Difference between revisions of "Team:UCopenhagen/Human Practices"

 
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          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. Reading through this page, we'll show you how human practices has shaped our project this year, and how:<br>
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Science is, and should be treated as, a social affair. Human practice is an integral part of iGEM that attempts to map the <b>societal, environmental, and ethical</b> implications of a scientific project. This is done by <b>reflecting</b> rigorously on how your project interacts with the world, and by integrating relevant <b>stakeholder</b> 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 <b>meaningful impact</b>. Here, we will show you how Human practice has shaped CIDosis.
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<li> ✧ We considered different aspects of the <b>ethical ramifications</b> of our project. </li>
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<li> ✧ We integrated expert feedback to develop a <b>modular</b> wet lab design.</li>
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<li> ✧ We decided <b>against</b> diagnostics based on expert and patient advice.</li>
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<li> ✧ We based the design of our patch on <b>patient feedback.</b></li>
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<li> ✧ We integrated patient feedback into our dry and wet lab models by making sure that the <b>time</b> horizon of our patch (and thus amplification in our system) fit with patient needs.</li>
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<li> ✧ We developed an <b>ethics guide</b> to aid future iGEMers in their HP work.</li>
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         <h5>The challenge</h5>
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         <h5>How We Approached Human Practice</h5>
                It is estimated that <b>60% of deaths</b> are due to <b>chronic inflammatory diseases</b> like chronic respiratory diseases, arthritis, inflammatory bowles diseases and diabetes <a href="#WHO" aria-describedby="footnote-label" id="WHO-ref"> </a>.
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              The CIDosis team made an extensive effort to reflect on the societal and environmental implications of our project. We relied on the input from <b>relevant patient groups, medical researchers, and doctors</b>. For doing integrated human practice work we developed an ethical framework. The <b>CID framework</b> (short for <b>Consideration, Interview, and Decision</b>) helped us structure our human practice endeavor in a systematic way.  
                Chronic inflammatory diseases are debilitating, often life-long illnesses. It increases mortality and therapy and care are expensive.
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                <br><br>Up to <b>one-third of patients</b> do not respond to medication. Doctors often 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 <b>invasive</b> methods of testing done on-site at the hospital. For example, Rheumatoid patients can undergo <b>drastic changes</b> in their disease that go unnoticed between tests. When testing is done, effective treatment may be too late.
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             <h5>Our Solution</h5>
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             <h5>Main Human Practice Outcomes</h5>
 
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              The CIDosis patch is a <b>supplement</b> to traditional forms of testing.
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We integrated expert feedback to develop a <b>modular wet lab design</b>
              By providing a cheap, non-invasive test for inflammation that can
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              be used <b>at home</b>, we can create a clearer picture of the disease.
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              The core of our idea was to give patients more autonomy over their
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              medical treatment plans. Furthermore, we wanted to provide the necessary data for continuous treatment adjustment, to increase the patients' <b>quality of life.</b>
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<i>Based on interviews with Henrik, and other experts</i></ul><br>
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              We decided to focus on <b>monitoring inflammation</b>, instead of diagnosing it.
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<ul>&bull;
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<i>Based on interviews with Benedicte, Troels and Dinithi</i></ul><br>
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We based the <b>design of the patch</b> on patient feedback.
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<i>Based on a general survey, and a survey for Crohn's and Colitis patients</i></ul><br>
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We integrated patient feedback into our <b>dry lab models</b> and changed our <b>wet lab work</b> to fit more with <b>patient needs</b>.<br>
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<i>E.G. We adjusted how long the patients have to wear the patch before <b>getting a result</b>.</i></ul>
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<br>
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We developed an <b>ethics guide</b> for future iGEM teams. This guide is also one of our <b>contributions</b> this year.
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In total, we interviewed a total of <b>10 experts</b> and received input from <b>86 patients</b> (4 from interviews, 82 from surveys).
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             <h2>Our Motivating Values</h2>
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             <h2>Foundational Values</h2>
             <div text >Like many iGEM projects, our motivating values are founded on the <b>UN sustainability goals</b>. Our team felt a strong passion about ensuring  “good health and well-being” for the world population. After sketching out two motivating values that we personally found important, namely increasing <b>patient autonomy</b> and reducing <b>patient suffering</b>, we set out to brainstorm how we could use the iGEM platform to achieve those goals.</div>
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             <div text >Our motivating values are founded on the <b>UN sustainability goals</b>. 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 <b>patient autonomy</b> and reducing <b>patient suffering</b>, we set out to brainstorm how we could use the iGEM platform to achieve those goals.</div>
 
