Team:OhioState/Human Practices
Sharing Knowledge through Biocontainment Consulting
Collaborations with MichiganState, Stony Brook, Costa Rica, BITSPilani-Goa India, MIT_MAHE, IISER-Pune-India, Lund, FCB-UANL, UNILausanne, Thessaly
Biocontainment is a field that requires attention and finesse. To this day, PhDs are devoting their career to perfect these systems. In order to translate these high devotion areas of synthetic biology into iGEM projects, teams must fully understand all precautions. In order to best facilitate this synthesis of information, we decided to offer our expertise in biocontainment and assist other teams that implement biocontainment systems into their project.
Through promotion in the global iGEM slack and social media, multiple teams contacted us with biocontainment questions. We offered our consultation service to ten other iGEM teams. Our team advised, designed plasmids, shared resources and papers, and steered teams in the right direction to implement useful systems into other team projects.
Teams responded greatly to our services. Many teams commended our assistance, unpromptedly saying, “This help was very, very useful”, "Thank you very much, you are being very helpful”, and “You guys did a very good job helping us".
Understanding iGEM Biocontainment Part Implementation Experiences and Hardships
Through outreach, we came into contact with 8 other iGEM teams in order to understand the hardships and shortfalls of the current biocontainment infrastructure. We asked questions regarding the igem part registry, the shortfalls of this parts page, the type of biocontainment part used, what the most useful resources were, and what would make the process easier. This was an integral portion of our human practice outreach so that we could adapt our project to the most prevalent needs of the iGEM community.
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Interviewee |
How much experience with iGEM have you had? |
Have you used the registry to find a biosafety part? |
Tell us about your experience if you have used it |
Have you considered using a biosafety part? (if so which one) |
What resources did you use to find a biosafety part information? |
What do you think would make the process easier? |
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BITSPilani-Goa_India |
Institute's first year doing iGEM. Team of 12. |
It was nightmare to find the part. They ended up not using the biosafety section of the registry. Instead they individually searched from promoters and toxins that best fit their system. |
They had a negative experience using it and found it very difficult and time consuming. They also had a negative experience with SynBioHub. They found that the registry was outdated. |
Yes, they found individual promoters and toxin/antitoxin systems from the registry . They had to consider using a biosafety part because it is a fundamental aspect to making their project useful. It is vital to have a kill switch in order to make their project viable. |
They mainly used the registry to find parts. They also used SynBioHub a bit. |
They noticed that the parts did not have solid characterization data which made the process difficult. They weren't sure which part would be best because there was not solid data avaliable in regards to if the part works. They suggest there should be more references and documentation to improve the registry situation. A streamlining of the registry would also be useful, for it is not orgnaized well. |
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MIT_MAHE of India |
Institute's first year doing iGEM. Team of 21. |
They have not looked at the biosafety iGEM registry. |
none |
They considered a biosafey part after looking at other probiotic projects that had a kill switch safety system. They thought that this would be a good way to refine their project. |
none, reaching out to us was their first step. |
n/a |
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Lund of Sweeden |
Team of 8. |
iGEM biosafety pages when filling out the biosafety page |
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FCB-UNAL of Mexico |
2012-2014 and then from 2019-2020. Team of 15. |
They've only used tetR from the registry and did not look at the biosafety registry. |
most teams use other means such as ncbi or other gene databases |
yes, look at the FCB-UNAL 2019 biocontainment section of their wiki. |
Only used the registry to find tetR, he didn't find any other parts. He just used google, first to see what biocontainment is about, then he narrowed his search results just to find specific kill switch parts. He eventually found the parts he wanted to use from gene bank. |
He thinks it would have been easier, especially for those outside of iGEM. Most iGEM teams are looking for a new gene and a new use, they are most concerned with finding a new part. For researchers outside of the competition it would be really useful. The registry is a sort of gallery for new parts, it is not too useful in terms of finding parts to include in one's project. However, our project would be extremely useful for people doing a thesis. Overall, he thinks it would be a great idea to make our database. |
