Notes, thoughts, and news on synthetic biology.

Glowing Futures


Back in 2010 I was a teaching fellow for a group of undergraduates competing in the International Genetically Engineered Machines competition (iGEM) with a project on "personalized" genetic engineering of plants. We designed genetic modifications that would alter flavor, color, vitamin production, and the presence of allergens, so that a gardener could customize seeds to suit his or her whims and needs. As a proof of principle, we built BioBrick plasmids and transformed the model plant Arabidopsis with the gene for miraculin and genetic constructs that could theoretically decrease the expression of allergen genes. We also designed a prototype genetic engineering kit, the iGarden, that future gardeners might use to optimize seeds using genetic parts from the iGEM registry. These prototypes, in the form of genetic constructs, lab experiments, and nonfunctional kits also served as design provocations meant to ask questions about the way that biotechnology works now and could work in the future. Could plant genetic engineering be done outside of the current industrial model? Could genetically modified plants be open source, less resource intensive, educational, fun? What would it take to build and distribute such a kit, beyond the DNA sequences to transform the plants? How might such a system deal with unintended consequences?

We were just one team of many hundreds who have participated in iGEM since it began almost ten years ago, each with a unique project proposing a different application for synthetic biology, building on the open source designs and data of previous teams to develop increasingly ambitious projects. iGEM has captured the imagination of thousands of students, leading to many provocative questions about the future of biotechnology and how it will be taught, practiced, regulated, and sold.

In recent months, a proposed synthetic biology project has again captured the imagination of thousands of people, sparking new conversations about how biotechnologies are funded, designed, made, and distributed. Genome Compiler's "Glowing Plant" project has raised over $425,000 on Kickstarter so far, promising rewards that range from stickers and t-shirts to engineered seeds and a kit where, like with our iGarden, you can theoretically genetically modify your own Arabidopsis plants at home with genes from bioluminescent bacteria.

Genome Compiler Corp Glowing Plant Project

The support, media coverage, and financial backing for the project has been overwhelming and largely positive, reflecting a wider enthusiasm for the potential of crowdfunding and open source technologies in many industries. In its design and in its success, the Glowing Plant project is providing access not only to the sequences of (already available) bioluminescent gene constructs but also openly highlighting some of the evolving tensions in the ways that innovation, regulation, intellectual property, and commercial interests intersect. Like much of the work in synthetic biology that the Glowing Plant project builds on, this is a project that is about much more than the direct applications proposed, prompting critical reflection and debate about topics ranging from government oversight to technological hype.

Engineering Bioluminescence

The genes that make fireflies and some bacteria luminescent have been used in molecular biology experiments for decades as visual reporters of gene expression. Unlike the more commonly used Green Fluorescent Protein from jellyfish, which requires input of blue light to fluoresce, the luciferase protein produces light as long as its substrate molecule luciferin is present. The 2010 iGEM team from Cambridge University focused on engineering biobricks for the expression of luciferase in E. coli along with pathways for the metabolic recycling of luciferin. Without having to externally add luciferin to the system, the bacteria engineered with these BioBricks were brighter than typical luciferase expression systems, visible after a few minutes of adjustment to a pitch black room (for more details on their project and a perspective on the Genome Compiler Project, check out this excellent post from one of the team members).

Cambridge iGEM 2010

While the team worked with bacteria due to the time constraints of the iGEM competition schedule, they were inspired by the possibility of one day being able to make luminescent plants as streetlights, modeling some of the efficiency requirements that would be necessary for such a system to be feasible and producing a mock-up architectural drawing of glowing tree lined streets. At the iGEM Jamboree that year our teams talked excitedly about the potential of future iGEM teams combining the Cambridge team's luminescence genes with our BioBrick expression system for plants.

Cambridge iGEM 2010 E. Glowli

Of course many other researchers, artists, science fiction writers, and gardeners have been inspired by the possibility of glowing plants before. The first report of luciferase expression in plants was in a 1986 Science paper (PDF), demonstrating that luciferase could be expressed in tobacco plants "watered" with luciferin. The figure from the paper showing the cross section of the plant glowing brightly is beautiful and quite striking. However, the image also shows some of the challenges of using luciferase to make any significant light. The image is not a photograph, but made by placing the plant directly onto film in a darkroom. It's unlikely that such a plant would be able to make a significant amount of light that would be as striking to the naked eye.

