Team:NTU-Singapore/IHP
Integrated Human Practice
A Glimpse of Our Journey
With the recent advance on CRISPR technology and a growing topic in the national conversation in Singapore, our iGEM project is at the heart of such a discussion. How far should we as a society accept technologies that change our genetic makeup? What are the important concerns that people may have? And even more fundamentally, how can our society become informed about such a niche topic, when it is now so close to our life?
With all the questions at our heart, we started to engage with our community to inform them about gene editing and understand their concerns. Through our public education and engagement, we had an intuitive understanding about people’s attitudes and we realized some mismatches between our focus and the concerns that other people have. Therefore, to fully convince ourselves, we decided to conduct a comprehensive analysis of the general attitude towards gene editing in this region. Below is what we have learned.
Motivation
To ensure our experience is not subjective and unique, we first started off by collecting and analyzing the different views of Singaporeans about gene editing technologies on different media platforms. We believe the different stands and the different arguments being raised would inform us about the main issues in the discussion.
Summary of Arguments
In Singapore, proponents of gene editing argue that it is a great tool for us to cure genetic diseases. With the CRISPR/Cas system, target efficiency and specificity have been greatly improved. It promises an affordable solution for curing rare genetically linked diseases, the cost of which is unimaginable for many families. Lastly, many believe that it is important for many parents with genetic diseases to have an equal opportunity to have their children.
However, opponents against gene editing argue that no one is born to be perfect, so we should not deliberately change our genetic makeup to eliminate disease causing-genes. Many also think that germline gene editing objectifies humans and violates bodily integrity. More importantly, many question the safety of such treatment, fearing for the variation in the results and the consequences that come after.
In general, the discussions in Singapore are capable of reaching the consensus that at the very least, we should treat it just like traditional medical methods, where the technology itself is morally neutral, but its morality depends on how people use it. Majority of the voices agree that only applications in disease treatment should be allowed but not for enhancement purposes, to prevent the unregulated use of gene editing and they call for all stakeholders, including scientists, politicians, and the public to bear the responsibility of regulating gene editing together.
For example, Singapore has Bioethics Advisory Committee made up of a group of specialists, professors, and doctors in the medical field to review relevant laws and rules associated with gene editing. Where necessary, it engages public and reviews all the ethical, legal and social implications arising from gene editing and suggests to the government bodies what are the best actions to be taken. This exemplifies how different stakeholders shall cooperate and the recent call for legalizing mitochondrial replacement therapy is a realistic example. A summary of all arguments can be found here.
Our Takeaway
There is a myriad of views towards gene editing, especially for germline editing, with some arguing that it is a social leveler while some others arguing the opposite. The most discussed issues regarding gene editing are the social ones. People are worried about the social change that will be caused by gene editing technology.
Most Singaporeans hold an attitude of cautious acceptance towards gene editing. They look forward to its power, meanwhile take caution on its potential negative effect. Their assurance is partly for the fact that Singapore has relevant authorities to keep research and application in gene editing under careful observation.
Our Actions
The overall attitude towards gene editing in Singapore is a receptive one, so we are assured that our research will be supported by the public and will hold a good opportunity to be applied in Singapore’s society. However, we still see many issues being raised, like affordability and safety. We should measure and rank their relative importance. Hence, from the pilot testing of our survey in National Junior College, we decided to expand this survey further.
Motivation
With a properly designed survey, we hope to draw a rigorous conclusion from the analysis of survey data. More specifically, we want to understand the following:
• To better understand the awareness level, concerns and preferences about gene editing of the general public.
• To put the public opinion of Singapore in the context of our region, by comparing with other countries.
• To correlate people’s attitude towards gene editing with educational background.
Survey Design
In order to obtain meaningful results, we invested great effort to design our survey questions and methodology to minimize the biases it may introduce. As such, we first established the following before our start.
Goal
Determine public awareness, concerns, and acceptance towards use of gene editing and therapy.
Covering letter
Cover letter provides information about the survey and get informed consent from the respondents.
Approach
Both interpersonal collection in outreach events as well as digital collection through Google Form.
Minimizing Bias
We formed and evaluated the following matrix of criteria, taking necessary steps to minimize the potential bias in our survey and ensures the validity of our survey results.
1. Neutral Wording
Words that carry connotations or emotions are avoided. Scientific definitions given where necessary.
2. No Leading Questions
Incorporate Likert-scale questions where possible. [1] Open-ended question given to allow discussion.
3. Readability
Tested with Dale-Chall Readability Formula, Gunning Fog Index, and Flesch-Kincaid Readability Test [2], all show a tenth grade level.
