Human Practice

Introduction

From our online research (based on published papers), there are increasing interests to having engineered probiotics that have therapeutic function but researchers have raised concerns about their the use potential harmful side effects to the human body,[1](will continue to add more) as well as the unknown effects that the GMO will have on the natural ecosystem. These issues must be addressed before engineered probiotics can be approved for consumption in the market.

Approach

NUSGEM believes that the killswitch is the gateway to unlocking a new era of medicine. As a human practices, we like to find out from our potential users their opinions of such engineered probiotics. For iGEM2017, we focus on engineered probiotics as a case study.

Firstly, our team identified the stake-holders relevant to our project. In it’s finalized version in the form of a genetically engineered probiotic as a form of medication, members of public are the largest group of people who directly ingest these products but might not understand the potential risk accompanied with the medicine. The second group of people are the experts in the field of synthetic biology who researched on probiotics or synthetic killswitches. They would be core source of knowledge towards building a successful system and understand the challenges faced in building such a system. The final group are the conservationist who study or work in-depth with the flora and fauna and they would know what are the possible dangers or benefits that synthetic biology could offer with our natural environment.

We proceeded with creating surveys for different groups of people for our interview to gather revelant information. (survey link for researchers, survey link for public, survey link for conservationist(needs to be created)

First Group – Scientific Researchers in the field of synthetic biology

We attended the recent Synthetic Biology 7 event held locally in Singapore which garners top experts in the field of synthetic biology whom have come forward to showcase their projects.

During the 4-day event, our team surveyed close to 40 attendees(survey link) about our project (figure 1. About half of those surveyed are students whom are currently pursuing their PHD/Masters in the field of synthetic biology. About 20% of those surveyed are from synthetic biology related industries. We inquired for their opinion on releasing genetically engineered probiotics out onto the market. From Figure 2, about 89% of those surveyed were supportive towards having engineered probiotic circulate into the market for public consumption. However, from Figure 3, half of these experts surveyed raised concerns including potential health risk imposed upon consuming genetical modified probiotics, another third argued that the unknown interactions that engineered microbes upon accidental release into the natural environment could have adverse implications on the natural biodiversity and ecosystem.

However, from online research, there was many researchers whom opposed the use of probiotics due to their unknown nature and potential harmful side effects to the human body,[1](will continue to add more) as well as the unknown effects that GMO will have on the natural ecosystem. These issues must be addressed before engineered probiotics can be approved for consumption in the market. From figure 3, about half of those surveyed stated health concerns as their top priority to address. (i.e. side effects from taking such medicine) Furthermore, one-third of the experts were concerned that such genetically engineered microbes could implicate our biodiversity and natural habitat.

Second Group – members of the public

Moving on to engage the second group of “customers”, our team then went out to different parts of Singapore to survey members of the public on the potential side effects of genetically engineered probiotics. We simplified most of the complex jargon(GMO, Probiotics,etc.)(survey link) and explained all the necessary terms to elicit a clearer response. While many participants were neutral towards GMO(Figure 4(support GMO)), they were able to give clear reasoning(Figure 5(top concern GMO) about the topic of GMO by stating ecological concerns, ethical dilemmas and consumption safety. However, from our survey, because members of the public could not link GMO and genetically engineered therapeutic probiotics in the same category. Therefore, they presumed that genetically engineered probiotics were another form of medicine and only considered raised issues with regards to consumption safety.(Figure 6) Team NUSgem concluded that there is a gap in knowledge among members of the public which warranted the need to educate them about the benefits and dangers of GMO and more importantly, the development of a killswitch mechanism to control our genetically modified bacteria while it is traversing through the human GI pathway because we realized that it is not possible to reach out and educate everyone about our kill-switch mechanism with time constraint and manpower resource problems.

Third group - Talk with conservationist

Results

Takeaway from the surveys

1. Importance of a killswitch mechanism embedded into genetically engineered therapeutic probiotics.

To address the concern of potential health risk associated with consumption of genetically engineered therapeutic probiotics.
Environmental risk associated with accidental release of genetically engineered therapeutic probiotics.

2. Current methods to integrate killswitches into genetically engineered organisms are not well defined.

3. Education for members of the public to bridge gap in knowledge.

Outcome

Actions taken after learning from the survey

Educational Outreach

On October 27, team NUSGem headed down to NUShackers to give a talk about the importance of our killswitch in GMO.

Need for a framework that make engineering of killswitches easily (because of the importance)
Need to also consider the safety of the killswitch, what if it fails inside the human body.
Design Considerations

Our team listed out the most common factors about medicine that would be relatable to members of the public. We then asked survey participants to rank from a choice of 1-5 with 1 being most important and 5 being least important to understand what are their needs about medicine.

The 5 factors we listed out were Cost, Performance(number of times of consumption of medication in one day), treatment duration( how long did it take to treat the symptoms), mode of delivery and lastly side effects. (explain more about how we come about identifying these 5 reasons)

We tabulated a table calculating the various ranks as shown in Figure 7.(can talk about how to derive results) We determined that Performance, Side effects and Treatment Duration are the top 3 factors. In the next section, we will be talking about what could be done to improve the current design of our system in the context of the genetically modified probiotics.

Performance

How to prevent our killswitch system from inducing too much metabolic stress onto our system. How to prevent it from interfering with the function of the probiotic.

Side Effect

what if the system failed? What are the possible side effects. Where did the system fail at(in the body, outside the body). How to address the problem.

Reference

Sanders, M. E., Akkermans, L. M., Haller, D., Hammerman, C., Heimbach, J. T., Hörmannsperger, G., Huys, G. (2010). Safety assessment of probiotics for human use. Gut Microbes,1(3), 164-185. doi:10.4161/gmic.1.3.12127
Harrison, K. L., Geller, G., Marshall, P., Tilburt, J., Mercer, M. B., Brinich, M. A.,Sharp, R. R. (2012). Ethical Discourse about the Modification of Food for Therapeutic Purposes: How Patients with Gastrointestinal Diseases View the Good, the Bad, and the Healthy. AJOB Primary Research,3(3), 12-20. doi:10.1080/21507716.2012.662574

Team:NUS Singapore/HP/Gold Integrated