A pilot program for synthetic biology education via a scalable distributed network model of distance-based laboratory learning can be accessible globally across disciplines and backgrounds.
The advent of synthetic biology (synbio) in the 2000s marked a new era for human innovation1,2. Dramatic technological advancements have revolutionized our ability to manipulate DNA, allowing us to inexpensively and accurately rewrite the blueprint of life on this planet. These tools will be instrumental in tackling urgent global challenges, from sustainable agriculture to pandemic response. Yet the self-replicating nature of biology could result in devastating consequences for entire ecosystems if synbio tools are used unethically, maliciously or without the critical awareness of unintended outcomes.
Consequently, synbio education has been recognized as a critical step to public acceptance and ethical development in the field3. While the tools and techniques of synbio have been widely adopted across the science, technology, engineering, and math (STEM) fields, synbio education has lagged and is still largely viewed as too complex and prohibitively expensive for most students, making these technologies inaccessible to most of the world’s population. A 2017 examination of the US public’s attitudes on synbio revealed that the majority of the public does not feel sufficiently informed about the field and tends to oppose the use of or federal funding of synbio technology4.
There have been several synbio outreach efforts5,6,7,8,9 to engage younger students and the general public in proactively framing the public dialog and building trust, including BioBuilder10 and the International Genetically Engineered Machine (iGEM) competition11, which have worked to introduce synbio education in school curricula at the high school and university levels. The efforts of Global Community Bio Summit and many budding community biology labs across the world foster the spread of synbio knowledge at the community level and beyond. The network of community laboratories grew significantly in recent years from two bio labs in the US in 2009 to over 60 bio labs in 2021 (ref. 12). Private companies such as Amino Labs, Bento Labs, BioBits8,13 and The Odin have recognized the growing demand for synbio education and have developed educational products including learning kits, curricula and workshops. However, there is still a gap between the advanced training provided to graduate-level STEM students and those designed to build interest among the general public. Thus, most people, including non-STEM students and professionals who are interested in incorporating synbio into their own disciplines and STEM students outside of elite research institutions and universities, still lack access to quality synbio education opportunities that are comprehensive, practical and applicable to their own interest and use.
An early comprehensive global synbio curriculum was designed by researchers at the Massachusetts Institute of Technology (MIT) and Harvard to expand access to synbio education through the “How To Grow (Almost) Anything” (HTGAA) course. This course was inspired by the MIT “How To Make (Almost) Anything” course’s ethos of democratizing digital fabrication techniques and tools, teaching students, regardless of background, how to prototype hardware, engineer a computer and 3D-print objects. The HTGAA team asked, “What if students in the future could prototype biomolecules, engineer biological computers and print biomaterials for our sustainable future?”
HTGAA aims to equip everyone, regardless of their background, with access to cutting-edge knowledge, skills and laboratory equipment for executing their ideas, while incorporating the latest in biosafety and bioethics. The foundation of the HTGAA approach is teaching the fundamentals of synbio as quickly, deeply and safely as possible through hands-on exercises and creative projects across a variety of scales and contexts. While the pedagogy has remained consistent throughout the last six years that the course has been offered, there have been adjustments and variations in curriculum flow, topics and exercises to ensure that the course is dynamic and evolving.
The initial HTGAA class was launched in 2015 primarily to the network of Fab Labs, through Fab Academy14, the global version of MIT’s How to Make (Almost) Anything course. While still lacking experimental work, the 2015 pedagogy was similar to today’s, consisting of one topic per week taught by a global expert through an intensive deep dive into the science and technology of that field, with related design-based homework. In years 2 and 3 of the course, tuition was charged, as at the Fab Academy, and experimental homework was built and supply chains organized. However, extreme variation in lab infrastructure globally and challenges with reagent and equipment availability in some locations resulted in logistical challenges, while the substantial variation in student backgrounds was challenging for instructors. In 2018, the HTGAA instructors decided to bring HTGAA back to MIT so that the curriculum could be refined with MIT resources and students. In 2019, the introduction of a pre-semester Bio Bootcamp helped to mitigate the challenges presented by differences in student educational backgrounds by providing the foundational scientific knowledge necessary to succeed in the HTGAA course.
