Cultured Cannabinoids

Cannabis is a fascinating and rapidly growing industry, predicted to reach $57 billion worldwide by 2027. As legalization spreads, so too does our understanding of the potential benefits of the many different molecules present in the plant.

Beyond the better known THC and CBD, cannabinoids present in tiny quantities in the plant have the potential to be valuable in a range of pharmaceutical applications. Ongoing research has shown potential medicinal uses for indications such as chronic pain, nervous disorders, nausea, weight loss, and some mental illnesses.

But to unlock the value of these molecules, we first need to be able to access them. Today we’re announcing a partnership with Toronto-based Cronos Group to produce a range of different cannabinoid molecules through fermentation of engineered yeasts. It’s a large-scale and long-term deal, involving up to $22M for R&D along with a total of up to $100 million worth of Cronos common shares upon achieving pilot commercial scale.

The Science:
There are hundreds of different cannabinoids produced by different varietals of the plant. Long term breeding has led to strains that produce large amounts of THC(A) and CBD(A) (the A stands for acid, a different chemical form that is converted to THC and CBD when heated) but other molecules such as CBC, CBG, and THCV are present only in trace amounts, meaning that they are impractical or impossible to extract and purify from the plant. Without a cost effective supply, research into the pharmaceutical properties of these molecules has also been hampered. THCV, for example, has been shown at low doses to offer relief from anxiety without the appetite stimulating effects of THC, but so much is still unknown.

By transferring the DNA sequences for cannabinoid production into yeast, using the foundry and our existing high-throughput fermentation processes, we’ll work to construct strains that produce a range of different cannabinoids at high quality and purity, identical to those extracted from the plant with traditional methods. By capitalizing on the power of biological manufacturing, we can unlock access to medically important cannabinoids that can be scaled up and produced reliably.

An engineer works with an automated bioreactor system in Ginkgo's foundry

Why Cronos:
We’re so excited to be working with the Cronos Group on this landmark partnership. Cronos, based in Canada and with a presence across four continents, is a vertically integrated cannabis company that operates two licensed producers regulated under Health Canada’s Access to Cannabis for Medical Purposes Regulations. Cronos, with access to an array of varietals and a deep expertise in plant genetics, has gathered extensive data on cannabinoids and their properties. This allows them to generate the best recipes for the full spectrum of cannabinoids, not just the most common ones.

We’ll be working to develop strains of yeast that can produce eight different cannabinoids. All the R&D work we’ll be doing at Ginkgo will of course be conducted in compliance with all U.S. federal laws regarding controlled substances, and we’re currently waiting for approval from from Federal and State agencies. Cronos Group intends to produce and distribute the cultured cannabinoids that result from our partnership globally, and has received confirmation that this method of production is permitted under the Cannabis Act—the legal framework that will regulate cannabis in Canada.

Cronos Group

As Ginkgo has grown, we’ve seen the power of biological engineering and fermentation to unlock the potential of a huge variety of molecules in several industries, from flavor and fragrance to pharmaceuticals. We’re thrilled to be working with Cronos as they build the world’s most innovative cannabinoid platform to bring these products to life.

For more, check out this article by Kristine Owram at Bloomberg: “Cronos Partners With Ginkgo to Develop Lab-Grown Cannabis”

***

Cultured Cannabinoids image at the top of the post by Karen Ingram.

Posted By: Jason Kelly

Our work on biosecurity

Our mission is to make biology easier to engineer—that hasn’t changed for the ten years we’ve been building Ginkgo. The ability to read, write, and design DNA code is having profound positive impacts in medicine, agriculture, and manufacturing, from engineered cell therapies that can target a person’s cancer cells, to probiotics for plants that can reduce the need for nitrogen fertilizers, to sustainably grown materials.

We are working to unlock the enormous power of biology: its ability to grow sustainably, to process information, and adapt to changing environments. But we’re not naive to the potential risks. We understand that as it becomes easier to engineer biology, it will become easier to engineer the part of biology that’s dangerous to humans, animals, and plants—the pathogens and parasites that can infect us. Since researchers synthesized the polio virus in 2002, it has been technically possible to chemically synthesize viruses that infect humans

To date, the work done on synthesizing viruses has been intended for medical research and other peaceful purposes, but there is a concern that someone could theoretically produce a virus or other pathogen with the intent to harm. The intentional use of pathogens to harm others is abhorrent and something that I believe that we should never do under any circumstances—as a company and as human beings. The international community agrees with me on this: 180 countries including the United States are parties to the UN Biological Weapons Convention, which was first signed in 1972 and states that we are “never in any circumstance to develop, produce, stockpile, or otherwise acquire or retain: Microbial or other biological agents, or toxins…that have no justification for prophylactic, protective or other peaceful purposes.”

