My first brush with Synthetic Biology, 13 years ago, was a baptism by fire, but exciting nonetheless. It was late in 2000 while I was working as part of the NewcoGen Group (a Flagship Ventures fund) where we founded a synthetic biology company called engeneOS (Engineered Genomic Operating Systems). The business plan included innovative but optimistic strategies to develop engineered genomic parts that could be assembled to provide bio-organisms with a range of novel properties. We also envisioned assembly of whole modified organisms, such as bacteria that could be used to coat houses with polyethylene sheet (e.g., similar to Tyvek), and biosensors of airborne-biothreats. Though some of the designs were quite interesting, and commercially useful, early companies were limited in a practical way, by the cost of assembling novel genes. Applying engineering approaches to gene assembly, which often involve many cycles or trial and error, were simply too expensive when the costs of DNA synthesis and sequencing are too high. We were also missing critical biological information to make many of our ideas reality. engeneOS was ahead of its time and never was a commercial success but some of the technology was incorporated into companies like Compound Therapeutics (sold to Adnexus Therapeutics) and Epitome (sold to Millipore).
So what has changed since 2000? In the last decade, the significant advancements in gene sequencing, gene synthesis, gene editing, and bioinformatics have laid the ground work for this industry to flourish. Investigators such as Jim Collins at Boston University and George Church at Harvard have made great strides building gene toggle switches and circuits. In 2010, Craig Venter announced the first “synthetic cell“. These scientific advances have breathed new life into the business side of Synthetic Biology. So we may be looking at the re-birth of synthetic biology if we fast forward to the recent announcements such as: Intrexon Corp, just raised $150M, and Gen9, with Kevin Munnelly at the helm, raised $21M from Agilent as a strategic investment. Intrexon is an industry leader who has truly demonstrated that they can successfully engineer complex multigenic systems. Gen9 is built on breakthrough methods to dramatically increase the throughput and decrease the cost of synthesizing DNA. They also leverage Next-Gen Sequencing strategies to provide the much needed quality control, and report that through the combination of the synthesis and sequencing advances that DNA sequences have very few errors. Combined, the effects of these recent developments are not too dissimilar to the effects of technological improvements made in DNA sequencing itself, in the last decade.
So the excitement is just beginning. An announcement in GenomeWeb this month, stating that the number of Synthetic Biology companies has tripled over the last four years, is perhaps a bellwether of a new trend and more things to come. With new capabilities driving the market we may be back to the point where true engineering approaches to synthetic biology are possible at low cost. When trial and error becomes practical for exploring many modified genes and assemblies in parallel, we are only limited by our imagination. Check out George Church’s talk about how this area will reinvent ourselves. We are far from solving all of the obstacles of making daily advances in synthetic biology, but the industry seems poised to advance, and there are some intriguing ideas on how these could be applied. Here are just a few:
– Strategies for bringing back extinct species; check out Steve Brand’s Ted Talk.
– Engineered sensors for safer food. Sample6 uses programmable phages to detect food pathogens
– Improved therapeutics. Check out a new antimalarial drug that was partially developed using Synthetic Biology approaches at UC Berkeley.