In 2021, the COVID-19 pandemic served as a catalyst for rethinking HTGAA as a hybrid laboratory-based course once all courses at MIT transitioned to distance-based learning. The resulting hybrid course described here was jointly offered to a set of global learners, who are student and non-student participants from around the world with different backgrounds and education but a shared interest in synbio. The tools developed to overcome the challenges of experiment- and project-based learning during the pandemic resulted in progress toward the fulfillment of the original vision of HTGAA as a global synbio course and can be expanded as a model for the democratization of synbio education globally.
Hybrid distance-learning approach
Hands-on experimentation is a key component in synbio education5,15,16. As a result of the unique teaching circumstances during a pandemic, the HTGAA instructors and teaching assistants (TAs) devised a hybrid distance approach to mitigate the lack of physical access to lab spaces (Fig. 1). Remote lab work was conducted in one or more modalities ranging from (i) student-run home laboratory experiments using low-cost equipment (‘home lab’), (ii) student-executed cloud simulations (‘cloud lab’), (iii) student-programmed robot-assisted experiments in Biosafety Level 1 (BL1) labs (‘robot-assisted’)17,18, and (iv) TA-assisted laboratory work in which the experiment was designed by the student followed by in-lab execution by a teaching assistant (TA) with a live video stream (‘TA-assisted’). All exercises contained a design component that required students to study, research and describe a solution to a problem in the field. These design-based approaches were critical for enabling students from diverse backgrounds to integrate their field of expertise with new knowledge acquired in the virtual lecture portion of the class.
The HTGAA pedagogy is designed to be incremental and iterative. Each week includes a live lecture, which is recorded, and a design-oriented exercise (Fig. 2; see Supplementary Notes for detailed curriculum, homework and protocols). The following day, a virtual recitation and laboratory experiment is introduced. Classes build on previous knowledge each week, none of which requires prerequisites in biology. For students lacking a background in biology, a Bio Bootcamp preceded the course to provide the necessary fundamentals. Automation and access to predesigned parts allow students to carry out experiments and enable students with little to no background in synthetic biology to build and explore biological systems with increasing complexity. The use of iteration and experimentation allows students to better grasp abstract concepts and topics that make up the field of synthetic biology. Quick experimentation kits along with lab automation capabilities can allow students to fail fast and cheaply while facilitating documentation and reproducibility. Open-source software such as Benchling, which is freely available without an institutional or commercial license, was selected over commercial software to facilitate access for global learners. The virtual sessions of the class were recorded over Zoom and later shared online to enable students in different time zones to follow along. For experiments unsuited to the robot-controlled modality, results from the TA-assisted experiments were shared in the online collaborative platform (Slack) dedicated to the class. All experiments included in the course underwent review and approval by the MIT Environment, Health & Safety representative, ensuring the safety of students and educators.
Robot-controlled distance learning
A key element in the approach presented here is the application of lab robots for distance education. At the core of the educational system (Fig. 3) is a robotic liquid handler (Opentrons OT-2) and Code Lab Notebooks (CLN) (see Supplementary Notes). The robot can be directly programmed to transfer liquids at microliter precision and modulate temperatures, thus allowing a wide range of BL1 and above protocols such as PCR, cloning and transformation into bacterial cells. Students reserve an allotted time slot and connect directly to the robot via Remote Desktop. The robot is equipped with live cameras, so students can watch in real time as their code is executed. For each exercise, the course staff fabricates custom robot modifications to support each experiment, such as 3D-printed Petri dish holders or a shaking incubator. For each weekly module, students are given a code template for the experiment — for example, a restriction digest reaction template with all of the required reagents (enzyme, DNA, buffer, water) but the volumes left blank. CLNs are simulated on the students’ personal computers. The simulations help students to catch errors early, such as transferring a liquid volume using the wrong pipette. Before each session, the TA feeds the robot with the input reagents. The CLN serves as an explicit interface between the TA and the student, by programmable specification of the types of reagents needed and their locations. At the end of the session, the samples are stored at 4 °C within the robot until the TA removes them to prepare for the next remote session.
The robotic system holds a few key advantages beyond the ability to conduct remote experiments without BL1 lab access. Simulated CLN execution offline enables students to freely and creatively experiment with no loss of materials or safety hazards. Furthermore, code and protocols are iterated upon from week to week, allowing students to progress and design more complex experiments as the class advances.