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MichiganState of US |
Members we interviewed were 1st year iGEMers, but their institute has participated in iGEM for a few years. Team of 9. |
Little experience experience with the iGEM registry. Searched for parts they wanted and if the registry showed up (or something hosted by igem) they would use it. |
none |
They are not going to do a kill switch, but will have a toxin/antitoxin system for a way to prevent HGT |
At first they did research on general biocontainment. If it looked promosing then they pursued it and continued to look into it. Found promoter ideas from grad students and professors they talked with. Just read papers to find more information. They did not really look at specific igem parts. |
A central place for biocontainment papers that described different things would be useful. They are using a bacteria that is not very well documented. However, it might have been helpful, if they were pusuing something else, to have a table of ecoli constitutive promoters, different terminators, and stronger promoters in order to piece things together. |
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Waterloo of Canada |
Interviewed members in their 2nd year of iGEM. There has been a team at Waterloo for a while. Team of 40. |
Have not implemented a kill switch into a project. |
Have used the iGEM registry or used papers like ncbi. The registry was outdated and not enough for their project. |
Not in recent years, for the members that we have met with. |
Used literature for parts for their project |
List of common parts in iGEM reigstry, are not updated so it makes them hard to find infomation. Recommend updating the iGEM registry |
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UNILausanne of Switzerland |
Little Experience with iGEM. Team of 12. |
They have not looked into specific parts yet. |
none |
They are trying to build a kill switch because their organism is to go into the human gut |
Found a toxin anti-toxin paper and looked at other iGEM team's biosafety portion of their projects |
Have a run down of everything one needs to do regarding implementing a biocontainment mechanism. |
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Thessaly of Greece |
The University's 2nd year participating in iGEM. Team of 10. |
Mostly used other team's wiki and literature |
The most useful portion they used was other team's wiki's and the citations they included. |
Yes, iGEM heavily emphasizes the importance of biosafety. And they came across the importance of a kill switch to keep it contained. Found the Mazf system. They chose this since it has the most data. |
They used the parts registry, academic papers, biosafety parts library, previous teams wiki's and they found citations from other team's wiki's |
It would be easier if the process needed to implement a kill switch was standardized |
Exploring Current Public Fears and Misconceptions of GMOs
Public perception of genetically modified organisms varies greatly, ranging from pungent supporters to staunch opponents. Intrinsic biocontainment in the form of genetic kill switches has the potential to convince opponents of the great safety of genetically modified organisms. In order to best speak on kill switches when considering an audience who may be opposed to the applications of the technology, the OhioState iGEM team researched the anti-GMO project and public anti-GMO opinions present on social media. Independent team research was conducted and intra-team communication and round table discussion was held in order to best fathom and unpack the complex public perception of GMOs. This research shaped our project and ensured that OhioState’s mode of communication is most useful and beneficial for all.
Great care was taken throughout the continuation of our project to ensure that the perspective of those frightened by genetically modified organisms was considered. The way in which we phrased our project shows the public the great benefits of kill switch systems. Furthermore, we were cautious when using words that may induce unnecessary fear such as toxin, induced death, and other similar terms.
Engaging with Ohio State faculty
The OhioState iGEM team looked first at the tools available at our own institution to gain interdisciplinary knowledge regarding biocontainment implementation. OhioState engaged with many Ohio State University faculty members including Dr. Sarah Short, Dr. Pete Piermarini, Professor Patti Zettler, Dr. Seth Faith, Mr. Ethan Rivera, Mr. Sam Malloy, and Dr. Mike Oglesbee, Applications of these conversations induced a greater appreciation for fields expanding beyond synthetic biology. Dr. Short and Dr. Piermarini study disease in mosquitoes, and this expanded our horizon for a useful application of kill switches in mosquitoes for future years. Our extended conversations with Professor Zettler encouraged our work on biotechnology related regulations.
