Difference between revisions of "Team:Oxford/Practices"

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        <h3>Questionnaire Results</h3>
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<div class="container-fluid page-heading" style="background-image:url(https://static.igem.org/mediawiki/2015/5/5c/Ox_practicesheader.jpg)">
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    <h3>Practices</h3>
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            <div class="section" id="practices_overview">
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                    <h2>Overview</h2>
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                        Coordinated action is required to minimize emergence and spread of antibacterial resistance (ABR). The World Health Organisation have recently (May 2015) endorsed a global action plan to tackle <a class="definition" title="antimicrobial resistance" data-content="Bacteria adapt to their surroundings, and can become resistant to powerful antibiotics if allowed to survive. The risk of developing antimicrobial resistance increases when you don’t finish your course of antibiotics.">antimicrobial resistance</a>.
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                        The plan sets out 5 objectives:
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                    <ol>
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                        <li>Improve awareness and understanding of antimicrobial resistance</li>
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                        <li>Strengthen surveillance and research</li>
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                        <li>Reduce the incidence of infection</li>
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                        <li>Optimize the use of antimicrobial medicines</li>
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                        <li>Ensure sustainable investment in countering antimicrobial resistance</li>
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                    </ol>
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                    <br>
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                    <p>
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                        Our work is focused on the first two WHO objectives. In our <a href="https://2015.igem.org/Team:Oxford/Project">project</a>, we are developing the use of bacteria as living therapeutics to provide an alternative to administering antibiotics, thereby addressing objective number two. However, ABR cannot be overcome with research alone in view of the fact that misinformed antibiotic use contributes a large part to the increasing worldwide acquired ABR.
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                    </p>
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                    <p>
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                        In line with the first objective of the WHO global action plan, to improve awareness and understanding of ABR, our project relies on a three way conversation between the team, the public and experts. This influences every aspect of our project, from our choice of application to the details of our delivery system. The emphasis of our Policy and Practices is to take an iterative approach to developing our idea, continuously taking input from the public and healthcare professionals, so as to ensure that our project could become a realistic method to overcome ABR.
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                    </p>
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                    <p>
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                        The practices approach of our project has been inspired by the Royal College of General Practitioners TARGET Antibiotics Toolkit. TARGET stands for: Treat Antibiotics Responsibly, Guidance, Education, Tools.<a href="#references"><sup>1</sup></a> Our guidance comes from healthcare professionals and the public; in terms of education we have worked on increasing awareness of ABR and synthetic biology; and our tools are based around using engineered bacteria as therapeutic agents. The targeted nature of our solution is achieved by building the project around our practices, constantly feeding back and forth between the two.
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                    <p>
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                        We want to make our website as accessible as possible to all readers, regardless of their level of expertise. Words with a <a class="definition" title="Dotted Blue Underline" data-content="Yep, just like this one">dotted underline</a> will show a definition when you click them.
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            <div class="section" id="practices_discourse">
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                    <h2>Discourse</h2>
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                    <div id="practices_approaching-the-public">
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                        <h3>Approaching the public</h3>
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                        <p>
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                            From the offset we wanted to tackle a problem raised to us by the public. We sent out an <a href="https://2015.igem.org/Team:Oxford/Questionnaires#first_questionnaire">initial questionnaire</a> to the public to ask what big problems they wanted solving and to hear about what they thought about synthetic biology. We took the questionnaire to schools, to the streets and to our friends. Examples of their suggestions for the applications of synthetic biology included bacteria which:
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                        </p>
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                        <ul>
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                            <li>Remove carbon dioxide from the atmosphere</li>
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                            <li>Target and kill cancerous cells</li>
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                            <li>Help treat Alzheimer's disease</li>
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                            <li>Produce energy</li>
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                            <li>Sew up holes in clothes</li>
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                            <li>Produce teeth glue</li>
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                            <li>Indicate how long someone has been dead</li>
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                            <li>Combat antibiotic resistance</li>
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                        </ul>
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                         <h4>Antibiotic resistance</h4>
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                         <h2>First Questionnaire</h2>
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                         <p>
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                         <div id="q1_aim">
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                            Of the responses to our initial survey, 40 of the 86 were related to Medicine and Health. Inspired by a talk given by Professor Dame Sally Davies:  <a href="https://www.youtube.com/watch?v=Q5H8Z9CkoTk">“A ticking time bomb: the infectious threat of antibiotic resistance”</a> and the public responses, antibiotic resistance stood out to us as an issue we could tackle with synthetic biology. To confirm that we were on the right track, we approached the public again with the question: <a href="https://2015.igem.org/Team:Oxford/Questionnaires#q2_antibiotic_resistance"><em>To what extent do you feel that antibiotic resistance is a problem that needs addressing in society today?</em></a> This graph clearly shows that, according to the general public, antibiotic resistance is an important problem that needs solving.
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                            <h4>Aim:</h4>
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                                To find out what the public want synthetic biology to do for them.
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                            <img src="https://static.igem.org/mediawiki/2015/b/b8/Ox_q2_antibiotic_resistance2.png">
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                            </p>
 
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                        <div id="q1_introduction">
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                             <h4>Introduction</h4>
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                        <h3>Urinary Tract Infections (UTIs)</h3>
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                        <p>
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                             It was our team member George Driscoll’s work at the Hornsey <a class="definition" title="UTI" data-content="An infection in the bladder or kidney, symptoms include inflammation, needing to urinate more frequently, and occasionally blood in the urine. Treatments currently rely on antibiotics, and typically follow a two week course. 50% of women acquire one in their lifetime.">UTI</a> clinic in London which helped us to select UTIs as a specific cause to focus on. Due to the unaesthetic nature of the infection, it often receives less attention with regard to research. Having worked in the clinic, George knew first-hand that UTIs are a problem for a significant proportion of the population, and that resistance to the antibiotics used to treat UTIs is growing. In fact the clinic’s primary treatment method is long, high-dose courses of multiple antibiotics to overcome long-lasting infections despite the clinic’s awareness that their treatment choice may lead to further resistance.
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                        </p>
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                             <p>
 
                             <p>
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                                 UTIs are the most common healthcare-acquired infection. Among UTIs acquired in the hospital, approximately 75% are associated with a urinary <a class="definition" title="catheter" data-content="A small, flexible tube inserted into the body to remove fluid. Urinary tract infections are a common side effect of using these.">catheter</a>.<a href="#references"><sup>2</sup></a>
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                                 We conducted this survey in the Christmas vacation, with the idea that the results from this survey could inform our choice of project. The responses we got back were very varied, with some very interesting and detailed possibilities, and other, less thought-through options, such as "stop racism".
 
