Last Wednesday the SynBioBeta conference got kicked off at Imperial College. Central topic was the current state of synthetic biology and how (commercial) value can be gained by supplying tools and platforms. In the keynote by Tom Knight from Ginkgo Bioworks, and the afterwards chat with his old PhD student Ron Weiss (now professor at MIT), a few interesting points came by that illustrate the path synbio has taken over de last two decades.
Ginkgo Bioworks founder Tom Knight (Photo courtesy of Twist Bioscience)
Tom started of with a quote from Douglas Adams “if you try and take a cat apart to see how it works, the first thing you have on your hands is a non-working cat” to illustrate the current (or not so far in the past) state of biology in general. He used the old ‘systems engineering’ of a Boeing 777 example to highlight where synbio should be going in his opinion. As in: 1. design using CAD 2. build 3. it works. So no more tinkering and endless design-build-test cycles. In order to do so he argued for an extra loop in the cycle, the simulate component. This would allow the end-user to design and simulate a layout before actually building and testing it. However, he was quickly to note that we are currently lacking a lot of insights into the biology of a single simple cell, for exmample the Mycoplasma mycoides of which 149 of the 473 remain of unknown function but are essential for cell survival.
An improved version of the design cycle proposed by Tom Knight
Also the VSLI analog was brought up and the panel noted that Voigts group last week came a step closer to this paradigm by rationally designing circuits and building them.
On the questions whether synbio is progressing fast enough Ron Weiss replied that it is not “as fast as we want”, he recalled the last chapter of his thesis describing a synthetic biology program language, which he laughingly categorized as “completely useless back then”. However the state of mind back in the 2000’s was “that within a year or 5” we would be able to build circuits with at least 30 gates (Voigts paper from last week showed a ‘Consensus circuit’ containing 12 regulated promoters). Tom was a bit more optimistic saying that “You overestimate what is going to happen in 5 and underestimate what happens in 10 years”. Bottom line was the central need to be able to make robust systems that can work in the real world and in order to do so more information is needed such as whole cell models. The session ended with a spot-on question from riboswitch pioneer Justin Gallivan, now at DARPA; “who is going to fund research this research to gain basic knowledge?”. For example, who is going to elucidate the function of the 149 proteins of unknown functions? One suggestion was that Venter should just pull out his checkbook again…
The investors’ perspective
Next on the program was the investors round table geared towards the commercialization aspect of synthetic biology. It was debated whether the use of the term ‘synbio’ would negatively affect your final product or whether it would boost sales, Veronique de Bruijn from IcosCapital argued that the “uneducated audience will definitely judge you” so she suggested to use the term ‘synbio’ cautiously. Business models, an ever debated topic, stroke more consensus among the investors, they all agreed that it is difficult for a platform technology to go out, hence it can be extremely difficult to apply the technology to the optimal specific product. Karl Handelsman from Codon Capital noted that when you do have a product company it is important to engage with customers early, so you build something they really want. Related to this he recalled that a product company at the West Coast typically exits for 60-80 million USD, so you should be aware that you can never raise more than ~9 mUSD throughout the lifetime of a company. When it came to engaging with Corporate Venture Capital, the panel unanimously appraised them for their expertise came, but care should be taken that your exit strategies are not getting limited by partnering up with them. The session was rounded off with a yes/no on the positive impact of Trump as president on synbio, only Karl was positive because this would definitely direct lots and lots of funding towards Life-On-Mars projects.
Applications of synbio by the industry
In the ‘Application Stack’ session five companies pitched their take on synbio and how this can be used as a value creator. Ranging from bacterial vitamin production by Biosyntia to harnessing the power of Deinoccocus. Particular interesting was Darren Platts’ talk who showing one of Amyris in-house developed tools on language specification in synthetic biology. The actual challenge here was not to write the software “pretty straightforward”, it was more difficult to get the users engaged in the project and adapting the tool. Their paper was published recently in ASC Synbio and the code is soon released on Github.
Is there place for synbio in big pharma?