Researching world legislation and policy
The Ohio State iGEM team recognizes the potential expansion of the field of synthetic biology with the continued perfection of biocontainment systems. An international approach to the implementation of synthetic biology systems and biosafety parts must be taken. We recognize that differing countries have differing policies and considerations of such technology. For this reason, the OhioState iGEM team took an approach to fathom these differing regulations to ensure our project could be the most useful for the world as a whole, rather than just one country. OhioState iGEM team collaborated with BITSPilani-Goa and FCB-UANL iGEM teams to compare the regulation policies among India, Mexico and the United States.
Gaining perspective from biocontainment experts
The OhioState iGEM team relied greatly on the advice and commentary of biocontainment experts. Multiple conversations were held with Dr. Dan Mandell, CEO of GRO Biosciences. It was in these conversations that our project ideas were finalized. Our next conversation was with Dr. Lexi Rovner, CEO of 64-x Bio, who directed our kill switch thought process to the ideals of environmental release, policies, and the EPA. Dr. Pam Silver, who has conducted research in the area of biocontainment, spoke on her work and reaffirmed the importance of these systems and brought to our attention fine details to consider while working on our project. Dr. George Church is a staple in biocontainment. We were very thankful for our conversation with him, as he introduced to us very unique perspectives on kill switches.
Increasing accessibility to synthetic biology education
We increased accessibility to synthetic biology education through the creation of educational videos. Through collaboration with 5 additional colleges, we ensured that the most knowledge was integrated and accessible to the community. Our target population consists of anyone with access to youtube with the intention of relaying our gained knowledge to the public. This is a necessary step to ensure that the discrepancy among those with and without a higher education in biology can stay up to date regarding modern biotechnologies We aimed to make biocontainment and synthetic biology more accessible through educational videos published on youtube. With the StonyBrook iGEM team, we saw the necessity to explain the benefits and the common misconceptions of the biocontainment system. Therefore, we focused many of our efforts perfecting our biocontainment video.
Gaining feedback regarding practicality and functionality of project-- Infectious Disease Institute at The Ohio State University.
The OhioState iGEM team presented a project progress update during an Infectious Disease SCOPE meeting at the Ohio State Battelle Center. During this meeting, the OhioState team detailed our current progress and welcomed feedback from the audience of law students, research scientists, virologists, microbiologists, and computer program modelers on our project updates. A few key points were brought up: Dr. Faith mentioned that our use of the terminology "toxin" may get a few different reactions depending on the audience to which we are informing. This reiterates a thought we have had in the past and we will, in the near future, create a standard term that describes a toxin without invoking fear of harm in our audience. Mr. Malloy, a research scientist, expressed the need to refine our human practice ideas and invest all of our efforts in few ideas rather than spreading ourselves thin.
Other than this example, OhioState also pulled from all collaboration conversations with other iGEM teams, biocontainment experts, and other university and industry professionals to ensure that our project is practical and functional.
Gaining feedback regarding practicality and functionality of project--iGEM Teams
Through speaking with other teams and scientists, we integrated their expertise and advice into our project in order to ensure that we produced the greatest quality tool to offer both iGEM teams and the surrounding scientific community.
In addition to offering our consulting services to these teams, we decided to tailor our project to the needs of the teams we assist. Though the teams we assisted benefitted from our shared information, we also gained vital knowledge regarding the current shortfalls of the current biocontainment information and infrastructure of accessibility to biocontainment information. We asked a short series of questions regarding the experience that these previously mentioned teams experienced. We used these teams responses to ensure our project was useful to the entire iGEM community
Therefore, we conducted a short tele-survey with 8 iGEM teams. We wanted to make sure that the vast scope of iGEM was represented, thus we ensured that we heard responses from undergraduate and overgraduate team, including a mix of new and experienced teams from different countries. Our scope continued to diversify as we spoke with teams ranging from first year teams to more experienced and developed iGEM programs.
As a result of the tele-survey, vital information was shared with us. And we therefore integrated the results of this survey into our project. We shaped our project to the needs that these teams expressed to us. Since we are providing a tool for other iGEM teams, we wanted to ensure that we were making something that would be useful to the teams we are tailoring our project to.
