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SynBio is Booming

In this third part of our review of 2015, sourced from synthetic biology community, we cover five aspects that relate to developments in automation and commercialization. Synbio is booming, a 2014 report estimated the market could be worth $38 billion by 2020. The responses we received reflected the excitement within the community, but they also highlighted some of the challenges that must be addressed in order to prevent the bubble bursting.   

1. The 100M bp Question

Development of scaling tools to cut back the excruciating uncertainty of strain development in SynBio will release the tiger.”

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Advanced Liquid Logic uses the electrowetting effect to precisely manipulate droplets within a sealed microfluidic cartridge. Image from http://www.liquid-logic.com/#!prettyPhoto/1/

This quote from Ron Shigeta of Indie.Bio strikes to the heart of the issue; scale-up is perhaps the biggest challenge to making the leap from lab to market, and it is one we have seen before during the biofuel crash of the late naughties. For Dr. Steve Shih “the development of new automation technologies in #synbio has been the most exciting [aspect of 2015]” because “it has pushed the boundaries on how we can engineer organisms – from chip-based gene synthesis (Twist Bioscience) to developing new automation platforms for organism engineering  (Zymergen)”. Other notable examples of clever automation tools included Illumina’s Advanced Liquid Logic technology and Oxford Nanopore’s VolTRAX.

The most eye catching example of synbio working at scale was nominated by Khalid K. Alam, who picked “Ginkgo Bioworks Ordering 100M basepairs of DNA from Twist Bioscience”. This is a truly dizzying amount of DNA for anyone to handle, and as Khalid commented “in the past decade we have been able to read DNA at scale, to the point where we can sequence an entire genome for $1000. This deal symbolizes our forthcoming ability to write the genome at scale. Our ability to read, write, and rewrite the code of life will drive the bioeconomy of the 21st century and impact humanity in ways we have yet to realize.”

2. Towards Computer Aided Design

To capitalize on the ability to synthesize DNA cheaply it will be necessary to adopt an automated design process using standard parts. Towards this aim, 2015 saw the Plant Synthetic Biology community establish a common syntax for exchange of biological components. However, there is still a long way to go, and problems with a lack of characterization and documentation remain key issues (check out this video by BioFaction on standarization in synbio for more info).

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Antha ‘Making biology simple, reproducible and scalable’. Image from https://www.antha-lang.org/

As a molecular biologist, I know I wouldn’t want to be design 100M bp worth of vectors by hand, it would also be stupid. Gone are the days of designing plasmids in text files! Ben Mackrow who works for LabGenius commented “engineering biology requires big data analysis and advances in machine learning will be needed to permit such intelligent reprogramming of the complex natural world.” Referring specifically to LabGenius’ synthetic DNA libraries he explained “the need for software solutions to obstacles created by infinitely vast genetic landscape [is key]”. This is something that is equally relevant to any application when beginning to work at scale, and 2015 saw the continued development of software tools that will be vital for automating laboratory workflows, one of which was highlighted by Dr. Daniela Quaglia:

“The achievement of better automation and standardisation in biological experimental processes is fundamental to the synthetic biology revolution. Antha, a first-generation [open-source] high-level programming language for biology recently released by Synthace, is in line with this idea and promises to be of great help in making biology more reproducible, hence more shareable. I believe this to be one of the most exciting developments of the year!”

Antha is written in Google’s Go script, and one of its main advantages is it overcomes difficulties in interfacing between multiple pieces of hardware by converting device specific, proprietary file formats into standard (JSON) data (a good blog piece about it can be found here). Antha is one of several initiatives such as Synthetic Biology Open Language (SBOL) Visual and PrPr that offer great promise for lab automation; it is currently used by Synthace and has been adopted by Dow AgroSciences and Merck, making 2015 the year when these approaches started to enter into mainstream use.

