Team:Oxford/Design
Practices
Introduction
Our project relies on a three way conversation between the team, the public and experts. It touches every aspect of the project, from our choice of application to the details of our delivery system. We promoted Synthetic Biology and iGEM through outreach programs to inspire the next generation.
Urinary tract infections are a huge problem globally with millions of cases reported each year. We’re producing a guide for everything you need to know about urinary tract infections, as well as a treatment to beat antibiotics, which are rapidly becoming ineffective.
We want to make our website as accessible as possible to all readers, regardless of their level of expertise. Words with a dotted blue underline will show a definition when you hover over them.
Project Choice
Approaching the Public
To decide on our project idea, we sent out an initial questionnaire to the public to hear about what they thought about synthetic biology. We asked what big problems they wanted solving. We took the questionnaire to schools, to the streets and to our friends.
Examples of their suggestions for the applications of synthetic biology include bacteria which:
- Remove carbon dioxide from the atmosphere
- Target and kill cancerous cells
- Help treat Alzheimer's disease
- Produce energy
- Sew up holes in clothes
- Produce teeth glue
- Indicate how long someone has been dead for
- Combat antibiotic resistance
Of our responses, around 40 were related to Medicine and Health [1]. This led us to choose that track for our project. However, it was our team member George Driscoll’s work at the UTI clinic in London which helped us to select UTIs as a specific cause. Due to the un-aesthetic nature of the infection, it often receives less attention with regard to research.
A large proportion of our responses expressed concern for how Synthetic Biology would be used in society, with several references to the issues of contamination and exploitation for profit. With this in mind, we constructed a second questionnaire about our project, to test whether the public would get behind it.
Initial Feedback
We sent a second questionnaire to find out more about whether the public would use a Solution from synthetic biology to treat Urinary tract infections. We asked more about whether they had heard of genetic engineering or synthetic biology, and how much they trust a recommended treatment by a doctor. In collaboration with UCL, we also filmed some of these responses on the street. The results were overwhelmingly positive.
Our Inspiration
Jorge Talk
Churchill Hospital, Oxford
Our first visit to the hospital was to the outpatient clinic during which we spoke with Jan, one of the nurses on the ward. Jan told us about a case of a person getting septicaemia as a result of a urinary infection. The patient had received antibiotics for seven days and had come back for a check up. Their urine sample was clear and all seemed fine but then the patient had started to shake. The bacteria were now in their blood as it had travelled back up the ureter to the kidney. Even though this was a rare case, it was shocking to hear about such a serious case and made our project feel very relevant.
Jan also made the following points:
- People with infections have a catheter because they need a way to empty the bladder; else the urine travels up the ureter and back into the bladder
- If a patient becomes septic the catheter has to be removed or can be fatal
- UTIs are not just contracted by the catheter and it is important to also consider community based UTIs
- “UTIs are very common and can be quite painful”
- No separate ward for UTIs – they are treated in every ward
- The protocol for treatment is to take a urine sample, see if there is an infection, and prescribe antibiotics that the bacteria are most sensitive to
- Elderly hospital wards are likely to have many cases of UTIs
We took a lot from this initial conversation. We went onto investigating the pros and cons of the current methods of treating urinary infections and compared these to what Solution could offer. We realized that we needed to consider the catheter more from a hospital/medical perspective as up to this point we had confused its function, thinking it was more to do with administering medication rather than emptying the bladder. Following this meeting, the design of the catheter became an integral part of the project.
John Radcliffe Hospital, Oxford
We still wanted to learn more about urinary infections as well as to get some feedback from nurses abourtour idea. We organized a trip to the Adams Ward (Geratology) to learn more about how urinary infections affect elderly people.
First interview with Laura Evans, Adams Ward
What is the procedure for treating UTIs?
- Dip urine
- If the test comes back as positive, treat with a wide spectrum antibiotic
- Whether or not the catheter is inserted with prophylactic antibiotic treatment is the doctor’s decision
What happens when a patient tests positive for a urinary infection?
Whether or not the catheter is removed if a patient tests positive for a urinary infection depends largely on the reason that the catheter has been fitted. On the whole, the catheter remains fitted and the patient is treated with a large dose of antibiotics.
Is antibiotic resistance a problem?
Yes, particularly on this ward. As we treat elderly patients with recurring infections, their UTIs are frequently resistant to antibiotic treatment. We try different combinations of antibiotics but recurring infections are a significant problem.
Our project involves designing a catheter that prevents the formation of a biofilm on its surface. What do you think of this idea?
A catheter like that would be useful, but it depends on how long your catheter would work for. Patients can have catheters fitted for 3 months or longer. Catheters are also removed for other reasons, for example if they become blocked. Blockage is particularly an issue when the patient is suffering from a urinary infection.