The final session of the first day was titled ‘ Synthetic Biology for Biopharmaceuticals’ and here if found the talks of Marcelo Kern from GSK and Mark Wigglesworth from AstraZeneca especially interesting, they gave their ‘big pharma’ view on how to incorporate synthetic biology into the established workflows. GSK for example focused on reducing the carbon footprint by replacing chemical synthesis with enzyme catalysis. Another great example was the use of CRISPR to generate drug resistant cell lines to for direct use by the in-house screening department.
The first day was rounded of by Emily Leproust
from Twist Bioscience
, announcing that they would be happy to take new orders from June (!) on.
The future of synbio
The second day started of with a discussion on ‘Futures: New technologies and Applications’ by Gen9 CEO Kevin Mundanely and Sean Sutcliffe from Green biologics. Both showed examples of partnering by their company with academic institutions to get FTO into place. Sean also made an interesting comment that it took them about 4 years to commercialize “technology from the ’70” so he estimated it would take around 12 years before the CRISPR technology, now trickling into the labs, can be used on production scale in the fermenters.
A fun-and-fast-paced ‘Lightning Talks’ session gave industry and non-profit captains a platform of exactly 5 minutes to pitch their vision. Randy Rettberg gave a fabulous speech about the impact of iGEM on the synbio sector and concluded that iGEM helps cultivating the future leaders of the field. Gernot Abel from Novozymes highlighted a ‘citizen science’ project where the ‘corporate’ Novozymes worked together with biohacker space Biologigaragen in Copenhagen to successfully construct an ethanol assay. Along these lines Ellen Jorgensen from the non-profit Genspace pitched their “why a new generation of bio-entrepreneurs are choosing community labs over incubators/accelerators” at a price point of 100$/month versus 1000$/month. Dek Woolfson (known for his computationally designed peptides and cages) gave an academically tasting talk about BrisSynBio but finished his pitch that they are looking for a seasoned business person to help making their tools available for a broader public.
What happens when synthetic biology and hardware meet?
The hardware and robot session showcased, among others, Biorealize who are constructing a tabletop device to transform cells and incubate and lyse them, Synthase who just released an open source data management platform Antha and Bento Lab (currently running a very succesfull kickstarter campaign) highlighting their mobile PCR workstation. An interesting question was posed at the end as to how much responsibility Bento Lab was putting on the DNA oligo synthesis companies by democratizing and making PCR available to the general public. Bento Lab defended that they are supplying an extensive ethical guide with their product and that they don’t supply any reagents. Unfortunately this very interesting discussing was terminated due to a tight conference schedule.
Tabletop transformations, incubations and lysis in one go using Biorealize
A healthy microbiome using GMO’s?
In the final session of SynBioBeta a few examples of synbio applied to the microbiome came by. Boston based Synlogic is planning on starting the IND (Investigational New Drug) process on their E.coli equipped with ammonia degrading capabilities to combat urea cycle disorder. Xavier Duportet showed an example of Eligo Bioscience using CRISPR systems delivered by phages that selectively kill pathogens, such as Staphylococcus aureus, part of this exciting work was published in 2014 in Nature Biotech using mice models.
After all these dazzling applications of synthetic biology, captain John Cumbers wrapped up SynBioBeta by also announcing the next event in San Fransico at 4th-6th October and in London next year again around April.
Personally I think the conference did a great job at gathering together the industrial synthetic biology community, from both early start-up to big pharma. Although the sentiment is that we are not as far as we want to be, there have been some considerable advancements over the last 15 years. From an investors perspective there is still a lot of uncertainty surrounding the run-time (and the inherently coupled rate of return) of synbio projects, however the recent numbers on VC funding are indicating there is an eagerness to take the leap. Taking together, a jam packed two days with high end exciting synthetic biology applications, it will be very interesting to see if Moore’s law also applies to synbio.
Disclaimer: The above write up is strongly biased by my own interests, so revert to the twitter hashtag #SBBUK16 to get a more colorful overview of the past two days.