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

Treatment

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.