Laura’s response regarding how long a catheter remains in place spurred us into researching how we could keep our Solution bacteria alive. This is what we found.
The Problem
Following our inspiring visits to the Churchill and John Radcliffe hospitals, we wanted to find out the public thought about the problem of antibiotic resistance. We posed the question: To what extent do you feel that antibiotic resistance is a problem that needs addressing in society today?
Our survey clearly shows that, according to the general public, antibiotic resistance is an important problem that needs solving. Therefore we felf it was a useful area to direct our project towards. One of our team members, George, worked in a UTI clinic over the summer of 2014, so he knows first-hand that UTIs are a big problem for a lot of people and that, in severe cases, current methods of treatment are inadequate. When he brought this to our attention, we thought it was worthwile trying to find a solution to this problem.
Feedback from Oxford Experts
To gain a further insight into the feasibility of Solution, we gave two talks during the summer, one at the termly Corpus Christi College Biochemistry talks and another to a group of alumni from the Oxford Biochemistry department. Two important questions arose from these talks:
- Have you considered whether the proteins you planning on secreting are immunogenic?
- If you are to kill all of the pathogenic bacteria in the urinary tract, will that make fungal infections more likely?
Our Solution
Project Viability
Now that we had decided on our project choice, we needed to find out if it wolud be feasible and, if so, what obstacles we wolud need to overcome.
Bacterial Sustainability
We made our first steps in the right direction after visiting the Bedford Ward at the John Radcliffe Hospital. We spoke with one of the catheterised patients there called Mavis. She admitted to having had urinary infections in the past, but said she had not contracted a UTI since having a catheter fitted.
We found that Mavis would possibly use 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 and told us that it is not dissimilar to using antibiotics.
Ethics
To find out the public opinion on our project, we sent out a questionnaire to over 150 people, asking: '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?'. We also asked this question to a number of medical professionals during our visits to hospitals and clinics.
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 did have certain reservations about our idea.
This proportion of negative feedback, although small, highlighted to us that our dialogue with the public needed to be improved. 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 Increasing Awareness section below.
Nevertheless, this is very encouraging data for our project, and 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.
The UTI Clinic
Delivery Method
Now that we had focused our project towards treatment of CAUTIs, we needed a suitable catheter design. We needed some method by which we could expose the catheter, and bladder, to our anti-microbial proteins, and in a safe manner.
First, we considered the idea of having our bacteria implanted within the patient, in the confines of the catheter. It was of paramount importance that we make sure the bacteria would be safely contained, and not be able to escape into the bladder to cause further infection.
Our team member Ria Dinsdale made the suggestion of using sol-gel as a possible method of containment. Despite being a very convincing idea, we found that it would be too difficult to design under the time restraints of the summer.
However, we subseqently found an alternative containment method, which we resurrected from the Oxford iGEM 2014 project 'DCMation'. Our predecessors' project also had to find a method of bacterial containment.
BioBeads
First attempt at making the beads using Sodium Alginate
The 2014 team encapsulated their bacteria in agarose to form BioBeads. These BioBeads were then given an outer coating of cellulose acetate, to allow flow of molecules into and out of the bead, whilst preventing the escape of their bacteria.
This year, we have been able to significantly improve the BioBead concept, by changing our inner material to sodium alginate, and our outer material to polystyrene; something which is still a work in progress. For full details on our developements on BioBeads, check out our Design page!
Catheter design
Currently catheters are very cheap to produce, find out how much, therefore as part of our project we decided to look into how we could introduce the beads into the pipe during the manufacturing process. We spoken to a mechanical engineer, Steven Dinsdale, and he help us with a design for a machine that could do this. The machine would use the technique of extrusion to make the tube and then a second cooled inflow tube would introduce the beads. This would hopefully keep the bacteria cool enough so they are not killed yet the polymer would be hot enough to melt and then form the tube.
Manufacturing idea from mechanical engineer Steven Dinsdale
Potential problems:
- If this design were used for catheter production the bacteria would potentially not survive the sterilisation process at the end of the manufacturing.
- Steps further down in the manufacturing process could harm out bacteria.
- The bacteria may not survive in storage due to the length of time stored, temperature, etc
Increasing Awareness
To promote Synthetic Biology and iGEM, we’ve used a variety of approaches.
UNIQ Workshop
We met with 40 prospective Oxford students to teach them about Synthetic Biology. The students had in interest in Biochemistry but knew nothing about iGEM. 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 BioBricks. 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.
UTC Oxfordshire
A couple of us gave a presentation on antibiotic resistance to a class of GCSE students from UTC Oxfordshire (a local school specialising in science) at the Natural History Museum in Oxford, The Pitt Rivers Museum. 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 gene 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. 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.