Difference between revisions of "Team:Oxford/Practices"

Overview

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 antimicrobial resistance.

The plan sets out 5 objectives:

1. Improve awareness and understanding of antimicrobial resistance
2. Strengthen surveillance and research
3. Reduce the incidence of infection
4. Optimize the use of antimicrobial medicines
5. Ensure sustainable investment in countering antimicrobial resistance

Our work is focused on the first two WHO objectives. In our system, 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.

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 Practises 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.

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. [1] 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.

We want to make our website as accessible as possible to all readers, regardless of their level of expertise. Words with a dotted underline will show a definition when you click them.

Approaching the public

From the offset we wanted to tackle a problem raised to us by the public. We sent out an initial questionnaire 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:

• 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
• Combat antibiotic resistance

Urinary Tract Infections (UTIs)

It was our team member George Driscoll’s work at the Hornsey UTI 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.

Interaction with nurses

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.

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 uropathogenic 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 pros and cons of the current methods of CAUTI treatment, and compare these to what our solution could offer. Following this meeting, the design of the catheter became an integral part of our project.

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.

What happens when a catheterised patient tests positive for a UTI?

“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.”

Is antibiotic resistance a problem?

“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.”

Conversation with academics

In collaboration with Oxford University Scientific Society, we organised a public talk “Biofilms: role in health and disease, recalcitrance and in vitro modelling” 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.

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.

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 proteins we planned on secreting would be immunogenic. We explored this, and similar issues, in a report we wrote about the urinary biome. 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 Future section of design.

Return to the public

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.

We asked the public, “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 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.

We also asked, “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, the use of engineered bacteria as therapeutic agents will not progress from primary research.

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.

During this visit we were able to talk to Laura Evans again, this time to ask questions specifically about our project.

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 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.

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.

Increasing Awareness

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.

BBC Radio Oxford

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.

Mabel and Helen in the studio with Kat Orman!

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 DNA 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.

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: hopefully! Our section begins 1hr 6mins into the 3 hour show. Click here to have a listen!

UNIQ Workshop

Duke discusses the central dogma with UNIQ Summer School

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.