Expanding Human Practices to Community Engagement

Since 2010, the MIT iGEM team has chosen iGEM projects across multiple tracks: manufacturing, health & medicine, and information processing. While very different in their goals, all of the projects shared a commonality of working in mammalian systems – a still rare occurrence in the approximately 200 iGEM teams worldwide. However, it’s this familiarity with mammalian systems that has resulted in some very interesting discussion and debate on the phrase ‘human practices.’

Simply, when introduced to the majority of the scientific community, most of whom are unfamiliar with iGEM, at best, the phrase human practices conjures up thoughts of clinical trials or experiments using human subjects. When introduced to a larger community, human practices results in blank stares and confusion. While initial negative impressions and/or confusion can be effectively negated with healthy conversations as evidenced by the large number of iGEM team-lead surveys, it’s inevitably an uphill battle to rebrand terminology.

This year we remove the phrase ‘human practices’ from our vernacular and instead utilize the term ‘community engagement.’ This phrase effectively captures the core essence of human practices – the fact that laboratory science cannot exist in a vacuum but instead must evolve with varying economic/political/cultural forces whether that be industrial contacts or venture capitalists for translational research, policy experts to draft new guidelines for risk management, lawyers to address patent and idea protection, technical and non-technical audiences in educational outreach, or other iGEM teams for mutual benefit. Perhaps most importantly, it puts engagement as a critical component of projects rather than merely an afterthought to get an iGEM medal – encouraging the community to help refine project conception and execution.

MIT iGEM 2013 Engagement Efforts

We participated in a series of engagement exercises, educating our international collaborators to promote the formation of a new iGEM team, risk assessment of our project with Kenneth Oye, consulting with patients and doctors about potential application spaces for our research technology, educational outreach to the local Boston community, and collaborating with fellow iGEM teams to improve their projects and presentations.

International Education

In January of this year, we ran a student-run laboratory course at MIT for 2 weeks over IAP http://stellar.mit.edu/S/project/synbio-iap2011/. The curriculum we teach is half seminar and half in a biology lab, exposing neophyte researchers to the origins of synthetic biology and current best practices. We include lectures on iGEM, the parts registry, the use of abstraction, and how theory and experiments can be complementary. These lectures are followed with an intensive lab setting where teams of students utilize BioBricks to build 2 plasmids, forming an inducible bioluminescent circuit. This year, we doubled enrollment by co-teaching the class with a dozen students at the Universidad Adolfo Ibáñez in Santiago, Chile. We streamed our lectures to South America and additionally dispatched three MIT iGEM students to Santiago to run the lab sections. This international engagement will be fully realized for the 2014 competition year when UAI will host their own iGEM team for the first time – one that we will assist as well as have applied for funds to allow an exchange program for the two teams. In July of this year, the professor and lead instructor from Chile that will be forming the new team came to Boston to shadow the iGEM team for several days to learn and develop good habits of team management.

Safety and Risk Assessment

In addition to our international involvement, we also pursued several projects locally in the Boston area. The first was hosting Kenneth Oye http://web.mit.edu/polisci/people/faculty/kenneth-oye.html for an hour long seminar to the team on a discussion on the implications of our project ideas. During the course of our conversation with Professor Oye, we first went through several case studies in biological research before turning our attention in working to analyze our own project for risk, safety, legal, or ethical concerns.

Mammalian cells can be engineered through a variety of methods – the use of viral vectors that integrate into the genome, exogenous introduction of proteins or other factors, or transient transfection of non-replicating DNA. The use of viral vectors, while common in laboratory settings, would be a certain critical risk in containment and safety of our undergrad researchers due to the ability of some classes of viruses to infect humans in addition to test tubes of cells. The use of proteins or external cues did not afford the possibility to manipulate our mammalian cells in the necessary fashion and thus we chose to only use transient transfection. Because transient transfection does not use replicating DNA, it represents a negligible risk to users when decontaminated and disposed according to MIT Environmental Health and Safety regulations https://ehs.mit.edu/site/. We used similar risk matrices to arrive on decisions of what cell lines to engineer, the use of various reagents in our work, and the policy on necessary personal protective equipment during experiments.Project Refinement from Invested Parties

