Launch Grand Research Challenges to Unlock Leap-Ahead Capabilities

Congress must establish Centers for Biotechnology within the existing National Laboratory network to support grand research challenges.

The United States needs specialized and coordinated federal research infrastructure for biotechnology. Innovation in this sector requires interdisciplinary connections and access to key equipment.

The federal government has cutting-edge R&D facilities, including four Bioenergy Research Centers, two of which are led by DOE National Laboratories (i.e., Lawrence Berkeley National Laboratory and Oak Ridge National Laboratory). But these research centers tend to focus narrowly on early-stage R&D related to a specific mission and place less emphasis on translating research into products.²⁴⁹ Moreover, the United States lacks some R&D infrastructure that is critical for emerging biotechnologies, including:

• risk-assessment testbeds;
• data collection and computing power for biotechnology;
• advanced measurement development and instrumentation;
• chemical and material production using biology; and
• biotechnology scale-up innovation and infrastructure that span basic and applied research.

To achieve breakthroughs in biotechnology discovery akin to what Lawrence Livermore National Laboratory has done with fusion research or what Los Alamos National Laboratory has done with nuclear research, Congress must establish six Centers of Biotechnology within the 17 existing National Laboratories, each center with its own area of focus.²⁵⁰

The main purposes of these biotechnology centers would be to:

• provide facilities for interdisciplinary biotechnology research, discovery, and development;
• encourage large-scale research projects that have some risk of failure but could lead to huge leaps in the study, development, or adoption of biotechnology; and
• provide biotechnology practitioners access to expensive resources and instrumentation, such as supercomputers and advanced measurement capabilities.

These new Centers for Biotechnology would complement existing research efforts and enable biotechnology progress across the National Laboratory system, in collaboration with partners from academia and industry. They would also provide an opportunity for researchers across government, academia, and industry to access state-of-the-art equipment and instrumentation, similar to what the five Nanoscale Science Research Centers at the DOE have accomplished.²⁵¹ By providing instrumentation and interdisciplinary collaboration, these hubs would also enable progress on the grand research challenges proposed in this section.

The appropriate DOE office should manage each center. The DOE’s Office of Critical and Emerging Technologies (OCET) should facilitate the coordination of biotechnology efforts across the DOE, including the activities of all six biotechnology centers and other biotechnology capabilities at the National Laboratories. The OCET should help to lead a biotechnology group within the DOE that would develop a strategic plan for establishing and selecting the Centers for Biotechnology. The centers would be selected through a competitive process among the existing 17 National Labs.

Congress should initiate a grand research challenge focused on making biotechnology predictably engineerable.

While the United States has led the world in biotechnology innovation for many decades, that lead is at risk. This is largely owed to a lack of federal funding and prioritization for biotechnology research to unlock “leap-ahead capabilities,” or disruptive technologies that offer unprecedented new functionalities, in the United States. The U.S. research enterprise is either stagnant or falling behind in some key areas.

Funding for biotechnology research typically goes to ideas that represent incremental progress, and it is difficult to find funding for risky and innovative ideas. Some funding mechanisms, such as those at the Defense Advanced Research Project Agency (DARPA) or at Advanced Research Project Agencies (ARPA) within other departments, have long funded high-risk research, but they represent only a small portion of all government research funding.²⁵² New programs such as the National Science Foundation’s (NSF) Catalyzing Across Sectors to Advance the Bioeconomy (CASA-Bio) use interagency goals and interdisciplinary teams to seek common priority areas in biotechnology.²⁵³ But while CASA-Bio is a helpful mechanism through which an interagency group coalesced around important biotechnology goals, it is not a funding program.

To build on these programs, the United States needs to act boldly, inspiring its innovation base and encouraging a range of projects, small and large, across the country by initiating grand research challenges.

One of biotechnology’s most important quests is to make biology predictably engineerable. While the biotechnology community has worked toward this goal for decades, it has yet to reach the maturity of many engineering fields, including electrical engineering, computer engineering, and mechanical engineering, which have all reached a point where building end products is routine. Biotechnology is still in an earlier stage. Challenging the sector to harness nature in transformative ways that could benefit all would bring biological engineering to a similar maturity. Breakthroughs related to this goal could be applied to all different types of living organisms, including animals, plants, microbes, and fungi, and would subsequently enable advances in biotechnology and biomanufacturing.

Currently, however, broader funding by the federal government related to such a goal is sparse and diffuse, preventing breakthroughs.

