Team:UCopenhagen/Human Practices

The Problem

Human Practices

Integrated HP

Introduction

Science is, and should be treated as, a social affair. Human practice is an integral part of iGEM that attempts to map the societal, environmental, and ethical implications of a scientific project. This is done by reflecting rigorously on how your project interacts with the world, and by integrating relevant stakeholder input into your reflections and your execution of the project. Human practice work is important for evaluating the viability of your project, and for evaluating where you can make the most meaningful impact. Here, we will show you how Human practice has shaped CIDosis.

How We Approached Human Practice

The CIDosis team made an extensive effort to reflect on the societal and environmental implications of our project. We relied on the input from relevant patient groups, medical researchers, and doctors. For doing integrated human practice work we developed an ethical framework. The CID framework (short for Consideration, Interview, and Decision) helped us structure our human practice endeavor in a systematic way.

Main Human Practice Outcomes

We integrated expert feedback to develop a modular wet lab design

• Based on interviews with Henrik, and other experts

We decided to focus on monitoring inflammation, instead of diagnosing it.

• Based on interviews with Benedicte, Troels and Dinithi

We based the design of the patch on patient feedback.

• Based on a general survey, and a survey for Crohn's and Colitis patients

We integrated patient feedback into our dry lab models and changed our wet lab work to fit more with patient needs.

• E.G. We adjusted how long the patients have to wear the patch before getting a result.

We developed an ethics guide for future iGEM teams. This guide is also one of our contributions this year.

In total, we interviewed a total of 10 experts and received input from 86 patients (4 from interviews, 82 from surveys).

Foundational Values

Our motivating values are founded on the UN sustainability goals. We have a strong passion about contributing to “good health and well-being” for the world population. 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.

Inspired by our motivating values, we decided a step-by-step process that included talking to different stakeholders, such as CID researchers, patients and doctors, would give us a comprehensive overview of the seriousness of chronic inflammatory diseases

Ethical considerations

We sat down to brainstorm ethical and potentially controversial aspects of our project. This is the results:

1) Color of the patch: To avoid making the patch a constant reminder for CID patients, we initially thought the patch should be camouflaged on the skin. This raised an important ethical question. How do you define “skin color”?

• To avoid any discrimination, we settled for designing a transparent patch that serves two purposes. 1) it will be invisible on the skin and 2) it will serve as a contrast to the color change produced by the patch.
• This ethical consideration also resulted in the use of blue people on our wiki pages.

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.

• Therefore we focus CIDosis on patients with Chronic inflammatory diseases, whose inflammatory levels are sustained over time.
• We decided to just check the variations on inflammatory biomarkers under treatment regimes, so the variations are monitored over time.

3) Stress: An issue is potentially causing undue stress to patients if they see a color change that does not accurately reflect their inflammation level. Not only could that cause mental distress, but it might also lead to unnecessary visits to the hospital. Reflections on this culminated in an article

4) GMO safety: Current concerns about GMOs affecting health, and passing genes to other micro organisms, made us decide to eventually implement kill-switch or a life-switch to contain our GMO.

5) Wrong use of the patch: What if the user used our patch wrong? CIDosis is to blame if negative consequences occur as a result av subpar communication from our side.

• We developed a user guide to avoid any wrong use of the patch, and to improve the efficiency of the patch.

You can see how some of these considerations affected our design under proposed implementation.

Further Exploring Patient Stress and CIDosis as a stressor

Having a chronic inflammatory disease not only causes physical stress but can also cause mental distress. On the one hand, we like to believe that our product can relieve some of the mental distress caused by CIDs. The CIDosis patch is ideally placed to feature in treatment plans that focus on patient empowerment . Increasingly, patients with CID’s wish to take a more active part in their treatment. On the other hand, there is danger in partly taking healthcare professionals out of the testing procedure. If patients misread the results or misuses the patch, it can plausibly cause some mental distress.

We addressed some of our worries by conversing with people, such as Johan Burisch and Anna Fryxelius, who had experience in the area of self-testing as well as patients who would potentially use it. We found out that often CID patient valued having increased control of their disease. Increasing patient autonomy is a way to mitigate the negative mental health impacts of CIDs .

