Difference between revisions of "Team:Oxford/HP/Gold"

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<h2>Ethics and Safety</h2>
  
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<h2>Overview</h2>
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<p>After deciding on our final project design, based on extensive and continuous discourse with patients (for more information on this dialogue, click here (link to gold page)), we decided to investigate the issues that might prevent a probiotic treatment being approved by the government. We contacted an expert: Jane Kaye, Professor of Health, Law and Policy, and Director of HeLEX (Centre for Health, Law and Emerging Technologies). She advised us that policy regarding emerging technologies is often linked to public perception, and that in turn is linked to the safety and ethics research that has been done regarding the technology. This led us to investigate these issues further.
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<p>As seen on our Human Practices Silver Medal page (link), public perception and feedback have played a large part in the direction of our project and its design. Since its inception, one group have informed the design more than any other: the doctors and patients themselves. Throughout the project we have maintained a discourse between ourselves and patients in order to tailor our therapeutic to their requirements. These discussions have influenced our project through the design of our genetic circuitry and method of delivery.</p>
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For more information on the safety of our probiotic, please click here (link to safety page).
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<p>As we met with patients, they also raised concerns over the lack of awareness of Wilson’s Disease and other rare diseases in the general public. We integrated this into our public engagement activities.
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To determine the concerns of the public with the use of genetically engineered bacteria as medicine, we approached them with a survey to examine what they perceived to be the problems with using genetically engineered bacteria to treat disease, and why people might be against their use in this way.
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Content from Alex.
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<h2>Discourse</h2>
 