As the technology for synthesizing DNA code improves, groups from governments, industry, academia, and civil society have been developing frameworks for monitoring and assessing the safety and security of these new technologies. For example, we are a part of the international gene synthesis consortium, which developed standards for screening orders made to DNA synthesis companies. Our Head of Design, Patrick Boyle, was also recently on a panel convened by the National Academies of Sciences, Engineering, and Medicine to assess the risks of intentional misuse of synthetic biology.

Today we’re announcing Ginkgo’s biosecurity initiative that directly addresses some of these potential threats from engineered DNA sequences. Our current work on biosecurity focuses primarily on detecting potential threats using software that analyzes DNA sequences.

As part of IARPA’s (the Intelligence Advanced Research Projects Activity) Fun GCAT program, we are developing software to monitor DNA synthesis. This software is intended to ensure that no one orders DNA sequences that could have a pathogenic function. Think of this like a malware detector in computer programming—“programs” being written in synthetic DNA will go through the detector software, which will flag any sequences of concern before they are synthesized. The custom software we’ve developed for designing DNA sequences in our foundries is a useful start for a project like this—we need to be able to predict the function of enzymes based on their sequences in order to design new functions in our engineered microbes. Rather than predicting if an enzyme sequence could be used to produce, say, a fragrance or vitamin, here we’re applying the same types of algorithms to predict whether a given bit of code could be potentially harmful.

Unlike computer viruses, however, new biological viruses can also evolve in the wild. When a new virus emerges, researchers quickly sequence it to understand where it came from and how to best treat it and develop vaccines against it. We’re addressing this as part of another software-based biosecurity initiative, IARPA’s Finding Engineered Linked Indicators (FELIX) program. Here we are using deep learning to identify if the sequence of a new pathogen developed naturally or was engineered by humans. We’re leveraging our experience engineering the world’s largest library of engineered DNA sequences to help us train the software to detect whether something has been engineered.

Beyond developing software to guide the detection of threats, synthetic biology can also be important for responding to emerging diseases, for example making rapid response vaccines. It’s been almost a decade since the Venter institute partnered with Novartis on rapid synthetic DNA based vaccine development and the technology has been exponentially improving since then. Working alongside other companies, universities, and government agencies, we’re excited to be part of groups involved in developing tools to prevent, diagnose, and treat current and emerging diseases.

Ginkgo is the leading developer of genetic engineering tools we have an obligation to ensure that these tools are responsibly used. We are inspired by the words of Andy Weber, the former Assistant Secretary of Defense for Nuclear, Chemical & Biological Defense Programs under President Obama and a valued advisor to us here at Ginkgo on issues of biosecurity: we believe that while synthetic biology may lead to new risks, that these new tools also actually “offer the opportunity to take the global threat of biological weapons off the table.” By helping to develop software that can detect any threats before they materialize and develop the tools that can rapidly respond to emerging infectious diseases—natural or engineered—we hope to continue to drive the responsible growth of synthetic biology and realize its enormous potential for good.

For more on this story, check out Rebecca Spalding’s article in Bloomberg: “The DNA Cops Who Make Sure the World’s Deadliest Viruses Aren’t Rebuilt.

Posted By: Jason Kelly

Why innovate with biology? Because you can’t eat software

I’m happy to share we’ve been named to the CNBC Disruptor 50 list for the third year in a row. During these three years, Ginkgo has grown a lot, into new foundries and new industries. We’re now a team of almost 200 people and 65 robots and counting, still dreaming about how biology will change how we make things.

Crafting organisms | Illustration by George Kavallines for CNBC
image: George Kavallines for CNBC

Today, it’s a given that Silicon Valley and software are disrupting traditional ways of doing business, across media, financial services, logistics, transportation, healthcare, and many other things that once seemed to be far removed from computers and information technology. In 2011, Marc Andreessen aptly proclaimed that “software is eating the world”— in other words, that more sectors would be disrupted by and start to look like software companies.

A biotechnology company among a list of such disruptive companies could perhaps look like a software company, signaling just another sector eaten by software. But I think that would miss the point of innovating with biology.

In short, you can’t eat software.

Bits aren’t calories. A mobile app might help me decide what to eat for dinner and software will handle the logistics of how it gets to my door, but software doesn’t fill my stomach. I can’t taste software or smell it. I need more than just software to keep the lights on; I can’t wear it to keep warm. Software will help us discover important patterns in healthcare and medicine, but I can’t take a software pill to get well. Software can have many positive effects, but as Bill Gates has said about technology needs in the developing world: “When a kid gets diarrhea, no, there’s no website that relieves that.”