• We wrote an article. This materialized via a collaboration suggestion from two teams from Taiwan – CSMU and NCKU (see certificate below).
• The article itself is our take on how the CIDosis patch could help the target groups
• The article explored from a phenomenological perspective the nature of living with a CID, and how it negatively affects mental health. Such an analysis laid the groundwork for arguing that increasing patient autonomy improves mental health

Developing an Ethics Guide

When developing CIDosis, it gradually became apparent to us 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. In short, the guide help iGEM'ers define and decide on how to work with the ethical aspects of their project. The guide constitute our contribution to iGEM this year. You can read more about it here!

The Guide was developed in collaboration with SynthEthics, an organization working with ethical issues in biology.

The six steps of the guide is summarized in laymans term below.

1. Mapping out your case

• The project should be described in such detail that it becomes apparent where the moral ambiguities, or grey areas, lie. This is where your moral work should be focused.

2. Identifying relevant moral motto

• These are short, rule-like sayings that give moral identity to your case. For example, actions speak louder than words, honesty is the best policy, etc. In this step, you do not make judgments or conclusions but simply define the moral identity that apply to your problem.

3. Formulating a paradigm case

• Formulate an example case that illustrates a clear moral judgment. This paradigm case should share some similarities with the problem you wish to investigate. That means that at least one of the moral mottos that applies to your project should apply to the paradigm case.

4. Compare your case with the paradigm case

• Using the paradigm as an analogous case, you can investigate similarities and differences with your project. The paradigm case exemplifies a clear moral judgment, while your case does not. This means that the differences between your project and the example case make the moral conclusions distinct.

5. Practical reasoning and weighing the facts

• At this stage, you should try to evaluate the importance of the facts that differentiate your case from the paradigm case. You should now try to evaluate which of these facts are most important for making the moral conclusions different. There is no straightforward way to do this. It requires reliance on previous experience, contextual information, and common sense.

6. Sketching out the necessary conditions for you case

• You cannot with certainty claim that your case is morally permissible. But if your case is morally permissible, you can be certain that the facts that differentiate your case from the paradigm case, need to be in place

 

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. This work also lies within the bioethical realm. 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 framework as seen on our implementation page.
• We tested this framework by analyzing Aalto-Helsinki's project and thus laid the groundwork for mapping out our own environmental impact in the future.

Our meeting with Hanne Dalsgaard Nicolaisen, a master student in Environmental engineering, was instrumental for learning about the “cradle to grave” concept through a Life Cycle Assessment (LCA). She took us through a six step procedure for making a comprehensive analysis of our environmental impact. She also suggested some software tools necessary for performing such an analysis. To read more about how we in the future would proceed with such an evaluation of the environmental impact of the CIDosis patch click here.

Surveys: 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.
We also needed a broader picture of the opinions of potential end-user’s.
• Therefore, we decided to send a general survey and a survey for the Danish Crohn's and Colitis association. We received 82 patient responses.
You can view our whole survey, or you can find a snippet of the results we obtained below:

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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 expert interviews, over half of the patients have switched medication more than 2 times. This indicates that there is a need for CIDosis, as it is necessary to provided information on when medication change is needed

Graph 3: Despite our concerns about launching a GMO product, a majority is comfortable with our patch containing GMOs.

Graph 4: When the GMO is explained as modified Baker's yeast, it changes the patient's perception, and almost everyone is comfortable with having the modified yeast in the patch.


Our survey corroborates our conclusions from research and expert interviews regarding the need for a monitoring tool like our CIDosis patch for CID patients (read more below in integrated HP). When developing new medical devices it is essential to keep the patients in mind at all times. Our survey helped us confirm not only the need for new solutions, but also the patients' willingness to try our monitoring patch. Our intention with a patch for supplementary 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 nature of GMOs. If it is explained clearly, it can change people's perceptions drastically.

Introduction

We worked extensively with CIDosis stakeholders. This ensured that our science and project design was backed by a thorough understanding of the latest research and patient needs:
• 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 it also provided invaluable knowledge on how it should be executed.

Understanding Human Practice

When starting out, 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 our human practice approach. We decided to get some guidance from Signe Gybel, a previous iGEM participant.

