Next Steps to Grow the Bioeconomy

Policy and Regulatory Gaps

Advancing capability in synthetic biology results in new and expanded product categories. As a recent example, the US Food and Drug Administration has approved ³ the use of synthetic RNA as a positive control for severe acute respiratory syndrome coronavirus 2 testing in place of live virus-derived RNA for Emergency Use Authorization applications. This positive momentum carries forward many benefits for the bioeconomy, but the rapid pace means existing regulatory oversight methods may lose utility and impact. We find the 2017 National Academies of Science, Engineering, and Medicine study Preparing for Future Products of Biotechnology ⁴ is a strong resource in calling out the likelihood of overwhelming the current staffing and capabilities of US regulators as the bioeconomy expands. We share these concerns and experiences, and ask the White House Office of Science and Technology Policy to keep these issues front of mind as it plays a critical role in driving solutions and investment in workforce development. In particular, we ask them to pay attention to the 2017 study's cautionary words:

The profusion of biotechnology products over the next 5–10 years has the potential to overwhelm the U.S. regulatory system, which may be exacerbated by a disconnect between research in regulatory science and expected uses of future biotechnology products. The number and complexity of products, new pathways to risk-assessment endpoints, large range of types of products (for example, those for open release in the environment or marketed as direct-to-consumer), new actors (including DIY bioengineers, small- and medium-sized enterprises, and crowd funders), and complex alignment of potential future products with agency authorities are likely to change rapidly as biotechnology advances. A disconnect between research in regulatory science and its use in biotechnology research and product development creates a situation in which new products may be conceived and designed without sufficient consideration of regulatory requirements, which can lead to surprises and delays late in the development cycle. ⁴

The United States must invest in key regulatory agencies to develop timely, data-driven regulations that keep pace with evolving products. This will allow newer regulatory approaches to be both rooted in science as well as resource efficient. We recommend investments in regulatory science at the US Food and Drug Administration, the Environmental Protection Agency, the National Institute of Standards and Technology (NIST), the Department of Defense, and the US Department of Agriculture. Specifically, we encourage these agencies to develop clear frameworks for the regulation of novel products that cross traditional agency boundaries, such as the use of environmentally deployed microbial platforms that sense and respond to pathogens with agricultural significance to monitor risks to livestock. We further encourage these agencies to engage with undergraduate programs, law schools, public policy programs, and master's programs to educate students about a career path in regulatory science, to strengthen that workforce over time. Investments could be made financially through direct funding to academia and further investment in entities such as the Reagan Udall Foundation and public-private partnerships.

Additionally, we see an opportunity for the US government to intensify leadership of the coordination and dissemination of clear and regularly updated guidance to biotechnology companies on best practices for the management of American intellectual property assets. This is especially important for American companies operating in countries with limited adherence to the WIPO Convention. These efforts should parallel the approach taken by the Department of Homeland Security in their Critical Infrastructure Security program. Under this program, public-private partnerships promote the sharing of noncompetitive data on risks to cyber and physical infrastructure, along with best practices for the defense of these assets. A similar public-private partnership should be built around helping American companies to protect their intellectual property. Small, creative startup companies may not be aware of best practices and the importance of continual, active intellectual property protection. Support from the US government could include training material, documents, and coordinated networking with similarly situated companies to disseminate emerging threat information and intellectual property protection best practices.

The US government also has an opportunity to incentivize and require the use of products manufactured by companies headquartered in the United States. For example, research grants funded by the National Science Foundation (NSF) or National Institutes of Health (NIH) could require awardees to purchase DNA synthesis products from US companies that actively screen synthesis orders for biosecurity-related concerns—in accordance with 2010 guidance from the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response ⁵ —rather than from international vendors who do not screen. Adherence to this 2010 guidance should be a minimum requirement by NIH and other federal funding agencies. Not only would this promote the bioeconomy within the United States, but it would also foster adherence to global biosecurity norms. This approach has been successful in other areas of federal policy, including restrictions on Medicare payments to only US providers, and we suggest parity with this policy for the bioeconomy to strengthen the American marketplace.

Additionally, we encourage the US Department of Commerce to avoid overclassification of bioeconomy-related technologies as “emerging” or “foundational,” potentially triggering new export controls that reduce American competitiveness in global markets. Whenever possible, if the US government feels a new trade control is necessary, those controls should be implemented via multilateral arrangements—eg, via the Australia Group, ⁶ an informal group of 43 nations working to harmonize export controls for dual-use chemical and biological materials—to ensure a level playing field for American companies exporting to markets abroad. We further recommend the US Department of Commerce rely on and expand its existing technical advisory committees to assist in identifying specific candidate biological technologies or materials for new trade controls.

Lastly, the US Department of Commerce and the Census Bureau should extend the North American Industry Classification System (NAICS) to include more detailed codes to capture the growing diversity of materials manufactured using biological systems. A search of current NAICS codes ⁷ for “chemical” returns 82 distinct NAICS codes, while “biological” returns just 7, all of which are medical in nature. No NAICS code appears to properly capture the biology-based manufacture of traditionally chemically derived materials. This lack of appropriate codes limits the degree to which the Census Bureau can track and observe the growth of the bioeconomy.