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                        <div id="q1_results">
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                            <h1>Results</h1>
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                            <p>
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                                We decided to display the responses from this questionnaire as a word cloud. The size of each word in the word cloud is proportional to the frequency of its occurrence in the questionnaire responses, so that it is clear what the public consensus of useful project ideas is.
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                            </p>
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                                <img src="https://static.igem.org/mediawiki/2015/0/04/Ox_Wordcloud-white-background.png">
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                         <h3>Interaction with nurses</h3>
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                         <h2>Second Questionnaire</h2>
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                         <p>
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                         <div id="q2_aim">
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                            To learn more about catheter associated UTIs (CAUTIs), we visited the Churchill Hospital in Oxford. Our first visit to the hospital was to the outpatient clinic during which we spoke with Jan Harris, one of the nurses on the ward. Jan explained to us the current treatment of UTIs. The protocol for treatment is to first take a urine sample to test for the presence of bacterial colonies. If the dip test comes back as positive, the patient is treated with a wide spectrum antibiotic, after which an antibiotic treatment specific to the type of bacteria identified may be given. Whether or not a catheter is fitted with prophylactic antibiotic treatment is the doctor’s decision.
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                            <h4>Aim:</h4>
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                        </p>
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                             <p>
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                        <p>
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                                To find out the public's thoughts on genetic modification, and see whether they would consider a treatment involving modified bacteria if they were suffering with a <a class="definition" title="UTI" data-content="An infection in the bladder or kidney, symptoms include inflammation, needing to urinate more frequently, and occasionally blood in the urine. Treatments currently rely on antibiotics, and typically follow a two week course. 50% of women acquire one in their lifetime.">UTI</a>
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                            Up to this point, we weren’t fully aware of the potential seriousness of UTIs. Jan told us about a case of a person getting septicaemia as a result of a UTI. The patient had received antibiotics for seven days and had come back for a check up. Their urine sample was clear and but, despite this, the patient rapidly went into septic shock. This life threatening infection is caused by the uro<a class="definition" title="pathogen" data-content="Any organism or virus that can cause disease.">pathogen</a>ic bacteria rising up the ureter to the kidney. If a patient becomes septic the catheter has to be removed or CAUTI can be fatal. This shocking example made our project feel very relevant and we took a lot from this initial conversation. We went on to investigate the <a href="#practices_fc_prosandcons">pros and cons</a> of the current methods of CAUTI treatment, and compare these to what our solution could offer. Following this meeting, the <a href="https://2015.igem.org/Team:Oxford/Design">design</a> of the catheter became an integral part of our project.
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, as well as gauging their opinion as to whether antibiotic resistance is a problem.
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                             Laura Evans, from the Adams Ward (geriatric) in the John Radcliffe Hospital, also talked to us about the current treatment of UTIs, informing us that the use of antibiotics is often ineffective and therefore infections are recurrent. We asked Laura the following questions.
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                        </p>
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                        <p>
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                            What happens when a catheterised patient tests positive for a UTI?
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                        <p class="interview-response">
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                            “Whether or not the catheter is removed if a patient tests positive for a UTI depends largely on the reason that the catheter has been fitted. In most cases, the catheter remains fitted and the patient is treated with a large dose of antibiotics.”
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                        </p>
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                        <p>
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                            Is antibiotic resistance a problem?
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                        <p class="interview-response">
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                            “Yes, particularly on this ward. As we treat elderly patients with recurring infections, the uropathogens they succumb to are often resistant to antibiotic treatment. As a result, we have to try different combinations of antibiotics, but in many cases this does not stop recurrences of the infection.”
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                        <h3>Conversation with academics</h3>
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                        <p>
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                            In collaboration with Oxford University Scientific Society, we organised a public talk “<a class="definition" title="biofilm" data-content="A community of bacteria (or other microorganisms) adhering to a surface and each other, held together by secreted slime-like polymers that create a more favorable environment for the bacteria and protect them from environmental stresses and attack from a host’s immune system (in the case of pathogenic bacteria).">Biofilm</a>s: role in health and disease, recalcitrance and in vitro <a class="definition" title="model" data-content="A simplified or idealised description of a system or process, usually mathematical, that can be used to predict how it will behave.">model</a>ling” by Dr. Andrew McBain, Biofilm Research Group, Manchester Pharmacy School. This talk helped the team understand the role of biofilms in causing infection and why they are resistant to antibiotic treatment. During his talk, Dr. McBain explained the role of biofilms in infections and how they confer ABR. He talked to us about persister cells and their importance in the recalcitrance of biofilms to antibiotic treatment. Hence, in the project design, we looked at agents that specifically target these sessile, metabolically inactive persister cells and decided on Art-175 as one of our antibacterial agents.
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                         <div id="q2_introduction">
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                             <h4>Introduction</h4>
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                            <p>
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                                Throughout our project, we have been determined to engage with the public so that we can develop a project which will be as useful to as many people as possible. These questionnaires, along with interviews with medical professionals and posts on social media, comprise a dialogue that we have maintained with the public for the duration of our project.
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                         <div id="q2_questions">
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                             Professor Timothy K. Lu, from the Synthetic Biology Group at MIT recommended that we use endogenous anti-biofilm agents rather than designing them bottom up. He said that our idea to use synthetic biology as a means of fighting UTIs and ABR was “interesting” but raised to us the the problem of our bacteria being subject to resistance mechanisms depending on the agents used, but that we could overcome this by exploring combinatorial therapies.
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                             <h1>Questions</h1>
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                                <h3>Ages of participants</h3>
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                            During the summer, we also gave two talks, one at the termly Corpus Christi College Biochemistry talks and another to a group of alumni from the Oxford Biochemistry department. Again, the feedback we received in terms of our project idea was positive and our idea was described as “ambitious but achievable”. Max Crispin, Oxford Glycoprotein Therapeutics Laboratory raised the issue of whether the <a class="definition" title="protein" data-content="An essential part of all living organisms. They are long and fold up into complicated structures and are made up of amino acids.">protein</a>s we planned on secreting would be immunogenic. We explored this, and similar issues, in a report we wrote about the <a href="https://2015.igem.org/Team:Oxford/UTB">urinary biome</a>. Another question we were faced with concerned the issue of whether our solution would make fungal infections more likely. This issue is addressed in the <a href="#practices_further_considerations">Futher Considerations</a> section.
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                                <p>
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                <div id="practices_return-to-public">
+
                                    We included age brackets as part of the survey so that we could check that our data is roughly representative, and so that we could see to what extent people of different ages are informed about genetic modification and antibiotic resistance. We found that most older people (31+) have heard of genetic modification but not synthetic biology, and are less likely to allow genetically modified bacteria to be used as a treatment. Younger people (up to 30) tend to be more open to the new treatment ideas, and more of them have heard of synthetic biology. However, our results may be biased, due to the high proportion of our participants aged under 30. Different generations are likely to have had different educations; synthetic biology is a very new field, so it is likely not to have been taught in schools yet. Similarly, older people may be more aware, and sceptical, due to the previous GM food scare.
−
                    <div class="slim">
+
                                </p>
−
                        <h3>Return to the public</h3>
+
                            </div>
−
                        <p>
+
                            <div id="q2_awareness">
−
                            Having investigated the feasibility of our idea, we approached the public again to seek their opinion. The idea working on paper is one thing, but having the support of the public and the patients who would be using our solution is another aspect entirely.
+
                                <h5>Awareness</h5>
−
                        </p>
+
                                <div id="q2_antibiotic_resistance">
−
                    </div>
+
                                    <h3>To what extent do you feel that antibiotic resistance is a problem that needs addressing in society today?</h3>
−
                    <video class="image-massive" poster="https://static.igem.org/mediawiki/2015/0/06/Publictalk.jpg" controls>
+
                                    <p>
−
                        <source src="https://static.igem.org/mediawiki/2015/2/23/OxiGEM_Consulting_the_public.mp4" type="video/mp4"/>
+
                                        Our survey clearly shows that the public think that antibiotic resistance is an important problem that needs solving, therefore we feel that it is an appropriate and useful area to direct our project towards. One of our team members, George, worked in a UTI clinic last summer, so he knows first-hand that UTIs are a big problem for a lot of people, with current methods of treatment still being inadequate in severe cases. When he brought this to our attention while we were trying to decide on a project, we thought it was worthwile trying to find a solution to this problem.
−
                        Your browser does not support the video tag.
+
                                    </p>
−
                    </video>
+
                                    <div class="image image-full">
−
                    <div class="slim">
+
                                        <img src="https://static.igem.org/mediawiki/2015/0/02/Ox_THISONE.png">
−
                        <p>
+
                                    </div>
−
                            We asked the public, <a href="https://2015.igem.org/Team:Oxford/Questionnaires#q2_options"><em>“If you had the option of using two treatments for an infection, where one was antibiotics and one was bacteria that were designed to cure the infection, which would you choose?”</em></a>
+
                                </div>
−
                        </p>
+
                                <div id="q2_hospital_infection">
−
                        <div class="image image-full">
+
                                    <h3>Which of these do you think is the most common infection acquired in hospitals?</h3>
−
                            <img src="https://static.igem.org/mediawiki/2015/a/a0/Ox_q2_options2.png">
+
                                    <p>
 +
                                        Most of the public (45.5%) thought that MRSA is the most commonly acquired infection in hospitals, showing that they think that antibiotic resistance is a problem. However, with UTIs coming in quite far behind this (19.5%), it seems that the public are not aware of the risk of getting UTIs in hospital due to urinary <a class="definition" title="catheter" data-content="A small, flexible tube inserted into the body to remove fluid. Urinary tract infections are a common side effect of using these.">catheter</a>isation. This could be due to the fact that UTIs are advertised less than MRSA, but since this is an important issue, we looked into educating the public through sessions with summer schools and school students, as well as getting in touch with local media, such as BBC Radio Oxford, ad promoting our project across social media. We believe that this has helped raise awareness of problems associated with catheter-based infections, not only in the urinary tract, but also due to other catheterised parts of the body.
 +
                                    </p>
 +
                                    <div class="image image-full">
 +
                                        <img src="https://static.igem.org/mediawiki/2015/0/05/Ox_q2_hospital_infection2.png">
 +
                                    </div>
 +
                                </div>
 +
                                <div id="q2_genetic_engineering">
 +
                                    <h3>Have you heard of genetic engineering?</h3>
 +
                                    <p>
 +
                                        96.5% of the people we surveyed had heard of genetic engineering. However, we did not collect data for whether people thought it was a good thing or not. This would be something to pursue in further surveys.
 +
                                    </p>
 +
                                    <div class="image image-full">
 +
                                        <img src="https://static.igem.org/mediawiki/2015/2/28/Ox_q2_genetic_engineering2.png">
 +
                                    </div>
 +
                                </div>
 +
                                <div id="q2_synthetic_biology">
 +
                                    <h3>Have you heard of synthetic biology, before this questionnaire?</h3>
 +
                                    <p>
 +
                                        Compared to the question about genetic modification, the results for this question were much more evenly spread between yes and no, with 58% saying they had heard of synthetic biology. Again, it would be interesting to see whether those who have heard of synthetic biology have a good opinion of it or not, and this would be an avenue for future surveys.
 +
                                    </p>
 +
                                    <div class="image image-full">
 +
                                        <img src="https://static.igem.org/mediawiki/2015/3/3d/Ox_q2_synthetic_biology2.png">
 +
                                    </div>
 +
                                </div>
 +
                            </div>
 +
                            <div id="q2_treatment">
 +
                                <h5>Treatment</h5>
 +
                                <div id="q2_options">
 +
                                    <h3>If you had the option of using two treatments for an infection, where one was antibiotics and one was bacteria that were designed to cure the infection, which would you choose?</h3>
 +
                                    <p>
 +
                                        The majority (70%) of the people we surveyed said that they would take the advice of their doctor on this. This means that it is important that we talk to and get advice from doctors as to how we can improve out treatment, since if we can't convince doctors that this is a better treatment than any current treatment, the patients won't take it either. However, encouragingly, of those who wouldn't take the advice of their doctor, our treatment was favourite with just under half saying they would prefer the designed bacteria (48%), compared to 40% who would prefer antibiotics.
 +
                                    </p>
 +
                                    <div class="image image-full">
 +
                                        <img src="https://static.igem.org/mediawiki/2015/a/a0/Ox_q2_options2.png">
 +
                                    </div>
 +
                                </div>
 +
                                <div class="section" id="q2_doctor_recommendation">
 +
                                    <h3>If your doctor recommended a treatment for an infection, which involved the use of bacteria that had been engineered to treat the infection, would you use it?</h3>
 +
                                    <p>
 +
                                        Our survey showed that if a doctor recommended our treatment, only 6% would not consider it. This is very encouraging data for our project, but again highlights the importance of gaining support from doctors, because without their backing, this project is likely never to become as common a treatment as antibiotics.
 +
                                    </p>
 +
                                    <div class="image image-full">
 +
                                        <img src="https://static.igem.org/mediawiki/2015/c/cc/Ox_q2_doctor_recommendation2.png">
 +
                                    </div>
 +
                                </div>
 +
                            </div>
 +
                            <div class="section-spacer"></div>
 
                         </div>
 
                         </div>
−
                        <p>
 
−
                            The majority (70%) of the people we surveyed said that they would take the advice of their doctor on this. This reinforced to us the importance of nurses and doctors backing our project idea. However, encouragingly, of those who wouldn't take the advice of their doctor, our treatment was favourite with just under half saying they would prefer the designed bacteria (48%), compared to 40% who would prefer antibiotics.
 
−
                        </p>
 
−
                        <p>
 
−
                            We had very similar feedback when we spoke to patients. During a visit to the Bedford Ward at the John Radcliffe Hospital, we spoke with one of the catheterised patients there called Mavis. She admitted to having had UTIs in the past, but said she had not contracted a UTI since having a catheter fitted. We found that patients like Mavis could end up using the same catheter for up to 10 weeks. This enforced the importance of being able to keep our bacteria alive for a sustained period of time. When we asked her about treating infection with bacteria, she said she would be happy to, if it had been recommended to her by a doctor. She said, in her view, it is not dissimilar to using antibiotics.
 
