By Grant Vousden-Dishington
— SynBioBeta (@SynBioBeta) November 4, 2015
Two months ago, PLOS Synbio covered and sponsored the iGEM 2015 Giant Jamboree, where John Cumbers was one of the keynote speakers. Cumbers’s company, SynBioBeta, hosted its own eponymous event, SynBioBeta SF 2015, in early November at the UC San Francisco campus in Mission Bay, bringing together an eclectic crowd of entrepreneurs, biologists, students, and other synthetic biology enthusiasts near the heart of northern California’s burgeoning biotech start-up population. Spanning 11 presentation sessions and several panels over two days, there was no shortage of topics within synthetic biology to discuss between the more than 500 attendees, but several larger themes became apparent.
— SynBioBeta (@SynBioBeta) November 5, 2015
The Blue Sky Bio Competition
To understand how diverse the field is for synthetic biology, we need look no further than the three finalists for SynBioBeta’s inaugural Blue Sky Bio Competition. Aside from the impressive prize packs each group competed for, the aims of the companies were quite divergent.
- alGAS Biotechnologies seeks to create a biodegradable, non-toxic, rechargeable battery using synthetic biology.
- Gigagen aims to pioneer what it calls “synthetic immunology,” by create custom antibodies for disease therapy by sequencing genes from patients’ B-Cells.
- Koliber Biosciences designs probiotics intended to ameliorate and treat depression by ingestion and having targeted effects on patients’ microbiomes.
Each of these goals is very ambitious, having two with medical purposes and one aspiring to revolutionize the energy industry. After a round of voting by the audience, Koliber edged out Gigagen for first place. The margin of victory for Koliber may have to do with how near the issue of depression is to the audience. Depression may affect nearly 10% of the general population, but some estimate depression affects nearly one-third of entrepreneurs. The appeal of a probiotic is understandable.
Biotech Investment, Incubation, and Innovation
Many attendees of SynBioBeta SF 2015 plan to be or already are participants in the biotech industry, so a great deal of the meeting was dedicated to the best strategies for creating a thriving synthetic biology company. A recurring sentiment among speakers was that biotech is in a similar position to the software industry just as personal computers were becoming mainstream, and more than a few comparisons were made to software development. Even Silicon Valley investors, such as Sam Altman, President of the famed software start-up incubator Y Combinator, spoke at the event about why people like him are interested in this industry.
Perhaps surprising some, there was low emphasis from speakers regarding domain knowledge, specifically in the biosciences, and high emphasis on the need to be open and agile when pursuing synthetic biology. Jay Keasling, among others, explained this is because the scientific components of the business are often more reliable than the externalities — the conditions of the industry as a whole and its regulation. As such, resilience to these obstacles should take priority. The lesser importance of domain knowledge may be welcome news to some participants, as interest in synthetic biology has been drawn from traditionally non-biological fields, but time will tell if the relative difficulty of the science is really so simple.
— Swapnil (@Pipette_Ninja) November 5, 2015
Information and Automation
Having DNA and custom protein complexes is not sufficient to create a successful biotech enterprise. Creating new biological machines will mean mining, trying, and scrapping many potential genetic designs, a feat that will be impossible without an appropriate computational pipeline. Along with computation and analysis, companies will need scalable infrastructure to execute the experiments needed to validate and test these constructs. Ewa Lis, CTO of Koliber Biosciences, went a step further and suggested that machine learning, a field undergoing a resurgence of its own outside of synthetic biology, will be crucial for determining what genotype and phenotype features are important and guiding the direction of research. Easily accessible machine learning platforms for biosciences have yet to appear, but many “cloud lab” start-ups aim to bring automation to researchers, such as Arcturus BioCloud, Emerald Cloud Laboratory, andTranscriptic, all of which were in attendance. To make the design of experiments easier, many of these platforms are also focusing on helpful interfaces for visualizing the complexes that will be used and synthesized. Still more companies, like Ginkgo Bioworks, are starting up their own platforms to design, build, test, and iterate the genomes of interest to create the synthetic micro-organisms they need, and others like OpenTrons aim to make the necessary technology affordable enough that any entrepreneur or biohacker can participate by providing a low-cost liquid-handling robotic platform, capable of executing simple experimental protocols. The increasing availability of such options, as opposed to building an in-house laboratory, is another potential reason for the aforementioned emphasis on infrastructure over domain knowledge — tools like these will make it easier for non-experts to perform experiments, ideally without being detrimental to the quality of these experiments.
The Future of Bioengineering
No modern bioscience meeting could be complete without acknowledging the rapid advancement of genetic engineering. Due largely to the number of CRISPR-based tools now available, parallelized and precise genetic modification is now possible in nearly every lab-ready biological system. Driving home this point, there was a timely announcement on Day 2 of SynBioBeta SF 2015 from Editas Medicine CEO Katrine Bosley that genetic editing of human subjects could be underway as soon as 2017.
The aforementioned Koliber Biosciences is not the only company aiming to use metabolic engineering to address consumer needs, but as easy as CRISPR makes insertion and deletion of genes, this is only a subset of the engineering needed. The question of biotech’s future boiled down to “Will Synthetic Biology be the Source of the Next Google, Apple, or Tesla?” Several panelists responded that they hoped there wouldn’t be a Google, Apple, or Tesla in biotech, believing the best path to innovation is to remain as distributed as possible instead of few companies gaining such a strong foothold that they crowd out competitors, and if independent groups are to work together efficiently, standards will need to be set early. The risk, however, is that the biotech companies making the standards are the most likely candidates to become the kind of monolithic company panelists are wary of. If a single company in the future controls the way others interact with CRISPR, it will have significant influence on how the rest of the industry and its consumer-base moves, in much the same way Google shaped how users interacted with the world-wide web in establishing its prominence.
Founding a Collaborative Architecture for Synthetic Biology
The first of two keynotes at SBBSF15 was delivered by Tim O’Reilly, known for his namesake company O’Reilly Media, especially well-known for publishing widely-read references on programming and computer science. O’Reilly stressed the importance of openness and the ability to collaborate in biotech, urging synthetic biologists to worry less about open-licensing of products and focusing on what he calls “architecuture:” the rules and standards used by today’s biotech companies will become the de factostandards for tomorrow’s, so it’s important to be deliberate in selecting them. To make the point, O’Reilly pointed out that 60% of the world’s railways are built with beams in the same standard guage — 4 feet 8.5 inches — set by George Stephenson in 1822. He also pointed out that UNIX, the 40-year old operating system still at the heart of many operating systems today, was built collaboratively despite being licensed and owned by one company and being “just open enough” for collaboration to happen.
— Tim O’Reilly (@timoreilly) November 5, 2015
There was no shortage of optimism for synthetic biology in the second keynote of the event, delivered by Intrexon CEO Randal J. Kirk. Calling the coming wave of biotech innovation “arguably the most poignant moment in history,” Kirk also distinguished his talk by abstaining from the use of a slide deck, delivering his points entirely with speech. Among his key points was the idea that fear is a response accompanying nearly every industrial change, that this fear is valid, and that it is the natural course of innovation. Referring to the security concerns when the first ATM installations arrived, Kirk affirmed his belief that the industry would be able to overcome its own pitfalls, and that if synthetic biology can offer a tangible product to the world, it has an obligation to overcome those obstacles to deliver it.