Given the profound potential of genetic engineering to shape the world around us, ethics in this field are of crucial importance. It is the constant responsibility of the scientist to consider and be aware of the implications of their research. Scientists must be prepared for the complex situations that will undoubtedly arise.

When considering the ethical implications of our project, we used the excellent Ethics Handbook devised by the 2017 Technion iGEM team. Thus, we decided to breakdown our project into the main ethical issues associated with it.

Given that our treatment would involve the incorporation of genetically engineered L. reuteri into the microbiome we acknowledge that some patients might not be comfortable with ingesting live, genetically engineered bacteria.

Thus, we decided to talk to Zack Abbott, co-founder and CEO of ZBiotics, behind the world’s first GMO probiotic that is available for sale to the general public. ZBiotics uses genetically modified B. subtilis to facilitate the breakdown of acetaldehyde in the gut and thus reduce the effects of alcohol consumption . Zbiotics is marketed as a food and is thus FDA-compliant. Moreover, the B. subtilis of Zbiotics will pass through the gut without colonising it - a large difference compared to our bacteria.

Yet, whilst ZBiotics main users are healthy individuals that have no need to alter the gut microbiome, our C. difficile patients’ microbiome will already have been colonised by C. difficile. In fact, current antibiotic treatment of C. difficile infection dramatically alters and kills the gut flora. In contrast, our L. reuteri would target only the pathogenic C. difficile . Thus, our modification of the patient’s microbiome is minimal in comparison to the widely accepted treatment of antibiotics. Moreover, itself which has been shown to act as an anti-microbial probiotic by Spinler et al. (2017) and fulfills “all the requirements” of a probiotic as mentioned by Mu et al. (2018).

For some, the very notion of using synthetic biology to engineer organisms is completely unnatural.This was pointed out by Dr Frances Butcher, a medical doctor who now specialises in bioethics and biosecurity. In addition, as shown by our survey, opinions on genetic engineering vary greatly between different age groups. As a result, we engaged with both elderly individuals, in the form of interviews, and young school children via summer schools and talks.

Moreover, Dr Butcher led us to question the idea of including a kill switch within our system. She made it clear that the kill switch must have a scientific objective and “must not be used to solely treat societal anxieties.” In fact, including a kill switch might lead to a negative public perception as it invites people to question the safety and potential risks of our probiotic. As a result of this, we ultimately decided not to incorporate a killswitch into our ProQuorum bacteria and instead rely on the sensitivity of our detection system..

To further develop our understanding of the public’s ethical view of genetic engineering, we created a survey focusing on specific areas of ethical concern and their comfort levels with GMOs in therapeutics

The subsequent responses further informed our ethical outreach and education strategy. Notably, one major conclusion we were able to draw was that the public’s scientific understanding of genetic engineering plays a key role in its perception as ethical. As such, survey participants who described themselves as not very proficient and/or interested in medicine tended to be the most skeptical about genetic engineering.

Therefore, clearing misconceptions definitely plays an important part in enabling the public to make informed decisions. Furthermore, many comments of survey participants confirmed the huge importance of education in this matter:

“People can be very fearful about new technology and myths are spread. Educating people will benefit society by reducing people’s reservations about GMOs so they can get the most effective treatment possible.”

In order to truly engage with the public concerning their opinions on GM technology, we decided to discuss ethics with them face to face. We also provided them with basic, unbiased information to provide background to the discussions.

Given that ethics often lends itself to a wide variety of opinions, we decided to host multiple events focusing on educating the public about genetic engineering and engaging in lively discussion. This is because it is of fundamental importance that discussion doesn’t simply remain limited to science laboratories and scientific experts. The voice of the public should be heard loud and clear as they are the ones who will be most directly affected by our potential product.

In light of this, we ran a synthetic biology and bioethics summer school workshop with 16-17 year old high school students to broaden the knowledge of future generations so that they can make informed judgements of their own on this ethical quagmire. Later, we also hosted an interactive talk on the topic at the Museum of Natural History in Oxford, further detailed here. Notably, this talk held special emphasis on the question:

When are GM drugs ethical and thus, when would people consider taking them?

The consensus was that conditions would generally need to be life-threatening to justify the use of GM drugs. However, people did seem to confuse drugs containing or produced by GM organisms with the act of genetically engineering itself.

Furthermore, one of the main comments raised in our survey was that a video would be an optimal medium to explain the concepts of genetic engineering in a more interesting and accessible manner. Thus, we decided to team up with several other iGEM teams, notable iGEM Queens, to produce a short FAQ video based around genetic engineering, as detailed here.

Ethical Practices

Throughout all our outreach activities, we made sure to comply with general ethics guidelines, especially regarding confidentiality - notably, the anonymity of our survey participants. Our survey itself was designed following the ethical guidelines AAPOR Task Force report “Evaluating Survey Quality in Today’s Complex Environment”.