Introduction: Understanding challenges and addressing concerns about the implication of genome editing in the public domain.
With the rapid advancement of gene manipulation technology, the community is hopeful towards its vast potential. Riding on this wave, our team wanted to explore how we can harness the strengths of genome editing and yet remain vigilant to its pitfalls. Our project works on a fundamental ideal that applications will impact the society at whole, thus in order to optimize the public’s acceptance, we investigated the impacts.
In our Human Practice, we will share our commitment to understand public opinions, to practice responsible Science and to engage key stakeholders. To establish relevance, we started the process with #CasAsks where a survey was published to gather public opinion and perception on genome editing. Using the data gathered from our survey as the basis, we took #CasAsks one step further to consult expert opinion on genome editing. These experts include current scientists with strong knowledge of genome editing and Bioethicist to understand the societal impact further. This affirmed our choice to zoom into RNA editing.
Concurrently, we rolled out a multipronged public engagement effort in view of the misconceptions we collected during the survey. Our public engagement effort is broken down into three unique and yet concerted approach: #CasTalks (videos targeted at public), #CasTeaches (outreach talks targeted at students) and #CasWrites (discussion essays targeted at critical thinkers).
Together, these four components of our Human Practice will provide the public with a more in-depth and holistic understanding on the topic of genome editing in both the scientific advancement and its societal impact.
Read further on our Integrated Human Practice section to view our most crucial insights and how interactions with key stakeholders evolved our experiments and project design.
Integrated Human Practices
Integrated Human Practices was extremely valuable in shaping our project. In order to obtain the focus of our experimental design, we carried out a holistic ground research, considering the various stakeholders. From our multifaceted perspectives, we uncovered that the main hindrance of the public, for the hotly discussed CRISPR-Cas9 system, is attributed to the ethical concerns, which stems from the permanent alteration of the genome. Thus, we identified RNA editing as a safer and more relevant option and this helped in our choice to tackle RNA editing in our project. In response to opinions from key stakeholders, we launched a multi-pronged engagement to practice responsible Science.
We identified 3 main statements that drive our human practice: perception, risk and engagement.
The timeline of our Integrated Human Practice Process will illustrate how our project evolved over time and with the input from our valued stakeholders.
Theoretical Framework
Our Integrated Human Practice is based on the interaction between various stakeholders on the topic of genetic engineering. Science is a social institute that is completely influenced by other institutions – mainly economical frameworks, legal systems, religion and the research community. How will we integrate genetic engineering into the society? We aim to dissect the sociology of Scientific knowledge – focusing on the social conditions of Science, with the social structure and processes of scientific activity. Our ultimate objective was to act as a bridge between the stakeholders by shaping the direction of our project and designing methods to communicate Science more efficiently.
Timeline
Figure 1.
Perception
To gain extensive insight into the differing perspectives of stakeholders, we first identified the stakeholders involved in our project.
Figure 2.
We started by collecting data from the public about their understanding and perception towards gene therapy and genetic engineering to understand the ground knowledge. Through this data-driven approach, we identified misconceptions people had about genome editing. To better address these misinterpretations of the public, we sought the feedback of scientists in the research field and ethics regulatory board in Singapore. All these are documented in #CasAsks.
After the team decided on genetic editing as a broad topic, we were exploring between the well-researched DNA editing and the uprising RNA editing field. We investigated both the technical risks and ethical concerns arising from our project. These are some key opinions we heard from the experts/scientists that affirmed our choice to zoom into RNA editing.
Dr Kon Oi Lian: “RNA editing, because of the nature of RNA, I think should be safer because any adverse effects do not last forever. In terms of RNA editing, the ethical issues would be less complicated compared to DNA.”
Dr Calvin Ho: “RNA editing, at least the changes would be more transient than permanent. It would be interesting depending on the condition that we are intending to address. If it’s able to alleviate some of the safety concerns and prove a measured way forward, I think that will be extremely beneficial to holistic development. ”
Thus, after understanding the ethical conundrums surrounding genetic engineering, we chose to embark on transient RNA-editing as opposed to permanent DNA-editing due to the lesser concerns of non-permanent edits and hence a higher likelihood of public acceptance. Our fundamental research on RNA editing would contribute to the development of RNA-related diagnostics and/or therapeutics, which likely faces less ethical criticisms of infringing the sanctity of genetic material. Quoting Dr Kon, “Inflammatory conditions, infectious conditions, which of their very nature last only for days to week might be a good area in which RNA editing could be helpful because the effects is over when the infection is over. You need not worry about leaving a footprint in the person or the cells you have modified. "
Risk
As with all technological applications, there are definitely inherent risks. By talking to scientists working in the field of genetic engineering, we evaluated the possible sources of risk in our project and sought to alleviate these risks. We identified 2 main sources of risk stemming from our research: A main source of risk for this research is the off-target effects of the guideRNA, which would hinder the specificity of editing.
Quoting Dr. Autios, “When you design everything really well –you get the perfect guideRNA and use the best available Cas enzyme which has been improved in specificity, it can work very precisely.” With this, our modelling team came up with a guideRNA-designing programme that identifies the Kozak consensus sequence and makes a suitable guideRNA from it. Thus, this possibly decreases the likelihood of off-target sequences and improves the binding specificity. This is a technical issue related to our technology and the aim for modelling is to reduce the off-target risks to the largest extent possible.
Engagement
From our #CasAsks public opinion survey, we uncovered misconceptions and knowledge gaps that are rampant in the public. We identify the public as the greatest stakeholder as they are the eventual consumers of such genetic manipulation technology. Acting upon formative feedback obtained from the public, we dedicated majority of our human practices efforts into educating and engaging the public. Recognizing the need for enhanced scientific literacy and to generate discussion about genetic engineering, we had 3 target groups and action plans in mind:
#CasTalks – a series of videos targeting the public. We present a diversity of perspectives, from the application and potential of genetic engineering to the ethical concerns. We hope to dispel misconceptions and bridge knowledge gaps. This encourages members of the public to adopt a more informed stance, and further engage with government bodies to navigate the ethics with scientific advancement.
#CasTeaches – a series of outreach talks with the aim of garnishing students’ education with technicalities, therapeutics and diagnostics of gene editing. More so than the public, students need to be cognizant to such prevailing technologies that will be of increasing relevance to them in the future.
#CasWrites – a series of in-depth opinion-based discussion targeting readers who want to engage in more critical thinking and be exposed to theoretical epistemology behind ethical frameworks.
By coming up with 3 separate branches to target a diverse audience, our team hopes to be able to engage people of all walks of life and varying degree of knowledge in genetic engineering to gain insights on this topic. We also hope to develop their positive attitudes towards scientific research.
