Mapping the Synthetic Biology Industry: Implications for Biosecurity

Mapping the Landscape of Industrial Tools and Capabilities

A map of the landscape of tools and capabilities, the drivers of emerging biotechnology, is instructive to an understanding of how the industry is evolving and its potential for misuse. Our study found that the synthetic biology industry is characterized by significant growth and investment in horizontally applicable tools that support and feed into more traditional vertical industrial sectors. Basic tools such as DNA synthesis and genome editing tools form a foundation for more tailored capabilities, such as organism engineering, design software, and automated laboratory robotics. The companies that provide these tools and services are interconnected and interdependent as they compete to find their niche in a complex and international industry ecosystem. Figure 1 depicts how these tools and capabilities (horizontal bars) contribute to economic sectors (vertical bars) from pharmaceuticals and agriculture to materials and energy.

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Figure 1.

Horizontal and vertical landscape of the synthetic biology industry

Many companies that make up the synthetic biology industry are working within these horizontal bars to develop new capabilities and integrate them into existing product categories. At the same time, many large, established companies in these economic sectors are working to bolster their synthetic biology capabilities, either by partnering with companies that have these tools and services or by developing them internally. The framework in Figure 1 simplifies the complex set of tools and applications that make up the synthetic biology industry. It enables productive multi-stakeholder conversation, as synthetic biology practitioners and industry representatives can find themselves on this map, and biosecurity and policy experts can be specific about their concerns.

This framework enables a starting point for greater insight into the potential biosecurity impacts of such tools and capabilities. For example, much has been written about the democratization of synthetic biology as tools and capabilities for engineering DNA constructs, proteins, and organisms become more widely available. Perspectives range from excitement about the possibilities for citizen science ⁴ to concern that expanding access to these technologies will lead to catastrophe. ⁵ As synthetic biology tools advance and become more powerful, biosecurity concerns have continued to grow.

However, our in-depth examination of user access to different types of synthetic biology capabilities shows that significant barriers remain for individuals, do-it-yourself biology community members, and even most researchers in traditional labs. Subject matter experts in our study agreed that the most powerful tools and services require a high level of collaborative technical development and are very valuable from an investment perspective. They are closely held by the companies that develop them, and venture capital firms and other funders expect strong intellectual property protections. Customers for these advanced products tend to be large pharmaceutical, agricultural, or chemical companies that can best afford the costs, while the tools and capabilities that are available more broadly are less powerful and not as well supported.

As an example, laboratory robotics are quickly becoming a defining component of the canonical design-build-test-learn cycle for synthetic biology. Robotics that are widely available include products such as the Opentrons OT-2 pipetting machines (currently listed for $4,000), along with access to “cloud-based” labs such as Transcriptic, which will perform a limited set of specific protocols with samples provided by the customer. Although helpful, these products and services do not significantly change the underlying capabilities of their users.

In contrast, large synthetic biology companies such as Ginkgo Bioworks and Zymergen have been able to improve operations by orders of magnitude based on extensive laboratory automation that is fully integrated into the design-build-test-learn cycle—aided by sensors and machine learning algorithms that can test and optimize an ever-increasing number of genetic constructs and organisms. Companies such as Synthace and LabGenius work with customers (primarily other businesses) collaboratively to integrate this type of “smart” laboratory automation into their workflows.

Policy Implications

A leading concern about the misuse of synthetic biology is the potential to synthesize DNA sequences or whole genomes of pathogens or toxins that are otherwise unavailable or difficult to obtain. ⁶ In the United States, the Department of Health and Human Services (HHS) Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA ⁷ was issued in 2010 to address this concern, and this guidance has been reasonably well adopted by leading DNA synthesis companies (though some challenges remain).^8,9 When this guidance was developed, the primary customers for synthetic DNA were researchers, who used the DNA primarily for studies in research and academic institutions. Today, however, our interviews and discussions indicated that the customer base for synthetic DNA is dominated by companies; in addition to large companies pursuing specific types of applications that rely on synthetic DNA (eg, pharmaceuticals or chemicals), there are now a wide range of synthetic biology companies that purchase synthetic DNA to develop and provide value-added products (such as optimized DNA constructs, custom vectors, and engineered organisms) to end users.

