University of Calgary Faculty Presentation

In May 2018, our team held a informational presentation outlining our preliminary ideas and plans for researchers, doctors, and general interest groups at the University of Calgary. We presented a 10 minute pitch of our project, then opened the floor to questions, comments and criticisms from the experts in attendance. Logistical comments were made regarding different transfection methods and whether to use wild type Cas9 or nickase. However, an unexpected yet repeated message from a few experts was to stray away from gene therapy and instead focus on using our toolkit for gene integration. The argument specified that gene therapy is filled with unknowns and hurdles, both physical and ethical, and navigating this landscape would not be worth the effort when our system could be readily applied to any gene integration applications within basic research. The main champion of this viewpoint was Dr. Ian Lewis, a professor at the University of Calgary whom we proceeded to meet with down the road. The specifics of these meetings can be found lower down on this page. This presentation provided us with some tangible laboratory knowledge regarding ideal procedures and methods, however the more salient impact was the effect on our team direction. This faculty session was the first time that we considered pivoting from gene therapy, and instead focusing on developing a gene integration toolkit for broader application in research.

Safety and Ethical Considerations in Literature Review

With consideration of the potential impact of our work on the surrounding society and world, we consulted literature that discussed the safety and ethical considerations attached to gene therapy, CRISPR, and regulation of modified organisms. Although focused on optimizing our system to be both efficient and safe, it was valuable to examine the negative implications that our work could have if unregulated. Further we recognized the influence Snip, Equip, Flip, could have on fields beyond therapeutics, while our system addresses one of the largest current challenges to gene therapy, it can also be applied to present issues in large-scale gene integration. This promoted the significance with which we focused on the specific targeting, size, expression and isolation of our insert.

In consulting present literature, we found it of utmost importance to involve ourselves in ongoing discussions on current issues of bioethics and biological safety and security, as it is our scientific and moral responsibility to address implications of our own project. Particularly, we thought it would be beneficial to engage individuals that have backgrounds internal and external to the realm of synthetic biology, whether that be within a laboratory or a public context. These meetings were used to verify preliminary research done on bioethical topics to determine if the surrounding community echoed the sentiment of present literature. In addition, our meetings would inform the framework with which we designed our project.

Meeting with Dr. Ian Lewis

Dr. Lewis works as a Chair for Alberta Innovates: Health Solutions in Translational Health. He also is involved in Metabolomics and is an assistant professor at the University of Calgary. His work centres on connecting metabolic adaptation and virulence of human pathogens, and developing new diagnostic methods and novel antimicrobial therapies. As an interested party, he attended our faculty presentation earlier in the summer and provided initial thoughts on our project. He was worried about the difficulty of addressing a topic as large as gene therapy, and thought that the sheer amount of unknowns and barriers involved with such an endeavour would prove problematic. He counselled us to use our gene integration framework for generic research purposes.

Later on in the project we met with Dr. Lewis again to talk about our progress and potential applications for our work. He was particularly interested in our project's applicability as a molecular modification tool, due to its wide usability in several fields of work. He thought the project could be used in molecular biology and gene analysis because it pertains to functions in metabolic disorders (his specialty) in a eukaryotic, human context. Particularly in his lab, work being done on DCMA syndrome (a metabolic disorder) could be advantaged by the use of a tool that allows for the knock-in of genes to characterize their function in the disorder. In a general context he described the potential of Snip, Equip, Flip as an “anvil”, whereas current technology such as CRISPR, could be likened to that of a “sword”. Emphasis put on our project’s utility as a tool for understanding biology further justified a shift toward expanding the scope of our project to become a toolkit for researchers, as opposed to a strict gene therapy system.

Spiritual Care Advisory Committee Calgary Zone Meeting

The Spiritual Care Advisory Committee members we spoke with consisted of Spiritual Health Practitioners, a family physician, and a community member from various religious denominations including Christianity, Sikhism, Islam and Buddhism. These individuals work closely with families and patients to support in counseling and spiritual well-being, whether it be active listening or the provision of rituals or ceremonies. Particularly they provide a conduit between public and spiritual views, while having first-hand experience in patient care.

We discussed the views of the public and religious faiths on the ideas of genetic modification, biotechnology, and potential implications of gene therapy. Although it was determined that therapies that improve the livelihood of humanity were beneficial, there were reservations in its use as a tool that can be viewed as altering the natural order. It was evident from our conversation that current society is not wholly prepared for wide-scale use of genetic modification for therapeutic purposes. Particularly the potential for alterations to the human genome for the sake of enhancement or targeting embryonic modifications were topics that were met with caution. Interestingly, the topic of eradicating cultures associated with genetically linked disorders such as deafness or dwarfism was brought up as a negative consequence to gene therapies. Ultimately, it was determined that our team was not equipped to fully counter the negative connotations and safety concerns that accompany the project’s therapeutic applications on a large-scale. As a result, we felt it was apt to limit the scope of our project to an equally important issue facing current gene therapies as well as genetic modification as a whole: gene delivery and activation.