Ow et al. Science, 1986.

Excerpted figure from Krichevsky et al. PLoS ONE 2010. Photograph of glowing plant taken with a five minute exposure.

Since then, luciferase as well as other visual markers like fluorescent proteins have been used countless times in many plant species for a range of experiments in plant biology, using sensitive instrumentation that can quantify light output in very small ranges. Attempts to use luciferase for the production of glowing plants as decoration or lighting are much less common, but have also recently been developed by several groups. In a recent paper published in late 2010, just after we were speculating about glowing plants at the iGEM jamboree, a group of researchers from Stony Brook University reported having engineered tobacco plants to express luciferase and the luciferin recycling pathway, creating autoluminescent plants that could glow dimly without addition of luciferin.

So what's different between these past glowing plants and the plants proposed by Genome Compiler? At a technical level, besides using their software to optimize the genetic code for a different host organism (the Genome Compiler team is using Arabidopsis, not tobacco), not much. But this project isn't really about reproducing past work and trying to make cool plant night-lights. In fact, Omri Amirav-Drory, the founder and CEO of Genome Compiler, was quoted in the Wired UK article about the project saying "To be honest, it's actually annoying that I have to do it. I wish that other people would do it--I wish that 100,000 people would use my software to to solve another 100,000 problems in the world." This project isn't about this particular genetic engineering project, it's about the potential of all future genetic engineering projects.

Like the BioBricks foundation, iGEM, and the many projects and proposals of synthetic biology researchers, the Glowing Plant project is about exploring the potential for what might be possible if teams of biologists and engineers could build off of the open source work of others. It's about exploring the limits of current technologies, economic and regulatory frameworks, and patent regimes, to make genetic engineering more effective and efficient, more fairly distributed, and as safe as possible. However, there's one important difference between the work of students and academic researchers and Genome Compiler: this project is about more than simply inspiring others, it's about inspiring people to use their product in future genetic engineering projects. It's about selling the idea that open source synthetic biology can solve problems and that you should use their closed source software to do synthetic biology.

Selling a story

Amirav-Drory continues in the Wired interview saying, "We chose Kickstarter for a reason -- we're trying to sell a story more than anything." The story is a triumphant one of the future of open source synthetic biology, crowdsourced design and crowdfunded production solving big problems, doing "something that people on the street would consider science fiction," designed using the Genome Compiler interface and printed by their DNA synthesis partner company, Cambrian Genomics. This is about using Kickstarter as a marketing platform not for a product but for an idea, an idea about "democratizing the tools of creation" with a proprietary software tool. The imagery and rhetoric of the Kickstarter campaign and of Genome Compiler's product intentionally blurs the old and the new, the proprietary and the open, the technologically feasible with the technologically "innovative," science fact and fiction, to create this story and to garner significant attention and crowdfunding.

A Slide from Genome Compiler CEO Omri Amirav-Drory's Solve for X presentation

The image of the glowing plant from the 1986 Science paper that the team is using as the logo of their campaign combines many of the tensions present in the design and marketing of the project. First of all, the image is a direct copy of the work of past researchers, copyrighted by Science, and used with ambiguous citation in promotional materials, proposed Kickstarter rewards like t-shirts, advertising and branding on their website and their software. The use of this copyrighted image to raise funds is a symptom of a larger issue with how intellectual property is being dealt with in this story (more on that later), but more importantly the image provides the team both credibility in terms of feasibility of the project as well as in terms of "wow"-factor. The image of the glowing plant shows that this is technology that has been around for a long time--nearly 30 years!--but is also misleadingly reminiscent of the science fiction plants from the movie "Avatar," which are frequently cited as inspiration.

Demonstrating that something is technically feasible (and that you are competent enough to do it) while still being innovative and working on more than an incremental improvement to what has been done before is the key challenge when asking for money, whether in a grant proposal to the NSF or to the wider "crowd" on Kickstarter. The Genome Compiler team cites the previous work of others on glowing plants and the open-source luciferin recycling pathways from iGEM on their site as proof of concept and then briefly discusses some possible experiments they could do to make the plants brighter, with some of the possible designs available in the "cloud" through their software interface. With the level of funding they have received, they will be able to synthesize and test many version of the design and will likely improve incrementally on previous work on bioluminescence in plants.

