Bold Goals for U.S. Biotechnology and Biomanufacturing

B OLD G OALS FOR U.S. B IOTECHNOLOGY

AND

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BOLD GOALS FOR

U.S.

BIOTECHNOLOGY

AND BIOMANUFACTURING

HARNESSING RESEARCH AND DEVELOPMENT

TO FURTHER SOCIETAL GOALS

MARCH 2023

B OLD G OALS FOR U.S. B IOTECHNOLOGY

AND

B IOMANUFACTURING

Bold Goals for U.S. Biotechnology

and Biomanufacturing

Harnessing Research and Development to Further Societal Goals

er Executive Order 14081

Compiled by

The White House Office of Science and Technology Policy

Including sections by

U.S. Department of Energy

U.S. Department of Agriculture

U.S. Department of Commerce

U.S. Department of Health and Human Services

U.S. National Science Foundation

arch 2023

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Table of Contents

Introduction ................................................................................................................................................. 1

Biotechnology and Biomanufacturing R&D to Further Climate Change Solutions ............................ 3

Executive Summary ................................................................................................................................... 4

Bold Goals for Harnessing Biotechnology and Biomanufacturing ........................................................... 5

Bold Goals Explored ................................................................................................................................. 6

Enhancing Biosafety and Biosecurity ...................................................................................................... 11

Opportunities for Public-Private Collaboration ....................................................................................... 12

Biotechnology and Biomanufacturing R&D to Further Food and Agriculture Innovation .............. 15

Executive Summary ................................................................................................................................. 16

Bold Goals for Harnessing Biotechnology and Biomanufacturing ......................................................... 17

Bold Goals Explored ............................................................................................................................... 18

Enhancing Biosafety and Biosecurity ...................................................................................................... 24

Opportunities for Public-Private Collaboration ....................................................................................... 24

Biotechnology and Biomanufacturing R&D to Further Supply Chain Resilience ............................. 26

Executive Summary ................................................................................................................................. 27

Bold Goals for Harnessing Biotechnology and Biomanufacturing ......................................................... 28

Bold Goals Explored ............................................................................................................................... 29

Enhancing Biosafety and Biosecurity ...................................................................................................... 34

Opportunities for Public-Private Collaboration ....................................................................................... 34

Biotechnology and Biomanufacturing R&D to Further Human Health ............................................. 37

Executive Summary ................................................................................................................................. 38

Bold Goals for Harnessing Biotechnology and Biomanufacturing ......................................................... 39

Bold Goals Explored ............................................................................................................................... 40

Enhancing Biosafety and Biosecurity ...................................................................................................... 46

Opportunities for Public-Private Collaboration ....................................................................................... 47

Biotechnology and Biomanufacturing R&D to Further Cross-Cutting Advances ............................. 49

Executive Summary ................................................................................................................................. 50

Bold Goals for Harnessing Biotechnology and Biomanufacturing ......................................................... 51

Bold Goals Explored ............................................................................................................................... 52

Enhancing Biosafety and Biosecurity ...................................................................................................... 58

Opportunities for Public-Private Collaboration ....................................................................................... 59

ppendix A. Agency Research and Development Efforts ..................................................................... 61

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Introduction

The world is on the cusp of an industrial revolution fueled by biotechnology and biomanufacturing.

Emerging biological technologies are and will continue to transform the foundation of our physical

world – everything from clothing, to plastics, to fuels, to concrete. Through biomanufacturing, sustainable

biomass across the United States can be converted into new products and provide an alternative to

petroleum-based production for chemicals, medicines, fuels, materials, and more. While the most

prominent applications today are related to human health, biotechnology and biomanufacturing are

expanding to build products that will be everywhere in our lives and support climate and energy goals,

improve food security, and grow the economy across all of America. Our Nation’s bioeconomy –

economic activity derived from biotechnology and biomanufacturing – is strong. However, maintaining

our global leadership in research and development (R&D) and reaping the full benefits of the bioeconomy

requires more action from across the public and private sectors.