Key statements from our conducted tele-suvey that shaped our project. Thus ensuring our project met the most prevalent biocontainment needs in the iGEM community.
Integrated Human Practices
Collaborating and networking with scientists and community played a large part in the outlook and scope of our project. Here we present summaries and pieces of our conversations with those we networked with that were influential for our project. These suggestions and comments were either integrated into our project or shaped the direction of our project.
Dr. Dan Mandell
Co-Founder and Chief Executive Officer of GRO Biosciences, Inc.
Dr. Mandell made the analogy: design the "seatbelt before the car" when thinking about implementing kill switches into GMOs.He suggested we design a kill switch that is simple and has minimal escapees, and horizontal gene transfer chances. When advertising a kill switch we should never say that it is fool proof (because that's impossible), but we should emphasize that while there may be escapees, it's impossible that it'd never establish a colony.
In another conversation, He suggested that we start simple with designing our kill switch, and also mentioned that there are many ways to improve current biocontainment. Dr. Mandell was very fond of the idea of making guidelines to explain GMO/synthetic biology regulations, and he suggested that we first send out surveys to groups of people in order to understand the current public perception on GMOs and what needs added to current guidelines.Mathematical predictive modeling may be difficult because there are many implicit assumptions that go into this, whereas we might need a more explicit model.
Project Impact, Wetlab refinement: took to heart Dr. Mandell’s comment regarding the necessity to improve already existing biocontainment systems. DRYLAB refinement changed our first idea of using AI, we decided to switch our scope to web scrapers and web crawlers.
Dr. Lex Rovner
Co-Founder and Chief Executive Officer of 64-x GRO
Dr. Rovner talked more on company policies than the actual design of the organism. She expresses the importance of biocontainment to companies by stressing that regulations could increase by the time the product is finished. She's noticed that a lot of people ignore including a kill switch until it becomes a problem. For a new system design, she recommends having several layered mechanisms to limit the risk of failure, but at the same time, the less one does to the host, the better. She also informed us that the EPA won't approve field release because of the risk of HGT (horizontal gene transfer). However, there would be a big market for the kill switch if the risk of HGT were eliminated.
In an additional conversation with Dr. Rovner, she said that there has not been much done environmentally in regards to biocontainment, so this would more than likely be able to have a big impact if we focused on something more environmental. Dr. Rovner also said that the FDA is not as concerned with biocontainment as the EPA, so focusing on FDA guidelines and making ways for less chances of moratorium for projects gone wrong would be a good path.
Project Impact, Human Practice Refinement: This conversation paved a central spot for human practices to focus on: legislation regarding environmental release. Dry lab refinement: Focused our attention on assisting teams to implement environmental kill switches.
Dr. Sarah Short and Dr. Pete Piermarini
Principal Investigators at OSU
Current idea to kill mosquitoes that bite humans would likely not be effective in any population that uses humans as a significant food source. It could be better to incur a negative fitness change when biting humans, a positive change when not biting humans, a negative change (possibly death) when infected with pathogens. We could also drive a gene through the population to make them respond to a chemical that can then be used as an insecticide/repellent. We need to make sure that whatever gene we use can spread through the entire population.
Project Impact, Wetlab Refinement: Reaffirmed that we could potentially pursue this project path in future years.
Dr. Pamela Silver
Professor and Research Investigator at Harvard
Dr. Silver recognizes the importance of biocontainment mechanisms. People who are in chronic pain are more open to solutions even if they involve GMOs (Insulin for example). This knowledge also helps understand why 3rd world countries are more accepting of GMO food to feed themselves whereas countries like America, who have enough land to grow “natural” food for now, have the choice to be against GMOs. It will likely be harder to change opinions now that politics are so involved with GMOs, but the Impossible Burger is a success. People know it is a GMO yet Burger King sells it so people are okay with it. People also might be more open-minded when a bio-economy offers jobs to all levels of education/background. Dr. Silver also mentioned that GMO food also provides the opportunity to know exactly what is in the food whereas nature is kind of a gamble.