Outcomes and challenges
The course curriculum covers a wide array of disciplines and skills that together reflect the state of the art in synbio. A key outcome of the class is the final project. Each student produces a prototype piece that serves as a demonstration of newly collected skills and the student’s creative agency. Fig. 4 illustrates example projects built by students from the 2021 cohort — some with no previous synbio experience. Projects covered a broad range of applications, such as an open-source, portable bioreactor for do-it-yourself biosensor testing and deployment; a microfluidic chip for nanodroplet synthesis, fabricated in Taiwan by global students; synthetically engineered bacteria to produce biological art, remotely synthesized and patterned via a lab robot in the United States by a student in Germany; and an extension lab robot module to modulate various light conditions when incubating optogenetics experiments with microbial samples.
Judging by students’ feedback and engagement, the experimental approach for hybrid distance learning proved generally successful. However, several challenges arose with the model. First, the final cohort of local and global learners was small compared to that in the beginning of the class. The retention issue for an online class is expected and could be improved upon. However, the small cohort provides an advantage for staff and teaching assistants to fully focus and support each student, especially in the new robot-controlled and TA-assisted modalities. Scaling up the number of students would require more resource sharing and efficient interfaces between staff, teaching assistants and students. Possible improvements include a shared robot time slot (for example, perform liquid handling while the robot is running a thermocycling program). Furthermore, the final project timeframe, from zero background to a working biological prototype, proved challenging over the course of a single semester due to supply-chain issues of custom synthetic parts. As in iGEM, a preordered library of diverse synthesized parts could facilitate quicker experimentation and fabrication cycles. Importantly, the distance learning approach and modalities presented here lack a key element of in-person collaboration among students. As a result of the physical distance constraints imposed by COVID-19, students could no longer experiment side by side on a single lab bench, exchange experiences and construct fruitful collaborations. Nonetheless, the uniform interface for programming the lab robot did provide a platform for students to discuss and compare their protocols in a clear, jargon-free way.
Vision for global synbio education
The original HTGAA vision of global synbio education for all was plagued by inequities in the biotechnology supply chain and lack of access to state-of-the-art laboratory equipment that made implementing this program a challenge. However, the global pandemic and resulting closure of physical laboratory access served as a creative catalyst that directly led to the development of our hybrid distance learning model. This method leverages the resources available at MIT to enable hybrid hands-on synbio experimentation for students anywhere in the world. Building from the HTGAA course during the pandemic, we envision that a multi-node community lab network will be the key to enabling scalable synbio education and development forward. Borrowing from lessons in the fields of computation and digital manufacturing, the network would be composed of multiple nodes that, when combined, can allow low-resource communities to access state-of-the-art equipment, talents and facilities. Each node will have specific characteristics that allow the entire network to manage tradeoffs involving resource availability and decentralization or outreach.
This network approach will enable learners from all around the world, regardless of local resources beyond an Internet connection, to access knowledge resources (mentorship and teaching by global experts) and the physical infrastructure to execute cutting-edge experiments, which could lead to the exchange of ideas, best practices and specifically robot code, protocols and digital artifacts. Further, the infrastructure would foster interdisciplinary peer learning among highly diverse groups (cultural, technical, geographic and creative backgrounds) through sharing camaraderie and fellowship. For example, a group in Hawaii could do a comparative genomic profiling to understand their local biodiversity together with a group in Latin America. This productive global collaboration would organically form through the network.
Community lab network
As illustrated in Fig. 5, we propose three types of nodes for this network: (i) local nodes, (ii) regional hubs and (iii) super-core sites. This is inspired and built on by the progress of the global community bio movement and its programming that fosters collaborations among regional labs with various resources and expertise.
Local nodes correspond to the first layer of the network, which will have the highest distribution and availability. These types of nodes will allow synbio to reach student communities with high resource scarcity and will act as a democratized gateway into the network. Local node facilities have the fewest resources and will require only basic lab equipment and a stable Internet connection, but will need a strong community leader to become part of the network. These frugal and do-it-yourself science resources and tools are not expected to be parts of global biotech supply chains. Experimental work that can be completed at these local nodes will vary on the basis of member interests and equipment, and will likely have more focused interests such as biodiversity or address locally relevant challenges. Local nodes provide not only learning materials, but also rigorous biosafety lessons.