Designing DNA makes it possible to fundamentally disrupt the many unsustainable ways we make things today, to improve how we produce food, design medicines, and manufacture materials and chemicals. Learning from the wisdom of three billion years of biological evolution, we can tap into the ways living things grow, heal, and adapt in deeply circular and interconnected ways to make technology that is rooted in nature. From meat to medicines, vitamins, flavors, and everyday household products, biology companies are rethinking our manufacturing system and transforming cells into living factories to grow the products that will help meet growing global demand. 

Even two industries that are fundamentally about biology—pharma and agriculture—are being biologically transformed by new ways of engineering cells. In 2016, 25% of pharma sales were from biologics like proteins and antibodies that are produced through genetic engineering. Today, we are seeing the beginning of a new generation of living therapeutics and engineered cell therapies, like those we are developing with Synlogic. In ag, new innovation is targeting the chemical inputs necessary for large-scale farming, replacing them with more sustainable biologic products. Just last year we founded Joyn Bio, our joint venture with Bayer to develop probiotics that could decrease the amount of chemical fertilizer – a major contributor to greenhouse gas emissions – needed in agriculture.

Fermentation engineer Kar Mun Neoh works in Bioworks2

But because we are biology, the stakes for disruption are also much higher for biotechnology. The power of biology is what inspires us and drives us to build this industry, but it’s also something we have great respect for and must approach with humility. Evolution has 3 billion years on us, and we don’t take that lightly.

With respect for biology at its core, the disruption that biotechnology offers is one that is going to enable more sustainable manufacturing, less fossil fuel intensive agriculture, smarter medicines, and so much more. We’re so excited to be part of that.


See the full CNBC Disruptor list here and read more about Ginkgo and our approach to synthetic biology on CNBC here: “Why Bill Gates is betting on a start-up that prints synthetic DNA”

Posted By: Jason Kelly

Why the Future of Synthetic Biology Needs a Platform

SynBioBeta San Francisco 2017: Why the Future of Synthetic Biology Needs a Platform

Today, the Ginkgo team and I are attending the 6th annual SynBioBeta conference in San Francisco—an annual meeting that brings together leaders in the synthetic biology industry. I’m kicking off the day discussing why biology is the most powerful and advanced technology on the planet and Ginkgo’s mission is to make biology easier to engineer.

We’re witnessing an exciting shift in the biotech world. Companies big and small across a variety of industries—from enzymes to fragrances to agriculture—are realizing the power of biology as a better way to make everyday ingredients and products.

Last month, we partnered with Bayer to launch a new company—along with a $100M Series A investment—to improve plant-associated microbes, focusing on nitrogen fixation. Nitrogen fertilizer is a significant contributor to greenhouse gas emissions and water pollution, and we’re proud to be at the forefront of solving such a major problem with biology.

We hope this partnership serves as a major indicator for synthetic biology’s potential: big companies are looking to solve big problems with this technology. But more importantly, we believe the potential for biology doesn’t have to come with a $100M investment. Smaller companies are also rethinking manufacturing through biology, and we’re committed to being a platform that’s accessible to companies of all industries and all budgets.

Today we have three announcements that help cement our vision for being a universal and accessible platform for the biotech world:

• We’ve long-admired Transcriptic’s mission to make lab work less expensive and faster thanks to the power of automation. Today we’re investing over $10 million to bring their software into our foundries, to further improve our automation processes.
• We’re teaming up with Geltor, an 8-person company creating texturizing proteins for foods and cosmetic products, to help it make products faster and more efficiently. With our foundry, Geltor’s team can focus on product design and development, and more importantly make biotech timelines compatible with business cycles in the CPG markets.
• To support our growth, we’ll be purchasing one billion pairs of synthetic DNA from our longtime partner Twist Bioscience. It’s a historic purchase, and ensures we’re ready to support the needs of today’s customers and tomorrow’s partners.

I’m incredibly proud of what our team has built so far. We’ve designed a platform that powers  big and small customers, while allowing partners to build on top of our technology to create something even greater.  At the same time, I’m humbled by what lies ahead. We’re looking forward to meeting other consumer biotech companies this week at SynBioBeta to learn about their roadblocks and hope that Ginkgo can play a role in contributing to their success!

Posted By: Jason Kelly

2017 So Far:  Growing our Technology & Our Team

2017 So Far:  Growing our Technology & Our Team
Jason Kelly, Ginkgo Bioworks co-founder and CEO

The first half of 2017 has been nothing short of incredible for Ginkgo. We acquired Gen9 in January to bring their DNA synthesis capabilities in-house, and last month announced successful commercial-scale fermentation of an ingredient with our partner Robertet. Both of these were significant milestones in our work on continuing to scale our technology, but we know there’s more work to do.