             <div class="txt" style="display: flex; border-top: solid pink; border-bottom: solid pink; margin-top:5%; margin-bottom: 5%;align-items: center; justify-content:"><div style="display: flex; flex-direction: row; align-items: center; justify-content: center; width: 85%;"><img style="width: 32.5%; flex:1;" src="https://static.igem.org/mediawiki/2020/6/63/T--UCopenhagen--Health_SDG.png"><img style="margin-top: -5%; margin-bottom: -5%; flex:4;" src="https://static.igem.org/mediawiki/2020/9/93/T--UCopenhagen--SDG_but_no_copyright_this_time.svg"></div></div>
 
             <div class="txt" style="display: flex; border-top: solid pink; border-bottom: solid pink; margin-top:5%; margin-bottom: 5%;align-items: center; justify-content:"><div style="display: flex; flex-direction: row; align-items: center; justify-content: center; width: 85%;"><img style="width: 32.5%; flex:1;" src="https://static.igem.org/mediawiki/2020/6/63/T--UCopenhagen--Health_SDG.png"><img style="margin-top: -5%; margin-bottom: -5%; flex:4;" src="https://static.igem.org/mediawiki/2020/9/93/T--UCopenhagen--SDG_but_no_copyright_this_time.svg"></div></div>
            In order to develop a project that respected our motivating values, and accorded with the above-mentioned UN sustainable development goals, we decided to take the process step-by-step and talk to different stakeholders in an orderly fashion. Approaching different stakeholders was necessary to get a comprehensive overview on the seriousness of chronic inflammatory diseases and the myths surrounding it. This included talking to researchers, patients and doctors.*/
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          <div> Inspired by our <b>motivating values</b>, we decided a <b>step-by-step process</b> that included talking to different stakeholders, such as <b>CID researchers, patients and doctors</b>, would give us a comprehensive overview of the seriousness of chronic inflammatory diseases</div>
 
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             <h2>Ethical considerations</h2>
 
             <h2>Ethical considerations</h2>
             Ethical considerations always arise when developing a scientific project. When we sat down to brainstorm potential controversial aspects of our project or stages where ethical questions could be raised, we listed the following: <br><br>
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             We sat down to brainstorm ethical and potentially controversial aspects of our project. This is the results: <br><br>
 
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               <ol><b>1) Color of the patch: </b>in order to avoid making the patch into a constant reminder for the patients that they have a CID, we thought that the patch should be camouflaged 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 <b>transparent patch</b> that served two purposes it would be <b>invisible</b> on the skin and it would 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.</ol>
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               <ol><b>1) Color of the patch: </b>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”?
               <ol><b>2) False positives: </b>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.</ol>
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               <ol><b>3) Stress: </b>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 <b>mental distress</b>, but it might also lead to <b>unnecessary visits</b> to the hospital. As you will see, this is an issue we grappled with for a long time. </ol>
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               <ol><b>4) GMO safety: </b>we tried to ensure in the best way possible the containment of GMOs by creating a <b>kill-switch</b> or a <b>life-switch</b>. </ol>
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To avoid any discrimination, we settled for designing a <b>transparent patch</b> that serves two purposes. 1) it will be <b>invisible</b> on the skin and 2) it will serve as a contrast to the color change produced by the patch.  
               <ol><b>5) Wrong use of the patch:</b> The perspective of the user was also considered, and a <b>user guide</b> was developed to avoid any wrong use of the patch and to improve the efficiency of the patch. </ol>
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&bull; This ethical consideration also resulted in the use of <b>blue people</b> on our wiki pages.</ol></ul>
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<br>
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               <ol><b>2) False positives: </b>If a person suffers from other sorts of acute inflammation, such as an <b>infection or allergies</b>, the patch could give a false positive.
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&bull;
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Therefore we focus CIDosis on patients with Chronic inflammatory diseases, whose inflammatory levels are <b>sustained over time</b>. <br>
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&bull;
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We decided to just check the variations on inflammatory biomarkers under treatment regimes, so the <b>variations are monitored</b> over time.</ul></ol>
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<br>
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               <ol><b>3) Stress: </b>An issue is potentially causing <b>undue stress</b> to patients if they see a color change that does not accurately reflect their inflammation level. Not only could that cause <b>mental distress</b>, but it might also lead to <b>unnecessary visits</b> to the hospital. Reflections on this culminated in an article </ol>
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<br>
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               <ol><b>4) GMO safety: </b> Current concerns about GMOs <b>affecting health</b>, and <b>passing genes</b> to other micro organisms, made us decide to eventually implement <b>kill-switch</b> or a <b>life-switch</b> to contain our GMO. </ol>
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<br>
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               <ol><b>5) Wrong use of the patch:</b> 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.
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<br>
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<ul>
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&bull;
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We developed a <b>user guide</b> to avoid any wrong use of the patch, and to improve the efficiency of the patch. </ul> </ol>
 