Getting Introduced to Human Practices

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:

1) One should investigate as many avenues as possible
2) One should be willing to improvise based on the responsiveness to our investigations.

Feeling much more informed about the nature of human practices, we set out to integrate the opinions and advice of relevant groups.

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 opinions 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

Main Consideration: Could our patch be used as a diagnostic device, or would it be better to focus on monitoring?

We knew we wanted to make a non-invasive sweat based test kit for inflammation, but we needed to know where such a device would be most useful. Would such a device be best suited for diagnostics, or is it best to focus on monitoring? We set out to talk with some experts to see where a CIDosis patch would fit best.

Tuberculosis as a Potential Target Area

Troels Lillebæk, Head of Department Tuberculosis and Mycobacteria, SSI - May 7th

One of the first target areas we considered was tuberculosis. In tuberculosis (TB), inflammation is part of the pathogenesis. We thought it would 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:

• We should combine several biomarkers for optimal precision
• We should focus on supplementing tests, instead of substituting them
• Precise, non-invasive, at-home testing already exist for tuberculosis

To read more about the interview click here

IBD and EoE as Potential Target Areas

Benedicte Wilson, Chief Physician, Department of Gastroenterology – April 24th

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:

• Inflammatory Bowel Disease (IBD) and Eosinophilic Esophagitis (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

Focusing on Monitoring vs Diagnostics

Dr. Dinithi Iddawela, MD, Internal Medicine, UCSF Fresno - April 26th

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 were:

• 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

Focusing on General Inflammation

Henrik Hasseldam, Lector at Biomedical Institute, University of Copenhagen – May 4th

Henrik echoed the insights offered by Dr. Iddawela. The main takeaways from this meeting were:

• 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

Main Decision: Look into the possibility of making a monitoring tool for general inflammation

We started out with an idea for a non-invasive at-home test for inflammation. By interviewing different experts, we managed to exclude specific inflammatory diseases and diagnostics as potential focus areas. Furthermore, we started to get a clear idea about the scientific feasibility of developing a monitoring tool for general inflammation. We started talking about the possibility of making a modular design, so we could expand to different biomarkers depending on the patient's illness and needs.

How HP Affected the Proposed Implementation

Main consideration: Getting patient input on designing our project

Patients are arguably the most important stakeholders in our product. Getting their perspective could give us clarity on how the patch should look, what ethical considerations to keep in mind, how long they would be willing to wear the patch, the preferred color, and their feelings about using a GMO product. Furthermore, we needed to know if there were any CID group that would especially benefit from our product. Each CID is somewhat specific and has specific treatment needs. We spoke to patients with different chronic inflammatory diseases and sent out surveys to get a broader perspective.

Considering EoE patient Perspective

Jessica Chzarn, Eosinophilic Esophagitis (EoE) patient – April 24th

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 takeaways from the meeting were:

• There is not known cure for Eoe. Dietary restriction 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 endoscopy. An invasive procedure that relies on potentially dangerous anesthetics.

To read more about the interview click here

Considering Crohn's and Colitis Patient Perspective

Survey for Crohn's and Colitis Association – May 26th

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.

Considering COPD patient perspective

Maria Martin and Justo Herraiz, COPD patients – August 31st

Maria and Justo suffer from Chronic Obstructive Pulmonary Disease (COPD), which we thought could be another target group for CIDosis. The main takeaways from the meeting were:

• 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 as a Potential Target Group

Jakob Seidelin, Inflammatory bowel disease (IBD) specialist, Herlev Hospital – October 7th

Our meeting with Jakob served us as a confirmation that our patch would be needed. The most important takeaways from this meeting were:

• 1/3 of treated IBD 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

Main Decision: Based on patient feedback, we decided to develop a monitoring tool for general inflammation

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

Main Consideration: Get expert insight for developing the scientific parts of our project

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.

Learning how to Model

Marcus Medom Ryding, MSc in Bioinformatics and Systems Biology– June 28th

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 were:

• How to standardize the modelling and lab work one is doing, and how to integrate the two
• 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 – June 22nd

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. They introduced us to the concept of USER cloning and proposed that we use this method in the development of our project. Such a method would make it possible to construct a modular biosensor. USER cloning became an integral part of our project.