Evolving Scientific Funding and Translational Research

The Research Roadmap for the Next Generation Bioeconomy, produced by the Engineering Biology Research Consortium (EBRC), ⁸ represents US industry and academic consensus on prioritization of research funding. We encourage the use of this document within the US government to guide, execute, and implement strategies to support advancement of American engineering biology capabilities and expand the bioeconomy.

We also recognize a critical need to harmonize global research funding roadmaps with US basic science funding priorities. Complementary funding strategies across nations for basic, precompetitive science can drive synergies internationally. If this spending remains uncoordinated, resources will be spent across nations on the same goals, duplicating effort and slowing overall global basic scientific progress. The EBRC has made efforts in this direction with its recent Global Forum on Engineering Biology, in which representatives from 13 countries met to share spending levels and technical area prioritization within their nations. We support their findings and approach on next steps and encourage the US government to take a leadership role in implementing this policy.

We also believe NSF should revisit the sizing requirements for its Industry-University Collaborative Research Center (IUCRC) program ⁹ and allow new IUCRCs with fewer, smaller industry partners. While the IUCRC approach is powerful, the current requirements for establishing a new IUCRC require more companies of larger size than the current bioeconomy can easily muster. Lowering this threshold would allow smaller coalitions to form IUCRCs and still reap the benefits of synergistic research.

Many bioeconomy companies are smaller than traditional defense or other government contractors and do not always have the necessary financial controls and other contract management staff required by more traditional government contracting vehicles and reporting requirements. Other Transaction Authority agreements offer a more achievable entry point for smaller companies but use of these agreements by agencies is limited. ¹⁰ We suggest a renewed emphasis by agencies on use of Other Transaction Authority-type agreements to provide more lightweight funding vehicles to a wider array of bioeconomy companies.

We encourage the US government to expand its commitment to the existing Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. ¹¹ These programs direct US federal agencies to focus a fixed percentage (currently 3.2%) of their funding on investing in small business technology innovation. An expanded commitment to these programs could increase this percentage (eg, from 3.2% to 3.5% or even 4%) of agency budgets directed to SBIR/STTR funding or increase the per-grant maximums for biotechnology-related companies, recognizing that engineering biology research and development can often be more capital-intensive than in other high-tech industries like software. Temporarily (eg, for a period of 5 to 10 years) earmarking the entirety of this increase in allocation of agency budgets specifically to grants with impact on the bioeconomy would be a powerful step to directly increase US competitiveness and expand technology transition to the private sector.

Advancing Workforce Development

A growing bioeconomy needs a growing workforce, we support a continued focus and dramatically increased funding for the National Science Foundation, National Institutes of Health, and Department of Defense research programs to fund universities and institutions to conduct engineering biology research and development. This funding would expand support for existing laboratories and allow creation of new laboratories with more postdoctoral, graduate, and undergraduate students. This expansion is critical as the United States works to maintain our leadership in this industry worldwide. We strongly encourage the US government to prioritize funding academic partners with geographic, ethnic, and gender diversity. The industry remains less than optimally diverse, which will severely limit the potential expansion of the bioeconomy over time as diversity encourages innovation and invention. Federal investment can play a powerful equalizing role in supporting the development of new bioeconomy hubs across the country, ensuring the benefits of a booming bioeconomy are shared broadly across the US workforce.

We also recognize the pressing need for new training approaches to expand the skilled labor force, such as production laboratory operators and fermentation technicians, available to work in the larger and more numerous biomanufacturing facilities driving the bioeconomy. We suggest the US government support and drive funding for programs that expand both vocational opportunities at technical schools as well as certificate programs within existing 2- or 4-year degree programs to ensure we have a skilled labor workforce to support the rate of growth in the bioeconomy.

Augmented course offerings for a professional laboratory career should be based on training in traditional molecular biology processes and techniques such as polymerase chain reaction testing, DNA quantification, and DNA or protein purification as well as microbiology techniques including media preparation, plating, and fermenter operation. Government funding should include a focus on community colleges and vocational schools to purchase equipment used in commercial settings to provide training. This government funding would bring the technology companies are currently using into the classroom, helping provide students and trainees with skills that have immediate application to job opportunities. This direct link, supported by government, could serve as a model for other industries. Specifically, we recommend funding access to advanced liquid handling and laboratory automation tools. Because workforce development and training will continue to evolve rapidly, we suggest convening a stakeholder group twice annually to focus on recruitment, training, and real-time solutions to driving the bioeconomy.

Recruiting foreign talent via H-1B and other visa options drives US companies' success and provides a barrier to foreign competitors. Given the choice, the majority of top-tier researchers would choose the United States over competing foreign countries. We should leverage this desire to benefit the US ecosystem and establish a broader policy allocating visas to researchers and their families to ensure the United States continues to be researchers' first choice.