3. Transforming Industry – First Things First – Food!

Once you have the technology, you need a market and a product. As one of the major aims of synbio is to decouple design and production processes, it was encouraging that we had a couple of responses nominating projects involving collaboration between designers and scientists. For Dr. Markus Schmidt of BIOFACTION, the highlight of 2015 was seeing “Plenty of start-ups and VC taking sybio from the lab to the real world. Artists, filmmakers and designers become more prominent in experimenting with, reflecting and shaping synbio.”

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Second Skin. Macroscopic view of the bio- hybrid film that reacts to sweaty skin. Image from http://tangible.media.mit.edu/project/biologic/

Victoria Geaney, who was interviewed for this blog earlier in the year, chose a specific example – “the “Second Skin” project by the [Tangible Media Group] at MIT. [It] is a really exciting project using responsive Bacillus subtilis natto as living actuators in a garment to react to perspiration. The use of growing bacterial actuators could be really applicable in sportswear and as a concept is very futuristic and a great and innovative Synthetic Biology and Fashion project.” If you haven’t seen the promo videos – they are definitely worth a view, the second skin project looks like it belongs to the realm of science fiction, and that creativity is what democratization of the design process can bring.

As for the major synbio companies making progress this year, Emily Leproust of Twist Bioscience wrote an excellent introduction in September which is well worth a read. Highlighted in our survey were firms dealing in sustainable foods and natural products:

“The rise of consumer biotech is one of the most fascinating development of 2015 with a number of companies using synbio as a tool to make better, more sustainable food: Afineur, Muufri, Clara Foods, Modern Meadows, etc”

Dr. Camille Delebecque, Founder and CEO of SynBioConsulting

“For me it was Google’s attempt to buy impossible foods for $200m. It really validated the entire engineered food space, and I think it’s just a start.”

Ryan Bethencourt, Indie.Bio Program Director and Venture Partner.

It remains to be seen what the public’s attitudes to these products will be, but as Tim Treis commented, goods such as “3D printed synthetic Rhino horns, [made by] @pembient [and shark fins made by] @NewWaveFoods” are really exciting, as “not only are they sustainable, but [they] also tackle quite a bloody market.”

4. Colossal start-up fundraising

Scaling up requires money, and the amount of investment in synbio this year was nominated as a key development by a number of  people:

“The biggest development was the record investment in the field of SynBio. Over half a billion dollars in 2015 alone.”

John Cumbers,  Founder of synbiobeta

“A lot more venture capital dollars poured into synbio in 2015 than in any previous year. Given that the mission of synbio is to make biology easier to engineer, it’s a big deal to see these transformative commercial entities attract the resources they need to achieve their goals.”

Dr. Aditya Kunjapur, Post-Doctoral Research Fellow MIT

“Increasing investment and ever-growing involvement from more traditional silicon valley investors has been invigorating for SynBio in 2015, the line between biotech and classical tech continues to blur.”

Ben Mackrow, LabGenius

Blue-Sky-Bio-CompetitionIn addition to conventional venture capitalist (VC) involvement, 2015 saw continued investment in synbio startups from organisations such as Ycombinator (as covered by Christopher Harrison), Indie.Bio, Illumina Accelerator and SynbiCITE as well as from schemes like the Rainbow Seed Fund to facilitate the transition from the lab to market. Also of note was the introduction of the BlueSkyBio competition at SynBioBeta as a boost for startups (winners were reported here and here).

A detailed list of the investment synbio companies have raised can be found on AngelList, and for a great summary I recommend this piece written by Dr. Aditya Kunjapur for our blog. Key restraining factors include fears about biosafety and biosecurity, but the most important sectors are likely to include DNA synthesis and IT, as well as Industrial and Agricultural Biotech (as recently reviewed by Calvin Schmidt in a synbiobeta blog post).

