Our silver practices encompasses the interviews conducted with each user group: novices, hobbyists, and experts. We used their feedback to determine the type of system that would benefit all three groups and what design principles we would incorporate. In addition to our user group interviews, we spoke with individuals who are involved with aspects of biosecurity to help with our understanding of current legislation and how to address the dual-use of our cell-free system. Overall, these interviews guided us in our design of Next vivo.
The current curriculum is lacking synthetic biology
Winston Churchill High School Science Department
We contacted members of the science department from Winston Churchill High School, a local high school, and asked the department about how synthetic biology is integrated within the Alberta science curriculum. The current focus is on the nature of science and how it can relate to technology, society, and the environment. The curriculum works to utilize the scientific method and to integrate First Nations, Metis, and Inuit perspectives. They said their students are interested in learning about the human system, how technology and science work together, and enjoy hands-on activities. In their opinion, synthetic biology is largely absent from the current curriculum, with the exception of the grade 12 biology course, and that current scientific research is hard to discuss. They suggested synthetic biology could be easily integrated but there is a need for updated language and relevant examples, as well as an earlier introduction of synthetic biology concepts to benefit students in the long run. When asked what we would need to include in a teaching aide for topics such as transcription and translation they emphasized an easy to use, small, and cost effective solution. For cost effectiveness, a higher upfront cost for the tool with affordable replacement packs containing the necessary components would work best. For the safety considerations of using it in a classroom, they suggested it would need to have appropriate labelling and a clear disposal mechanism. They also suggested professional development (PD) day workshops, where teachers could learn synthetic biology concepts and experiments to then teach in class. PD day workshops would be necessary for teachers to obtain the background knowledge required to use the tool effectively.
Utilize the modularity of your system
Derek Masterman, High School Teacher
A member of our team discussed experimental design of our system with Derek Masterman, a high school science teacher with a background in biochemistry. He suggested that it would be effective for us to design an experiment that utilizes the modularity of our system. One idea was that an experiment would involve separating the transcription and translation components. Without certain components, the system would not be able to transcribe mRNA or translate a gene product with a visual output to indicate to the students if the experiment was successful or not.
Problems in the world can be solved using science
Sheanne Cox, Middle School Teacher
As a part of our collaboration, members of the High School team interviewed Sheanne Cox, a Grade 6 teacher in Lethbridge School District 51, who was involved with curriculum development at the Grade 5 level for many years. From this interview, we gained insight into what the focus of the Alberta curriculum is for younger age groups. The main focus is problem solving and getting the students to see how problems the world is facing can be figured out using science. For the educational tool, she suggested that the kit would need to be easy to assemble and durable, as it would likely be passed between different class section. Additional consideration is required to identify if the tool would be a class set (one for each student) or a single kit large enough for every student to see. She recommended having digital resources, like PowerPoint or smartboard compatible components, to increase the usability of the teaching aide. The kit would also require instruction booklets to explain components of the kit to the teachers, as well as how to use the tool.
Increase hands-on learning opportunities
Brent Runnett, Elementary School Principal
A member of our team spoke with Brent Runnett, an elementary school principal, about the Alberta curriculum. In regards to science curriculum, a major focus is on the development of basic skills, as well as piquing students interest in science. For synthetic biology to be incorporated, it needs to fit within the current curriculum initiatives, which include: Attitudes, Knowledge, Science, Technology and Society, and Skills. He suggested to make a kit that would include these objectives and that we would need to present our tool as a resource for increasing hands-on learning opportunities within the classroom. He also said that we would need to include supplementary materials for teachers.
Consider questions that students will ask
Justin Pahara and Julie Legault, Amino Labs
Members of our team had the opportunity to interview the co-founders of Amino Labs, Justin Pahara and Julie Legault. Amino Labs is a start up company that produces innovative mini-labs and kits for people aged 12 and up. We conferred with them how to develop a kit for educational purposes using a cell-free system. We discussed how we should market our system as a kit to teachers in a way that is easy for them to understand. They told us that we should write simplified instructions for teachers since we won’t know the science backgrounds of the people wanting to use it. Julie also recommended that we write the instructions while thinking of questions the students may have. This will allow teachers to do some research if they are unsure of how to answer the potential questions. Julie also mentioned that we should look at the safety procedures that other science kits include and that we should push users of the cell-free kit to have good safety practices, even though there is a low risk of contamination. They also told us that labeling can be an issue and to make sure that package labels comply to the standards in each country that the kit could be distributed to.
