Can the reengineering of biology be coupled to the spread of tools and knowledge sufficient to improve the health of people and the environment worldwide? We believe the answer is yes, albeit with much work to be accomplished both technically and culturally. Practically, a comprehensive overhaul of the process by which living systems are engineered is needed. Legal, political, and cultural innovations are also required to collectively insure that the resulting knowledge and tools are freely availably to those who would use them constructively.
We do not know how to make biology easy to engineer (think playing with Legos or coding software with Java). However, technical inventions prototyped over the past six years point the way to a future in which biology is much easier to engineer relative to today. For example, in the summer of 2009, a team of undergraduates at the University of Cambridge won the International Genetically Engineered Machines (iGEM) competition by engineering seven strains of E. coli, each capable of synthesizing a different pigment visible to the naked eye. The resulting set, collectively known as E. chromi, required rerouting the metabolism of the bacteria so that natural precursor chemicals are converted across a palette of seven colors, from red to purple; such genetic color generators can be used to program microbes to change color in response to otherwise invisible environmental pollutants or health conditions. A few years ago such a project would have required several PhD-level experts in biology and metabolic engineering and would have likely taken a few years. Today, undergraduates can perform such work in months. This change in reality is due to two advances—tools and sharing—both of which are ready for their own revolutions.
The Cambridge iGEM students benefited from a preexisting collection of free-to-use standard biological parts, collectively known as the BioBricks collection. This collection of standardized DNA, although still incredibly immature, represents a radical advance in the underlying technology and cultural framing of biotechnology. For example, the enzymes needed to produce the red and orange pigments were available via a DNA kit that the students received at the start of their project. And, in completing their project the students gave back new DNA—created via advanced gene synthesis tools—encoding enzymes that produce brown, violet, light and dark green, and blue pigments, so that others who follow can readily make use of these additional materials. The students’ “give and get” and “standard biological parts” philosophy stands in stark contrast to current biotechnology practice, which depends upon an ad hoc genetic artistry and is dominated by hoarding of both materials and property rights.
How can the students’ experiences impact global biotechnology and, in particular, the conceptualization, development, and application of indigenous biological technologies of local relevance? One net positive impact would be to make accessible methods to produce needed chemicals and materials that are now unavailable or too expensive. More specifically, a reduction in capital and research costs associated with biotechnology research and development would allow a greater diversity of teams to work on many now ignored challenges, such as orphan diseases, that mainly affect poorer people who lack significant purchasing power. For example, the Gates Foundation funding of a public-benefit partnership led by Jay Keasling of Berkeley produced an engineered strain of yeast that is capable of converting sugar into the antimalarial drug, artemisinin, at a fraction of the cost now associated with extracting the same drug from the bark of the sweet wormwood tree. What if we could enable thousands of artemisinin projects, each hoping to improve the human condition or our environment? What if we could enable the very people whose livelihoods now depend on intensive and expensive methods of manufacturing and production—such as wormwood tree farming—to help conceive, enable, and benefit from a transition to a human civilization that is implicitly and responsibly partnered with the living world?
Practically, the phenomenon of orphan diseases points to a broader challenge underlying all innovation and development. Many powerful new technologies migrate slowly, if at all, to developing world populations. More critically, the upstream choice of which technological advances to pursue often depends on market conditions or the wealth of different national governments, which means that the unique needs of developing world populations tend to go unaddressed or are not voiced during the early stages of a technology’s development. Thus, translating the promise of any new field of research, such as synthetic biology, into concrete benefits requires more than technology alone, especially when it comes to helping underserved populations in the developing world. It requires supportive legal, institutional, and commercial environments, and coordination among researchers to pool efforts toward solving shared problems.
With these challenges in mind, synthetic biologists and colleagues from Harvard, MIT, and Stanford now lead the BioBricks Foundation, an independent non-profit organization dedicated to supporting the open development of synthetic biology through the promulgation of new technical standards and legal instruments. For example, among its projects, the BioBricks Foundation is now participating in the creation of a “BioFab,” a public-benefit factory dedicated to the professional production of sets of reliable, standardized biological parts that will collective constitute an free operating system for biotechnology. By focusing on application-agnostic tools, collections of standardized, interoperable biological parts can be developed that make all kinds of biological engineering easier. This would mean that all possible downstream uses become simpler as well, with a much greater potential for positive impact on understudied problems and underserved populations.
As a second example, the BioBricks Foundation is working to ensure that synthetic biology develops in an open manner, legally and institutionally. The focus of this effort so far has been the drafting of the BioBricks Public Agreement (BPA), which is a new legal instrument for sharing synthetic biological parts. The BPA is an attempt to bring open source innovation into synthetic biology. Open source products (such as Linux software) have traditionally been favored by developing world governments and companies, as they provide access to new technology at low cost. The BioBricks Foundation hopes that the BPA will enable open platform-based synthetic biological tools to be used, transformed, and strengthened through the efforts of researchers around the world, including those in developing countries.
In more detail, readers familiar with open source licenses in software may be accustomed to thinking of open source products as imposing conditions on their users (for example, through “give-back” or “share-alike” clauses). By contrast, the BPA imposes very few restrictions on what users can—or can’t—do with the materials they receive. Instead, the agreements are structured not as licenses to use existing intellectual property, but as contracts between two parties (the “user” of the materials and “contributor” of the materials”) with a promise by the contributor not to assert any intellectual property rights, including patents, against the user. In other words, contributors to the BPA disavow any control of intellectual property in relation to users who agree to certain conditions. The decision to use a non-assertion promise rather than a licensing agreement was a complex one that involved careful consideration of the different legal and financial landscapes around patented uses of genetic materials rather than copyrighted software. The simplicity of the BPA should help the community of synthetic biologists grow without the cost or complexity of navigating the patent system. Those who wish to continue to use the patent system and other intellectual property frameworks (outside of the sharing system established via the BPA) are free to do so.
We believe that open and broadly useful genetic technology platforms will encourage and enable the growing community of synthetic biologists in both academia and industry. Through the BioFab and the BPA, the BioBricks Foundation is working with its partners to ensure that the benefits of the next generation of biotechnology are widely shared and do not neglect the needs of populations in developing countries. No such endeavor is perfect, and there are many problems to solve, but the BioBricks Foundation embodies the ideas that the open development and free sharing of improved tools will result in widespread innovations both underling and defining the future of biological technologies.
Drew Endy is a biological engineer at Stanford University. Mark Fischer, an intellectual property attorney in Boston, and David Grewal, a member of the Harvard Society of Fellows, both co-authored this essay.
Originally published March 3, 2011