As with many cases in biotechnology, however, patents and intellectual property raise complex questions about what levels of openness are best for incremental advances and true "innovation" in this story. Do patents stifle innovation, blocking others from making progress with lawsuits and expensive licensing? Or do patents protect innovative people, allowing them to be fairly compensated for their work when it is used by for-profit corporations? Can there be a different model where sharing is incentivized with different structures of attribution, compensation, and innovation? Is biotechnology and the patenting of DNA sequences or living organisms a special case?

In general I don't agree with biotechnology patents and I support the efforts of the BioBricks foundation to explore different arrangements and licensing schemes. It is difficult to tell what the role of Genome Compiler will be in the long run of the debate about intellectual property in biotechnology, and it's difficult to tell what role patents will end up playing in the Glowing Plant story. The language of the kicktarter campaign and of the Genome Compiler software is language of the open source movement, emphasizing sharing and "democratization" over profit. However, while Genome Compiler cites the PLoS ONE paper from the Stony Brook team, they fail to mention the fact that this group has started a company, BioGlow Inc., to produce and sell ornamental glowing plants, and that this company holds a broad patent on bioluminescent plants (there are a number of other patents on transgenic bioluminescent plants as well). Does the power of the story of openness on the part of Genome Compiler trump the previous work of the BioGlow group? What or who is being democratized, who is being protected or infringed on here? Do crowdfunding "rewards" infringe on patents the same way that a product for sale would?

Genome Compiler Corp. has gotten into patent trouble before, not over uses and applications of their software, but with the actual software itself. The DNA synthesis company DNA 2.0 has a patent on their version of "drag-and-drop" synthetic biology design software called Gene Designer, and has sued Genome Compiler for infringement. Fortunately, many other options for this kind of software exist, including some well developed open source options that allow you to edit, build on, and contribute to the future development of the software itself rather than just releasing your designs to a corporation's "cloud" so that they might one day decide to do a Kickstarter about your idea too. These include programs like Clotho or TinkerCell to name just two of many, as well as a host of much simpler DNA viewing tools that allow users to design small-scale plasmids, not to mention the open and completely free databases of genetic sequences that anyone can access like the National Center for Biotechnology Information or the iGEM Parts Registry.

Same as it ever was

In an email exchange with the Marketing Manager of Genome Compiler Corp. about the patent situation, the company stated that "[We] initially thought of doing some kind of defensive patent, but we decided not to in the end. Genome Compiler was built with the thought of democratizing creation and we would be thrilled if someone wanted to use or alter the design. The design is already up for anyone to see on Genome Compiler in the cloud. We were not concerned with other patents since we were using a different method."

But how different is it, really? When people have raised concerns about the uncontrolled release of genetically modified seeds and DIY Agrobacterium engineering kits to backers according to the Kickstarter rewards structure, the team's response has been to emphasize similarity over difference, claiming: "We are using the term 'synthetic biology' in its most general sense, the technology we are using is functionally the same as that which has been used in the creation of many other biotechnology products over the last two decades." (PDF) While distinguishing themselves from BioGlow, Inc. when it comes to patent regulation, they claim significant similarity and overlap when it comes to government oversight and regulation so that the conditional USDA approval of BioGlow's product (PDF) might cover the Genome Compiler Glowing Plant as well.

So is it the same or is it different? While aggressively selling themselves as something new and something inherently moral and democratic, Genome Compiler is unfortunately acting out a very familiar story. They are a for-profit corporation trying to wedge themselves into a crowded market of DNA-based services that has many viable open source alternatives, exploiting the ideas, work, and the enthusiasm of idealistic people excited about the potential of synthetic biology, overpromising and overhyping the potential of the technology in the short term in order to market their derivative, proprietary software tools and themselves as leaders in the future of the field.

Like the provocations of iGEM designs and prototypes, this project asks many more questions than it answers. Amirav-Drory says that the Glowing Plant project is "so obviously beautiful, and non-dangerous and legal and ethical," but there's nothing obvious about the future of synthetic biology, especially when we're talking about where these technologies will go in the future, when 100,000 people will be working on 100,000 projects. Will we someday have glowing plants lighting our streets, "solving" the problem of electricity use for lighting? Probably not. Will corporations continue to try and exploit others and their ideas to make a profit? Unfortunately yes.

The views expressed are those of the author and are not necessarily those of Scientific American.

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