4. Random Sampling
Distributed online and social media for anyone to fill in. Not limited to the people around us.
5. Anonymity
Name or contact information is not collected and individual answer is not published.
6. Appropriate Length
Able to be completed just over three minutes.
7. Demographic at the end
Demographic questions are intrusive, and may affect answers by reminding social status. [3]
8. iGEM Past-Examples
Researched on the past studies in iGEM. Wording checks by Harvard Survey Research Tip Sheet [4].
9. Pilot test
Pilot test of 30 samples conducted in NJC outreach to validate our survey. Results were not used.
After our own evaluation, we then consulted Prof Rosenthal from Wee Kim Wee School of Communication and Information, Nanyang Technological University [5] to confirm the validity of the above criteria and our survey. He is an expert in the field of public understanding of science and research methodology. He gave us valuable feedback on how to further improve the survey questions such as fine-tuning some of the phrasing and organization of the entire survey. Here shows a sample of our survey should you become a participant.
Survey Results
From the survey, we collected 581 survey responses from Singapore, Indonesia and China in total. Figures below show the gender, and age distribution of our respondents.
Figure 1. Pie chart of the gender of respondents from all three countries.
Figure 2. Histogram of age of respondents from all three countries.
Among all respondents, over 50% of the respondents are able to correctly identify at least one disease caused by genetic defects, with diabetes and down’s syndrome being the most frequently mentioned diseases for all three countries. This suggests that most respondents have some degree of awareness of the genetic diseases around us.
Figure 3. Word cloud for responses to known diseases caused by genetic defects
From left to right are results for Singapore, Indonesia and China respectively.
However, cancer, being one of the most common genetic disorders, is surprisingly not as frequently mentioned. It only ranks 4th most frequently identified genetic diseases for Indonesia and ranks even lower in the other two countries, indicating that cancer is not classified as a genetic disease according to most of the respondents. Therefore, we can conclude that though most respondents are able to name one or a few genetic disorders, they are less familiar with what constitutes a genetic disease.
Next, we compared the public attitudes towards gene editing in the three countries we surveyed. Generally, people are receptive of gene editing on the purpose of curing lethal diseases, as it holds the highest proportion of “agree” and “strongly agree”. As of the other three applications of gene editing, the trend differs. In Singapore, people support more on curing minor diseases, followed by improving physical trait, and lastly intelligence. In Indonesia, people support slightly more on curing non-lethal diseases, followed by improving intelligence and physical features. In China, the graphs hold the same shape for all three other applications of gene editing. There is no obvious difference in the support level.
Figure 4. Attitude towards different applications of gene editing
Then we tested how much the respondents perceive themselves to know about gene therapy. It also leads to the next question of the different factors to consider when making a choice about gene therapy. From the graph below, Singapore and Indonesia showed similar trends where there is a bulk in the middle. Most of the people in these two countries perceive themselves to have some degree of confidence when they need to make a decision on gene therapy. Whereas for people in China, there is no obvious peak or valley, suggesting an equal distribution.
Figure 5. Confidence level of making an informed choice regarding gene editing
In terms of factors in decision making, Singaporean are most concerned about the safety of the technology and the price as Singapore ranks first in these two categories, followed by China and Indonesia. China and Singapore are more concerned with ethics than Indonesia. Indonesia ranks lowest for all three factors of cost, safety, and ethics. In weighing DNA editing over RNA, from the responses with a choice made, all countries show a higher percentage of people choosing RNA editing over DNA editing. In Singapore, there are 42% of the respondents choosing RNA editing, relatively higher than those choosing DNA editing, which is 30%. Therefore, the public in Singapore favor towards RNA editing.
Figure 6. Significance of factors in affecting decision regarding gene editing
From the results, we are able to conclude that there is a significant value in developing RNA editing technology and the important factors we should think about are safety and cost. There are more interesting observations we observed from the survey. You can view our complete report here.
Our Actions
As the general public prefers RNA editing, we decided to expand our research to include RNA editing. As the public deems safety and cost to be the most important factors, we also researched in ways to ensure safety level and reduce the cost of current gene editing technologies. However, we still think it is necessary to engage the other stakeholder in the context of gene therapy, the doctors, who will be giving professional advice to patients who need gene therapy. We want to hear their views on the concerns and choices of the public and possible ways to address these issues.