−
                        </p>
 
 
                     </div>
 
                     </div>
 
                 </div>
 
                 </div>
−
                 <div id="practices_return-to-nurses">
+
                 <div class="section" id="third_questionnaire">
 
                     <div class="slim">
 
                     <div class="slim">
−
                         <h3>Return to nurses</h3>
+
                         <h2>Third Questionnaire</h2>
−
                         <p>
+
                         <div id="q3_aim">
−
                            During this visit we were able to talk to Laura Evans again, this time to ask questions specifically about our project.
+
                            <h4>Aim:</h4>
−
                        </p>
+
−
                        <p>
+
−
                            Our project involves designing a catheter that prevents the formation of a biofilm on its surface. What do you think of this idea?
+
−
                        </p>
+
−
                        <p class="interview-response">
+
−
                            A catheter like that would be useful, but it depends on how long your catheter would work for. Patients can have a single catheter fitted for 3 months or longer. Catheters are also removed for other reasons, for example if they become blocked. Catheter blockage is a common issue for patients suffering from UTIs.
+
−
                        </p>
+
−
                        <p>
+
−
                            Both Laura’s and Mavis’ response regarding how long a catheter remains in place inspired us to research how we could keep our Solution bacteria alive, the results of which can be found in design. Jan Harris, Churchill Hospital, raised the issue that our solution does not tackle intracellular bacterial communities (IBCs) and community UTIs. Jan made the point that UTIs are not just contracted through catheterisation, and it is important for us to also consider community based UTIs. IBCs and community UTIs are complex issues to solve but we have explored the potential of commensal bacteria as a treatment approach (See <a href="#practices_delivery_commensal">Commensal Bacteria</a>).
+
−
                        </p>
+
−
                    </div>
+
−
                </div>
+
−
                <div id="practices_feedback-from-doctors">
+
−
                    <div class="slim">
+
−
                        <h3>Feedback from doctors</h3>
+
−
                        <div class="quote quote-full">
+
 
                             <p>
 
                             <p>
−
                                 "Years from now we will treat most infections with bacteria and not antibiotics."
+
                                 To return to the public with a variety of delivery methods for our bacteria, so that they can provide feedback on what they like and don’t like about the options, and to see which they would like to see in use.
 
                             </p>
 
                             </p>
−
                            <h3>Professor James Malone-Lee<br>Barlow Professor of Geriatric Medicine</h3>
 
 
                         </div>
 
                         </div>
−
                         <p>
+
                         <div id="q3_intro">
−
                            Our interaction with the public highlighted the importance of gaining doctor’s support for our project. With this is mind, George went back to Hornsey UTI clinic to speak with Dr. Sheela Swamy and Professor Malone-Lee, the consultant clinician as well as the principal investigator of the laboratory associated with the clinic. The Professor’s feedback on our project was extremely positive. “Biofilms have a profound effect on antibiotic resistance and so bacteria that can penetrate through biofilms strikes me as a very sensible project direction.”
+
                             <h4>Introduction:</h4>
−
                        </p>
+
                             <p>
−
                        <p>
+
                                Having last surveyed the public on how receptive they would be to treatments involving engineered bacteria, and received very positive results, we decided to work on a selection of delivery options. Having designed several containment options with physical and molecular barriers to unwanted colonisation, we returned to the public to see which they would prefer.
−
                            Dr. Sheela Swamy, Hornsey UTI clinic, said:
+
                             </p>
−
                        </p>
+
−
                        <p class="interview-response">
+
−
                             “We get through so many buckets of antibiotics here, if your product could prevent infections or reduce our reliance on those antibiotics that is hugely appealing as a practitioner.”
+
−
                        </p>
+
−
                        <p class="interview-response">
+
−
                             “It will be really great if we actually have bacteria engineered to achieve biofilm and cellular penetration and a bactericidal effect will be a total seller. That may be the answer to the Chronic UTI if we can get it to work.”
+
−
                        </p>
+
−
                        <p>
+
−
                            The doctors at the UTI clinic left us with a few points to bear in mind as we are currently focused on only killing <a class="definition" title="E. coli" data-content="The fastest-growing strain of bacteria that we know everything about. Certain strains can make you ill, but you won’t find those ones in the lab."><em>Escherichia coli</em></a> and <a class="definition" title="P. aeruginosa" data-content="Like E. coli, it is a well documented, fast-growing bacteria. It is more dangerous than E. coli and is harmful to humans, so we would need higher permissions to work with it in the lab."><em>Pseudomonas aeruginosa</em></a>:
+
−
                        </p>
+
−
                        <ol>
+
−
                            <li><em>The bladder biome is complex with many culturable and nonculturable pathogens. What role each of these have and what concentration they need to be in to cause UTI symptoms is unknown.</em></li>
+
−
                            <li><em>Uropathogens listed in literature are not the only organisms responsible for UTI as they are also present in normal controls yet don't cause symptoms.</em></li>
+
−
                            <li><em>Bacteria are opportunistic and a skin commensal if in the bladder can cause symptoms, and we have had many women with pyuric UTIs even though they only grew a Staphylococcus so you may have to try develop something that works on a wide spectrum of bacteria.</em></li>
+
−
                        </ol>
+
−
                    </div>
+
−
                </div>
+
−
                <div id="practices_speaking-with-patients">
+
−
                    <div class="slim">
+
−
                        <h3>Speaking with Patients</h3>
+
−
                        <p>
+
−
                            During his time meeting with Dr. Sheela Swamy and Prof. Malone-Lee, George was invited to attend a pair of clinic sessions in which chronic urinary infection patients came to see doctors and change their treatment plan or give samples for urinalysis. During these sessions George sat in on 8 consultations and interviewed 6 urinalysis patients to gain an understanding of their symptoms and the way their infection is currently managed. George was also given the chance to interview each of these patients and learn what they thought about antibiotic regimes, catheter-based delivery and our synthetic biology solution to their infections. From the 14 interviews conducted George drew these particular conclusions from his conversations with Hornsey’s patients:
+
−
                        </p>
+
−
                        <ul>
+
−
                            <li>That comfort levels with catheterisation are reliant on previous experience with catheterisation.</li>
+
−
                            <li>That antibiotic use often has side effects that significantly decrease the quality of life of patients often through nausea but also induced faecal incontinence.</li>
+
−
                            <li>Most patients are comfortable with the idea of GM solutions to infection given the backing of the practitioners in the clinic.</li>
+
−
                        </ul>
+
−
                        <div class="image image-full">
+
−
                            <img src="https://static.igem.org/mediawiki/2015/a/af/Ox_lysiscartoon.jpeg">
+
−
                        </div>
+
−
                    </div>
+
−
                </div>
+
−
            </div>
+
−
            <div class="section-spacer"></div>
+
−
            <div class="section" id="practices_delivery">
+
−
                <div class="slim">
+
−
                    <h2>Delivery</h2>
+
−
                    <div class="quote quote-full">
+
−
                        <p>“Is there a material for the catheter or its coating that is suitably permeable to this mystery molecule(s) yet entirely able to contain the source of microbes without any leaks?”</p>
+
−
                        <h3>Professor Jef D. Boeke<br>Director, Institute for Systems Genetics<br>NYU Langone Medical Center</h3>
+
−
                    </div>
+
−
                    <p>
+
−
                        Asked by others and by ourselves, our thoughts on how to practically implement Solution has shaped the project and forced us to tackle the problem from many angles. We needed a method by which we could expose the catheter, and bladder, to our anti-microbial proteins, and in a safe manner. Safety was a key consideration when designing delivery methods. We looked at a range of different approaches, including a variety of different catheter coatings, a semi-permeable membrane inside the catheter and encasing our bacteria within <a class="definition" title="sodium alginate" data-content="Anionic polysaccharide is distributed widely in the cell walls of brown algae, where through binding with water it forms a viscous gum.">sodium alginate</a> beads. For more information, check out our <a href="https://2015.igem.org/Team:Oxford/Safety">safety</a> and <a href="https://2015.igem.org/Team:Oxford/Design">design</a> pages.
+
−
                    </p>
+
−
                    <div id="practices_delivery_commensal">
+
−
                        <h3>Commensal Bacteria</h3>
+
−
                        <p>
+
−
                            We thought further about the discussions we had had at Hornsey UTI clinic and were inspired by what Prof. Malone-Lee said to us:
+
−
                        </p>
+
−
                        <p class="interview-response">
+
−
                            “Biofilms have a profound effect on antibiotic resistance … bacteria that can penetrate through biofilms strikes me as a very sensible project direction.”
+
−
                        </p>
+
−
                        <p>
+
−
                            At the clinic they talked to us out using competing species of bacteria to replace the common uropathogens.
+
−
                        </p>
+
−
                        <div class="quote quote-full">
+
−
                            <p>“Patients keep taking probiotics while being treated with antibiotics in our unit and they don't seem to mind ingesting 20-40 billion acidophilus bacteria without a second thought.”</p>
+
−
                            <h3>Dr. Sheela Swamy</h3>
+
−
                        </div>
+
−
                        <p>
+
−
                            With these conversations in mind, we went back to the drawing board. Our data showed us that we needed a high local concentration of anti-biofilm and antimicrobial agents to be able to break down a biofilm. We thought about how we could create these high local concentrations and came up with a new solution: to introduce free living bacteria into the urinary tract. Whilst we are aware that current GMO regulations would not permit this, we have explored the possibility of it becoming an option in the future.
+
−
                        </p>
+
−
                        <p>
+
−
                            Many people perceive the use of GMOs to be unethical and this has far-reaching impacts on society, such as the enaction of anti-GMO legislation. To explore these ethical questions and find out the public’s opinion on our project, we sent out a <a href="https://2015.igem.org/Team:Oxford/Questionnaires#second_questionnaire">questionnaire</a> to over 150 people, asking: <a href="https://2015.igem.org/Team:Oxford/Questionnaires#q2_doctor_recommendation"><em>If your doctor recommended a treatment for an infection, which involved the use of bacteria that had been engineered to treat the infection, would you use it?</em></a> We also asked this question to a number of medical professionals during our visits to hospitals and clinics.
+
−
                        </p>
+
−
                        <p>
+
−
                             Whilst the majority of feedback was very positive, we did encounter some valuable criticism, as shown in the graph below. Most medical professionals we spoke to had positive responses, though one nurse had reservations about our idea.
+
−
                        </p>
+
−
                        <div class="image image-full">
+
−
                            <img src="https://static.igem.org/mediawiki/2015/c/cc/Ox_q2_doctor_recommendation2.png">
+
 