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<h3>Dr Garry Brown</h3>
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<h2>Public Engagement and Education</h2>
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<p>“The therapies used today are the same as those in the 1980s – zinc and copper chelators. The chelators DO work, but with severe side effects, and there has been little interest in research looking new treatment methods since.”</p>
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Public engagement and education play a big part in iGEM, with acceptance of synthetic biology only being possible through education and increased awareness. As our project consists of us developing a probiotic treatment for use by humans, we knew that we would likely be facing an uphill climb when trying to encourage acceptance of this and similar technologies.  
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<p>The initial idea for our project came from a lecture by Dr Garry Brown on inborn errors of metabolism. Dr Brown has had previous experience with Wilson’s Disease, having treated sufferers earlier in his career. He informed us of some of the issues he perceived with current treatments, which have not been improved upon since the 1980s due to lack of research into other options.</p>
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We approached engagement and education on 3 levels: local, national and international.
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<p>Following this meeting, we began our research into specific copper-binding proteins that our bacteria could constitutively express to chelate excess copper. See how dry and wet lab research informed our chelator choices here (link).</p>
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<h3>Valerie Wheater, patient and Treasurer of the Wilson’s Disease Support Group (WDSG)</h3>
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<h3>Local<h3>
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<p>We then contacted the Wilson’s Disease Support Group (WDSG), hoping to get the opinion of current patients on our idea and ask them about their concerns with current treatments. We first spoke to Valerie Wheater, the group’s treasurer. She expressed her dissatisfaction with current treatments, particularly the high dosage frequency. She also expressed the general desire among patients for a longer term treatment.
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<h3>Patients at the 6th AGM</h3>
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<span style="font-weight:bold;">Natural History Museum</span><br>
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During the summer, we contacted the Oxford Natural History Museum to collaborate with them. This involved us carrying out a workshop with a group of young researchers, aged 16-17, who were carrying out 3 week summer research projects in conjunction with the museum. We introduced them to the concept of synthetic biology and the iGEM competition, through a short presentation and a series of synbio puzzle activities, and invited them into the lab to get a taste of undergraduate research.  
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<p>Following our introduction to Valerie, we attended the 6th AGM of the WDSG and presented our project idea before talking to patients to get their feedback. They expressed 3 key limitations with current treatments: side effects, price, and the high dosage frequency. We examined these limitations and returned to the drawing board, altering the design of our project to address these disadvantages.</p>
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<h2>Side Effects</h2>
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<p>Concern: Trientine Dihydrochloride and Penicillamine are currently used to treat Wilson’s Disease. Both have severe associated side effects, particularly Penicillamine. Despite this, due to it being the subject of more in-depth research, penicillamine is usually the first treatment prescribed, followed by trientine if adverse effects are observed.</p>
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<p>Serious adverse effects such as bone marrow suppression, anorexia, vomiting and diarrhoea are observed in 20-30% of cases (1). Infrequently, there may be cases of nephropathy (kidney disease) and hepatotoxicity (drug induced liver disease). Side effects associated with Trientine Dihydrochloride include nausea, skin rash, severe stomach pains, diarrhoea, and anaemia (2).</p>
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<p>Impact on design: Following the discussion of side effects, we investigated the risks associated with probiotic bacteria, further information can be found here (link to safety page). Side effects from probiotics, if any, tend to be mild and digestive. This concern primarily influenced the choice of chassis that we would ultimately want to use for our therapeutic.</p>
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<p>Insert table from Eric here concerning different bacteria.</p>
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<p>From this and discussion with Professor Kevin Foster (see below), we decided that ideally we would use E. coli K-12 Nissle 1917 to express our chelation system. Further information on risks specific to this strain can be found here (link to safety page chassis choice). </p>
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<h2>Price</h2>
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<p>Concern: Both Penicillamine and Trientine Dihydrochloride are very expensive. Trientine Dihydrochloride production in the UK is under the monopoly of a single company, and over the last 2 years there has been a 600% increase in the cost of the drug, despite the relatively inexpensive production costs. At £3,400 per 100 capsules, it is becoming increasingly difficult for the NHS cover the cost of the drug, particularly as the standard dose is 4 per day. The yearly treatment costs for a patient are approximately £50,000, meaning that the NHS are spending millions of pounds per year on treatments. In the USA, the situation is even worse, with both Penicillamine and Trientine Dihydrochloride having a price of over $22,000 per 100 capsules. These price hikes are making it very difficult for patients to get the treatment they need to prevent their condition from regressing.</p>
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<p>Impact on design: One of the intrinsic benefits of developing a probiotic therapeutic is that our therapeutic has the capacity to provide a significantly cheaper treatment as bacterial cell cultures are relatively inexpensive to maintain.</p>
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<p>The impact that price had on the development of our genetic circuit is related to the patient’s desire for a longer term treatment, which is discussed below under “High Dosage Frequency”.</p>
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<h2>High Dosage Frequency</h2>
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<p>Concern: One of the significant issues that patients expressed with the current treatment regime was the requirement for medicine to be refrigerated, whilst also being taken 4 times daily. Obviously, this requirement is limiting, and patients were keen for the development of a longer term treatment.</p>
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<p>Impact on design: Initially, our idea was to produce bacteria that would constitutively express copper chelators. Patients would take these in conjunction with a meal, and excess copper would be bound and excreted. However, this would require constant applications of the treatment.</p>
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<p>Following our discussion with patients, where they expressed their concerns with current treatments prices and the high dosage frequency, we decided that a longer term treatment would be necessary. We redesigned our genetic circuitry so that chelator expression would be under the control of a copper-sensitive promoter. This has the advantage of conferring safety benefits - the chelator is only expressed when required, meaning that it is unlikely that an excess of copper will be chelated that could result in copper deficiency. In addition, the metabolic load imposed on the bacterial cells is lowered, meaning that they are more likely to successfully and competitively persist in the gut microbiome. For information on the other safety measures we explored, please click here (link to safety). To see how wet and dry lab informed the development of our circuit designs, please click here (link to appropriate page).</p>
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<h3>Professor Kevin Foster</h3>
 
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<p>Upon deciding to produce a long term probiotic treatment, we spoke to Professor of Evolutionary Biology, Kevin Foster, about how we could ensure that our bacteria persist in the gut. He advised us to consider the distribution of different bacteria in the small intestine when deciding on our chassis. In addition, he advised us to think about colicins when designing our system, in order to make our probiotic more competitive in the gut flora. This contributed to our choice of E. coli K-12 Nissle 1917 as our final chassis - as this strain produces colicins, allowing it to successfully compete with other E. coli strains, including pathogenic strains (3).</p>
 
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<h3>Return to patients and the public</h3>
 
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<p>Having designed genetic circuitry and decided to produce a probiotic therapeutic, we returned to the public to determine whether they would be willing to take a treatment of this sort.</p>
 
