Human Practice

Introduction

From our online research, interest towards usage of engineered probiotics incorporated with therapeutic function is rapidly expanding. However, researchers have raised major concerns about the unknown effects that GMO could have on the natural ecosystem ^[1-3]. These issues must be addressed before engineered probiotics are approved for consumption in the market.

In our project, we are developing kill switch for engineered probiotics and at the same time developing a methodology which includes toolkits to allow easier design of kill switches for various applications. This has potential impact on various stakeholders including the members of the public and experts in the field of synthetic biology. Hence, for our Human Practice, we like to seek the opinions of these stakeholders on the importance of biocontainment using kill switch for GMO. Using the results, we then like to refine our project and take actions accordingly. For iGEM2017, we have surveyed the views of scientists, members of the public and conservationist on kill switches used in engineered probiotics as a case study to provide a more relatable context. In total, we surveyed over 70 people in person!

Approach

Firstly, our team identified the stakeholders relevant to our project. As genetically engineered probiotic could be a form of medication, members of the public would be the largest group of people who directly ingest these products but might not understand the potential risks, including the hazards to the environment. The second group of people is the experts in the field of synthetic biology who do research on GMO and synthetic kill switches. They would be a core source of knowledge towards building a successful system and understand the challenges faced in building such a system. The final group is the conservationist who studies or work in-depth with the flora and fauna and has first-hand experience of the possible dangers or benefits that synthetic biology could offer to our natural environment.

We proceeded with creating surveys and interviewing different groups of people to gather relevant information. (Researchers , members of the public)

First Group – Scientific Researchers in the field of synthetic biology

We attended the recent Synthetic Biology 7 event held locally in Singapore which garnered top experts in the field of synthetic biology who came to showcase their projects.

During the 4-day event, our team surveyed close to 40 attendees (Figure 1) About half of those surveyed are students who 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 their opinion on releasing genetically engineered probiotics out into 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 group surveyed raised concerns including potential health risk imposed upon consuming genetically modified probiotics. Another one-third of those surveyed here 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.

Team NUSgem at SB7.0

Figure 1. Statistics of suryvees at SB 7.0

Figure 2. Opinion on Genetically Engineered Probiotic

Figure 3. Concerns about GMO

Second Group – members of the public

Moving on to engage the second group of “customers”, our team went out to different parts of Singapore and surveyed members of the public on the potential side effects of genetically engineered probiotics. We simplified most of the complex jargon (GMO, Probiotics, etc.) and explained all the necessary terms to elicit a clearer response. While many participants were neutral towards GMO (Figure 4), they were able to give clear reasoning (Figure 5) about the topic of GMO by stating ecological concerns, ethical dilemmas and consumption safety. However, through the interactions that we had with the public, they could not grasp the concept of genetically engineered probiotics. Therefore, they presumed that genetically engineered probiotics were another form of medicine and only raised issues with regards to consumption safety. Based on the results, we concluded that there is a gap in knowledge among members of the public which warranted the need for education about the benefits and dangers of GMO and more importantly, the development of a kill switch mechanism to control our genetically modified bacteria while it is traversing through the human GI pathway.

Figure 4. Public's opinion on GMO

Figure 5. Public's top concern on GMO

Third group - Talk with conservationist

We attended a talk given by conservationist Dr. Madhu Rao and Dr. Chia-Da Hsu. We introduced our project about kill switches for use in genetically engineered probiotics and asked about the possible consequences of introducing our genetically engineered probiotics into the environment. Both answered that in the past genetically engineered organisms did more harm than good to our natural ecosystem. A strain of genetically engineered bacteria could have potentially both adverse and beneficial effects on the natural flora and fauna, but ultimately could lead to species extinction if left unchecked. They emphasized a need to regulate GMO in the natural habitat and welcomed our team’s idea of incorporating the kill switch system into probiotics. Our team asked if there were successful examples of GMO that had no adverse effect on the wildlife. They acknowledged that the introduction of genetically modified organisms into the ecosystem is bound to have some form of an effect on the natural biodiversity but trying to minimize this impact is a key strategy to ensuring the safety of nature’s inhabitants. Dr.Rao advised us to consider the potential areas of limitation in our kill switch system and to identify possible solutions to circumvent the identified limitations as the way forward.

Survey results

More education for members of the public to bridge gap in knowledge is needed.
The importance of a kill switch mechanism embedded into genetically modified organisms was emphasized.

There is a need 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 should be addressed.

Current methods to integrate kill switches into genetically engineered organisms are not well defined.

Action Plan from survey results

Framework to make engineering kill switches easier (Link to Human Practise Gold Action taken: Table 1 and Table 2 at Human Practise Gold page)

Discuss with researchers at NUS Synthetic Biology programme, SynCTI

What are the challenges faced in integration of kill switch (performance)
What could be the potential cause of side effects.

Safety Considerations of the kill switch failing in the human body. Action taken: Table 3 at Human Practise Gold page

How it fail
Where it fail
what are the consequences if it fails

Outreach

A need to outreach and educate members of the public about our work and the synthetic biology as a whole. See Education section below.

Outreach

We approached NUS Hackerspace to give a talk to interested parties about the importance of synthetic biology and our kill switch system in GMO. NUS Hacker is an open platform for everyone to pool their knowledge about computer coding which extensively studies the various computer languages (C++, MATLAB, Python, Javascript) to create complex algorithms and automated systems.

Team NUSgem endeavours to connect with this part of the community because:

Both fields of synthetic biology and computer coding have almost no relation with one another in terms of the fundamental knowledge involved. NUSgem believe that our outreach to this group could help expand their knowledge in synthetic biology and its potential benefits.
Our project is heavily dependent on the modelling aspect that utilizes MATLAB and thus interaction with aficionados in the field of computer programming can provide NUSgem with new insights on how to maximise the efficacy of our modelling system.

Our team member Wenhao giving details about the nature of synthetic biology

We drafted our presentation in the following format:

Timeline introduction of the field of synthetic biology with important advancements explained.
Introduction to the components of synthetic biology in simplified terms for easier understanding.
Brief introduction to GMO and kill switch, how the two are linked and our project rationale for the importance of kill switch to be incorporated into GMO.
Explained how the usage of modelling guided our project.

In the Q&A section, the audience asked an array of insightful questions. Some of these questions included:

How do you insert the DNA construct into the cell and achieve its intended function?
Won't there be too much metabolic stress in bacteria?
What if the toxin was poisonous and somehow affects our body?
What is your team considerations about potential future work, e.g. testing on experimental strains in the human body?

At the end of the presentation, we received generally positive feedback - the audience understood our presentation. They mentioned that although there were a little too many technicalities, they were explained thoroughly. Team NUSgem hopes that through this outreach effort, we are better able to educate the public on the aims synthetic biology and that our project has been meaningfully understood.

Our team member Wilbert explaining the importance of modelling in our project

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
D’Silva I. Recombinant technology and probiotics. Int J Eng Technol. 2011;3:288–93.
Amalaradjou, M. A., & Bhunia, A. K. (2013). Bioengineered probiotics, a strategic approach to control enteric infections. Bioengineered, 4(6), 379-387. doi:10.4161/bioe.23574

Team:NUS Singapore/HP/Silver