Proof reading and Learning how to Communicate our Modeling

Researchers at our host lab, Team Aalto-Helsinki

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.

Main Decision: Develop our project with USER cloning

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 cloning here. Lastly, we decided that Rosetta would be a useful tool for us.

How HP Affected the Ethics of the Project

Main Consideration: Investigate the ethical implications of our 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 monitor themselves.

Exploring the world of Self-Testing

Johan Burisch, Researcher in Inflammatory Bowel Disease – August 12th

Johan told us about the testing procedures patients with Crohn's Disease and Colitis undergo. The key takeaways from this meeting were:

• 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.
• According to Johan, 80 % of people diagnosed with Crohn’s Disease have had at least one medication change one year after diagnosis.

To read more about the interview click here

Learning About Patient Empowerment

Anna Fryxelius, Case Manager at Norwegian Rheumatoid Association – August 12th

Anna works in the Norwegian Rheumatoid Association and is herself a Rheumatoid Arthritis (RA) patient. As such, she was able to give us both expert input and first-hand patient perspective. The key takeaways from the meeting were:

• The notion of patient empowerment is important for many people in the rheumatoid community. Many people are looking for tools to manage their disease themselves. According to her, 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 depends on the level of inflammation.
• RA patients change their medications frequently. It is not unusual for patients to have changed their medications up to 20 times.

To read more about the interview click here

Working Through Ethical Issues - Nordic Ethics Workshop

Nordic Ethics Workshop with Copenhagen, Helsinki, Stockholm, Trondheim and Uppsala

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

Main Decision: Look into the possibility of CIDosis being a tool for mental distress relief.

These sets of interviews were important for our reflections on the ethical issues associated with 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.

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 develop a business plan alongside the science and laboratory work. We also hope to reach out to people who can help us in the subsequent steps that include making mock-up patches for the people to test the comfort, allergy, skin reactions, color, and design of the CIDosis patch.

1. https://www.who.int/nutrition/topics/2_background/en/ ↩
2. Castro, E. M., Van Regenmortel, T., Vanhaecht, K., Sermeus, W., & Van Hecke, A. (2016). Patient empowerment, patient participation and patient-centeredness in hospital care: A concept analysis based on a literature review. Patient Education and Counseling. https://doi.org/10.1016/j.pec.2016.07.026 ↩
3. Sunyaev, A., & Chornyi, D. (2012). Supporting chronic disease care quality: Design and implementation of a health service and its integration with electronic health records. Journal of Data and Information Quality. https://doi.org/10.1145/2184442.2184443↩
4. Naik, A. D., Dyer, C. B., Kunik, M. E., & McCullough, L. B. (2009). Patient autonomy for the management of chronic conditions: A two-component re-conceptualization. American Journal of Bioethics. https://doi.org/10.1080/15265160802654111↩
5. Herrera Izaguirre, J. (2007). International Law and GMOs: can the Precautionary Principle Protect Biological Diversity? Boletín Mexicano de Derecho Comparado. https://doi.org/10.22201/iij.24484873e.2007.118.390↩
6. Owen, R., Bessant, J., & Heintz, M. (2013). Responsible Innovation: Managing the Responsible Emergence of Science and Innovation in Society. In Responsible Innovation: Managing the Responsible Emergence of Science and Innovation in Society. https://doi.org/10.1002/9781118551424↩

Troels

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Troels told us we could combine more than one biomarker to detect different tuberculosis phases (latent, atypical, and active tuberculosis). He also highlighted that PCR and Sputum smear tests are already precise and that we could focus on supplementing them, instead of substituting them. He also suggested we look at making a patch that could diagnose TB in immunocompromised patients (i.e. HIV positive) and children since the existing tests are of little help in these cases.

The takeaways of this meeting were to consider the use of more than one biomarker to have a more specific picture and to consider the option of supplementing, rather than substituting, tests.

