Meta Analysis of Biobricks

        The Registry of Standard Biological Parts has been a longstanding partner of iGEM. The promotion of synthetic biology communication and cooperation have become tenants of every iGEM team. The database was an incredible step forward in biological research and standardization. And for this reason, we must now reevaluate the registry.

Moore's Law and Biology

        Moore’s Law is a principle developed in 1975 claiming the maximum number of transistors per microchip doubles every two years. Analogous to the technological limits in computer engineering, biology has seen a similar trend in the cost of sequencing and synthesizing DNA. The high cost of synthetic biology is what initially drove the movement to physical databases of biological parts. For example, a gene segment costing $800 when the Registry of Biological Parts was conceived, while only costing around $30 by modern standards. In the last decade and a half, synthesis prices have halved approximately every 2.5 years.

       This registry, if it serves as a replacement and utility to the physical construction of biological parts, is a rapidly depreciating database due simply to the trend in technological costs. This direction has prevented the registry from gaining momentum in research groups. Only 11% of the 70 iGEM team we contacted said to have used the registry to order parts. At the time of this study (August 28th, 2015), only 69% of requests made to the registry were processed. Of the requests that were completed, it took on average 7.5 days to process the request internally. Additionally, only 2.5 requests were made per day in 2015 with each part averaging $130 from IDT (each part was pulled from the request form and processed through IDT in our study). Furthermore, studies have suggested 5’ cut sites can have significant impacts on gene expression and function (Lou 2012).


Today's Registry

        Maybe there still is value in the registry, and maybe it does save groups synthesis costs and time. After all, current saves researchers $325 on average a day. But when we return to this conversation in 5 years and the savings is only about $80 a day? The National Science Foundation (NSF, $37 million over 10 years), and Defense Advanced Research Projects Agency (DARPA, undisclosed grant), and National Institutes of Health (NIH, undisclosed grant) funnel hefty grants as well as the International Genetically Engineered Machines (iGEM) competition to develop and contribute to the physical stock of parts. Should we be investing in this type of technology?

        In addition to the physical database, we were interested in the meta-analysis of biobricks. Are parts highly used in other projects? What do the usage statistics look like? We contacted the iGEM staff to determine whether they would release the complete list of Biobricks with usage data and our request was denied.

       But we had computers and we had website scraping tools, so we scraped all parts web pages for every iGEM team part from 2005 to 2014 for their usage information. Processing this information, we can get a snapshot of what is happening with the all the information this organization has accumulated. Biobricks are unconnected to any other Biobrick 72% the time, and 92% are used less than once a year. 61% of part usage is within the same team in the same year. Despite these trends, the superb parts had an entirely different story to tell.



The Best of the Registry

       Below, the top 1.3% of Biobricks by usage were mapped to all Biobricks they were used in and processed in Gephi as a network of information. The resulting image is the marvel of what the Registry of Standard Biological Parts has achieved. With each point representing a Biobrick, each color representing a year of competition, you can see the interconnectivity of iGEM at its best. Teams across the world and years building from others work and linking their work into this network of information.

       And this is what we believe the best direction is for the registry and iGEM as a whole. There has been this emphasis on forcing projects into this physical standard of biobricks and punished teams for omitting submission of a registry part. These leaves massive portions of the registry dark, untouched. The registry was a revolutionary idea initially, but the registry must evolve to coexist with the modern scientific environment. Drop the physical system and commit the registry to be a haven of synthetic biology research focusing on the scientific network, not the part number.



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Proposal for a Renewed Genetic Registry: Revisiting the founding ideals of iGEM

Biotechnology has seen many advances in the last decade and (perhaps accordingly) has been targeted with skepticism from the public eye as those unfamiliar with the new technologies become wary of unanticipated risks.

As iGEMers, we’re encouraged to promote transparency through tackling pressing issues of public opinion, ecological impact, and other contextual concerns of emerging GE technologies—but are we equally tuned to the most current methods for applied open science and industrial relevancy in how we share our genetic products through the BioBrick registry?

iGEM formed in 2003 as a leading effort in a revolutionary marriage of synthetic biology and open science. Since then, the organization has grown tremendously (with numerous additions of teams, tracks, and objectives) and continues to be a hub for innovative projects aiming to reinvent the way we tackle real world issues. We’re curious though—over 12 years after its conception, isn’t it time to reimagine the BioBrick system as well to reflect all the scientific advances of the last decade?

As the premier synthetic biology conference in the nation, iGEM inhabits an important niche in helping engage, educate, and prime prospective biotechnology professionals and/or synbio researchers. As such, iGEM both provides an excellent launching pad for interested young adults but also has a responsibility to the students to represent timely science, issues, and perspectives.

The BioBrick repository was designed to fit a vision of synthetic biology where genes could act like discrete parts of a well-calibrated machine. For the field of synthetic biology, developing a set of standardized parts that could be interchanged in biological circuits would simplify this type of genetic engineering to expert-level Lego creations, essentially, where the sequence of assembly is the sole determinant of the final product.

However, the reality of engineered biological circuits in vivo has proved to be not so simple.

The exciting frontier of engineering novel genetic pathways is still burgeoning over a decade later, but our toolbox has significantly expanded alongside greater understanding of the intricacies of systems biology. DNA sequencing and primer synthesis are exponentially cheaper and restriction enzymes are no longer a staple in engineering labs.

Essentially, the BioBrick format is no longer a revelation, but a relic.

Now this is not to say the library should be burned (so to speak)—actually far from it.

While for all intents and purposes the BioBrick format is no longer relevant technology for assembling genetic sequences in lab, the founding pillars of the registry—transparency and accessibility of open science—remain pertinent ideals across the scientific community.

Lead scientists at worldwide biotech corporation Cargill believe that a reliable, detailed catalog of different parts, their genetic context in which they were characterized, and quantified expressions would be useful food for thought and resource for industry professionals who are designing a new project. In essence, for maximum utility, the BioBrick catalog needs to focus on quality, not quantity.

In terms of the iGEM competition and the hundreds of undergrad, overgrad, and high school teams who participate in this important event each year, we feel that we need to push for an updated framework around how we modularize our gene constructs for the repository. We also feel like requirements for medals should no longer include making a BioBrick.

As culmination to our summer-long contemplating of our project and the structure of the overall iGEM competition and project standards, we would like to propose a specialized track within iGEM next year that focuses on ways we can improve the BioBrick system to suit more modern methods and better use of our teams’ time, both in terms of the wetlab burden of creating a BioBrick-compatible part as well as effectiveness of the registry as a resource.

Through pooling efforts and innovative minds from teams across the globe, we believe the next iGEM competition could yield greatly-needed proposals for a reformed BioBrick registry—a repository that could better serve both iGEM student teams and the broader biotech community.

In the spirit of open science, transparent biotechnology, and crafting forward-thinking solutions to contemporary problems, hosting a collective critique and reform of our current system would be a crucial tribute to iGEM’s founding ideals.