Regional hubs will be created to manage, organize and support the variety of lower resourced local nodes in the area and will have extended capabilities over those of the local nodes. These regional hub nodes will have broader access to low-cost and open-source equipment and will have capabilities similar to those found in a BL1 or above laboratory. The regional hubs will serve as the links between local nodes and as the main exchange channel with the super-cores. We envisage regional hubs being the nodes within the network with the most exchange of resources, talent, capabilities and ideas. The experienced members of the regional hub who receive extra training on bioethics and biosafety could serve as a steering committee for the local nodes.
Finally, super-cores are nodes with the highest resource capabilities and will be based in large private and public academic institutions with access to the most resource-intensive machinery and processes. Super-core nodes will be highly connected with regional hubs to facilitate virtual and remote use of their capabilities by regional and local hub users. Cooperation of super-cores with regional and local hubs will allow the entire network to gain access to state-of-the-art machinery and processes, including access to scientific equipment such as BL2 facilities, high-end microcopy, mass spectrometry, tissue culture, next-generation sequencing and synthesis platforms. People in the three types of learning environments could have periodic virtual meetings to exchange knowledge and ideas, provide training for node leaders and support bioethics discussion and safety review. Different learning environments could have various financial models to sustain the organization, from seeking grants to private and government sponsorships or crowdfunding.
Building on the success of our 2021 pilot program and the above community lab network vision, we expanded our global networks and capabilities for the 2022 How to Grow (Almost) Anything course. We now have five Opentrons robots at MIT, and the 2022 cohort was capped at 15 enrolled MIT and Harvard students, 30 global committed listeners who completed projects, and over 300 applicants and weekly global listeners. We are working to expand on these successes as we continue to grow our networks. As an example of how the full network might function, a student with interest in synbio living in a community in Guerrero, Mexico, would arrive at a local hub set up by local community leaders. The local hub would provide the student with their first mentors and access to all the online information and projects within the network. As the student is exposed to the learning materials, the student may have an idea that involves transforming bacterial cells to fight sea water pollution. The local node would connect the student with a regional hub in Mexico City that is able to help the student with initial designs and preliminary experimentation of the devices through the remote use of a low-cost lab automation robot and basic wet-lab equipment. The regional hub would also be able to give the student access to a group doing similar research in a regional hub in Taipei, Taiwan. The student reaches out to the team in Taiwan and begins collaborating with them. As the newly formed team iterates through multiple versions of the project, they realize that they will need highly specialized measuring and imaging equipment to validate their results. The regional hubs then connect them to imaging facilities found at the super-core node. Once their project is validated, the team could also gain access to super-core biofoundries to scale its implementation to make a real-world impact.
Synthetic biology holds the promise of solving some of the most critical challenges facing humankind, from climate change to global pandemics, but also threatens unimaginable destruction. Our hybrid distance learning approach and network model of synbio education envisages a solution to accessibility issues while also building in safeguards that should alleviate much of the public fear that has been a barrier to global synbio education efforts. We believe that this approach could enable collective intelligence that fosters knowledge sharing in the global synbio community. To achieve this, we must make synbio accessible to a diverse community of problem solvers who can provide insight through their own experiences to champion the potential of this new public-facing technology for a better future.
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We gratefully acknowledge all of the faculty instructors, teaching assistants and students who have participated in How To Grow (Almost) Anything. We would also like to thank the MIT Biology Department, Technical Instructor Anthony Fuccione, Senior Technical Instructor Vanessa Cheung, MIT’s Environment, Health, and Safety Office, Ginkgo Bioworks and the Institute of Preventive Medicine, National Defense Medical Center, Taiwan. The course has received support from Twist Biosciences, Opentrons, Waters Corporation, Takeda and the Program in Media Arts & Sciences at the MIT Media Lab.
The authors declare no competing interests.
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Perry, E., Weber, J., Pataranutaporn, P. et al. How to grow (almost) anything: a hybrid distance learning model for global laboratory-based synthetic biology education. Nat Biotechnol 40, 1874–1879 (2022). https://doi.org/10.1038/s41587-022-01601-x