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             <div>You can see how some of these considerations affected our design under <a href="https://2020.igem.org/Team:UCopenhagen/Implementation"> proposed implementation. </a></div>
 
             <div>You can see how some of these considerations affected our design under <a href="https://2020.igem.org/Team:UCopenhagen/Implementation"> proposed implementation. </a></div>
  
             <h2>Mental Distress relief</h2>
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             <h2>Further Exploring Patient Stress and CIDosis as a stressor</h2>
             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 CID. 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. 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 for the patient.
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             Having a chronic inflammatory disease not only causes <b>physical stress</b> but can also cause <b>mental distress</b>. On the one hand, we like to believe that our product can <b>relieve</b> some of the mental distress caused by CIDs. The CIDosis patch is ideally placed to feature in treatment plans that focus on <b>patient empowerment</b> <a href="#endre1" aria-describedby="footnote-label" id="endre1-ref"> </a>. Increasingly, patients with CID’s wish to take a more <b>active part</b><a href="#endre2" aria-describedby="footnote-label" id="endre2-ref"> </a>  in their treatment. On the other hand, there is danger in partly taking healthcare professionals out of the testing procedure. If patients <b> misread the results</b> or misuses the patch, it can plausibly cause some mental distress.
 
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             <br><br>
Some of our worries were addressed by conversing with people who had experience in the area of self-testing, as well as patients who would potentially use it. Furthermore, our reflections around this topic materialized into an <a href="https://2020.igem.org/Team:UCopenhagen/Collaborations#PHD"> <b>article</b></a> that was facilitated by a collaboration suggestion from two teams from Taiwan – CSMU and NCKU (see certificate below).
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We addressed some of our worries by conversing with people, such as <b>Johan Burisch</b> and <b>Anna Fryxelius</b>, who had experience in the area of <b>self-testing</b> as well as patients who would potentially use it. We found out that often CID patient valued having <b>increased control</b> of their disease. Increasing patient autonomy is a way to mitigate the negative mental health impacts of CIDs <a href="#endre3" aria-describedby="footnote-label" id="endre3-ref"> </a> .
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We wrote an <a href="https://2020.igem.org/Team:UCopenhagen/Collaborations#PHD"> <b>article.</b></a> This materialized via a collaboration suggestion from two teams from <b>Taiwan – CSMU and NCKU</b> (see certificate below).
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The article itself is our take on how the CIDosis patch could help the target groups
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The article explored from a <b>phenomenological perspective</b> 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</ul></ul>
 
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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 <b>expert input</b>. 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. <br><br>
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             <h2>Ethics Guide</h2>
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             <h2>Developing an Ethics Guide</h2>
             <div> 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.
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             <div> When developing CIDosis, it gradually became apparent to us that <b>ethical issues</b> permeate all aspects of it. Taking advantage of the Philosophy background of one of our team members, we decided to <b>develop an Ethics Guide to help other future iGEM teams</b> 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 <b>contribution</b> to iGEM this year. You can read more about it <a href="https://2020.igem.org/Team:UCopenhagen/Contribution">here!</a>
 
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<br><br>
The guide is based on the philosophical method of <b>casuistry</b>. The method emphasizes <b>mapping out the facts</b> of your case, identifying its <b>moral ambiguities</b>, and comparing it to a <b>paradigm case</b> exhibiting a clear moral judgment. You can find the guide under our contribution page <a href="https://2020.igem.org/Team:UCopenhagen/Contribution">here!</a>
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The Guide was developed in collaboration with <b>SynthEthics</b>, an organization working with ethical issues in biology.
 