|Need simplified protocols and kits that are easy-to-use|
|Need standardized parts for learning one system|
|Need modularity for simple experiments|
|Need to promote good safety practices|
Creating a powerful tool for the scientific community
Hans Wilms, Biotechnology Consultant
We conducted an interview with Hans Wilms, a PhD student who is working as a synthetic biology consultant with The ODIN. The ODIN is a biotechnology company that makes Do-It-Yourself (DIY) kits for anyone interested in genetic engineering. Hans said that by making our system open-source , we are creating a powerful tool that allows members of the scientific community to modulate our parts collection. He also agreed that using a cell-free system would help to reduce concerns that people have when working with microorganisms like E. coli. He did not foresee hazards using our system, since it is non-proliferating and would not be able to survive in an environment. He suggested we regulate our terminology appropriately, depending on how involved people want to be in the DIY biology community. We also discussed how to promote genetic engineering in a positive manner. He said that it is about creating an open community and showing other people what projects you are working on. In terms of how The ODIN could produce cell-free system kits, Hans said that there would not be any restrictions on what they could produce as long as they are safe and easy to use . He suggested that it would be preferable that the company would not have to construct the kit contents in-house, allowing for faster shipping to consumers.
There is a need to move towards cell-free systems
Heather Underwood, Denver Bio Labs
Members of our team interviewed Heather Underwood, a co-founder of Denver Bio Labs, a community lab based in Denver, Colorado. Heather started this lab in 2015 as a way for the community to have a place to learn about synthetic biology. The lab also competed in the iGEM competition in 2016. During our interview we discussed the potential uses of cell-free systems in a community lab. Heather and her colleagues try to be as transparent as possible with the people in Denver and also work closely with the Environmental Protection Agency and their local FBI representative to ensure they are providing a safe place for the community. Their lab has a standard training procedure and requires its members to have certification on equipment before they are allowed to start working in the lab. Heather said their lab is wanting to introduce the concept of cell-free systems due to issues with plasmid assemblies and the associated costs. She also suggested that it would be great to have open-source simplified protocols available for their members to understand the procedures for their projects. Currently the lab is a non-profit and is run with the help of volunteers. In terms of the projects conducted in the lab space, they are chosen by individual lab members. They are in the process of creating community-based projects for multiple people to work on and wish to work with us on the types of projects that can be adapted to use as a cell-free system. She recommended that it would be great if we had a repository of ideas for projects that can be used with cell-free systems as well.
|Need for cell-free systems in DIY Biology|
|Need for open-source and standard parts to allow more people to use them|
|Need simplified protocols|
|Kits need to be safe|
Modularity is key to break the cellular process into pieces
Dr. Ute Wieden-Kothe, Biochemistry Professor
We interviewed Dr. Ute Wieden-Kothe, a biochemistry professor in the Department of Chemistry and Biochemistry at the University of Lethbridge whose research focuses on RNA (specifically RNA modifications) and protein. We asked her questions related to the types of systems she uses in her lab, which includes in vitro transcription assays to synthesize RNA made in-house. For protein work, she said that her lab is normally able to purify protein products directly from the cell, although they have had issues with this method in the past. She said cell-free systems have the fundamental advantage of allowing precise control in the biochemistry work she does. On the other hand, she highlighted that cell-free systems may miss interactions that normally occur in vivo, but that the development of more complex cell-free systems could improve on this limitation. For her research, a cell-free system including the transcription machinery required in E. coli and Yeast systems would be useful. She also said modularity is key to separate cellular processes into different pieces, allowing researchers to choose the elements to include that are most imperative for their work. This could help with potential troubleshooting of our system as a whole and she suggested we think of a set of positive controls that could be included. With making our system open-source, she advised that we would need to communicate effectively on how people can access our parts.
|Need for cell-free systems in research|
|Modularity is key|
|Need to communicate how to access parts effectively|
|Need a well characterized and developed system for researchers|
Minimal risk for a cell-free system
Justin Pahara and Julie Legault, Amino Labs
Another part of our interview with Amino Labs centered around the biosecurity aspects of our project. In addition to his role as a co-founder, Justin is also a part of the Emerging Leaders in Biosecurity Initiative fellowship, so we asked questions related to how our system would be regulated. We asked Justin if he knew how a cell-free system would be regulated within Canada. He told us that it would depend on the end product being produced. If a toxin was produced, then it would be regulated under the Human Pathogens and Toxins Act. He also told us that he had not come across any specific regulations for cell-free systems. When asked them about exporting internationally, they told us that each country can be different and that it is up to companies and consumers to know how products will be regulated in their respective countries. When we asked about the system that we would develop as an educational tool and what safety recommendations we would have to consider, Justin thought that we would mainly have to do an internal risk assessment. He also told us that the main risk would be environmental, though he thought that risk would be minimal.