On September 12, 2022, President Biden signed an Executive Order (E.O.) on “Advancing Biotechnology

and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy.” In the

E.O., the President laid out his vision for a whole-of-government approach to advance biotechnology and

biomanufacturing by creating a research agenda that outlines the foundational and use-inspired R&D

needs that will lead to innovative solutions in health, climate change, energy, food security, agriculture,

supply chain resilience, and national and economic security. The E.O. also launched a National

Biotechnology and Biomanufacturing Initiative to ensure that, beyond R&D, we have the domestic

capacity to make in the United States all the bio-based products that we invent here. This will create new

jobs, build stronger supply chains, and contribute to our climate goals.

The President’s E.O. calls on Federal departments and agencies to harness biotechnology and

biomanufacturing innovation to further societal goals and transform industries related to: (1) climate

change solutions, (2) food and agriculture innovation, (3) supply chain resilience, (4) human health, and

(5) cross-cutting advances. This document includes five sections responsive to the E.O., individually

authored by the Department of Energy (DOE), Department of Agriculture (USDA), Department of

Commerce (DOC), Department of Health and Human Services (HHS), and National Science Foundation

(NSF), respectively, with input from other Federal departments and agencies.

Bold Goals for U.S. Biotechnology and Biomanufacturing R&D

Each of the five sections presents bold goals that highlight what could be possible with the power of

biology. These goals are intended to provide a broad vision for the U.S. bioeconomy and what can be

achieved with concerted action from industry, academia, nonprofits, the Federal Government, and other

organizations. The bold goals set ambitious national targets for the next two decades to help establish

R&D priorities that will be critical to advance the bioeconomy. They are not meant to represent

commitments by an agency or department to undertake specific activities. Each section also outlines the

essential R&D needed to achieve these bold goals for the U.S. bioeconomy, opportunities for public-

private collaboration, and recommendations for enhancing biosafety and biosecurity. Underpinning all

this work is the Administration’s commitment to growing the U.S. bioeconomy safely, ethically, and

equitably.

Achieving these goals will require significant prioritization of R&D investments and other efforts across

the U.S. government, as well as actions from the private sector; state, local, and tribal governments; and

international partners. Although a single agency or department is the lead author of each section,

advancing the bold goals in each sector will require efforts from multiple agencies and departments, as

shown in Appendix A. In the upcoming months, the White House Office of Science and Technology

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Policy will lead the development of a strategy and implementation plan to execute on R&D priorities and

other actions identified in this report.

Bold goals for the U.S. bioeconomy include, for example:

• Climate: In 20 years, demonstrate and deploy cost-effective and sustainable routes to convert

bio-based feedstocks into recyclable-by-design polymers that can displace more than 90% of

today’s plastics and other commercial polymers at scale.

• Food and Agriculture: By 2030, reduce methane emissions from agriculture, includi

ng by

inc

reasing biogas capture and utilization from manure management systems, reducing methane

from ruminant livestock, and reducing methane emissions from food waste in landfills, to support

the U.S. goal of reducing greenhouse gas emissions by 50% and the global goal of reduci

ethane emissions by 30%.

• Supply Chain: In 20 years, produce at least 30% of the U.S. chemical demand via sustainable

d cost-effective biomanufacturing pathways.

• Health: In 20 years, increase the manufacturing scale of cell-based therapies to expand access,

decrease health inequities, and decrease the manufacturing cost of cell-based therapies 10-fold

• Cross-Cutting Advances: In 5 years, sequence the genomes of one million microbial species and

understand the function of at least 80% of the newly discovered genes.

Reaching these bold goals will require progress in other areas beyond R&D to ensure that innovation can

lead to safe, effective, and equitable products in our daily lives which grow the bioeconomy across all of

America and with our partners globally. In forthcoming reports and plans, departments and agencies will

outline recommendations and steps that are underway to advance the following:

• Data for the bioeconomy – establishing a Data Initiative to ensure that high-quality, wide-

ranging, easily accessible, and secure biological data sets can drive breakthroughs for the U.S

oeconomy.

• Domestic biomanufacturing infrastructure – expanding domestic capacity to manufacture all the

biotechnology products we invent in the United States and support a resilient supply chain.

• Workforce development – growing training and education opportunities for the biotechnolo

nd biomanufacturing workforce of the future.

• Regulatory clarity and efficiency – improving the clarity and efficiency of the regulatory process

for biotechnology products to help ensure products come to market safely and efficiently.