5. The Rise of Moonshots

While synthetic biology has the potential to disrupt marketplaces with novel products, Dr. Charles Ebikeme made an interesting point about the effect markets are having on science itself:

The one thing that really excited me [this year] was Google’s shakeup/restructuring to Alphabet and the announcement of Google Life Sciences being under that umbrella… it is another example in how the worlds of biology and tech are moving closer together. And how, more and more, we are seeing a tech-startup approach (think moonshots) to the way we do science.”

With funding agencies emphasizing the need for impact in grant applications, it becomes increasingly necessary to pursue research with tangible benefits. Taking this logic further, for those looking to commercialize their research, VCs are interested in big returns and look for leaps in progress, not small steps. This kind of thinking is being fueled by organizations such as Google Alphabet’s ‘Verily’ (as described by the head of GoogleX, Astro Teller) and the Life Sciences XPrize. We now have moonshots for heart disease, cancer and understanding the human brain. Moonshot thinking drives scientists to push the limits of what is achievable, and has sparked projects that range from re-engineering the genetic code to incorporate novel bases to the ‘creation’ of artificial life itself.

The Synbio Ecosystem

The developments of 2015 point towards a key aspect of commercialization – the beginnings of a synbio ecosystem. Taking the 100M bp Ginkgo-Twist deal as an example, it would not have occurred without (1) improvements in tools for scale-up of DNA synthesis, (2) the establishment of Ginkgo’s Bioworks1 robotic laboratory for automation of strain engineering, (3) developments in software and molecular biology for using standardized parts and automated design, (4) a market for Ginkgo Bioworks’ products (which incidentally also lead to my favorite tweet of the year) and a market for the DNA (5) VC backing of synbio companies and (6) a moonshot approach to biotechnology.

In a recent talk I attended by Amy Weatherup of i-Teams, the need for trust between investors and entrepreneurs was emphasized as a key component of growing a business. As synbio is a relatively new sector, investors face a number of challenges that have been discussed previously, and it takes time to build relationships. The increasing involvement of members of the corporate world in running synbio companies may be speeding up the process, as for example seen in the management board of Amyris, but future growth might be driven by the movement of established business into the area; Google was mentioned twice in our survey – it will be interesting to see what the future holds.

We want to say a big thanks to all those people who contributed. For those of you that have an interest in scale-up, SynBiCITE are running an event in February next year. More information about the companies mentioned can be found by following the links embedded, and for LabGenius on facebook, twitter and online.

Declarations: The author has no affiliation with, involvement in, or financial interest in any of the companies included in this post.

Discussion
  1. The last paragraph regarding trust between investors and entrepreneurs really hit home for me. Managing expectations is one of the greatest challenges for entrepreneurs, who by nature must be optimistic (or why start the business?).

    The trust can break down quickly when the first couple of deals fall through, and the entrepreneur says, “the big deal is right around the corner”. I’ve seen such situations drive investors crazy and lead to a breakdown in trust that results in the management team being replaced.

    The key for the entrepreneur is not so much reiterating that they have great science, but to keep a realistic perspective on what it really takes for a customer or partner to adopt their great science. Entrepreneurs who are able to do this often are able to maintain the trust of investors longer, and through trying times.

  2. […] SynBio is Booming “Ben Mackrow who works for LabGenius commented “engineering biology requires big data analysis and advances in machine learning will be needed to permit such intelligent reprogramming of the complex natural world.” Referring specifically to LabGenius’ synthetic DNA libraries he explained “the need for software solutions to obstacles created by infinitely vast genetic landscape [is key]”. This is something that is equally relevant to any application when beginning to work at scale, and 2015 saw the continued development of software tools that will be vital for automating laboratory workflows, one of which was highlighted by Dr. Daniela Quaglia: “The achievement of better automation and standardisation in biological experimental processes is fundamental to the synthetic biology revolution. Antha, a first-generation [open-source] high-level programming language for biology recently released by Synthace, is in line with this idea and promises to be of great help in making biology more reproducible, hence more shareable. I believe this to be one of the most exciting developments of the year!” […]

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