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A summary of the guide can be found below.
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The <b>six steps</b> of the guide is summarized in laymans term below.
 
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<ul><h3>1. Mapping out your case </h3>
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The project should be described in such <b>detail</b> that it becomes apparent where the <b>moral ambiguities</b>, or grey areas, lie. This is where your moral work should be focused. </ul> </ul>
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<ul><h3>2. Identifying relevant moral motto</h3>
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These are short, <b>rule-like sayings</b> 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 <b>moral identity</b> that apply to your problem.</ul></ul>
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<ul><h3>3. Formulating a paradigm case</h3>
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Formulate an example case that illustrates a <b>clear moral judgment</b>. This <b>paradigm case</b> 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. </ul></ul>
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<ul><h3>4. Compare your case with the paradigm case</h3>
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Using the paradigm as an <b>analogous case</b>, 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. </ul></ul>
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<ul><h3>5. Practical reasoning and weighing the facts</h3>
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At this stage, you should try to evaluate the importance of the facts that <b>differentiate your case from the paradigm case</b>. 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.</ul></ul>
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<ul><h3>6. Sketching out the necessary conditions for you case</h3>
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You cannot with certainty claim that your case is morally permissible. But <i>if</i>  your case is morally permissible, you can be certain that the facts that differentiate your case from the paradigm case, <b>need to be in place</b></ul></ul>  
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             <h2>Considering Our Environmental Impact</h2>
 
             <h2>Considering Our Environmental Impact</h2>
             Given that we are <b>modifying nature</b>, 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 <b>safe</b> throughout and comply with national and international <b>environmental laws</b>. Therefore, we made an </b>environmental analysis framework</b> 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.  
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             Given that we are <b>modifying nature</b>, 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 <b>safe</b> throughout and comply with national and international <b>environmental laws</b><a href="#endre4" aria-describedby="footnote-label" id="endre4-ref"> </a> . Therefore:
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&bull; we made an <b>environmental analysis framework</b> as seen on our implementation page.
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&bull; We tested this framework by <b>analyzing Aalto-Helsinki's project</b> and thus laid the groundwork for mapping out our own environmental impact in the future.  
  
             <h2>Tailoring to Patient Needs</h2>
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             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 <b>relevant patient groups</b>. In order to gain this input, we made some <b>personal interviews</b> with several patients, but we also needed a broader picture of the opinions of potential end-user’s. Therefore, we decided to send a <b>general survey</b> for which we received <b>68 patient responses</b>. You can view our whole <a href="https://static.igem.org/mediawiki/2020/a/aa/T--UCopenhagen--HP-General-Survey.pdf">survey</a>, or you can find a snippet of the results we obtained below:
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                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.
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             <h2>Surveys: Tailoring to Patient Needs</h2>
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             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 <b>relevant patient groups</b>.
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<ul>
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&bull;
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In order to gain this input, we made some <b>personal interviews</b> with several patients.</ul>
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We also needed a broader picture of the opinions of potential end-user’s.  
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<ul>
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&bull;
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Therefore, we decided to send a <b>general survey</b> and a survey for the <b>Danish Crohn's and Colitis association</b>. We received <b>82 patient responses</b>.</ul>
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You can view our whole <a href="https://static.igem.org/mediawiki/2020/a/aa/T--UCopenhagen--HP-General-Survey.pdf">survey</a>, or you can find a <b>snippet of the results</b> we obtained below:
 