• Biosafety and biosecurity – creating a Biosafety and Biosecurity Innovation Initiative to reduce

risks associated with advances in biotechnology and biomanufacturing.

• International engagement R&D – pursuing cooperation through joint research projects and data

sharing, while mitigating risks and reaffirming democratic values.

These “Bold Goals for U.S. Biotechnology and Biomanufacturing” align with other recent Administration

actions, such as the National Biodefense Strategy, the Executive Order on America’s Supply Chains and

resultant 100-Day Review, the Net-Zero Game Changers Initiative, the American Pandemic Preparedness

Plan, the National Strategy on Hunger, Nutrition, and Health, and the Cancer Moonshot, among others.

Furthermore, the recent CHIPS and Science Act unlocks new R&D opportunities, spurs regional

innovation, and advances workforce development in biotechnology and biomanufacturing. All these

actions support the growth of the American bioeconomy and bolster the R&D needed to fully harness

biotechnology and biomanufacturing to build on our Nation’s unique strengths of innovation, agricultural

and biomass production, and entrepreneurship.

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Biotechnology and Biomanufacturing R&D to

Further Climate Change Solutions

In collaboration with other U.S. Federal Government departments and agencies,

this report was authored by the U.S. Department of Energy

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Executive Summary

Transforming the U.S. economy to achieve net-zero greenhouse gas (GHG) emissions by 2050 will

necessitate major advances across many economic sectors. To meet this transformational goal, action is

needed now to spur focused research and development (R&D) that translates innovations in bioscience

and biotechnology to broad scale implementation to mitigate the effects of climate change.

This report on climate change solutions provides an overview of ten bold goals and associated R&D

needs to safely harness rapid developments in biotechnology and biomanufacturing to dramatically

decrease GHG emissions, increase carbon sequestration, and develop innovative products. Achieving

these goals in partnership with the private sector will help mitigate the effects of climate change and

contribute to a strong and resilient bioeconomy with multiple benefits across broad geographic regions

and socio-economic strata within the United States.

These bold goals for climate solutions are cross-cutting and will require efforts across the U.S.

government and the private sector. The ten bold goals are grouped into four themes where biotechnology

can play a critical role in reducing GHG emissions and removing carbon from the atmosphere.

Theme 1 addresses the need to develop more carbon-neutral transportation and stationary fuels by

expanding renewable feedstock availability and producing more sustainable aviation and other strategic

fuels. New ways to produce such fuels are needed to shift the United States from fossil-based fuels toward

renewable liquid fuels, which will likely still be required by a subset of transportation and other

applications currently difficult to electrify.

Theme 2 seeks alternative processes to produce chemicals and materials from renewable biomass and

intermediate feedstocks by developing low-carbon-intensity product pathways and promoting a circular

economy for materials. Achieving these goals will position the United States at the forefront of a vibrant

global bioeconomy while producing net-zero or net-negative emissions, reducing use of and reliance on

fossil fuels, and increasing use of recyclable-by-design chemicals and materials like bio-based products.

Theme 3 seeks to develop climate-focused agricultural systems and plants and includes bold goals to

develop restorative and resilient feedstock production systems, engineer better plants tailored as

bioeconomy feedstocks, improve usage of current feedstocks, and engineer more efficient protein

production systems. These efforts will generate a variety of biomass feedstocks with increased resilience,

yield, and nutrient use efficiency, laying the foundation for the expanding U.S. bioeconomy.

Theme 4 addresses carbon dioxide (CO

) removal. The goals within this theme expand landscape-scale

biotechnology solutions to store carbon within soils and enable biomass to remove and store carbon.

Implementation of these solutions will dramatically increase CO

removal from the atmosphere across

whole ecosystems through landscape-scale carbon sequestration and management techniques.

The U.S. National Blueprint for Transportation Decarbonization | U.S. Departments of Energy, Housing and Urban

Development, and Transportation, and U.S. Environmental Protection Agency

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Bold Goals for Harnessing Biotechnology and Biomanufacturing

The following goals for climate change solutions provide a broad vision for the U.S. bioeconomy but are

not commitments by the U.S. Department of Energy (DOE) to undertake specific activities. Achieving

these goals will require significant prioritization of R&D investments and efforts across the U.S.

government, as well as actions from the private sector and state, local, and tribal governments.