                         </div>
 
                         </div>
−
                         <p>
+
                         <div id="q3_results">
−
                             This proportion of negative feedback, although small (6%), highlighted to us that our dialogue with the public needed to be improved, as well as telling us that getting our treatment recommended by doctors is the key to getting it used as common practice. We believe that, through improving people's understanding of our project, we can convince pessimists that genetic engineering is now a force for good. This also led us onto holding talks to student groups, which you can find in the <a href="#practices_outreach">Outreach</a> section below. Nevertheless, this is very encouraging data for our project, and again highlights the importance of gaining support from doctors for this to become a realistic treatment option.
+
                             <h1>Results</h1>
−
                        </p>
+
                            <div id="q3_results_sealed">
−
                        <p>
+
                                <h3>Sealed within a section of catheter</h3>
−
                            We also approached the public later on with a variety of different delivery option for them to choose from, including the idea of introducing free-living, genetically engineered bacteria into the urinary tract, alongside different catheter-associated treatments. 44% of the 50 people we asked were most happy with the free living bacteria, due to its effectiveness at treating the infection. This was by far the most popular option, followed by 20% opting to have the bacteria sealed within a catheter, since this balanced efficiency with safety.
+
                                <p>
−
                        </p>
+
                                    For a description of this option, check out our safety page <a href="https://2015.igem.org/Team:Oxford/Safety#project-safety-within-catheter">here</a>. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.
−
                        <div class="image image-full">
+
                                </p>
−
                            <img src="https://static.igem.org/mediawiki/2015/7/7b/Ox_public_preference.png">
+
                                <h4>Pros:</h4>
−
                        </div>
+
                                <ul>
−
                        <p>
+
                                    <li>No contact between patient and bacteria (11)</li>
−
                            The public’s biggest concern for this option is side effects from the engineered bacteria colonising the urinary tract. However, over 2/3 of the people who raised this concern said that they would be happy to use the method if they got a clear explanation of how it worked from a health care professional. Additionally, the concern was outweighed by the public’s opinion of having a safe kill switch, and that this treatment is the most effective. Again, full results can be seen <a href="https://2015.igem.org/Team:Oxford/Questionnaires#third_questionnaire">here</a>.
+
                                    <li>Extra safeguard should the bacteria escape (6)</li>
−
                        </p>
+
                                    <li>Good compromise between encasing and ability to sense (3)</li>
−
                    </div>
+
                                    <li>Very safe (2)</li>
−
                    <div id="practices_delivery_safety">
+
                                    <li>Simple (1)</li>
−
                        <h3>Safety Considerations for Free-living Bacteria</h3>
+
                                </ul>
−
                        <p>
+
                                <h4>Cons:</h4>
−
                            For the idea of introducing our engineered bacteria into the human body to be feasible, there need to be sufficient safety considerations in place. Whereas for the physically contained options, ensuring that if the bacteria escape, they die is important, it is especially important to make sure that molecular containment is in place for the free-living delivery option.
+
                                <ul>
−
                        </p>
+
                                    <li>Less effective (14)</li>
−
                        <p>
+
                                    <li>Long treatment time (6) – cost to NHS (1)</li>
−
                            We have created theoretical kill switches for each of the situations that our engineered bacteria might find themselves in, to allow us complete control over when they die. Since the kill switches are based on the lac operon, if there are any concerns about the action of the bacteria, we can kill the whole population immediately, by introducing IPTG through the catheter. Furthermore, the kill switch is also sensitive to other elements which could be present (AI2 for free-living bacteria, valine for bacteria in media) to allow extra degrees of control. The kill switch options were another aspect we surveyed the public on. The results were that they were happy to use them, provided their healthcare professional ensured that it was safe. For more details, check out our <a href="https://2015.igem.org/Team:Oxford/Safety">safety</a> and <a href="https://2015.igem.org/Team:Oxford/Questionnaires">questionnaire</a> pages.
+
                                    <li>catheter uncomfortable (4)</li>
−
                        </p>
+
                                    <li>Bacteria block catheter? (3)</li>
−
                        <div class="image image-full">
+
                                    <li>Bacteria can’t be safely replaced (1)</li>
−
                            <img src="https://static.igem.org/mediawiki/2015/7/78/Ox_resistancecartoon.jpeg">
+
                                    <li>Will agent be able to pass through catheter? (1)</li>
 +
                                    <li>Resistance (1)</li>
 +
                                </ul>
 +
                                <br>
 +
                                <p>
 +
                                    The most common concern for this option was that it would be less effective than other methods, and would hence have a longer treatment time, causing discomfort to the patient and cost to the NHS. This concern was not outweighed by the number of people who liked that there was no contact between patient and bacteria, suggesting that the public would rather have a more effective treatment than one which was deemed to be “more safe”.
 +
                                </p>
 +
                                <h4>Other Concerns</h4>
 +
                                <p>
 +
                                    <em>Will the bacteria block the catheter?</em> We would address this concern in the design of the bacterial compartment in the catheter, so that it does not impede the flow of water and urine.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Can the bacteria be safely replaced?</em> We would investigate this further, and if it turned out that we couldn’t due to lack of sterility, we would suggest that another of our catheters were inserted, as a “disposable” solution.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Will the agent be able to pass through the catheter?</em> We would need to investigate the nature of <a class="definition" title="protein" data-content="An essential part of all living organisms. They are long and fold up into complicated structures and are made up of amino acids.">protein</a> folding in urine-like conditions, something that we haven’t been able to achieve given the timescale of the project, but if the protein folds well, the agent would be able to diffuse out into the urinary tract. If not, it may be worth attempting to modify the protein structure to make it more stable in the conditions of the urinary tract.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Can the <a class="definition" title="pathogen" data-content="Any organism or virus that can cause disease.">pathogen</a>ic bacteria gain resistance?</em> The agents produced by our bacteria are designed to break up the <a class="definition" title="biofilm" data-content="A community of bacteria (or other microorganisms) adhering to a surface and each other, held together by secreted slime-like polymers that create a more favorable environment for the bacteria and protect them from environmental stresses and attack from a host’s immune system (in the case of pathogenic bacteria).">biofilm</a> that gives the pathogenic bacteria protection. Resistance arises when an antimicrobial agent fails to kill the entire population of targeted bacteria. We expect that, due to the design of our system, the entire population would be killed, so that resistance is not a problem.
 +
                                </p>
 +
                            </div>
 +
                            <div id="q3_results_beads">
 +
                                <h3>Beads containing bacteria contained within a section of catheter</h3>
 +
                                <p>
 +
                                    For a description of this option, check out our safety page <a href="https://2015.igem.org/Team:Oxford/Safety#project-safety-beads">here</a>. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.
 +
                                </p>
 +
                                <h4>Pros:</h4>
 +
                                <ul>
 +
                                    <li>Extra degree of containment (12)</li>
 +
                                    <li>Multiple safety measures (3)</li>
 +
                                    <li>Kill switch (2)</li>
 +
                                </ul>
 +
                                <h4>Cons:</h4>
 +
                                <ul>
 +
                                    <li>Less effective (21)</li>
 +
                                    <li>Infection won’t be completely cleared due to dulled sensing capacity (5)</li>
 +
                                    <li>Restriction of flow (4)</li>
 +
                                    <li>Do bead cases break down in body? (3)</li>
 +
                                    <li>Long treatment time (3)</li>
 +
                                    <li>More expensive (2)</li>
 +
                                    <li>catheter uncomfortable (2)</li>
 +
                                    <li>More hospitalisations (1)</li>
 +
                                    <li>Replacement of bacteria (1)</li>
 +
                                </ul>
 +
                                <br>
 +
                                <p>
 +
                                    Again, the most common concern was over the efficiency of this option, with additional related concerns about the number of hospitalisations, length of treatment, and the chance that the infection won’t be completely cleared. This was, as before, not outweighed by those who thought the extra degree of containment was a good idea. This provided further evidence that the public would prefer a more effective treatment.
 +
                                </p>
 +
                                <h4>Other Concerns</h4>
 +
                                <p>
 +
                                    <em>Will flow of water/urine be restricted?</em> We would design the bead compartment around this concern, so that there is plenty of catheter diameter to allow sufficient flow.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Do the beads break down in the body?</em> This is something that we would test. <a class="definition" title="sodium alginate" data-content="Anionic polysaccharide is distributed widely in the cell walls of brown algae, where through binding with water it forms a viscous gum">Sodium alginate</a> (the substance from which the beads are made) is sometimes used in the food industry, which suggests that it could be broken down. What we would need to test is whether the <a class="definition" title="enzyme" data-content="A molecule which speeds up a chemical reaction - a biological catalyst. The reaction does not involve these molecules.">enzyme</a>s involved are only present in the digestive tract, or whether they are present in the urinary tract as well.
 +
                                </p>
 +
                                <p>
 +
                                    <em>This treatment option would be more expensive due to the materials involved.</em> This is true, but we believe that the comparative cost is negligible due to the very low cost of sodium alginate. We would investigate other materials which have the same sort of properties, and whether these materials are any less expensive.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Can the bacteria be safely replaced?</em> Again, something for further investigation. If, like in the option above, it is not possible, we would suggest our catheters are used as disposable, so that when the bacteria need replacing, the whole catheter is replaced.
 +
                                </p>
 +
                            </div>
 +
                            <div id="q3_results_attached">
 +
                                <h3>Attached to the end of a catheter</h3>
 +
                                <p>
 +
                                      For a description of this option, check out our safety page <a href="https://2015.igem.org/Team:Oxford/Safety#project-safety-attached-catheter">here</a>. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.
 +
                                </p>
 +
                                <h4>Pros:</h4>
 +
                                <ul>
 +
                                    <li>More effective (19)</li>
 +
                                    <li>Kill switch (6)</li>
 +
                                    <li>Balance between containment and efficiency (5)</li>
 +
                                    <li>Still physically contained (4)</li>
 +
                                </ul>
 +
                                <h4>Cons:</h4>
 +
                                <ul>
 +
                                    <li>Introduction of another bacteria (8)</li>
 +
                                    <li>Diffusion rate of antibacterial agent (1)</li>
 +
                                    <li>Immune response (1)</li>
 +
                                    <li>Bacteria escape to kidney? (1)</li>
 +
                                    <li>Slower treatment (1)</li>
 +
                                    <li>Resistance (1)</li>
 +
                                    <li>catheter uncomfortable (1)</li>
 +
                                </ul>
 +
                                <br>
 +
                                <p>
 +
                                    The primary concern for this treatment is that if the physical containment fails, another type of bacteria will be introduced to the urinary tract, and since their infection was caused by bacteria, this makes the public more wary. However, this is counteracted by the fact that more than twice as many people think that this treatment is more effective, and roughly the same number feel that it strikes a good balance between containment and efficiency.
 +
                                </p>
 +
                                <h4>Other Concerns</h4>
 +
                                <p>
 +
                                    <em>Will the diffusion rate of the antibacterial agent be too low to be effective?</em> As long as we have enough of our engineered bacteria secreting the agents, we will be able to get a sufficient concentration of antibacterial agent to make this treatment effective. We are <a class="definition" title="model" data-content="A simplified or idealised description of a system or process, usually mathematical, that can be used to predict how it will behave.">model</a>ling how many bacteria would be “enough”.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Will the attached bacteria result in an immune response from the body?</em> This is something that we would test. We don’t believe it would, since the chassis we are using has had all the pathogenic properties removed. We think that the immunogenicity of the agents is more of an issue that the immunogenicity of the bacteria, and an article on that can be found here.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Will the bacteria be able to escape to travel up to the kidney?</em> This would be a long journey for the bacteria to make. They shouldn’t be able to make it, since the kill switches would start to work as soon as they were out of range of the pathogenic bacteria, and result in the deaths of all the escaped bacteria.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Will the distance between the catheter and infected site result in slower treatment?</em> Yes it will, but the treatment will be faster that if the bacteria are contained within the catheter. However, if we had more time, we would also work on improving the efficiency of agent production, so that, whatever the distance, our solution would be more effective.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Can the pathogenic bacteria gain resistance?</em> The agents produced by our bacteria are designed to break up the biofilm that gives the pathogenic bacteria protection. Resistance arises when an antimicrobial agent fails to kill the entire population of targeted bacteria. We expect that, due to the design of our system, the entire population would be killed, so that resistance is not a problem.
 +
                                </p>
 +
                            </div>
 +
                            <div id="q3_results_free">
 +
                                <h3>Free-living Bacteria</h3>
 +
                                <p>
 +
                                      For a description of this option, check out our safety page <a href="https://2015.igem.org/Team:Oxford/Safety#project-safety-free-living">here</a>. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.
 +
                                </p>
 +
                                <h4>Pros:</h4>
 +
                                <ul>
 +
                                    <li>Most effective (23)</li>
 +
                                    <li>Safe kill switch (11)</li>
 +
                                    <li>Swift treatment (6)</li>
 +
                                    <li>Two types of bacteria (5)</li>
 +
                                    <li>More comfortable for patient (4)</li>
 +
                                    <li>Prevention (1)</li>
 +
                                    <li>No need to be in hospital (1)</li>
 +
                                </ul>
 +
                                <h4>Cons:</h4>
 +
                                <ul>
 +
                                    <li>Side effects of engineered bacteria colonisation (11)</li>
 +
                                    <ul>
 +
                                        <li>just want a clear explanation from health care professional (8)</li>
 +
                                    </ul>
 +
                                    <li>Kill switch concerns (5)</li>
 +
                                    <li>Opportunistic pathogens (2)</li>
 +
                                    <li>Any self-sacrificing bacteria left once all UTI-causing bacteria are killed? (1)</li>
 +
                                    <li>More difficult to monitor (1)</li>
 +
                                </ul>
 +
                                <br>
 +
                                <p>
 +
                                    The public’s biggest concern for this option is side effects from the engineered bacteria colonising the urinary tract. However, over 2/3 of the people who raised this concern said that they would be happy to use the method if they got a clear explanation of how it worked from a health care professional. Additionally, the concern was outweighed by the public’s opinion of having a safe kill switch, and that this treatment is the most effective.
 +
                                </p>
 +
                                <h4>Other Concerns</h4>
 +
                                <p>
 +
                                    <em>How do you know whether the kill switch will be effective?</em> The kill switch we have designed works in theory, but we will not know properly until it is tested. However, many other teams have used similar kill switches, and they have worked, so we don’t have a reason to suggest that it won’t work. The people who wrote this as a concern said that “if it can be proved to work, I’d be happy with it”, suggesting that their concern is that they haven’t heard of this type of thing before, and are wary of it for that reason, since it is harder to visualise than, for example, a physical containment option.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Will opportunistic pathogens take advantage of the niche that was previously occupied by the pathogenic bacteria?</em> We are hoping that our bacteria will occupy that niche until the infection has been cleared up, and then allow the urinary tract’s natural flora to recolonise. Obviously, we would need to test this in vivo, but we think it would be good to use this treatment in combination with a preventative treatment against opportunistic pathogens, at least until conclusive evidence has been collected.
 +
                                </p>
 +
                                <p>
 +
                                    <em>What will happen if there are any self-sacrificing bacteria left once all the pathogenic bacteria are killed?</em> We would use a very basic additional kill switch where we could get rid of any remaining engineered bacteria at the end of treatment by adding IPTG.
 +
                                </p>
 +
                                <p>
 +
                                    <em>Won’t this make the bacteria more difficult to monitor?</em> If this solution were to proceed to clinical trials, one of the things we would test would be how long it took to clear up an infection, so we could base treatment courses on this. We would be more likely to monitor the symptoms of the infection rather than the bacteria themselves.
 +
                                </p>
 +
                            </div>
 +
                            <div id="q3_preferred">
 +
                                <h3>The Public's preferred method of treatment</h3>
 +
                                <div class="image image-right">
 +
                                    <img src="https://static.igem.org/mediawiki/2015/7/7b/Ox_public_preference.png">
 +
                                </div>
 +
                                <p>
 +
                                    From the survey results, we found that the public were most happy with the free living bacteria option (44%), due to it's effectiveness at treating the infection, resulting in greater comfort for the patient. The next most popular option with 20% was sealed within a catheter, since this balanced efficiency with safety. Attached to a catheter and bacteria contained within beads both got 16%, these being less popular because one aspect (safety or efficiency) outweighed the others too heavily. Only 4% said that none of the options appealed, which is very encouraging for our treatment, since treatment of infections with engineered bacteria is a very new concept. It gives our project and synthetic biology as a whole a confident outlook that the public are so receptive to this idea.
 +
                                </p>
 +
                            </div>
 
