from this meeting was:
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Marcus provided information on how to standardize the modelling and lab work one is doing, and how to integrate the two
• Marcus introduced us to ordinary differential equations (ODEs), which are important for modelling the molecular processes necessary for developing this project.
To read more about the interview click here
Workshop with Irini and Simon – 22nd June 2020
Researchers at our host lab
The workshop held by Irini and Simon taught us about cloning strategies and how to simulate on a supercomputer. They made the science behind synthetic biology more understandable.
Team Aalto-Helsinki
Researchers at our host lab
Our partnership with Aalto started off as a dry lab collaboration. We discussed the importance of figures and visual representations when it comes to communicating dry-lab to whoever is interested. For example, Graphs should be as intuitive and simple as possible in order to facilitate easy understanding. We also discussed the need to continually add comments to our code, so that our work is as transparent as possible.
The first few meetings culminated in us deciding to use Rosetta to formalize the simulation objective and run the simulation on a supercomputer. You can read more about it here on our dry lab section.
After getting some information on how to use ODEs and user cloning strategies we decided that we should pay extra attention to the units of our model, that we should avoid relative units, and that USER cloning should be a part of our project. You can read more about our use of USER here. Lastly, we decided that Rosetta would be a useful tool for us
How HP Worked with the Ethical Implications of the Project
Throughout working on this project some ethical issues became apparent. We worried that our product might not be environmentally friendly compared to other types of inflammation tests. Furthermore, there is always the issue of containing GMOs in the patch and preventing contamination of nature. We also had some concerns regarding our end-users, such as how we could prevent misuse of our product, and whether we were potentially causing undue mental distress by having patients test themselves.
Researcher in Inflammatory Bowel Disease – 12th August 2020
Meeting with Johan Burisch
Johan told us about the testing procedures patients with Crohn's and colitis undergo. The key takeaways from this meeting were:
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• Testing of Crohn's and Colitis patients in Denmark is part of a platform called "E-health". E-health is a self-testing platform for inflammation.
• How information is conveyed in self-testing tools is important for minimizing the potential mental distress felt by patients.
To read more about the interview click here
Case manager at Norwegian Rheumatoid Association – 12th August
Anna Fryxelius
Anna is works in the Norwegian Rheumatoid association and is herself a Rheumatoid patient. As such, she was able to give us both expert input and first-hand patient perspectives. The key takeaways from the meeting was:
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The notion of patient empowerment is important for many people in the Rheumatoid community. Many people are looking for tools to manage their disease thenselves. CIDosis could be such a tool
• "treat to target" is a new movement within Rheumatoid treatment practices. Treat to target requires frequent testing in order to get a clear picture of the disease. How aggressive the treatment plan should be is dependent on the level of inflammation.
To read more about the interview click here
Nordic Ethics Workshop
In order to answer some of these questions we, together with the iGEM team from Aalto, set up an ethics workshop for the iGEM teams in different Nordic countries.
The Nordic Ethics Workshop was insightful, to say the least. The Stockholm, Aalto, Uppsala, and NTNU teams raised some valid questions about our project. They all suggested we try an environmental impact of our patch and analyze what would be the best way to dispose of a patch containing GMOs in households while upholding safety and patient compliance. Questions regarding allergies to certain materials were raised. This question turned out to be salient as some CID patients are prone to yeast allergies. To read more about the workshop visit our partnership page
The Nordic Ethics Workshop was insightful, to say the least. The Stockholm, Aalto, Uppsala, and NTNU teams raised some valid questions about our project. They all suggested we try an environmental impact of our patch and analyze what would be the best way to dispose of a patch containing GMOs in households while upholding safety and patient compliance. Questions regarding allergies to certain materials were raised. This question turned out to be salient as some CID patients are prone to yeast allergies. To read more about the workshop visit our partnership page
Hanne Dalsgaard Nicolaisen – 27th Aug 2020
Master’s student in Environmental Engineering at Technical University of Denmark (DTU)
Hanne enlightened the HP team on the “cradle to grave” concept through a Life Cycle Assessment (LCA). To read more about the evaluation of the CIDosis patch and its environmental impact click here.
These sets of interviews were important for our reflections on the ethical issues facing us during the development of our project. The interviews with Johan and Anna gave us some reassurance regarding the mental distress aspect of our product. The patient empowerment movement within Rheumatoid arthritis communities inspired an article arguing that our product is potentially beneficial for the mental health of CID patients.
We also got a newfound appreciation for the complexities associated with making an environmental impact analysis. Making such an analysis is complicated and time-consuming. We did not get the time to make one, but we realized that if our product would be taken to market, such an analysis would be necessary.
Our conversations with different people with varied backgrounds were extremely beneficial in ideating the CIDosis patch and its design. We also integrated the input from advisors and experts in entrepreneurship. After iGEM, we hope to continue our interactions and collaborations with the business gurus and design a business canvas alongside the science and laboratory work. We also hope to reach out to people who can help us in the next steps that include making mock-up patches for the people to test the comfort, allergy, skin reactions, color, and design of the CIDosis patch.
We also got a newfound appreciation for the complexities associated with making an environmental impact analysis. Making such an analysis is complicated and time-consuming. We did not get the time to make one, but we realized that if our product would be taken to market, such an analysis would be necessary.
Concluding Remarks
Our conversations with different people with varied backgrounds were extremely beneficial in ideating the CIDosis patch and its design. We also integrated the input from advisors and experts in entrepreneurship. After iGEM, we hope to continue our interactions and collaborations with the business gurus and design a business canvas alongside the science and laboratory work. We also hope to reach out to people who can help us in the next steps that include making mock-up patches for the people to test the comfort, allergy, skin reactions, color, and design of the CIDosis patch.
- https://www.who.int/nutrition/topics/2_background/en/ ↩