Benedicte

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For gastrointestinal inflammatory diseases like IBD they have started to get patients to take photos of their feces for a monitoring app. She likes the idea of a patch to replace this. IBD and EoE are diseases that can require frequent monitoring. Sometimes CIDs like IBD can have sudden inflammation spikes without co-occurring symptoms. As such, a monitoring patch could be useful for this.

However, we needed to know whether our product could fit with other CID groups. We wanted to get a clear picture of how often patients with other CIDs were getting tested. Testing frequency varies, but Benedicte gave us a good reason for being optimistic. According to Benedicte, CID patients get tested frequently, some as often as every four to six months.

After our meetings with Troels and Benedicte, we decided to choose general inflammation over tuberculosis for the following reasons: Many on the team know people who suffer from CIDs, which partially made it a personal choice. The feasibility of focusing on CID was reinforced by our talk with Benedicte. We realized that there was a need for novel patient testing. The final motivation was the outreach opportunity offered by choosing a target group that could be reached easily in our local community.

Johan

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According to Johan, 80 % of people diagnosed with Crohn’s have had at least one medication change one year after diagnosis. This means there is an obvious need to monitor inflammation in order to see if medication is working

Johan also introduced us to a platform called “E-health”, a platform developed for the same purpose as CIDosis The patients are sent tubes containing a solution that determines the level of C-reactive protein in their feces. The patients then take a photo of the solution containing feces. An app then informs the patients about their inflammation level through a color scheme, where red is “bad”, yellow is “moderate” and green is “good”. Johan explained that if you inform the patients, they usually do not feel the need to know the exact level of inflammation. The color scheme is enough, as it is easy to relate to. In this way, the patients can track their inflammation states and take appropriate action, while the actual biomarker values are only shown to the medical professionals, who can identify the right course of action.

We thought the color scheme was a great idea, and we would have implemented this into our project if not for time constraints. However, this became one of the main points for the design of a modular wet lab system through adjustment of G-alpha affinity to the beta-gamma complex in the yeast pheromone pathway, and the amount and placement of TEV recognition sites. If more time could be spent, we would do further sensitivity modeling to better differentiate between the biomarker values that represent green, yellow and red color. This would be the next step of our integrated human practice design.

Anna

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Anna introduced us to the concept of “patient empowerment”. It is a concept that involves engaging patients more in the treatment of their disease, by informing and educating them on their condition in order to facilitate shared decision-making regarding monitoring and treatment plans. Anna also directed our attention to the new “treat to target” movement - a treatment strategy that involves frequent testing to monitor disease progress and switching medications quickly if desired effects are not achieved. Naturally, a non-invasive home test patch for inflammation would fit nicely with such a treatment plan. Frequent testing would be made easier with our patch.

While we agree that it is long overdue that the health system moves away from the paradigm of “provider-knows-best" and incorporates the desires and needs of informed patients, our thoughts were that the knowledge that the patient receives should be tangible for them to understand. But we had no real idea about what “too much information” for the patient meant. This would become a key ethical concern for us. Our product would ideally be used as a tool that gives the patient a feeling of empowerment. However, we worried that partly removing the doctor from the testing procedure could cause undue mental distress if the information provided was not conveyed properly.

Jessica

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EoE is a genetic condition. Proton pump inhibitors and antacids are prescribed to relieve some of the pain caused by the disease, but unfortunately, there is no known cure. Diet control is the most common way of controlling the disease. Jessica, her mother, sister, and brother, all suffer from EoE. While Jessica and her mother are asymptomatic, her sister and brother are not, and often feel discomfort, nausea, or pain whenever they eat certain types of food.

In order to test for EoE as well as to check if diet modifications have caused internal inflammation, the patients undergo endoscopy. It is a lengthy procedure because it requires the administration of general anesthetics. A 5-10-minute procedure ends up taking 2-3 hours. Furthermore, frequent administration of anesthetics can be dangerous.

Iddawela

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Dr. Iddawela was the first to suggest that instead of a diagnostic tool, we could try to develop a general monitoring device for checking the efficacy of Rheumatoid arthritis medications. She emphasized the importance of knowing whether a treatment plan is successful in managing inflammation. She echoed Benedicte's statements and said that many patients need to get frequent blood tests to check the efficacy of the medication. A non-invasive method could increase patient compliance and make monitoring easier and more precise.