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<span style="font-weight:bold;">Bang! Magazine</span><br>
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<p>We found that the majority of individuals would be happy to take a probiotic treatment, if prescribed and recommended by their doctor. Another portion of those surveyed were unsure, hopefully by providing further information, these individuals may be able to be persuaded to embrace a probiotic treatment.</p>
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We wrote an article detailing our project for Bang! Science magazine, which will be published in the forthcoming issue.  
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<h2>Delivery</h2>
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<p>Once we had determined our genetic circuitry, we reached out to patients and members of the general public to determine how best to deliver our probiotic. We carried out a survey in conjunction with the iGEM team from Vilnius, Lithuania, to compare results from our two countries.</p>
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<p>Insert Julia’s Survey 3 analysis</p>
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<p>From the results of our survey, we decided to use a “jelly-like” bead to deliver our bacteria to the intestine. Building upon the work done by the 2014 and 2015 Oxford iGEM teams, we decided to use an alginate bead coated in multiple layers of chitosan. Read about our results here (link).</p>
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<h2>References</h2>
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<p>(1). Grasedyck, K. (1988) ‘D-penicillamine--side effects, pathogenesis and decreasing the risks’,Zeitschrift für Rheumatologie, 47(Supplement 1: 17-9).
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<p>(2). Frequently asked questions (no date) Available at: http://www.trientine.com/frequently-asked-questions/#faq9 (Accessed: 8 April 2016).
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<p>(3). Sonnenborn, U. and Schulze, J. (2009) ‘The non-pathogenic Escherichia coli strain Nissle 1917 – features of a versatile probiotic’, Microbial Ecology in Health and Disease, 21(3-4), pp. 122–158. doi: 10.3109/08910600903444267.
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</p>
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<span style="font-weight:bold;">JackFM</span><br>
  
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We spoke to Oxfordshire-based radio station, JackFM, about synthetic biology and its uses. We also used this platform to increase awareness of rare diseases, discussing Wilson’s disease and the recent hike in the prices of the drugs used to treat it.
  
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JackFM has a weekly audience reach of 107,000 adults in the Oxford area, and our piece was played multiple time.
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<h3>National</h3>
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<span style="font-weight:bold;">Summer Schools</span><br>
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We organised summer school events for national students at 2 Oxford colleges. We began with a short presentation discussing the development of synthetic biology, its current applications and uses, the future of the subject, and the iGEM competition itself. Following this, we split the students into 4 groups to run small activities.
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We ran a variety of activities related to the use of biobricks and the construction of working parts. These included getting the students to build biological circuits whilst explaining the importance of different regions of different parts, troubleshooting potential genetic circuits to see whether they may or may not work as expected, investigating protein structure using PyMOL, and introducing the students to the concept of PCR and primer design.
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<span style="font-weight:bold;">WDSG AGM</span><br>
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During the summer, 3 of our team members visited Cambridge to attend the 6th AGM of the Wilson’s Disease Support Group. Here they gave a presentation explaining our project and received feedback from patients and doctors. To see how our discussion with patients impacted our project, please click here (link to Gold HP page).
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<h2>International</h2>
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<span style="font-weight:bold;">Presenting a poster at the London International Youth Science Forum (LIYSF)</span><br>
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One of our team members attended the LIYSF to present our project to 475 representatives from 75 countries. The presentation discussed the contact we had made with patients and the importance of finding alternative treatments for Wilson’s Disease, with the goal of raising awareness of rare diseases in addition to synbio. Most of the participants were unaware of Wilson’s Disease and showed interest in the issue.
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<span style="font-weight:bold;">Visiting Cyprus</span><br>
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As iGEM took place during our summer vacation, at some points members of the team took some time away from the lab to visit family and friends or go on holiday. One of our team members, Andreas, visited his home in Cyprus for a short time. Whilst he was there, he visited his old school to give a presentation covering a brief history of genetic manipulation, what synthetic biology is, and the kind of problems that it can solve. The presentation then discussed the use of synthetic biology to generate medical therapeutics and how treatments developed in this way might be used to alleviate the symptoms of Wilson’s Disease.
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<p>
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The presentation was well attended by high school students, chemistry and biology teachers, parents, and University of Cyprus (UCY) undergraduates. Cyprus has never before hosted an iGEM team, and at the end of his talk, Andreas was approached by an undergraduate student that showed an interest in starting a team for the competition next year. Hopefully this idea will come to fruition, and more students will be exploring synbio with iGEM next year!
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</p>
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<h2>Social Media</h2>
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Update at the end.
  