We support the Bio-Belt concept ² from SynBioBeta and suggest that Congress formalize this program, provide a framework for investment, define metrics for success, and allocate sufficient resources to build capabilities. Large agricultural centers in the Midwest and around the United States would be prime sites for biomanufacturing facilities, when paired with investment to educate a new generation of workers in engineering biology, fermentation-based manufacturing, and other relevant trades. The retooling of declining industries—including mining and textiles—would offer upside for localities and companies alike. Vocational schools and community colleges could step in to equalize opportunity and bolster these efforts. We believe this would allow rapid scale up to expand the skilled labor candidate pool and build toward a widely distributed workforce.

Supporting a Next-Generation Biological Computing Environment

Most of the original US government investment in information infrastructure in biotechnology focused on the National Center for Biotechnology Information (NCBI). NCBI has long served as a resource and repository of vast biological databases and tooling. As capability in engineering biology has advanced, the US government investment in infrastructure has, instead, been more widely distributed, leading to many different data sets and tools spread across diverse agencies (eg, the Joint BioEnergy Institute) and academic centers (eg, Boston University's CIDAR). This makes it difficult, if not impossible, for more junior researchers and small companies to discover free and open tools and data that may help them in their research goals. In the extreme case, this leads to researchers reinventing the wheel—using federal research dollars to build tools that already exist. We recommend the US government improve on this and charge (and fund) NCBI with coordinating a national information infrastructure for engineering biology. This may take the form of a federated discovery of resources across many national public and private providers or the collection of these tools and information resources into NCBI's compute infrastructure directly.

The United States currently makes all this infrastructure available globally at no cost, advancing synthetic biology worldwide. While this remains appropriate for basic science, we submit that data collection and nonpublic use for applied science should balance the advancement of synthetic biology globally with US domestic economic and security interests. For example, The Cancer Genome Atlas (TCGA) ¹² provides sequenced human genome data only to researchers who comply with the privacy and ethical regulations required by the NIH and complete a data use certification agreement. This agreement ensures that researchers who require controlled access to the data will comply with TCGA policies, such as maintaining participants' privacy, accessing the data securely, and following TCGA publication guidelines. However, TCGA does not make the data from these genomes globally available for anyone to download. This balance between scientific utility, economic value, and data privacy should be explored in many more engineering biology-related contexts.

We further recommend that NCBI invest in large-scale improvements to its user interface and site navigation, ideally working with 18F (an office within the General Services Administration that focuses on delivery of government services through technology) or the US Digital Service (a component of the Office of Management and Budget that helps agencies build digital tools) to modernize its user interfaces and API tools. Because it manages so many important resources, its current web interface can be complex to navigate, resulting in resources that go unused and driving inefficiency. An improved interface could allow a larger community of users to leverage the incredibly valuable tools and databases that NCBI has created and curates, promoting both efficient use of publicly funded resources and more rapid scientific advancement.

Standards and Secure Information Exchange

We strongly support the bioeconomy and believe it requires the capability to engage in trusted information sharing. The United States needs a mechanism to store data encrypted at rest and freely share information between government, academic institutions, and companies securely without public release. This approach to information handling has usually only been applied to settings where personally identifiable information is present; but many other data types produced by and related to the bioeconomy should also be governed by this approach to data security. These data can be economically valuable; therefore, maintaining the integrity and security of these data in transit and during use is an issue of global economic competitiveness. We need a trusted information platform for US entities and suggest Congress secure funding and direct agencies to create a working group to drive execution within a 2-year timeframe. This is critical to maintaining the US advantage in our industry in the global landscape.

We further believe NIST should have the resources needed to work quickly to standardize measurement and data transfer for all data types important in engineering biology research and commercialization. This includes participation in International Organization for Standardization activities so that the United States ensures these international standards optimize for competitiveness and an even playing field. Without this investment and prioritization, the United States may be forced to engage at a disadvantage or to accept and use standards designed by competitor nations. NIST has a long history of strongly and positively impacting US industrial growth ¹³ by establishing trusted standards, and the bioeconomy should be no different in this respect.

Trusted information storage and access will become even more important as the industry grows. The current practice of releasing high-value data sets for free actually poses risk by potentially empowering competitor nations. We encourage striking a balance between being a good global scientific citizen, where basic research is concerned, and giving away data on applied scientific applications paid for by federal investment. We also encourage a thoughtful approach to evaluating the inherent tradeoffs and to including economic and scientific competitiveness among the priorities addressed by a given data strategy rather than just protection of personally identifiable information.

Ethical Research and Biosecurity

We suggest that graduate and undergraduate academic curricula include a robust discussion of methodologies for evaluating the security implications of student work and determine when and whether such work constitutes dual use research of concern. Graduate programs in biotechnology already incorporate a class teaching ethics and biosafety to students under the NSF Responsible Conduct of Research program. ¹⁴ Extension of this approach to incorporate evaluation of potential security implications of graduate and postdoctoral research projects will be an important next step in ensuring the bioeconomy grows and prospers without creating additional risk. We recommend the US government continue to support and make use of the outcome of the Department of Homeland Security-funded EBRC program for Improving Security Considerations in Engineering Biology Research. ¹⁵