                         </div>
 
                         </div>
 
                     </div>
 
                     </div>
 
                 </div>
 
                 </div>
 
             </div>
 
             </div>
−
             <div class="section" id="practices_outreach">
+
             <div class="col-md-3 contents-sidebar">
−
                 <div class="slim">
+
                 <ul id="sidebar" class="nav nav-stacked affix-top sm-hidden xs-hidden" data-spy="affix">
−
                    <h2>Outreach</h2>
+
                     <li>
−
                    <p>
+
                        <a href="#first_questionnaire">First Questionnaire</a>
−
                        In an attempt to improve the general public's understanding of Synthetic Biology, we used a variety of approaches. We thought we could help certain members of audience, who represent the 6% of pessimists we found in an earlier survey, to fully understand the concepts of genetic engineering, and realise the incredible gains that can be made from projects like ours in the field of synthetic biology.
+
                         <ul class="nav nav-stacked">
−
                    </p>
+
                             <li><a href="#q1_aim">Aim</a></li>
−
                    <p>
+
                            <li><a href="#q1_introduction">Introduction</a></li>
−
                        We asked the public: <a href="https://2015.igem.org/Team:Oxford/Questionnaires#q2_hospital_infection"><em>Which of these do you think is the most common infection acquired in hospitals?</em></a>
+
                             <li><a href="#q1_results">Results</a></li>
−
                    </p>
+
                         </ul>
−
                    <div class="image image-left">
+
                     </li>
−
                        <img src="https://static.igem.org/mediawiki/2015/0/05/Ox_q2_hospital_infection2.png">
+
                     <li>
−
                     </div>
+
                         <a href="#second_questionnaire">Second Questionnaire</a>
−
                    <p>
+
                         <ul class="nav nav-stacked">
−
                        Most of the public (45.5%) thought that MRSA is the most commonly acquired infection in hospitals, showing that they think that antibiotic resistance is a problem. However, with UTIs coming in quite far behind this (19.5%), it seems that the public are not aware of the risk of getting UTIs in hospital due to urinary catheterisation. This could be due to the fact that UTIs are advertised less than MRSA, but since this is an important issue, we looked into educating the public through sessions with summer schools and school students, as well as getting in touch with local media, such as BBC Radio Oxford, and promoting our project across social media. We believe that this has helped raise awareness of problems associated with catheter-based infections, not only in the urinary tract, but also with infections in other catheterised parts of the body.
+
                             <li><a href="#q2_aim">Aim</a></li>
−
                    </p>
+
                            <li><a href="#q2_introduction">Introduction</a></li>
−
                    <div id="practices_outreach-bbc-radio-oxford">
+
                             <li><a href="#q2_questions">Questions</a>
−
                        <h3>BBC Radio Oxford</h3>
+
                                <ul class="nav nav-stacked">
−
                         <p>
+
                                    <li><a href="#q2_age">Ages of Participants</a></li>
−
                            We were invited to talk about antibiotic resistance on BBC Radio Oxford. We went on the Kat Orman's morning show, alongside Monty Python's Michael Palin, and spoke about the increasing threat that antibiotic resistance poses, and what we're doing to combat it. We were asked questions about why we chose this area to pursue, whether our project was likely to be lincensed, and about the basics of synthetic biology.
+
                                    <li><a href="#q2_awareness">Awareness</a>
−
                        </p>
+
                                        <ul class="nav nav-stacked">
−
                        <div class="image image-right">
+
                                            <li><a href="#q2_antibiotic_resistance">To what extent do you feel that antibiotic resistance is aproblem that needs addressing in society today</a></li>
−
                             <img src="https://static.igem.org/mediawiki/2015/e/ec/BBC_Radio_Oxford.JPG"/>
+
                                            <li><a href="#q2_hospital_infection">Which of these do you think is the most common infection acquired in hospitals?</a></li>
−
                            <p>Mabel and Helen in the studio with Kat Orman!</p>
+
                                            <li><a href="#q2_genetic_engineering">Have you heard of genetic engineering?</a></li>
−
                        </div>
+
                                            <li><a href="#q2_synthetic_biology">Have you heard of synthetic biology, before this questionnaire?</a></li>
−
                        <p>
+
                                        </ul>
−
                            We answered this by using the analogy of computer hardware: if your computer hard drive is broken, you can buy a new model from the shop without worrying about whether it will fit or not, and it's the same with stretches of <a class="definition" title="DNA" data-content="Contains the genetic code for life, using only four types of molecules. It forms the familiar double helix structure and can self-replicate under certain conditions.">DNA</a> sequence that you can stick together. We were also asked about our outreach and the efforts we were making to change the mindset of a society that demands to be prescribed antibiotics.
+
                                     </li>
−
                        </p>
+
                                     <li><a href="#q2_treatment">Treatment</a>
−
                        <p>
+
                                        <ul class="nav nav-stacked">
−
                             Finally, Kat ended by asking if we thought we could change the world with our project. After a little nervous laughter, we gave our answer: <em>hopefully!</em> Our section begins 1hr 6mins into the 3 hour show. Click <a href="http://www.bbc.co.uk/programmes/p030s8vv#play">here</a> to have a listen!
+
                                            <li><a href="#q2_options">If you had the option of using two treatments for an infection, where one was antibiotics and one was bacteria that were designed to cure the infection, which would you choose?</a></li>
−
                         </p>
+
                                            <li><a href="#q2_doctor_recommendation">If your doctor recommended a treatment for an infection, which involved the use of bacteria that had been engineered to treat the infection, would you use it?</a></li>
−
                     </div>
+
                                        </ul>
−
                     <div id="practices_outreach-uniq-workshop">
+
                                     </li>
−
                         <h3>UNIQ Workshop</h3>
+
                                 </ul>
−
 