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<div class="format txt"><b>Graph 1:<div></b> We envision our patch as a <b>supplement</b> to current testing tools, and the survey results show that this approach is in line with the patients' needs and willingness to use CIDosis.<br></div>
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<div class="format txt"><div class="format"><b>Graph 1:</b> We envision our patch as a <b>supplement</b> to current testing tools, and the survey results show that this approach is in line with the patients' needs and <b>willingness to use CIDosis</b>.<br></div>
<b>Graph 2:</b> In accordance with our expert interviews, over half of the patients have switched medication more than 2 times.<br>
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<div class="format"><b>Graph 2:</b> 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<br></div>
<b>Graph 3:</b> Despite our concerns about launching a GMO product, a majority is comfortable with our patch containing GMOs.<br>
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<div class="format"><b>Graph 3:</b> Despite our concerns about launching a GMO product, a majority is comfortable with our patch containing GMOs.<br></div>
<b>Graph 4:</b> When the GMO is explained as modified baker's yeast, it changes the patient's perception, and almost everyone is comfortable with the modified yeast in the patch.</div>
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<div class="format"><b>Graph 4:</b> 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.</div></div>
 
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<h5 style="text-align: left;">Introduction</h5>
 
<h5 style="text-align: left;">Introduction</h5>
In order to ensure that our science and project design were backed by a thorough understanding of the <b>latest research</b> and <b>patient needs</b>, we worked extensively with the following CIDosis <b>stakeholders</b>:
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We worked extensively with CIDosis <b>stakeholders</b>. This ensured that our science and project design was backed by a thorough understanding of the <b>latest research</b> and <b>patient needs</b>:
 
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             <h5>Understanding Human Practice</h5>
 
             <h5>Understanding Human Practice</h5>
 
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             <br>
             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, .
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             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.
 
            
 
            
 
            
 
            
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<h5>The CID Framework</h5>
 
<h5>The CID Framework</h5>
 
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<div>
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 <b>AREA framework</b> inspiring. The AREA framework is a <b>cyclical method</b> for incorporating relevant community and expert opinion into the work you are doing. The AREA framework is a <b>European Commission</b> endorsed guide to responsible research and innovation. The framework weighs <b>Anticipating</b> the impact your work will have; <b>Reflecting</b> on the ethical, societal, and economic importance of that impact; <b>Engaging</b> with the people who can help to develop and design our project; and, lastly, <b>Acting</b> 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.</div>
+
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 <b>AREA framework</b> inspiring <a href="#endre5" aria-describedby="footnote-label" id="endre5-ref"> </a> . The AREA framework is a <b>cyclical method</b> for incorporating relevant community and expert opinion into the work you are doing. The AREA framework is a <b>European Commission</b> endorsed guide to responsible research and innovation. The framework weighs <b>Anticipating</b> the impact your work will have; <b>Reflecting</b> on the ethical, societal, and economic importance of that impact; <b>Engaging</b> with the people who can help to develop and design our project; and, lastly, <b>Acting</b> 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.</div>
 
             <img src="https://static.igem.org/mediawiki/2020/4/41/T--UCopenhagen--CID_framework.png">
 
             <img src="https://static.igem.org/mediawiki/2020/4/41/T--UCopenhagen--CID_framework.png">
 
             <li>
 
             <li>
               <ul><b>Considerations: </b>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.</ul>
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               <ul><b>Considerations </b>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.</ul>
               <ul><b>Interview: </b>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.</ul>
+
               <ul><b>Interview </b>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.</ul>
               <ul><b>Decision: </b>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.</ul>
+
               <ul><b>Decision </b>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.</ul>
 
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                 <h2 id="troels" style="margin-top:0px;">Tuberculosis as a Potential Target Area</h2>
 
                 <h2 id="troels" style="margin-top:0px;">Tuberculosis as a Potential Target Area</h2>
             <h3 style="color:grey;">Troels Lillebæk, Head of Department Tuberculosis and Mycobacteria, SSI - 7th May</h3>
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             <h3 style="color:grey;">Troels Lillebæk, Head of Department Tuberculosis and Mycobacteria, SSI - May 7th</h3>
 
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                 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:
+
                 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:
 
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We should focus on supplementing tests, instead of substituting them<br>
 
We should focus on supplementing tests, instead of substituting them<br>
 
&bull;
 
&bull;
Precise non-invasive at home testing already exist for Tuberculosis
+
Precise, non-invasive, at-home testing already exist for tuberculosis
 
