Team:Lethbridge/human practices

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Policy and Practice

Interviews with Experts

In order to get a better perspective of the clinical applications of our project we interviewed Dr. Toni Winder who is a neurologist specializing in ischemic stroke. He elaborated on current stroke treatments and offered a clinical opinion on the use of genetic therapies for treating stroke and other traumatic brain injuries in patients. We also interviewed Dr. Randall Barley, an expert on cell culture therapy, to learn more about the current concerns with gene and cell culture therapy. These two interviews helped us become more aware of potential complication in our project and the clinical impact our work could have. We will be performing another interview with with a stroke victim, which allowed us to gain a better understanding of how this injury can affect a person’s daily life. The final interview will be available for viewing in at the Giant Jamboree this year in Boston.


Dr. Toni Winder
Neurologist
Lethbridge, Alberta

An interview with Dr. Winder discussing brain injury and his experience with treatment


Dr. Randall Barley
Ph.D. Experimental Surgery
Lethbridge, Alberta

An interview with Dr. Barley discussing cell and gene therapy

Concerns about Cell Therapy

With regards to human practice, because microglia can be derived directly from patient bone marrow cells, this study has the potential to provide a method of personalized, non-immunogenic neural rehabilitation [1]. In addition, we are also addressing the growing prevalence of bacterial antibiotic resistance around the globe [2].

Concerns about Gene Therapy

Antibiotic Resistance Reduction


“A post-antibiotic era – in which common infections and minor injuries can kill – far from
being an apocalyptic fantasy, is instead a very real possibility for the 21st Century.”

World Health Organization, 2014
In a report released this year, the World Health Organization warns that the growing resistance to antibiotics threatens to compromise our ability to treat even the smallest infections. Misuse of antibacterial drugs in medical, agricultural, and laboratory applications has led to elevated environmental levels of these drugs and increases the selective pressure for microbes to develop antibacterial resistances. This global concern, along with concerns specific to our project, has motivated our team to look elsewhere for plasmid selection mechanisms. In investigating potential methods of selecting for plasmids in culture, we came across an interesting RNA-IN – RNA-OUT paradigm, whereby an RNA stem-loop (RNA-OUT) acts in trans to base-pair with a stretch of mRNA (RNA-IN), obscuring the ribosome binding site, silencing expression (mutalik). By placing a “kill switch” gene, a T4 Holin lysis cassette or ccdB gyrase in our case, downstream of the RNA-IN sequence, the expression of this lethal gene can be prevented by blocking translation with RNA-OUT present on the plasmid. The RNA-OUT, inserted in the plasmid backbone in the place of the antibiotic resistance cassette, reduces the overall plasmid size, prevents the transfer of antibiotic resistance to human cells or microbiota, and reduces the levels of antibiotics in laboratory waste from cloning.

ethics and human practice.

Animal Ethics

In an effort to conduct our research in an ethically responsible manner, we used cell cultures rather than live animals for our initial tests (in accordance with the 3Rs principle defined by the Canadian Council on Animal Care). In anticipation of future testing in mouse models of stroke or traumatic brain injury, we have begun writing animal welfare protocols and initiated a discussion about obtaining consent for animal trials with the veterinarian at the Canadian Centre for Behavioural Neuroscience, Isabelle Gauthier, who is also a member of the University of Lethbridge's Animal Welfare Committee.

Collaboration with Public Health Agency of Canada

Together with the Public Health Agency of Canada (PHAC), we organized a discussion revolving around synthetic biology and the potential impact on public safety. One of our members, Suneet Kharey, travelled to Ottawa in October and presented at the PHAC our project details with emphasis on safety. This event was attended by over 70 participants (in person and via WebEx) from PHAC, Health Canada, and other departments including Environment Canada, Fisheries and Oceans, Foreign Affairs, Trade Development, and the Canadian Institutes of Health Research (CIHR). We participated in this conference from Lethbridge via WebEx.

During this conference, it became evident that there is a growing concern over the decreasing costs of DNA synthesis and the potential impact on public safety. Although the primary aim of synthetic biology is towards the development of biological parts for useful purposes, synthetic biology can easily be used for bioterrorism thereby raising the eyebrows of regulators and law-makers alike. In a controlled environment, the exploitation of DNA synthesis technology was demonstrated by the successful reconstruction of the Spanish Influenza Virus in 2005 (Science, 2005). It is nearly a decade since and the cost of DNA synthesis has decreased significantly (ref) and will continue to decline (ref) as technology is continually revolutionized.

It is clear that synthetic biology is dual-use, which was a major concern for PHAC and other authorities. Following the presentations by Suneet Kharey and a representative from PHAC, a round table discussion occurred with respect to policy and regulation development regarding current policies concerning synthetic biology. We discussed the risks and safety about doing synthetic biology in the institutional and/or professional environment and how this differs from do it yourself (DIY) labs. It was evident that policies and regulations need to be kept up to date with the current state and evolution of synthetic biology.

Most importantly, through this conversation we were able to develop the beginnings of a working relationship with PHAC as they were willing to collaborate with us and other iGEM teams in the future towards the goal of developing new and strengthening current policies. Since this conference, we have had preliminary talks with PHAC already about hosting an annual iGEM conference for Canadian teams moving towards fulfilling this goal.

References

[1] Hinze, A. & Stolzing, A. (2012). Microglia differentiation using a culture system for the expansion of mice non-adherent bone marrow stem cells. Journal of Inflammation, 9, 12.

[2] World Health Organization. (2014). Microbial resistance: global report on surveillance. Retrieved from http://www.who.int/drugresistance/documents/surveillancereport/en/