+
                             </li>
−
                        <p>
+
                         </ul>
−
                            We met with 40 prospective Oxford students to teach them about Synthetic Biology. The students had in interest in Biochemistry but knew nothing about <a class="definition" title="iGEM" data-content="Students doing something good with synthetic biology. Stands for International Genetically Engineered Machine.">iGEM</a>.
+
                     </li>
−
                         </p>
+
                     <li>
−
                        <div class="image image-full">
+
                         <a href="#third_questionnaire">Third Questionnaire</a>
−
                             <img src="https://static.igem.org/mediawiki/2015/d/d9/Ox_practices-uniq1.jpg">
+
                         <ul class="nav nav-stacked">
−
                        </div>
+
                             <li><a href="#q3_aim">Aim</a></li>
−
                        <div class="image image-full">
+
                            <li><a href="#q3_intro">Introduction</a></li>
−
                            <img src="https://static.igem.org/mediawiki/2015/f/f2/Ox_practices-uniq2.jpg">
+
                            <li><a href="#q3_results">Results</a>
−
                        </div>
+
                                 <ul class="nav nav-stacked">
−
                        <p>
+
                                    <li><a href="#q3_results_sealed">Sealed within a section of catheter</a></li>
−
                            We hammered home the key message of Synthetic Biology - that we achieve more progress by expanding a registry of standardised biological parts - through a 15 minute introductory presentation on <a class="definition" title="BioBrick" data-content="A specific base sequence that does something you want. Like a lego brick.">BioBrick</a>s.
+
                                    <li><a href="#q3_results_beads">Bacteria contained in beads within a catheter</a></li>
−
                        </p>
+
                                    <li><a href="#q3_results_attached">Attached to the catheter</a></li>
−
                        <p>
+
                                    <li><a href="#q3_results_free">Free-living Bacteria</a></li>
−
                             We then split them into groups and gave each one a mentor from our iGEM team. We worked through questions to test their understanding in a tutorial style and asked them to explain the constructs of previous iGEM teams. They finished by presenting their findings to each other.
+
                                    <li><a href="#q3_preferred">Public Preference</a></li>
−
                        </p>
+
                                </ul>
−
                        <p>
+
                            </li>
−
                            See the handouts we gave the groups <a href="https://2015.igem.org/Team:Oxford/UNIQ">here</a>. All the groups were given the Synthetic Biology page, and then one of the Group question pages.
+
                        </ul>
−
                        </p>
+
                    </li>
−
                    </div>
+
                 </ul>
−
                </div>
+
−
                <div class="image-massive">
+
−
                    <img src="https://static.igem.org/mediawiki/2015/8/8d/UNIQ_summer_school_picture.jpg"/>
+
−
                    <p>Duke discusses the central dogma with UNIQ Summer School</p>
+
−
                </div>
+
−
                <div class="slim">
+
−
                    <div id="practices_outreach-utc-oxfordshire">
+
−
                        <h3>UTC Oxfordshire</h3>
+
−
                        <p>
+
−
                            We gave a presentation on ABR to a class of GCSE students from University Technical College, Oxfordshire (a local school specialising in science) at the Natural History Museum in Oxford, The Pitt Rivers Museum. This was to spread awareness of ABR to a younger age group, inspiring them with the potential applications of synthetic biology.
+
−
                        </p>
+
−
                        <p>
+
−
                            Our talk covered the discovery of antibiotics, the advantages of them (including their use in laboratory work), how they work, and how bacteria can evolve to gain resistance to them, as well as concepts such as horizontal <a class="definition" title="gene" data-content="A section of DNA which codes for a protein.">gene</a> transfer and the consequences of antibiotic resistance on our everyday lives. It also covered our project outline, and pros and cons of Solution, showing how it should help combat antibiotic resistance.
+
−
                        </p>
+
−
                        <p>
+
−
                            At the end, we held a discussion between the students and our team about antibiotic resistance, and their perception of the concern. We also asked how they would feel about using our engineered bacteria, and the response was positive, with most of the students saying that if their doctor recommended the treatment, they would be open to using it.
+
−
                        </p>
+
−
                    </div>
+
−
                    <div id="practices_outreach-bang">
+
−
                        <h3>Bang! Magazine</h3>
+
−
                        <p>
+
−
                            An article was written about us and our Solution in Oxford University's science magazine, Bang! Read it <a href="http://www.bangscience.org">here</a>.
+
−
                        </p>
+
−
                        <div class="image image-full">
+
−
                            <img src="https://static.igem.org/mediawiki/2015/1/1c/Ox_frontcoverbang.png">
+
−
                        </div>
+
−
                        <div class="image image-full">
+
−
                            <img src="https://static.igem.org/mediawiki/2015/4/45/Ox_bangmag.png">
+
−
                        </div>
+
−
                    </div>
+
−
                </div>
+
−
            </div>
+
−
            <div class="section-spacer"></div>
+
−
            <div class="section" id="practices_further_considerations">
+
−
                <div class="slim">
+
−
                    <h2>Further Considerations</h2>
+
−
                    <div id="practices_fc_fungal">
+
−
                        <h3>Fungal Infections</h3>
+
−
                        <p>
+
−
                            “What about fungal infections?”
+
−
                        </p>
+
−
                        <p>
+
−
                            This question was asked following a talk we gave to Oxford alumni medical professionals. It was suggested that eliminating the bacterial population inside the urinary tract would increase the chance of the patient acquiring a fungal infection. Up to this point, we had not considered UTIs that are caused by fungi. The most common cause of fungal urinary infections are species of <em>Candida</em>. Infection with <em>Candida</em> usually occurs in patients with urinary catheters, typically after antibiotic therapy, although candidal and bacterial infections frequently occur simultaneously.  We then attended a talk by Dr. Haribabu Arthanari that discussed multidrug resistance in <em>Candida</em>, highlighting <em>Candida</em> as the second most common cause of fungal infection globally.
+
−
                        </p>
+
−
                        <p>
+
−
                            For a comprehensive treatment of UTIs, our solution also needs to target fungi. The most common species of <em>Candida</em> involved in infections, particularly in the urinary tract, is <em>Candida albicans</em> <a href="#references"><sup>3</sup></a>. Unfortunately, according to a fungi specialist (Professor Neil Gow, University of Aberdeen), “there is no fungal equivalent to bacterial exotoxins”, so anything we use to sense fungal virulence must be a constitutive part of the fungal cell. Additionally, if we use a hyphal cell wall protein (as suggested by Professor Gow), this would only allow our bacteria to sense <em>C. albicans</em>.
+
−
                        </p>
+
−
                        <p>
+
−
                          If we were to use our current system and adapt it to target fungi, we would propose incorporating a system into our bacteria that senses hyphal wall protein 1 (HWP1), a protein used for hyphal development and yeast adhesion to epithelial cells, which is only present when the <em>Candida</em> are virulent <a href="#references"><sup>4</sup></a>. We would then use our chassis to produce an antifungal agent that would target biofilm formation as well as breaking down the virulent fungal cells. An example of such an antifungal agent is the Echinocandin class of antifungals. The problem with this is that it is very complicated to engineer bacteria to produce these agents, so a better solution for using our current system to target fungi as well as bacteria would be to coat the catheter in pre-made Echinocandin to prevent <em>Candida</em> biofilm formation. <a href="#references"><sup>5</sup></a><a href="#references"><sup>6</sup></a>
+
−
                        </p>
+
−
                    </div>
+
−
                    <div id="practices_fc_prosandcons">
+
−
                        <h3>Treatment Pros and Cons</h3>
+
−
                        <table class="table table-striped">
+
−
                            <thead>
+
−
                                <th>
+
−
                                     Treatment
+
−
                                </th>
+
−
                                <th style="color:#57D064">
+
−
                                     Pros
+
−
                                </th>
+
−
                                <th style="color:#D90A40">
+
−
                                    Cons
+
−
                                </th>
+
−
                            </thead>
+
−
                            <tr>
+
−
                                <td rowspan="4" style="vertical-align:middle">
+
−
                                    <strong>Antibiotics</strong>
+
−
                                </td>
+
−
                                <td>
+
−
                                    Effective against many common infections
+
−
                                </td>
+
−
                                <td>
+
−
                                    Not effective against biofilms
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
                                    Easy to administer
+
−
                                </td>
+
−
                                <td>
+
−
                                    Bacteria can develop resistance
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
                                    Few side effects
+
−
                                </td>
+
−
                                <td>
+
−
                                    Some can result in side effects that exaggerate initial symptoms
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
                                    Inexpensive
+
−
                                </td>
+
−
                                <td>
+
−
                                    Can cause severe allergic reactions
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td rowspan="2" style="vertical-align:middle">
+
−
                                    <strong>Catheter coated with silver nanoparticles</strong>
+
−
                                </td>
+
−
                                <td>
+
−
                                    Bacteria cannot develop resistance
+
−
                                </td>
+
−
                                <td>
+
−
                                    There can be serious side effects
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
                                    Noninvasive in those who would otherwise be having a catheter fitted anyway
+
−
                                </td>
+
−
                                <td>
+
−
                                    Catheters support biofilm formation which can lead to recurring infections
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td rowspan="4" style="vertical-align:middle">
+
−
                                    <strong>Botox</strong>
+
−
                                </td>
+
−
                                <td>
+
−
                                    Increases comfort by lessening symptoms of incontinence
+
−
                                </td>
+
−
                                <td>
+
−
                                    Does not treat underlying infection
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
 