Project Impact, Human Practices Refinement: This conversation redefined how our human practice team approached science education and outreach, especially with educational videos.
Sir Richard Roberts
Chief Scientific Officer at New England Biolabs
Sir Richard Roberts emphasized the importance of GMOs in this world considering the ominous impact of global warming. The almost nonexistent negative impacts of GMOs are completely outweighed by the great benefits of drought resistant and flood resistant crops. Pest resistant crops/GMO crops are vital in order to feed those in developing countries. To quell GMO fears, one must emphasize the benefits, and express the naivety of an antiGMO mindset. In addition, it was expressed that the outreach with the greatest impact may be through the school system. Treating children like adults, having thorough discussions, and outreaching to populations in libraries have had the greatest impact in Sir Richard Robert’s own personal experience.
Project Impact, Human Practice Refinement: Inspired us to do GMO impact analysis modelling.
Prof. Patricia Zettler
Professor of Law at OSU
Prof. Zettler gave us advice on how to start working with Governmental regulations, and that is by focusing on a situation that is blocked by regulation or specific regulation that we have an issue with that also taught us a lot about how the agencies carry out their business and how they interact with the public.
Project Impact: Encouraged and informed our Human Practice efforts.
Dr. George Church
Professor and Principal Investigator at Harvard
Dr. Church’s thinking about biocontainment was quite different from what we have considered. He said that biocontainment is often negatively seen by entrepreneurs because it may require debugging and can cause the opposite effect of what the goal is. Additionally, he reiterated Dr. Silver’s point that those who are against GMOs are often those who are not in need. In regards to helping iGEM teams through the regulations, he said that it could be impactful if we set up a system where iGEM teams could talk with people from federal agencies to be walked through the process in an easy to understand way.
Project impact: Provided unique insight and perspective on biocontainment. Continued to allow us to see how our project is good for this world by challenging our initial viewpoints on biocontainment.
Rob Warden-Rothman
Discussed pathways to use for an E. coli switch. He recomended we use one gene each from different pathways. Most pathways will just make the bug 'sick' and not kill it, which wouldn't help any toxin/death mechanism we were to use. The bug will eventually die but that extended time allows it to fix the pathway. This could be okay for environmental/probiotic release because other bugs would kill it relativelyfast. When using a death mechanism, we need to use a very low leakage circuit.
Outreach: Use analogies where we want some kind of control over an otherwise dangerous tool that people now have no issue using to show why biocontainment systems are needed."
Wetlab Refinement: Reaffirmed that regulating E. coli metabolic pathways is a potential biocontainment strategy. Human practice refinement: Encouraged us to use analogies when explaining synthetic biology to people and gave examples of analogies for kill switches.
Integrated statements from conversations with iGEM Teams
Bits_Goa, Manipal Biomachines, FCB-UNAL, MSU, Waterloo, and UNILausanne.
“The kill switch process was time consuming and difficult process”
- Project impact: Shows us that our project does indeed address a need in the iGEM community.
“Parts don't have solid OR unified characterization. More references and documentation would improve the process”, ”if the process was standardized! It would be easier if the steps needed to implement a kill switch were standardized”
- Project Impact: Wet Lab wrote standardized procedures to characterize toxins and kill switch systems to address this shortfall.
“a central place to find biocontainment resources and papers would be useful”, “biosafety iGEM registry parts page is not update nor all inclusive”
- Project impact: OhioState decided to make this central place in addition to reorganizing the iGEM biosafety parts page.
“literature was the main source used to implement a safety switch”, ”used literature to find toxin antitoxin part”
- Project Impact: OhioState searched for useful literature and devoted a space to house biocontainment resources for future teams to use in order to address this verbalized statement.
”Other team’s citations and wiki’s were the most useful resources”
- Project Impact: OhioState created a web scraper that would scrape for certain pieces of information including resources and page titles in order to make other team’s wiki’s most useful.