Address issues directly with law makers
Ian Andrews, Legal Intern
We spoke with Ian Andrews about our legal research and the legal implications of the genetic re-coding aspect of our project. Ian is a graduate of the biochemistry program at the University of Lethbridge and is currently the legal intern with the technology transfer office at the University of Alberta (TEC Edmonton). Ian explained to us that the Canadian legal system is comprised of two elements: statutes and regulations. Statutes set out a general framework for what the law is, while regulations provide the specific mechanism for how their enabling statutes are enforced. Ian told us that statutes are often written years before the technologies that they are meant to control are fully developed. This means that, even though statutes may not specifically contemplate future technologies, they are often written so broadly so as to capture those future technologies. For instance, when we asked Ian if he had come across any statutory materials that mentioned cell-free systems, he said that it was unlikely that any statutes would specifically refer to such systems. The relevant statutes would have been written long before “cell-free” systems were contemplated by scientists, meaning that those statutes could not have been written with specific language encompassing cell-free systems. This is not to say, however, that cell-free systems are not captured by any existing statutes. Indeed, just because the subject of control is not mentioned specifically in a statute does not mean that it falls beyond the scope of that statute. Ian said that statutes like the Assisted Human Reproduction Act (AHRA) could impliedly regulate cell-free systems if such a technology were found to encroach on the statute’s broadly defined purpose (which, in the case of the AHRA, would be to control the use of technologies that could be used to modify the human genome). Ian also helped us focus on the important areas to cover in an overview of international legislation related to cell-free systems. He suggested that we group our international materials by legal system to aid in finding differences between pieces of legislation and to simplify the information presented.
For the genetic re-coding aspect of our project, we discussed with Ian the potential dual-use of our system. He said that laws are sometimes poorly designed to predict issues that may arise with new, rapidly-developing technology. This inability is particularly true for cell-free systems where the ability to expand the genetic code and use non-canonical amino acids is so novel. Ian said that the best practice for addressing any potential concerns is to raise those concerns with law-makers directly. Even where a concern is not likely to materialize in the near future, Ian suggested that it is still best to make law-makers aware so that they are able to contemplate specifically the technology in question when drafting new laws. We also discussed our proposed software solution with Ian. From a legal standpoint, he said that law-makers cannot predict every possible outcome that may arise from a new technology. Preemptively developing solutions to potential problems that law-makers may not consider on their own can be an excellent way to circumvent negative outcomes.
Encourage awareness about responsible research and potential misuse
Kathrina Yambao and Melanie Sabourin, Public Health Agency of Canada
We spoke with two representatives from the Centre for Biosecurity at the Public Health Agency of Canada: Kathrina Yambao, a senior policy analyst and a member of the iGEM Safety Committee, and Melanie Sabourin, a biosafety education officer with experience inspecting regulated laboratories in Canada. Both specialize on pathogen oversight under the Human Pathogens and Toxins Act. We approached them to learn more about how the Canadian legal system works in terms of regulating biotechnology and the potential impact of genetic re-coding using a cell-free system. We found that within Canada, the technology of our system is not specifically regulated; rather the potential products that can be produced from it may be subject to regulation under different federal jurisdictions. For example, polymers or biochemicals produced in a cellular or cell-free system that are used for environmental purposes may be regulated under the Canadian Environmental Protection Act. If toxins were to be produced by the system, the toxin may be subject to the Human Pathogens and Toxins Regulations. We also discussed considerations we would need to implement if our tool were to be used within schools as a teaching aide. While they did not see any issues with our tool itself being used, they encouraged us to utilize Risk Group 1 microorganisms, to ensure that the derived products are outside the scope of the Human Pathogens and Toxins Act, and to promote standard biosafety practices, such as wearing personal protective equipment and proper disposal. Through PHAC’s own outreach initiatives in promoting biosafety, they sent us resources to refer to while developing appropriate safety practices for our system.
With our system’s ability to utilize new and understudied genetic re-coding concepts, we felt it best to discuss any implications our system would have, and how they or other agencies could be affected. The main risk that was identified was the potential to circumvent current domestic international export controls if used for the production of select toxins. While the Public Health Agency of Canada has not been in contact with the International Gene Synthesis Consortium, they have been in contact with Germany’s ThermoFisher GeneArt and small scale Canadian synthesis companies to determine existing practices for screening gene synthesis orders. They recommended that the best way for this software to be deployed with a positive impact was for us to reach out to various security organizations and synthesis companies. They also encouraged us to raise awareness about responsible research and innovation by communicating the importance of addressing potential misuses of any research and technology during project design, planning, and deployment. Overall, they were interested in our ability to address a potential biosecurity risk and to come up with a solution to address it, keeping in tradition from the work done by the 2013 Lethbridge iGEM Team.
- Kits need to be safe
- No direct regulation of cell-free systems
- End-products will be subject to regulation
We successfully identified the benefit of cell-free systems for novices, hobbyists, and experts!
We successfully identified 4 core design principles (Standard, Modular, User-friendly, Safe)!
We successfully identified the steps to avoiding misuse of cell-free systems!