</ul>
 
</ul>
 
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             <h2 id="Benedicte" style="margin-top:0px;">IBD and EoE as Potential Target Areas – 24th April 2020</h2>
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             <h2 id="Benedicte" style="margin-top:0px;">IBD and EoE as Potential Target Areas</h2>
             <h3 style="color:grey;">Benedicte Wilson, Chief Physician, Department of Gastroenterology – 24th April 2020</h3>
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             <h3 style="color:grey;">Benedicte Wilson, Chief Physician, Department of Gastroenterology – April 24th</h3>
 
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             <h2 id="iddawela" style="margin-top:0px;">Focusing on Monitoring vs Diagnostics</h2>
 
             <h2 id="iddawela" style="margin-top:0px;">Focusing on Monitoring vs Diagnostics</h2>
             <h3 style="color:grey;"> Dr. Dinithi Iddawela, MD, Internal Medicine, UCSF Fresno - 26th April 2020,</h3>
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             <h3 style="color:grey;"> Dr. Dinithi Iddawela, MD, Internal Medicine, UCSF Fresno - April 26th</h3>
 
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                 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.
 
                 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.
                <br>
+
The main takeaways from the meeting were:
<br>
+
The main takeaways from the meeting was:
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             <h2 id="Henrik" style="margin-top:0px;">Focusing on General Inflammation</h2>
 
             <h2 id="Henrik" style="margin-top:0px;">Focusing on General Inflammation</h2>
             <h3 style="color:grey;">Henrik Hasseldam, Lector at Biomedical Institute, University of Copenhagen – 4th May</h3>
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             <h3 style="color:grey;">Henrik Hasseldam, Lector at Biomedical Institute, University of Copenhagen – May 4th</h3>
 
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               <img style="width:30%;" src="https://static.igem.org/mediawiki/2020/4/4f/T--UCopenhagen--HenrikogAje.jpg">
 
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                 Henrik echoed the insights offered by Dr. Iddawela. The main takeaways from this meeting was:
+
                 Henrik echoed the insights offered by Dr. Iddawela. The main takeaways from this meeting were:
 
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             </div>
 
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            <h2 style="margin-top:0px;">Investigating Potential Biomarkers</h2>
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<h3 style="color:grey;">Claus Henrik Nielson, Center for Rheumatology and Spine Diseases – 27th April</h3>
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                Claus validated our idea to make a monitoring tool. The main takeaways from this meeting was:
+
<br><ul>
+
&bull;
+
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.
+
<br>
+
&bull;
+
We had previously investigated whether Interleukin 6 would be a good biomarker for us to focus on, Claus validated our investigations. Present tests mostly focus on CRP levels, and IL-6 correlates well with CRP levels.
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<br><br></ul>
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<div class="format">To read more about the interview <a class="pretty_button" href="#seemore7"><b>click here</b></a></div>
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<img style="width: 20%;" src="https://static.igem.org/mediawiki/2020/f/ff/T--UCopenhagen--decisions.png?fbclid=IwAR00udihLNXVzgyu3ahkOB0KwoyGByZWfTLcC_wyQKv4MucQI1xvZj9fjrI">
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             <h2 id="jessica">Considering EoE patient Perspective</h2>
 
             <h2 id="jessica">Considering EoE patient Perspective</h2>
<h3 style="color:grey;">Jessica Chzarn, Eosinophilic Esophagitis (EoE) patient – 24th April</h3>
+
<h3 style="color:grey;">Jessica Chzarn, Eosinophilic Esophagitis (EoE) patient – April 24th</h3>
 
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                 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:
+
                 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:
 
<br><ul>
 
<br><ul>
 
&bull;
 
&bull;
There is not known cure for Eoe. Diet restrictions is the most common way to control the disease
+
There is not known cure for Eoe. Dietary restriction is the most common way to control the disease
 
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<br>
 
<br>
 
&bull;
 
&bull;
testing for internal inflammation is usually done by endoscpoy. An invasive procedure that relies on potentially dangerous anesthetics.
+
Testing for internal inflammation is usually done by endoscopy. An invasive procedure that relies on potentially dangerous anesthetics.
 