We figured that moving to a monitoring tool would be a good idea to help patients be more self-aware of their disease as well as helping doctors in personalizing medication for patients in a quicker way. However, we worried whether such a device would even be useful. A thought that occurred to us was that often patients would simply feel pain, nausea, or fatigue if they had an inflammation spike, and consequently, there would be no need for a monitoring device.

Claus

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He suggested that IL-6 is a good biomarker to focus on, as present testing methods mostly check for CRP, and IL-6 levels correlate well with CRP levels. He also said that patient compliance is low when it comes to monitoring because patients are reluctant to get tested periodically. This might be due to the invasive nature of current testing, and a patch might increase patient compliance.

Professor Nielsen was also one of the first Doctors to confirm, that self-monitoring at home would be a very useful tool for people with autoimmune diseases that are under biological treatment (ex. with antibodies) as only around 1/3 of patients are responders to these types of treatments and 1/3 of responders will loose the effect of the treatment.

Henrik

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Henrik suggested that we focus on developing a general inflammation biosensor, as tailoring it to specific diseases might not be feasible. Furthermore, Henrik emphasized that the potential use of such a device might be to measure therapeutic responses in relevant patients. An inflammation monitor could provide a solid foundation for dosage- and treatment personalization of medicine. He also answered our question on “feeling” inflammation and said that similar biomarkers are released in all chronic inflammatory diseases but what differs is the level of each biomarker in each condition.

Based on the information provided by Hasseldam and Dr. Iddawela, we decided to abandon the idea of monitoring specific diseases, and instead focus on monitoring general inflammation.

Justo and Maria

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When talking with Maria and Justo, we realized that changes in the medication for COPD patients was routine-based, and not on any type of testing or as a response to new symptoms. For that reason, we believe that COPD patients can benefit from our patch. Our patch could aid in confirming when medication is losing strength, and as such should be changed.

Moreover, Maria and Justo indicated that trust in the healthcare system is enormous, probably due to their dependence on it. At least that was the case for these two COPD patients in their 50’s. This trust was translated into not having any type of reluctance against the presence of GMOs in the patch. We realized that patients’ opinions on GMOs might vary depending on the patient group and their reliance on medicine due to their condition, together with the culture of the country they come from.

Based on the information provided by Hasseldam and Dr. Iddawela, we decided to abandon the idea of monitoring specific diseases, and instead focus on monitoring general inflammation.

Jakob

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Jakob mentioned that the CIDosis patch could substitute endoscopy in the case of IBS. For these patients, it is really difficult to reach “deep healing”, as often the inflammation is not manifesting any external symptoms, and biomarker levels do not change after a period of time. Maybe we could get some information from sweat that could be useful for this purpose.

Regarding the use of the CIDosis patch in the clinic, he proposed the use of an algorithm that would decide when to send the data to the hospital, and a double-check by a nurse that would ensure the data should be checked by a doctor. This would be a way to avoid the increase of work from the health care system due to this innovation.

Marcus

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When setting out to develop such a project it is necessary to have a solid scientific foundation. Marcus taught us how we should go about standardizing the work done in the wet and dry lab, and how we should integrate the two. As we are making a modular mechanism which ideally can be specified to detect different biomarkers, it is important to do our work in a way which allows others and ourselves to build on it in the future. One of the key aspects of the workshop was the introduction of ordinary differential equations. These are important for modelling molecular processes necessary for developing this project. He also suggested that one must always characterize more than is necessary. Lastly, he emphasized that it would be smart not to use relative units.
Marcus made the task seem a lot easier. Even the ones among us who had never done coding or used programming languages were a lot less intimidated by the end of the workshop. Thanks a lot, Marcus! You can read more about how we used MIRIAM, SBML, absolute units, and GTP function in α-G here.

About us

Comprising this team are nine ambitious students from various walks of life, who have come together to produce CIDosis - a non-invasive device that can help people with chronic inflammatory diseases visualize their level of inflammation.

Helpful Links

The Team
Promotional Video
Poster
Medals

Address

University of Copenhagen
Thorvaldsensvej 40, Frederiksberg C
Denmark

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