+
−
                                </td>
+
−
                                <td>
+
−
                                    May need to have a catheter fitted which increases incidence of infection
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
 
+
−
                                </td>
+
−
                                <td>
+
−
                                    Long term effect unknown
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
 
+
−
                                </td>
+
−
                                <td>
+
−
                                    Invasive
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td rowspan="3" style="vertical-align:middle">
+
−
                                    <strong>Methenamine hippurate</strong>
+
−
                                </td>
+
−
                                <td>
+
−
                                    Bacteria can’t develop resistance
+
−
                                </td>
+
−
                                <td>
+
−
                                    Have to take doses every day to prevent infection
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
 
+
−
                                </td>
+
−
                                <td>
+
−
                                     Requires additional supplements for effective treatment (Vitamin C, Cranberry supplements)
+
−
                                </td>
+
−
                            </tr>
+
−
                            <tr>
+
−
                                <td>
+
−
 
+
−
                                 </td>
+
−
                                <td>
+
−
                                    Relatively new treatment which hasn’t been tested in children, the elderly, or breastfeeding women, so this limits the number of cases it can be prescribed in
+
−
                                </td>
+
−
                             </tr>
+
−
                         </table>
+
−
                     </div>
+
−
                     <div id="practices_fc_sms">
+
−
                         <h3>Social Media Summary</h3>
+
−
                         <div id="p_fc_sms_t">
+
−
                             <h4>Twitter</h4>
+
−
                            <ul>
+
−
                                <li>396 tweets</li>
+
−
                                <li>495 followers</li>
+
−
                                <li>Retweeted by: The Wellcome Trust, the Royal Society, FRONT nurses (leading Research Nurses from across the UK), The Guardian Science, The Economist, and lots of other iGEM teams!
+
−
                            </ul>
+
−
                        </div>
+
−
                        <div id="p_fc_sms_f">
+
−
                            <h4>Facebook</h4>
+
−
                            <ul>
+
−
                                <li>321 likes</li>
+
−
                                <li>5.0/5 star ratings</li>
+
−
                                <li>6 reviews, all very positive</li>
+
−
                            </ul>
+
−
                        </div>
+
−
                        <div id="p_fc_sms_i">
+
−
                            <h4>Instagram</h4>
+
−
                            <ul>
+
−
                                 <li>24 posts</li>
+
−
                                <li>21 followers</li>
+
−
                            </ul>
+
−
                        </div>
+
−
                        <div id="p_fc_sms_wp">
+
−
                            <h4>Wordpress</h4>
+
−
                            <ul>
+
−
                                <li><a href="https://oxigem2015.wordpress.com/">https://oxigem2015.wordpress.com/</a></li>
+
−
                            </ul>
+
−
                        </div>
+
−
                    </div>
+
−
                </div>
+
−
            </div>
+
−
            <div id="references">
+
−
                <h2>References</h2>
+
−
                <ol class="references">
+
−
                    <li>TARGET Antibiotics Toolkit <a href="http://www.rcgp.org.uk/clinical-and-research/toolkits/target-antibiotics-toolkit.aspx">http://www.rcgp.org.uk/clinical-and-research/toolkits/target-antibiotics-toolkit.aspx</a></li>
+
−
                    <li>Catheter-associated Urinary Tract Infections (CAUTI), Centres for Disease Control and Prevention <a href="http://www.cdc.gov/HAI/ca_uti/uti.html">http://www.cdc.gov/HAI/ca_uti/uti.html</a></li>
+
−
                    <li><a href="http://www.cdc.gov/fungal/diseases/candidiasis/">http://www.cdc.gov/fungal/diseases/candidiasis/</a></li>
+
−
                    <li><a href="http://www.sciencedirect.com/science/article/pii/S0882401014000369">http://www.sciencedirect.com/science/article/pii/S0882401014000369</a></li>
+
−
                    <li>Morris MI, Villmann M (September 2006) "Echinocandins in the management of invasive fungal infections, part 1". Am J Health Syst Pharm 63 (18): 1693–703</li>
+
−
                    <li>Morris MI, Villmann M (October 2006). "Echinocandins in the management of invasive fungal infections, Part 2". Am J Health Syst Pharm 63 (19): 1813–20.</li>
+
−
                 </ol>
+
 
             </div>
 
             </div>
−
        </div>
 
−
        <div class="col-md-3 contents-sidebar">
 
−
            <ul id="sidebar" class="nav nav-stacked" data-spy="affix">
 
−
                <li><a href="#practices_overview">Overview</a></li>
 
−
                <li><a href="#practices_discourse">Discourse</a>
 
−
                    <ul class="nav nav-stacked">
 
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                        <li><a href="#practices_approaching-the-public">Approaching the Public</a>
 
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                            <ul class="nav nav-stacked">
 
−
                                <li><a href="#practices_approaching-the-public-ar">Antibiotic Resistance</a></li>
 
−
                            </ul>
 
−
                        </li>
 
−
                        <li><a href="#practices_urinary-tract-infections">Urinary Tract Infections (UTIs)</a></li>
 
−
                        <li><a href="#practices_interaction-with-nurses">Interaction with Nurses</a></li>
 
−
                        <li><a href="#practices_conversation-with-academics">Conversation with Academics</a></li>
 
−
                        <li><a href="#practices_return-to-public">Return to the Public</a></li>
 
−
                        <li><a href="#practices_return-to-nurses">Return to the Nurses</a></li>
 
−
                        <li><a href="#practices_feedback-from-doctors">Feedback from Doctors</a></li>
 
−
                        <li><a href="#practices_speaking-with-patients">Speaking with Patients</a></li>
 
−
                    </ul>
 
−
                </li>
 
−
                <li><a href="#practices_delivery">Delivery</a>
 
−
                    <ul class="nav nav-stacked">
 
−
                        <li><a href="#practices_delivery_commensal">Commensal Bacteria</a></li>
 
−
                        <li><a href="#practices_delivery_safety">Safety Considerations of Free-living Bacteria</a></li>
 
−
                    </ul>
 
−
                </li>
 
−
                <li><a href="#practices_outreach">Outreach</a>
 
−
                    <ul class="nav nav-stacked">
 
−
                        <li><a href="#practices_outreach-bbc-radio-oxford">BBC Radio Oxford</a></li>
 
−
                        <li><a href="#practices_outreach-uniq-workshop">UNIQ workshop</a></li>
 
−
                        <li><a href="#practices_outreach-utc-oxfordshire">UTC Oxfordshire</a></li>
 
−
                        <li><a href="#practices_outreach-bang">Bang! Magazine</a></li>
 
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                    </ul>
 
−
                </li>
 
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                <li><a href="#practices_further_considerations">Further Considerations</a>
 
−
                    <ul class="nav nav-stacked">
 
−
                        <li><a href="#practices_fc_fungal">Fungal Infections</a></li>
 
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                        <li><a href="#practices_fc_prosandcons">Treatment Pros and Cons</a></li>
 
−
                        <li><a href="#practices_fc_sms">Social Media Summaries</a>
 
−
                            <ul class="nav nav-stacked">
 
−
                                <li><a href="#p_fc_sms_t">Twitter</a></li>
 
−
                                <li><a href="#p_fc_sms_f">Facebook</a></li>
 
−
                                <li><a href="#p_fc_sms_i">Instagram</a></li>
 
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                                <li><a href="#p_fc_sms_wp">Wordpress</a></li>
 
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                            </ul>
 
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                        </li>
 
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                    </ul>
 
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                </li>
 
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                <li><a href="#references">References</a></li>
 
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            </ul>
 
 
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Revision as of 01:02, 19 September 2015

Questionnaire Results

First Questionnaire

Aim:

To find out what the public want synthetic biology to do for them.

Introduction

We conducted this survey in the Christmas vacation, with the idea that the results from this survey could inform our choice of project. The responses we got back were very varied, with some very interesting and detailed possibilities, and other, less thought-through options, such as "stop racism".

Results

We decided to display the responses from this questionnaire as a word cloud. The size of each word in the word cloud is proportional to the frequency of its occurrence in the questionnaire responses, so that it is clear what the public consensus of useful project ideas is.

Second Questionnaire

Aim:

To find out the public's thoughts on genetic modification, and see whether they would consider a treatment involving modified bacteria if they were suffering with a UTI , as well as gauging their opinion as to whether antibiotic resistance is a problem.

Introduction

Throughout our project, we have been determined to engage with the public so that we can develop a project which will be as useful to as many people as possible. These questionnaires, along with interviews with medical professionals and posts on social media, comprise a dialogue that we have maintained with the public for the duration of our project.

Questions

Ages of participants

We included age brackets as part of the survey so that we could check that our data is roughly representative, and so that we could see to what extent people of different ages are informed about genetic modification and antibiotic resistance. We found that most older people (31+) have heard of genetic modification but not synthetic biology, and are less likely to allow genetically modified bacteria to be used as a treatment. Younger people (up to 30) tend to be more open to the new treatment ideas, and more of them have heard of synthetic biology. However, our results may be biased, due to the high proportion of our participants aged under 30. Different generations are likely to have had different educations; synthetic biology is a very new field, so it is likely not to have been taught in schools yet. Similarly, older people may be more aware, and sceptical, due to the previous GM food scare.

Awareness

To what extent do you feel that antibiotic resistance is a problem that needs addressing in society today?

Our survey clearly shows that the public think that antibiotic resistance is an important problem that needs solving, therefore we feel that it is an appropriate and useful area to direct our project towards. One of our team members, George, worked in a UTI clinic last summer, so he knows first-hand that UTIs are a big problem for a lot of people, with current methods of treatment still being inadequate in severe cases. When he brought this to our attention while we were trying to decide on a project, we thought it was worthwile trying to find a solution to this problem.

Which of these do you think is the most common infection acquired in hospitals?

Most of the public (45.5%) thought that MRSA is the most commonly acquired infection in hospitals, showing that they think that antibiotic resistance is a problem. However, with UTIs coming in quite far behind this (19.5%), it seems that the public are not aware of the risk of getting UTIs in hospital due to urinary catheterisation. This could be due to the fact that UTIs are advertised less than MRSA, but since this is an important issue, we looked into educating the public through sessions with summer schools and school students, as well as getting in touch with local media, such as BBC Radio Oxford, ad promoting our project across social media. We believe that this has helped raise awareness of problems associated with catheter-based infections, not only in the urinary tract, but also due to other catheterised parts of the body.