Theme 1: Transportation and Stationary Fuels

Goal 1.1: Expand Feedstock Availability – In 20 years, collect and process 1.2 billion metric tons of

conversion-ready, purpose-grown plants and waste-derived feedstocks and utilize >60 million metric tons

of exhaust gas CO

suitable for conversion to fuels and products, while minimizing emissions, water use,

habitat conversion, and other sustainability challenges.

Goal 1.2: Produce Sustainable Aviation Fuel (SAF) – In 7 years, produce 3 billion gallons of SAF

with at least 50% (stretch 70%) reduction in GHG lifecycle emissions relative to conventional aviation

fuels, with production rising to 35 billion gallons in 2050.

Goal 1.3: Develop Other Strategic Fuels – In 20 years, develop technologies to replace 50% (>15

billion gallons) of maritime fuel, off-road vehicle fuel, and rail fuel with low net GHG emission fuels.

Theme 2: Chemicals and Materials

Goal 2.1: Develop Low-Carbon-Intensity Chemicals and Materials – In 5 years, produce >20

commercially viable bioproducts with >70% reduced lifecycle GHG emissions over current production

practices.

Goal 2.2: Spur a Circular Economy for Materials – In 20 years, demonstrate and deploy cost-effective

and sustainable routes to convert bio-based feedstocks into recyclable-by-design polymers that can displace

>90% of today’s plastics and other commercial polymers at scale

Theme 3: Climate-Focused Agricultural Systems and Plants

Goal 3.1: Develop Measurement Tools for Robust Feedstock Production Systems – In 5 years,

develop new tools for measurement of carbon and nutrient fluxes in agricultural and bioeconomy feedstock

systems that contribute to a national framework.

Goal 3.2: Engineer Better Feedstock Plants – In 5 years, engineer plants and manipulate plant

microbiomes to produce drought tolerant feedstocks capable of growing on underutilized land with >20%

improvement in nitrogen and phosphorus use efficiency.

Goal 3.3: Engineer Circular Food Protein Production Systems – In 5 years, demonstrate viable

pathways to produce protein for food consumption including from biomass, waste, and CO

that achieve

>50% lifecycle GHG emissions reduction and cost parity relative to current production methods.

Theme 4: Carbon Dioxide Removal

Goal 4.1: Develop Landscape-Scale Biotechnology Solutions – In 10 years, develop technologies to

expand implementation of landscape-scale soil carbon sequestration and management techniques on tens of

millions of acres, increasing soil health and drought resilience and supporting U.S. climate targets.

Goal 4.2: Enable Biomass with Carbon Removal and Storage (BiCRS) – In 9 years, demonstrate

durable, scalable biomass CO

removal for <$100/net metric ton, on a path to enabling gigaton-scale

removal.

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Bold Goals Explored

Climate change is expected to produce radical changes to the environment, including extreme weather

events, changing weather patterns, drifting ecological zones, and other rapid environmental changes that

may outpace Nature’s ability to adapt. Action is urgently needed to develop and implement less carbon-

intensive processes for producing the fuels, chemicals, and materials that support society, and to

implement practices that remove CO

from the atmosphere to ameliorate the long-term effects of climate

change. In addition, these approaches for reducing GHG emissions and CO

removal should also

minimize other harmful emissions, water use, habitat conversion, and other sustainability challenges.

These efforts will require a comprehensive approach effectively integrating discovery research, use-

inspired basic research, and applied research, development, demonstration, and deployment.

Given the cross-cutting nature of these all-of-government efforts, relevant goals for supporting climate

change solutions are also described in the other sections of this report led by the U.S. Department of

Agriculture (USDA), the Department of Commerce, and the National Science Foundation (NSF).

Theme 1: Transportation and Stationary Fuels

Context for the Bold Goals

Achieving overall net-zero GHG emissions in the United States requires major changes to shift the

economy from fossil-based fuels to sustainable sources for the liquid fuels needed to power economic

sectors that are traditionally difficult to power with sustainable approaches. The transportation sector

currently represents 29% of gross U.S. emissions,

with the difficult-to-abate sectors of aviation,

maritime, rail, and off-road transport contributing 26% of that total. As outlined in the multi-agency

Transportation Decarbonization Blueprint,

as battery electric vehicles and clean hydrogen begin to

reduce emissions from light-, medium-, and heavy-duty on-road vehicles, the share of emissions

associated with these difficult-to-abate sectors is expected to rise. Solutions will likely still require

sustainable liquid fuel production, with much of that relying on biomass and waste as feedstocks. In

particular, recognition of the importance of biomass in decarbonizing aviation led to the Sustainable

Aviation Grand Challenge which calls for producing more than 3 billion gallons of sustainable aviation

fuels (SAF) by 2030, rising to 35 billion gallons in 2050.