One critical project that developed due to meeting Professor Oye was establishing the connection between application and basic research. Our project aims to engineer cell-cell communication for use in therapeutic applications such as synthetic organoid development. These organoids could be used to augment natural failing organs in patients during the wait-time for donor organs or even function as a full solution in lieu of donors. In order to understand how our systems might be useful in a patient setting, we communicated with Samira Kiani, M.D. at MIT and Michele Annette Gadd, M.D. at the Massachusetts General Hospital and two patients within the Cambridge area that had been recipients of artificial ligaments during surgery. In written correspondence to the four individuals, we introduced our project and sought information on the transplant system and the need for replacement organs / systems. After meeting these doctors and an introduction to FDA regulations from one of our graduate instructors, we realized the need to better articulate our application space. Instead of synthetic organ replacement, we refined our application space to be the use of organoids for drug screening. The use of an in vitro system to examine novel therapeutics in a high throughput fashion may enable the design cycle of drugs to rapidly accelerate while serving as an initial trial for risk assessment in the use of genetically engineered mammalian organs. This use could then be used to collect data and usher in the development of best practices of mammalian organoids prior to extended investigation into future work in implantation or other applied work.

Outreach to the Non-Technical Community

As part of an ongoing thrust to introduce synthetic biology to the community at large outside of research universities, we pursued a partnership with the Museum of Science in Boston. A teammate’s friend was an intern at the Museum and we were able to secure a meeting between one of the outreach coordinators, Miriam Ledley, and our team on introducing a display into the Theater of Electricity on applying circuit design into the biological sciences. Miriam lead us through the specifications required of an exhibit – the educational content required, the build quality of an apparatus, the age-group of participants, and procedural aspects for biocontainment. For instance, initial ideas involved students streaking out rapidly dividing fluorescent bacteria on solid agar plates and visualizing their bacteria under a black light in the afternoon as well as assembling circuits using physical block abstractions. While we were able to design a unified lesson plan for inclusion in the exhibit, the balance between engaging children with biological material in a safe manner has become a much harder than anticipated challenge. The lack of a contained lab environment in the museum as well as the infrastructure necessary to house bacterial stocks, plates, and project supplies were above and beyond what our team could provide to the museum. We have since followed up with the MIT Center for Environmental Health and Safety (CEHS) to build off some of their experience using Lego DNA Kits in the Cambridge Science Festival and apply a similar LEGO model approach to synthetic biology as an activity. Tentatively, we are slated to assemble and deliver our first prototype kit for feedback from users in the Synthetic Biology Center in mid-November of this year.

Collaboration within the Academic and iGEM Community

In ambitious research projects, an extreme amount of collaboration must occur between far-flung research labs. This year, we had the opportunity to encounter several key research experiences during our project. The first was securing sequence and physical DNA in published literature from the originating lab. For multiple constructs, the lab’s principle investigators did not respond to DNA requests and made it very difficult for us to tackle our project. Thankfully, we were able to reverse engineer some constructs from existing literature methods sections as well as find suitable replacements from commercial or other academic sources. Speaking to researchers within the Synthetic Biology Center at MIT, this lapse in communication appears to be chronic in academia and illustrated to us the importance of standardized DNA repositories. For iGEM, the registry’s inclusion of both working and planning parts are instrumental in being able to push iGEM projects forward while other common repositories such as AddGene or NCBI GenBank serve the same purpose for the larger scientific community. The second challenge we faced was being ‘scooped’ this summer by a larger research lab on an idea we had conceived as part of our iGEM project. Throughout the course of the summer, we had elected to investigate the Cas9-CRISPR system’s use as a communicating message in exosomes and built a transcriptional activating version of Cas9, Cas9-VP16 https://2013.igem.org/Team:MIT/Cas9-VP16. However, several weeks into our iGEM project as we were testing our Cas9-VP16, a manuscript was published that effectively scooped our project with the protein Cas9-64, a transcriptional activator of similar design to our proposed construct http://www.nature.com/nbt/journal/v31/n9/full/nbt.2675.html. Thankfully, we were able to utilize the work in the manuscript to better our design but it was still an eye-opening experience that in future research endeavors we need to be aware about.

Finally, we worked to help our fellow Boston area teams in two avenues. In the first, we worked with Wellesley on testing their software programs to provide valuable feedback from an experimental background on their tools to help experimentalists https://2013.igem.org/Team:Wellesley_Desyne/Human_Practices. We also took them on tours of our facilities to enable them to get an understanding of our workflow from design -> data to allow them to further brainstorm on effective tool development. In the second Boston area engagement, we participated in NEGEM hosted by Boston University’s iGEM team. NEGEM is a gathering of local New England teams to give practice talks about their iGEM projects and garner feedback while building camaraderie.