Have you heard of genetic engineering?

96.5% of the people we surveyed had heard of genetic engineering. However, we did not collect data for whether people thought it was a good thing or not. This would be something to pursue in further surveys.

Have you heard of synthetic biology, before this questionnaire?

Compared to the question about genetic modification, the results for this question were much more evenly spread between yes and no, with 58% saying they had heard of synthetic biology. Again, it would be interesting to see whether those who have heard of synthetic biology have a good opinion of it or not, and this would be an avenue for future surveys.

Treatment

If you had the option of using two treatments for an infection, where one was antibiotics and one was bacteria that were designed to cure the infection, which would you choose?

The majority (70%) of the people we surveyed said that they would take the advice of their doctor on this. This means that it is important that we talk to and get advice from doctors as to how we can improve out treatment, since if we can't convince doctors that this is a better treatment than any current treatment, the patients won't take it either. However, encouragingly, of those who wouldn't take the advice of their doctor, our treatment was favourite with just under half saying they would prefer the designed bacteria (48%), compared to 40% who would prefer antibiotics.

If your doctor recommended a treatment for an infection, which involved the use of bacteria that had been engineered to treat the infection, would you use it?

Our survey showed that if a doctor recommended our treatment, only 6% would not consider it. This is very encouraging data for our project, but again highlights the importance of gaining support from doctors, because without their backing, this project is likely never to become as common a treatment as antibiotics.

Third Questionnaire

Aim:

To return to the public with a variety of delivery methods for our bacteria, so that they can provide feedback on what they like and don’t like about the options, and to see which they would like to see in use.

Introduction:

Having last surveyed the public on how receptive they would be to treatments involving engineered bacteria, and received very positive results, we decided to work on a selection of delivery options. Having designed several containment options with physical and molecular barriers to unwanted colonisation, we returned to the public to see which they would prefer.

Results

Sealed within a section of catheter

For a description of this option, check out our safety page here. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.

Pros:

  • No contact between patient and bacteria (11)
  • Extra safeguard should the bacteria escape (6)
  • Good compromise between encasing and ability to sense (3)
  • Very safe (2)
  • Simple (1)

Cons:

  • Less effective (14)
  • Long treatment time (6) – cost to NHS (1)
  • catheter uncomfortable (4)
  • Bacteria block catheter? (3)
  • Bacteria can’t be safely replaced (1)
  • Will agent be able to pass through catheter? (1)
  • Resistance (1)

The most common concern for this option was that it would be less effective than other methods, and would hence have a longer treatment time, causing discomfort to the patient and cost to the NHS. This concern was not outweighed by the number of people who liked that there was no contact between patient and bacteria, suggesting that the public would rather have a more effective treatment than one which was deemed to be “more safe”.

Other Concerns

Will the bacteria block the catheter? We would address this concern in the design of the bacterial compartment in the catheter, so that it does not impede the flow of water and urine.

Can the bacteria be safely replaced? We would investigate this further, and if it turned out that we couldn’t due to lack of sterility, we would suggest that another of our catheters were inserted, as a “disposable” solution.

Will the agent be able to pass through the catheter? We would need to investigate the nature of protein folding in urine-like conditions, something that we haven’t been able to achieve given the timescale of the project, but if the protein folds well, the agent would be able to diffuse out into the urinary tract. If not, it may be worth attempting to modify the protein structure to make it more stable in the conditions of the urinary tract.

Can the pathogenic bacteria gain resistance? The agents produced by our bacteria are designed to break up the biofilm that gives the pathogenic bacteria protection. Resistance arises when an antimicrobial agent fails to kill the entire population of targeted bacteria. We expect that, due to the design of our system, the entire population would be killed, so that resistance is not a problem.

Beads containing bacteria contained within a section of catheter

For a description of this option, check out our safety page here. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.

Pros:

  • Extra degree of containment (12)
  • Multiple safety measures (3)
  • Kill switch (2)

Cons:

  • Less effective (21)
  • Infection won’t be completely cleared due to dulled sensing capacity (5)
  • Restriction of flow (4)
  • Do bead cases break down in body? (3)
  • Long treatment time (3)
  • More expensive (2)
  • catheter uncomfortable (2)
  • More hospitalisations (1)
  • Replacement of bacteria (1)

Again, the most common concern was over the efficiency of this option, with additional related concerns about the number of hospitalisations, length of treatment, and the chance that the infection won’t be completely cleared. This was, as before, not outweighed by those who thought the extra degree of containment was a good idea. This provided further evidence that the public would prefer a more effective treatment.

Other Concerns

Will flow of water/urine be restricted? We would design the bead compartment around this concern, so that there is plenty of catheter diameter to allow sufficient flow.

Do the beads break down in the body? This is something that we would test. Sodium alginate (the substance from which the beads are made) is sometimes used in the food industry, which suggests that it could be broken down. What we would need to test is whether the enzymes involved are only present in the digestive tract, or whether they are present in the urinary tract as well.

This treatment option would be more expensive due to the materials involved. This is true, but we believe that the comparative cost is negligible due to the very low cost of sodium alginate. We would investigate other materials which have the same sort of properties, and whether these materials are any less expensive.

Can the bacteria be safely replaced? Again, something for further investigation. If, like in the option above, it is not possible, we would suggest our catheters are used as disposable, so that when the bacteria need replacing, the whole catheter is replaced.

Attached to the end of a catheter

For a description of this option, check out our safety page here. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.

Pros:

  • More effective (19)
  • Kill switch (6)
  • Balance between containment and efficiency (5)
  • Still physically contained (4)

Cons:

  • Introduction of another bacteria (8)
  • Diffusion rate of antibacterial agent (1)
  • Immune response (1)
  • Bacteria escape to kidney? (1)
  • Slower treatment (1)
  • Resistance (1)
  • catheter uncomfortable (1)

The primary concern for this treatment is that if the physical containment fails, another type of bacteria will be introduced to the urinary tract, and since their infection was caused by bacteria, this makes the public more wary. However, this is counteracted by the fact that more than twice as many people think that this treatment is more effective, and roughly the same number feel that it strikes a good balance between containment and efficiency.

Other Concerns

Will the diffusion rate of the antibacterial agent be too low to be effective? As long as we have enough of our engineered bacteria secreting the agents, we will be able to get a sufficient concentration of antibacterial agent to make this treatment effective. We are modelling how many bacteria would be “enough”.

Will the attached bacteria result in an immune response from the body? This is something that we would test. We don’t believe it would, since the chassis we are using has had all the pathogenic properties removed. We think that the immunogenicity of the agents is more of an issue that the immunogenicity of the bacteria, and an article on that can be found here.

Will the bacteria be able to escape to travel up to the kidney? This would be a long journey for the bacteria to make. They shouldn’t be able to make it, since the kill switches would start to work as soon as they were out of range of the pathogenic bacteria, and result in the deaths of all the escaped bacteria.

Will the distance between the catheter and infected site result in slower treatment? Yes it will, but the treatment will be faster that if the bacteria are contained within the catheter. However, if we had more time, we would also work on improving the efficiency of agent production, so that, whatever the distance, our solution would be more effective.

Can the pathogenic bacteria gain resistance? The agents produced by our bacteria are designed to break up the biofilm that gives the pathogenic bacteria protection. Resistance arises when an antimicrobial agent fails to kill the entire population of targeted bacteria. We expect that, due to the design of our system, the entire population would be killed, so that resistance is not a problem.

Free-living Bacteria

For a description of this option, check out our safety page here. Here is a list of the pros and cons of this treatment, as identified by the members of the public we surveyed, along with the frequency with which these were mentioned.

Pros:

  • Most effective (23)
  • Safe kill switch (11)
  • Swift treatment (6)
  • Two types of bacteria (5)
  • More comfortable for patient (4)
  • Prevention (1)
  • No need to be in hospital (1)

Cons:

  • Side effects of engineered bacteria colonisation (11)
    • just want a clear explanation from health care professional (8)
  • Kill switch concerns (5)
  • Opportunistic pathogens (2)
  • Any self-sacrificing bacteria left once all UTI-causing bacteria are killed? (1)
  • More difficult to monitor (1)

The public’s biggest concern for this option is side effects from the engineered bacteria colonising the urinary tract. However, over 2/3 of the people who raised this concern said that they would be happy to use the method if they got a clear explanation of how it worked from a health care professional. Additionally, the concern was outweighed by the public’s opinion of having a safe kill switch, and that this treatment is the most effective.

Other Concerns

How do you know whether the kill switch will be effective? The kill switch we have designed works in theory, but we will not know properly until it is tested. However, many other teams have used similar kill switches, and they have worked, so we don’t have a reason to suggest that it won’t work. The people who wrote this as a concern said that “if it can be proved to work, I’d be happy with it”, suggesting that their concern is that they haven’t heard of this type of thing before, and are wary of it for that reason, since it is harder to visualise than, for example, a physical containment option.

Will opportunistic pathogens take advantage of the niche that was previously occupied by the pathogenic bacteria? We are hoping that our bacteria will occupy that niche until the infection has been cleared up, and then allow the urinary tract’s natural flora to recolonise. Obviously, we would need to test this in vivo, but we think it would be good to use this treatment in combination with a preventative treatment against opportunistic pathogens, at least until conclusive evidence has been collected.

What will happen if there are any self-sacrificing bacteria left once all the pathogenic bacteria are killed? We would use a very basic additional kill switch where we could get rid of any remaining engineered bacteria at the end of treatment by adding IPTG.

Won’t this make the bacteria more difficult to monitor? If this solution were to proceed to clinical trials, one of the things we would test would be how long it took to clear up an infection, so we could base treatment courses on this. We would be more likely to monitor the symptoms of the infection rather than the bacteria themselves.

The Public's preferred method of treatment

From the survey results, we found that the public were most happy with the free living bacteria option (44%), due to it's effectiveness at treating the infection, resulting in greater comfort for the patient. The next most popular option with 20% was sealed within a catheter, since this balanced efficiency with safety. Attached to a catheter and bacteria contained within beads both got 16%, these being less popular because one aspect (safety or efficiency) outweighed the others too heavily. Only 4% said that none of the options appealed, which is very encouraging for our treatment, since treatment of infections with engineered bacteria is a very new concept. It gives our project and synthetic biology as a whole a confident outlook that the public are so receptive to this idea.