<br><br></ul>
 
<br><br></ul>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore5"><b>click here</b></a></div>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore5"><b>click here</b></a></div>
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             <h2>Considering Crohn's and Colitis Patient Perspective</h2>
 
             <h2>Considering Crohn's and Colitis Patient Perspective</h2>
             <h3 style="color:grey;">Survey for Crohn's and Colitis Association – 26th May</h3>
+
             <h3 style="color:grey;">Survey for Crohn's and Colitis Association – May 26th</h3>
 
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             <h2>Considering COPD patient perspective</h2>
 
             <h2>Considering COPD patient perspective</h2>
             <h3 style="color:grey;">Maria Martin and Justo Herraiz, COPD patients – 31st August</h3>
+
             <h3 style="color:grey;">Maria Martin and Justo Herraiz, COPD patients – August 31st</h3>
 
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Maria and Justo suffer from Chronic Obstructive Pulmonary Disease (COPD), which could be a target group for us. The main takeaways from the meeting was:
+
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:
 
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&bull;
 
&bull;
Their trust in the healthcare system was big, due to their dependence on it. This translates into a willingness to use GMO products.
+
Their trust in the healthcare system was big due to their dependence on it. This translates into a willingness to use GMO products.
 
<br><br></ul>
 
<br><br></ul>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore9"><b>click here</b></a></div>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore9"><b>click here</b></a></div>
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             <h2 id="Jakob">Inflammatory bowel disease as a Potential Target Group</h2>
 
             <h2 id="Jakob">Inflammatory bowel disease as a Potential Target Group</h2>
             <h3 style="color:grey;">Jakob Seidelin, Inflammatory bowel disease (IBD) specialist, Herlev Hospital – 7th October</h3>
+
             <h3 style="color:grey;">Jakob Seidelin, Inflammatory bowel disease (IBD) specialist, Herlev Hospital – October 7th</h3>
 
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             <div class="txt format">
               Our meeting with Jakob served us as a confirmation that our patch would be needed. The most important takeaways from this meeting was:
+
               Our meeting with Jakob served us as a confirmation that our patch would be needed. The most important takeaways from this meeting were:
 
<br><ul>
 
<br><ul>
 
&bull;
 
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             <h2>Learning how to Model</h2>
 
             <h2>Learning how to Model</h2>
             <h3 style="color:grey;">Marcus Medom Ryding, MSc in Bioinformatics and Systems Biology– 28th June 2020,</h3>
+
             <h3 style="color:grey;">Marcus Medom Ryding, MSc in Bioinformatics and Systems Biology– June 28th</h3>
 
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               <img style="width:20%;" src="https://static.igem.org/mediawiki/2020/e/e3/T--UCopenhagen--Marcus_workshop.png">
 
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                 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: <br>
+
                 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: <br>
 
                
 
                
 
<br><ul>
 
<br><ul>
 
&bull;
 
&bull;
Marcus provided information on how to standardize the modelling and lab work one is doing, and how to integrate the two
+
How to standardize the modelling and lab work one is doing, and how to integrate the two
 
<br>
 
<br>
 
&bull;
 
&bull;
Marcus introduced us to ordinary differential equations (ODEs), which are important for modelling the molecular processes necessary for developing this project.
+
Ordinary differential equations (ODEs), which are important for modelling the molecular processes necessary for developing this project.
 
<br><br></ul>
 
<br><br></ul>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore11"><b>click here</b></a></div>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore11"><b>click here</b></a></div>
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<div>
  
             <h2>Workshop with Irini and Simon – 22nd June 2020</h2>
+
             <h2>Workshop with Irini and Simon – June 22nd</h2>
 
             <h3>Researchers at our host lab</h3>
 
             <h3>Researchers at our host lab</h3>
 
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             <div class="txt format">
               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.
+
               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.
 
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<h3 style="font-size: 15px;"> <b>Main Consideration: Investigate the ethical implications of our project</b></h3>
 
<h3 style="font-size: 15px;"> <b>Main Consideration: Investigate the ethical implications of our project</b></h3>
<br> 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.
+
<br> 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.
  
 
             <h2 id="johan">Exploring the world of Self-Testing</h2>
 
             <h2 id="johan">Exploring the world of Self-Testing</h2>
             <h3 style="color:grey;">Johan Burisch, Researcher in Inflammatory Bowel Disease – 12th August 2020</h3>
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             <h3 style="color:grey;">Johan Burisch, Researcher in Inflammatory Bowel Disease – August 12th</h3>
 
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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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Johan told us about the testing procedures patients with Crohn's Disease and Colitis undergo. The key takeaways from this meeting were:
 
<br><ul>
 
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&bull; 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.
 