  

Revision as of 09:42, 16 September 2016

iGEM Oxford 2016 - Cure for Copper

Ethics and Safety

After deciding on our final project design, based on extensive and continuous discourse with patients (for more information on this dialogue, click here (link to gold page)), we decided to investigate the issues that might prevent a probiotic treatment being approved by the government. We contacted an expert: Jane Kaye, Professor of Health, Law and Policy, and Director of HeLEX (Centre for Health, Law and Emerging Technologies). She advised us that policy regarding emerging technologies is often linked to public perception, and that in turn is linked to the safety and ethics research that has been done regarding the technology. This led us to investigate these issues further.

For more information on the safety of our probiotic, please click here (link to safety page).

To determine the concerns of the public with the use of genetically engineered bacteria as medicine, we approached them with a survey to examine what they perceived to be the problems with using genetically engineered bacteria to treat disease, and why people might be against their use in this way.

Content from Alex.

Public Engagement and Education

Public engagement and education play a big part in iGEM, with acceptance of synthetic biology only being possible through education and increased awareness. As our project consists of us developing a probiotic treatment for use by humans, we knew that we would likely be facing an uphill climb when trying to encourage acceptance of this and similar technologies.

We approached engagement and education on 3 levels: local, national and international.

Local

Natural History Museum
During the summer, we contacted the Oxford Natural History Museum to collaborate with them. This involved us carrying out a workshop with a group of young researchers, aged 16-17, who were carrying out 3 week summer research projects in conjunction with the museum. We introduced them to the concept of synthetic biology and the iGEM competition, through a short presentation and a series of synbio puzzle activities, and invited them into the lab to get a taste of undergraduate research. Bang! Magazine
We wrote an article detailing our project for Bang! Science magazine, which will be published in the forthcoming issue. JackFM
We spoke to Oxfordshire-based radio station, JackFM, about synthetic biology and its uses. We also used this platform to increase awareness of rare diseases, discussing Wilson’s disease and the recent hike in the prices of the drugs used to treat it. JackFM has a weekly audience reach of 107,000 adults in the Oxford area, and our piece was played multiple time.

National

Summer Schools
We organised summer school events for national students at 2 Oxford colleges. We began with a short presentation discussing the development of synthetic biology, its current applications and uses, the future of the subject, and the iGEM competition itself. Following this, we split the students into 4 groups to run small activities. We ran a variety of activities related to the use of biobricks and the construction of working parts. These included getting the students to build biological circuits whilst explaining the importance of different regions of different parts, troubleshooting potential genetic circuits to see whether they may or may not work as expected, investigating protein structure using PyMOL, and introducing the students to the concept of PCR and primer design. WDSG AGM
During the summer, 3 of our team members visited Cambridge to attend the 6th AGM of the Wilson’s Disease Support Group. Here they gave a presentation explaining our project and received feedback from patients and doctors. To see how our discussion with patients impacted our project, please click here (link to Gold HP page).

International

Presenting a poster at the London International Youth Science Forum (LIYSF)
One of our team members attended the LIYSF to present our project to 475 representatives from 75 countries. The presentation discussed the contact we had made with patients and the importance of finding alternative treatments for Wilson’s Disease, with the goal of raising awareness of rare diseases in addition to synbio. Most of the participants were unaware of Wilson’s Disease and showed interest in the issue. Visiting Cyprus
As iGEM took place during our summer vacation, at some points members of the team took some time away from the lab to visit family and friends or go on holiday. One of our team members, Andreas, visited his home in Cyprus for a short time. Whilst he was there, he visited his old school to give a presentation covering a brief history of genetic manipulation, what synthetic biology is, and the kind of problems that it can solve. The presentation then discussed the use of synthetic biology to generate medical therapeutics and how treatments developed in this way might be used to alleviate the symptoms of Wilson’s Disease.

The presentation was well attended by high school students, chemistry and biology teachers, parents, and University of Cyprus (UCY) undergraduates. Cyprus has never before hosted an iGEM team, and at the end of his talk, Andreas was approached by an undergraduate student that showed an interest in starting a team for the competition next year. Hopefully this idea will come to fruition, and more students will be exploring synbio with iGEM next year!

Social Media

Update at the end.