A key tenet of the HHS guidance is customer screening to ensure that synthetic DNA is provided only to legitimate users. Again, our understanding of the synthetic biology industry ecosystem provides much needed context to the question of customer screening. In the case where a DNA provider sells DNA to other synthetic biology companies, it is difficult for that provider to determine if the end user is legitimate. DNA providers have made contractual agreements and other arrangements to address this issue, but these synthetic biology “middlemen” were not considered in the HHS guidance, and it is not clear that this is the best solution. Furthermore, it is likely that many more synthetic biology companies will be established, increasing the potential that the end user will be even further removed from the production of synthetic DNA. There is also the possibility of misuse of synthetic biology products or organisms downstream of initial DNA synthesis, and of other widely available tools, such as genome editing constructs and vectors, that do not rely on gene-length synthetic DNA at all. All of these factors suggest that customer screening may be a useful best practice to a much wider range of synthetic biology companies (not just DNA providers). Customer screening is widely used successfully in other industries and can be an added layer of assurance against misuse or other liabilities. Indeed, our interviews and discussions revealed that many, if not most, synthetic biology companies that have more than a few customers already conduct some type of customer screening.

In determining if a customer is a legitimate user of synthetic DNA, DNA providers currently check that the institution (eg, academic, nonprofit, community lab, company) is legitimate. However, with the changing landscape of the synthetic biology industry, there are a greater number of small companies for which it is difficult to determine legitimacy. The international nature of synthetic biology compounds this problem. More guidance on how to determine the legitimacy of synthetic biology companies would be helpful. Also, given that these current best practices depend on the legitimacy of the institution or company, those institutions should be made aware that they are responsible for their members or employees in this context. In addition to a shared responsibility for customer screening, synthetic biology companies of all types should have access to broad biosecurity training that includes the possibility of insider threats.

Another implication of the increasing diversity of synthetic biology companies is that the type and scale of DNA that is ordered is different from what it was 10 years ago. The synthetic biology industry now supports a wide range of economic sectors. Although biotechnology products have traditionally been more restricted to pharmaceuticals and agriculture, synthetic biology capabilities are being applied more broadly (see Figure 1). Also, as mentioned above, the amount of DNA that is ordered by some of these companies continues to grow exponentially. Nonprofit “biofoundries,” which aim to facilitate organism engineering, have also been established as major consumers of synthetic DNA. ¹⁰

All of these industry players intend to produce organisms that are more likely to meet regulatory requirements (such as “generally recognized as safe” for FDA or has a “history of safe use” for EPA) than to cause harm. The use of synthetic DNA as data storage also has the potential to become a significant driver of future DNA synthesis technology and business development,^11,12 though it is possible that this application will develop in a way that is largely orthogonal to uses in the life sciences. Under these circumstances, academic and nonprofit labs, and especially those that use pathogen or toxin DNA, are increasingly a niche market for synthetic DNA. As the industry grows and diversifies, it will be interesting to see if this niche develops its own specialized array of DNA providers and other services that may warrant more targeted biosecurity precautions.

Conclusions and Next Steps

Our project highlights the need for an ongoing venue for discussion between synthetic biology industry representatives and US government policymakers to better understand biosecurity risks and to identify paths forward. We found that the landscape of the synthetic biology industry features an emerging and diverse set of horizontal tools being applied across many vertical sectors in a complex and interconnected ecosystem of companies. The availability of these tools and how the industry will develop into the future has significant implications for policymakers and others concerned about the potential for misuse and the vulnerabilities of these capabilities. Biosecurity discussions should consider that the most powerful synthetic biology capabilities are primarily used by larger companies in collaboration with technology developers and are not available to a wide range of users. This more complex ecosystem of companies and customers also suggests that customer screening should not fall to synthetic DNA providers alone but should be shared much more broadly across the industry.

In addition to insights about the industry, our project also identified areas where the US government could work with synthetic biology companies to help identify and disseminate industry best practices. These included developing practices for customer screening, identifying potential risks that may arise from misuse of technologies or capabilities, and protecting company data and intellectual property in an international context. Each of these areas was cited as important by industry representatives within their own companies and by US government experts considering risks and vulnerabilities across the industry. Ongoing engagement between the US government and the synthetic biology industry should be a priority as the industry, its capabilities, and its practices continue to evolve.