Today, we’re officially announcing two new additions to our team here at Ginkgo who will play a huge role in our ability to continue to scale: Ena Cratsenburg, our chief business officer, and Will Schroeder, head of metabolic engineering. Ena has over a decade of business development experience in biotech, but also spent more than five years with Pixar.  She’s already brought that mix of practical experience and outside-the-box thinking to her role overseeing new partnerships and the commercialization of our tech and products. You can read more about Ena’s day-to-day experience at Ginkgo here, and how she found her way from Pixar to biotech.

Will serves as our new head of metabolic engineering, managing the teams of organism engineers designing the microbes that produce cultured ingredients for our customers. He comes to us from ADM and spent 12 years at Cargill. Both of these companies are partners of ours, and it’s great to have Will’s unique understanding of the industry and incredible expertise in enzymes (he’s the author or inventor of 16 publications and patents in the areas of microbial fermentation, molecular biology and enzyme catalysis!).

Please join me in welcoming Will and Ena to the team! You can read more about our commitment to diversity in our hiring practices here, and see open job recs here.

Posted By: Jason Kelly

State microbes

Since microbes are currently our favorite organisms to engineer here at Ginkgo, it was great to see Wisconsin recognize the first official state microbe! Of course they chose Lactococcus lactis, the bacterium used to make many popular cheeses.   Maybe we can convince Massachusetts to choose E.coli as a state microbe for all the biotech drugs it has produced — need to help Coli beat its bad rap!

Posted By: Jason Kelly

2 steps toward open DNA parts

Biological engineering today is increasingly built on a foundation of standard biological parts that engineers can use to build their systems.  These are the basic subroutines in our programming language.

It’s important that the parts that provide core functionality be free of restrictive IP rights and a couple recent developments deserve to be celebrated:

(1) Last week a district judge interpreted certain natural gene sequences to be primarily information rather than chemicals and hence not patentable.

Rob Carlson wrote up a nice summary and you can also read coverage from NYTimes and Genomics Law Report.  The ruling only applies to natural sequences, but it means that biological engineers can be a little more comfortable using  the massive amount of new DNA sequence that is added to GenBank daily.   Also nice to see the law catching up with the 60-year old realization that DNA is information.

(2) The  BIOFAB: International Open Facility Advancing Biotechnology (BIOFAB) was launched in December by the BioBricks Foundation with an initial bolus of funds from the National Science Foundation.

I heard the BIOFAB gang speak at the recent SynBERC conference in Berkeley and was excited to see the progress they had made.  The fab is set up to be an industrial-scale part production facility for generating open (IP-free), high quality biological parts.  The parts will hopefully be released under something similar to the the BioBrick Public Agreement that is a sort of GPL for biological parts.

Here’s hoping for more steps toward open parts in the future.

Posted By: Jason Kelly

Pearl Biotech Open Gel (Un)Box(ing)

pearlgelbox

Just received our gel box in the mail today.  Pearl has added a great tweak to the standard gel box with an illuminator that fits snuggly under the box.  The illuminator apparently does a good job of exciting SYBR Safe DNA stain so you can watch your DNA running in real time.  The design is open sourced and it would be great to see someone design a camera mount for the gel box to make a cheap gel imager.   All in all, the box looks solidly built and it’s exciting to see people innovating on tools for biological engineering.  Looking forward to seeing more from Pearl in the future.

Posted By: Jason Kelly

Bacterial Edge Detector

One of Ginkgo’s favorite biological engineers – Jeff Tabor, has just published his latest engineered biological system, a bacterial edge detector, in Cell Magazine.

edge-detector1

The edge detector is a great example of combining different biological parts (light sensors, cell-to-cell signaling molecules, reporters, and logic gates) to make a complicated engineered biological system.  In the final system, the engineered E.coli are spread in a lawn on a petri dish and light is shown on the dish in a particular shape.  The bacteria at the edge of the shape detect that they are at the interface between light and dark (this is the really amazing bit that requires communication between neighboring cells and some genetically-encoded logic) and express a reporter protein creating an outline of the shape.

This project was actually begun by Jeff and the UT Austin iGEM team in the 1st iGEM competition in 2004.  During the 4 months of the competition they didn’t manage to get the edge detector working, but they did build the first bacterial photography system (“Coliroid“) which was later published in Nature.

Hopefully Jefff’s success with the edge detector will be an inspiration for this year’s iGEM teams to go after ambitious projects!

Posted By: Jason Kelly