Interview with Medical Professionals
Motivation
After our survey, with the public concerns that we collected, we want to interview the last stakeholder in our conversation, the professional doctors, as they are the ones utilizing gene therapy in the future, therefore it is important to know what their attitude towards gene therapy is. They also know the needs of the patients from a professional standpoint rather than an emotional one, so they are able to provide us with valuable suggestions to address issues with the patients.
Professor Denise Goh
Professor Denise Goh is a Senior Consultant and heads the Division of Pediatric Genetics and Metabolism at the Khoo Teck Puat-National University Children's Medical Institute, National University Hospital.
She holds an optimistic view on gene editing, especially using AAV and CRISPR-Cas to treat genetic disorders. She hopes that gene editing can be made available in five years’ time, and to replace traditional methods of treatments, which are comparatively ineffective or cumbersome. For example, the enzyme replacement treatment for Hemophilia, she pointed out, requires the patient to receive the treatment continually and also posed to the possibility of a severe immune response.
When asked about DNA editing and RNA editing for disease treatment, she thinks that DNA editing has a major advantage over RNA editing, which is a relatively lower cost. As RNA editing needs to be tailored to the individual patient, and the effect is not as durable as DNA, the cost for customization and continual treatment would make it more expensive. On the issue of safety, she is not worried too much on that of DNA editing, as she believes that RNA editing, whose effect being transient, is also able to cause a severe immune response and result in organ failure in a short time. While the negative effect of DNA editing is long-lasting, its advantage of fixing the gene permanently, in her view, outweighs the potentially disastrous effect.
In spite of that, she also finds value in RNA editing — for cancer treatment, some are analyzing transcriptome to identify the disease-causing transcripts, one layer above protein profiling, because the same gene can produce multiple transcripts due to alternative splicing, therefore, when the genome is not erroneous, and when defective proteins are too many to be corrected, it is important to identify the transcripts and correct or knock down them. The major problem now, she asserts, is that RNA is very unstable as compared to DNA or protein, and the transcriptome changes from time to time, from cell to cell, making it especially hard to analyze.
Training Doctors from Duke-NUS Medical School
We also interviewed training doctors Dr. Tracy Koh and her fellow colleagues from Duke-NUS medical school to see how future doctors view such an issue.
Figure 7. Photo of our interviewer with training doctors
We raised the issue of safety to the interviewees, and they agreed that safety is indeed a big issue as the patients would be worried about the risks of receiving the treatment, especially when it is not so well-tested at this stage. From a technical point of view, apart from efficiency issues related with CRISPR-Cas, delivery system would also be a problem where target cells may not be reached. Only by having enough clinical trials can we ensure the safety level, which takes a long period to accomplish. From the public’s aspect, they may not have sufficient basic information about the risks related to gene editing. There are public concerns even about GMOs, not to mention having their own genes altered, as one of the interviewees mentioned. Therefore, public education is needed to establish a more objective view towards gene editing instead of a subjective one fueled with fear for change.
When we asked about the issue of cost, they affirmed that cost is going to be inevitably high at first, due to the fact that the technology is still at its early stage — even sequencing was very expensive at the start, one of the training doctors added. The general view towards cost is optimistic as they believe that as the research progresses, gene therapy will eventually become more affordable.
On the issue of DNA and RNA editing, they hold the view that both are important and it will depend on the particular disease. For a life-threatening disease such as cancer, DNA would be a better option while for a less severe disease with short-term effects, RNA editing might be a better option. Since most patients would have no idea of what DNA editing or RNA editing is, it would be important that the doctors have professional knowledge and advice the patients the best method according to the need of the patient. It is the patient who makes the ultimate decision, so it is equally important that the patients have some basic understanding of different forms of treatment.
Our Takeaways
Both DNA and RNA editing have their own values, as each has a unique advantage under different situations. Since gene therapy is still a rather unexplored field, we cannot be sure that one will definitely work better than the other. Therefore, we should research in both areas, especially gene editing on the RNA level, which is less developed and researched as compared to DNA editing.
Currently, DNA editing is likely to be preferred due to the possibly larger cost incurred from multiple treatments of RNA editing. In order to not limit ourselves to DNA editing only, we seek to reduce the cost of treatment at the very early stage — disease analysis. We could develop an easier sequencing technique and make it more affordable to identify the genetic mutations since current transcriptome analysis is too time-consuming and complicated.
Integration to Our Project
After all our effort to understand different opinions from stakeholders in the discussion of gene editing, we have reflected upon our project and decided on what may be good to stay relevant to the needs of our society. We felt the great importance in developing RNA editing techniques and in reducing the cost in the current transcriptome analysis. After researching more on literature, we expanded our project to include Project REPAIR and Nanopore.