&bull; 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.
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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. </ul>
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According to Johan, 80 % of people diagnosed with Crohn’s Disease have had at least one medication change one year after diagnosis. </ul>
 
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<div class="format">To read more about the interview <a class="pretty_button" href="#seemore3"><b>click here</b></a></div>
 
<div class="format">To read more about the interview <a class="pretty_button" href="#seemore3"><b>click here</b></a></div>
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             <h2 id="anna">Learning About Patient Empowerment</h2>
 
             <h2 id="anna">Learning About Patient Empowerment</h2>
             <h3 style="color:grey;">Anna Fryxelius, Case Manager at Norwegian Rheumatoid Association – 12th August</h3>
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             <h3 style="color:grey;">Anna Fryxelius, Case Manager at Norwegian Rheumatoid Association – August 12th</h3>
 
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Anna 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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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:
 
<br><ul>
 
<br><ul>
 
&bull;
 
&bull;
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. CIDosis could be such a tool
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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 themselves. According to her, CIDosis could be such a tool!
 
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"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.
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"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.
 
<br>
 
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&bull;RA patients change their medications frequently. It is not unusual for patients to have changed their medications up to 20 times.
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&bull; RA patients change their medications frequently. It is not unusual for patients to have changed their medications up to 20 times.
 
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             <h2>Working Through Ethical IssuesNordic Ethics Workshop</h2>
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             <h2>Working Through Ethical Issues - Nordic Ethics Workshop </h2>
 
  <h3 style="color:grey;">Nordic Ethics Workshop with Copenhagen, Helsinki, Stockholm, Trondheim and Uppsala</h3>
 
  <h3 style="color:grey;">Nordic Ethics Workshop with Copenhagen, Helsinki, Stockholm, Trondheim and Uppsala</h3>
 
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            <h2 id="hanne">Learning to Make an Environmental Impact Analysis</h2>
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            <h3 style="color:grey;">Hanne Dalsgaard Nicolaisen, Master’s student in Environmental Engineering – 27th Aug 2020</h3>
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                Hanne enlightened the HP team on 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.
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<img style="width: 20%;" src="https://static.igem.org/mediawiki/2020/f/ff/T--UCopenhagen--decisions.png?fbclid=IwAR00udihLNXVzgyu3ahkOB0KwoyGByZWfTLcC_wyQKv4MucQI1xvZj9fjrI">
 
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<h3 style="font-size: 15px;"> Main Decision: Look into the possibility of CIDosis being a tool for mental distress relief.</h3>
 
<h3 style="font-size: 15px;"> Main Decision: Look into the possibility of CIDosis being a tool for mental distress relief.</h3>
 
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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.
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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.
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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. If our product would be taken to market, such an analysis would be necessary.  
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<h5>Concluding Remarks</h5>
 
<h5>Concluding Remarks</h5>
 
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<br>
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 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.   
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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.   
 
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             <li id="WHO">https://www.who.int/nutrition/topics/2_background/en/ <a href="#WHO-ref" aria-label="Back to content">↩</a></li>
 
             <li id="WHO">https://www.who.int/nutrition/topics/2_background/en/ <a href="#WHO-ref" aria-label="Back to content">↩</a></li>
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<li id="endre1">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 <a href="#endre1-ref" aria-label="Back to content">↩</a></li>
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<li id="endre2">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<a href="#endre2-ref" aria-label="Back to content">↩</a></li>
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<li id="endre3">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<a href="#endre3-ref" aria-label="Back to content">↩</a></li>
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<li id="endre4">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<a href="#endre4-ref" aria-label="Back to content">↩</a></li>
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<li id="endre5">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<a href="#endre5-ref" aria-label="Back to content">↩</a></li>
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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.
 
                 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.
 
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                 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’ opinion 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.
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                 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.
 
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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.
 
             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.
 
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                 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.
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                 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.
 
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Latest revision as of 02:36, 28 October 2020


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. 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:
      1
      2
      3
      4

      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.
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    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
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