To inspire more biotechnology breakthroughs, Congress should initiate and fund a grand research challenge to make biology predictably engineerable. That grand challenge should be:

• an inspiring goal that captures the public imagination; 
• a mission the private sector is unlikely to pursue on its own; 
• a challenge requiring an interdisciplinary approach; 
• a project that fosters innovation and progress beyond the primary goal of the grand challenge; and 
• a goal that is broad and ambitious enough to be pursued across the research community and advanced by both incremental discoveries and major breakthroughs.

The U.S. government should appropriate a minimum of $5 billion over five years to achieve this goal. Any lesser investment would risk being too small to enable future biotechnology invention and product development in the United States.²⁵⁴

A portion of this new funding should be designed to reward success in solving hard, ambitious scientific challenges that unlock important leap-ahead capabilities. Structuring the funding in such a way would imbue grand research challenges with a spirit of constructive competition, while only deploying taxpayer dollars when ambitious goals are met. (For more detail on this grand challenge, including a potential funding structure, see Appendix D.)

This grand challenge would require bolstering the engineering paradigm of “make, model, and measure” for biological systems. Therefore, government funders should develop component challenges that break down predictable engineering into individual tasks. Some other key steps to implement this grand research challenge include:

• creating an interagency program and establishing a lead agency that would work with other departments and agencies toward this goal;
• consulting with the Director of the NBCO (see recommendation 1.1a) at the White House; and
• working with philanthropic funders to get buy-in on research areas and to increase the pool of money for funding research projects.

Congress should initiate a grand research challenge focused on making biomanufacturing scale-up predictable, rapid, and cost-competitive.

Biotechnology processes and production must also scale predictably—another challenge involving interdisciplinary science, technology, and engineering.

After decades of outsourcing the manufacturing of both legacy and next-generation biotechnology products, the United States has woefully deprioritized research that would reduce the complexity and costs of scaling biological processes.

Even with the U.S. biotechnology sectors’ tools and expertise, transitioning from small-scale research to large-scale production is inefficient, slow, and expensive.²⁵⁵ Expanding the United States’ number of physical facilities, while critical, is not sufficient on its own. Innovations in the science of biomanufacturing scale-up, in tandem with increased physical capacity, lie at the crux of ensuring that American biotechnology products make it to market. Advances in U.S. biomanufacturing spurred by solving scale-up questions in early-stage research—as well as equipment and technologies that span the bioprocessing chain—promise to unlock new ways of creating biomanufactured products.²⁵⁶ Prioritizing the science of scale-up would help create distributed, diversified, and flexible biomanufacturing across the United States.

To accomplish this, Congress should fund a grand research challenge to develop novel biomanufacturing technologies that make scale-up predictable, rapid, and cost-competitive. This grand challenge should prioritize interdisciplinary research focusing across four key research areas:

• chassis;
• feedstocks;
• process technology and equipment; and
• critical inputs.

Advancements in the first three research areas (chassis, feedstocks, and process technology and equipment) would expand the number of bioproducts that could be created with biomanufacturing, ensure that biomanufacturing is location-agnostic, and draw on plentiful raw material inputs such as location-specific agricultural biomass. Moreover, uniting and simplifying scale-up processes would decrease the money and expertise needed to transition bioproducts to the market.

Advancements in the fourth area (critical inputs) would diversify and secure the supply chain of low-margin chemicals and biological materials such as amino acids that are necessary to sustain scaled biomanufacturing. Demand for these materials is expected to greatly increase as the United States expands its biomanufacturing sector, but for the most part, these inputs are sourced abroad and often have market prices that are so low that they disincentivize innovations to cost-effectively produce them domestically.²⁵⁷

Other key implementation details for this grand research challenge include:

• congressional designation of a federal agency to lead efforts for each research area, based on considerations such as current or past agency efforts and mission spaces;
• collaboration among lead agencies and across the interagency to ensure that this multidisciplinary grand challenge draws on all relevant expertise within the federal government;
• coordination through the Director of the NBCO (see recommendation 1.1a) at the White House, to ensure collaboration, prevent duplicative research, and have a technical advisor to assess progress; and
• milestone-based funding, contingent on annual progress reports submitted by lead agencies to Congress. Congress could authorize incrementally larger funding amounts each additional year to ensure that funding is given in proportion to demonstrated progress. (Further further guiding detail on this scale-up grand research challenge, including suggested funding amounts and examples of lead agencies, see Appendix D.)

The four identified areas of scale-up research—chassis, feedstocks, process technology and equipment, and critical inputs—have implications for a wide range of biomanufacturing areas and can be applied broadly to biomanufacturing for chemicals, medicines, fuels, materials, and other biotechnology products. These areas also touch on biopharmaceuticals, especially when it comes to rapid vaccine production and new vaccine types.