Team:NUS Singapore-Sci/Cas Asks Interview

NUS Singapore Science: InterLab
Bridging the Gap: Interview keynote with expert scientists and bioethicists
Molecular biologists are at the forefront of the genome editing technology, exploring its immense potential for diagnostics, therapeutics and other out-of-the-box applications. This puts them in a perfect position to share the current advancements in genetic engineering and discuss ongoing challenges and limitations of the technology. We thus approached various molecular biologists to debunk the misconceptions surfaced during our survey. This can be found in #CasAsks: Survey.

Our team therefore hopes to become a bridge between the scientists who have the in-depth knowledge on genome editing and the general public who will be the eventual consumer of this technology. In this post, we distilled the keynotes highlighted by the expert scientists during our interviews to provide the general public with a wider perspective on the issue of genome editing.
Profile of our interviewees
Dr. Kon Oi Lian
is currently a Division head of the National Cancer Centre Singapore and has a Honorary Joint Professor position at the Department of Biochemistry in Yong Loo Lin School of Medicine, National University of Singapore (NUS).

Dr. Kon’s research focuses on cell therapy research in metabolic diseases. Currently, she is working on introducing a therapeutic gene to primary mammalian cells using zinc finger nucleases that aims to treat Haemophilia B here).



Dr. Matias Autio Currently a Senior Research Fellow in Professor Roger Foo’s Lab at A*STAR, Singapore.

Dr. Autio is researching on genome editing in stem cell models using the CRISPR technology. Foo’s Lab works on various projects related to the cardiac epigenome and heart-related diseases. (more information can be found here).



Dr. Calvin Ho Currently an Assistant Professor at the Centre for Biomedical Ethics at the Yong Loo Lin School of Medicine, National University of Singapore (NUS) and the co-Head of the World Health Organization Collaborator Centre on Bioethics, Singapore.

Dr. Ho’s research interest lies in global health law and ethics, research ethics and policy, as well as health policy and governance (more information can be found here).
Keynotes from Interview


1) CRISPR technology has great potential in the near future, especially for therapeutics
“There’s definitely potential there, there [are] thousands of people and companies working on these things and some of these ideas will be translated to the clinic eventually.”
- Dr. Matias Autio

“There is a lot of interest and excitement about the potential for genome editing for therapy.”
- Dr. Kon Oi Lian

“I think that [has] been a positive recent development, people I think are more interested in gene therapy, companies are rushing in to really take this further into the clinic.”
- Dr. Kon Oi Lian

“The public broadly speaking tends to be quite optimistic about the technology. [...] I think in the minds of certain individuals we are already there in terms of clinical applications. This may be true for a very limited number of somatic cell intervention in terms of gene editing or planning the gene editing technique but certainly not when we think about say, modifications at the germline level.”
- Dr Calvin Ho



Current genome editing techniques, including CRISPR, still face huge obstacles like low precision and off-target effects. We need to set realistic expectations for the whole society on what genome editing techniques can actually achieve.
“The thing is that you work on the reference genome. The reference genome is not yours or mine. [...] There’s always a possibility that even if you get a ‘perfect’ guide, maybe patient A unfortunately carries a mutation in whatever gene that makes the sequence now match to your guideRNA, and now you have an off-target.”
- Dr. Matias Autio

“I think that all the genome editing tools, even and especially CRISPR-Cas, one must be especially sensitive and aware of the fact that the accuracy is often not good. So, it’s not as advertised – you just make a particular modification and that’s all you do, that’s not true.”
- Dr. Kon Oi Lian

“We still don’t quite understand how the genome itself works. If we are hoping to rely on this technology for instance to have some changes in say behaviour or something as complex as intelligence, then clearly such an expectation will not be properly granted. But most immediately, if you are talking about particular disorders, such as [Huntington’s disease], at least we understand that we are not quite there yet in terms for being [sure] that is safe for patients.”
- Dr. Calvin Ho



3) Similar to any current treatment methods, using genome editing techniques like CRISPR for therapeutics definitely comes with its own risks. The key is setting an acceptable risk level when these technologies are introduced in the clinical setting.
“...there are going to be risks, there's no way that all the risk can be taken out of the picture for any potential therapies. And the question becomes like what is the acceptable risk?”
- Dr. Matias Autio

“...what are the standards of safety we are willing to accept before we take this into the clinic.”
- Dr. Kon Oi Lian

“It would depend on, whether the changes you have made, quite apart from whether they are accurate or precise, another aspect of the changes is, whether the changes you’ve made is biologically appropriate for the disease you’re trying to treat.”
- Dr. Kon Oi Lian



4) The introduction of the CRISPR technology has made genome editing much easier and cheaper than before. This could lead to possible abuse of the technology that perpetuates inequality and injustice in the society. Hence tight and well-established regulations on genome editing research will be necessary.
“Currently, I think the cost would be a consideration because the gene therapy products that have been approved are extremely costly. [...] The fairness of access would be something that we need to consider as a society. We will certainly not want to have good treatments that only the wealthy can access.”
- Dr. Kon Oi Lian

“I think the other consideration with a technology like CRISPR-Cas, because it becomes so easy to do, people are literally doing it in their kitchens. I think the question of biosecurity needs to be considered. Whether people could be using this for applications that the world would not approve of like bioterrorism, because now you can do a lot of things outside of a conventional laboratory.”
- Dr. Kon Oi Lian

“I think there are essentially issues that I will recognise. For instances, concerns about safety, concerns about fairness, concerns about how society would look like in the future, concerns about how this would affect the human race overtime, and concerns about our moral responsibilities. It may sound rather broad stroke but of course I think [it’s] very instructive, from certain past experience, to hear about how some of the justice concerns were for instance get articulated in a culturally defined and culturally appropriate manner.”
- Dr Calvin Ho



5) RNA editing techniques could open new possibilities in treatment methods for a wider range of diseases and disorders due to its short-lived effects.
“I think that RNA editing because of the nature of RNA, I think should be safer because any adverse effects don’t last forever anyway.”
- Dr. Kon Oi Lian

“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. So that might be an area for RNA editing.”
- Dr. Kon Oi Lian



6) Engagement of all key stakeholders is necessary and crucial, especially when genome editing techniques are introduced in the clinical settings.
“It’s always necessary to find out what the community knows, community concerns and what they want to happen in the society. What the community values are. It's a two-way process [for the BAC and the public]. [...] I think public consultations are extremely important and they should always happen”
- Dr. Kon Oi Lian

“...regulators need to engage all parties – the scientists that are doing the work and also the people who will be eventually affected when these things get to the clinic. You cannot expect the public to have deep discussion on the technical stuff but you have to get their opinion on what is acceptable or what avenues are acceptable.”
- Dr. Matias Autio

“I do think that [engagement] is first step in getting people involved, in this particular array of work. In others, I think it is more like moving into their social world, in a way that is meaningful for them, rather than expecting them to move out of their comfort zone into yours. So I think this step of moving out and reaching out is extremely important, and I do see this to some extent it’s a moral responsibility as knowledge holders, because we know this area, we have a greater moral responsibility to relate or to help others relate to what might be of interest to them”
- Dr Calvin Ho

For the full interview transcript, please refer to the files available below.
Dr. Matias Autio
Dr. Kon Oi Lian
Dr. Calvin Ho