Advances in harnessing biotechnology and

biomanufacturing to produce transportation and stationary fuels will require ongoing and expanded R&D

investments in three areas: expanding feedstock availability, producing SAF, and developing other

strategic fuels.

Goal 1.1: Expand Feedstock Availability. There is great potential for expanding the use of renewable

feedstocks in the United States due to a unique national strength in agriculture. The United States has an

unparalleled ability to grow, harvest, store, and transport agricultural products on a massive scale. While

this productivity is most evident for grain and oilseed crops, the potential exists to expand agricultural

production of purpose-grown crops for bioenergy and bioproducts. Currently, roughly 368 million metric

tons per year of biomass and biogenic wastes are available as feedstocks for conversion to a range of

products, and estimates indicate this could be expanded to more than 1 billion tons.

There are, however,

significant challenges to reliable and efficient biomass conversion to fuels and products stemming from

the compositional variability of sources such as agricultural and forest residues, organic municipal waste

streams, and dedicated herbaceous and woody crops. There are also opportunities to view CO

as a

feedstock in combination with renewable energy and clean hydrogen. These feedstocks will be critical for

Inventory of U.S. Greenhouse Gas Emissions and Sinks: 1990-2021 | U.S. Environmental Protection Agency

The U.S. National Blueprint for Transportation Decarbonization

Sustainable Aviation Fuel Grand Challenge Roadmap | U.S. Departments of Energy, Transportation, and Agriculture with the

U.S. Environmental Protection Agency

2016 Billion-Ton Report | U.S. Department of Energy

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achieving transportation and fuels goals as well as providing sustainable feedstock for decarbonization

efforts for chemicals and materials in Theme 2.

Goal 1.2: Produce SAF. Enhancements to increase sustainable feedstock production bring opportunities

to pursue priority market needs like renewable replacements for aviation fuels. U.S. commercial aviation

currently consumes approximately 10% of U.S. transportation energy and is projected to grow as a share

of fuel demand. Air travel, which represents most emissions from aviation, will be difficult to electrify

because batteries are not soon projected to achieve sufficient energy density to meet power and weight

requirements for long-haul air travel. Conversion of plant biomass and waste feedstocks, including

lignocellulosic biomass, municipal solid waste, and CO

, to sustainable aviation fuel in combination with

clean energy and hydrogen offers near-term potential to reduce aviation GHG emissions with minimal

changes to current airport infrastructure due to the potential “drop-in” nature of the fuel. Biotechnology

and complementary chemical catalysis approaches must be developed and deployed to maximize GHG

emissions reduction for new SAF mixtures beyond the 50% reduction qualifying floor to be eligible for

the tax credit established in the Inflation Reduction Act

and other policy frameworks. This includes the

stretch goal of achieving at least 70% GHG reduction on more than half of the potential biomass and

waste feedstocks outlined in Goal 1.1.

Goal 1.3: Develop Other Strategic Fuels. As light- and medium-duty vehicle liquid fuel use declines

with adoption of battery-powered electric vehicles, biofuels should be integrated into new markets with

limited medium- to long-term electrification potential. In addition to foreign demands, these markets

include maritime, off-road, and rail transport and will likely continue requiring energy-dense liquid

transportation fuels.

Stationary application fuels, like renewable natural gas, woody biomass, and low

carbon-intensity fuels for process heat, will also play important roles in economy-wide decarbonization.

R&D Needs

• Conduct research, development, and demonstration projects to reduce the carbon footprint of

feedstock production, collection, transportation, and preprocessing. (Goal 1.1)

• D

evelop technologies capable of cost-effectively and sustainably pretreating heterogeneous wast

treams and separating contaminants to increase the quantity and quality of available wast

eedstocks. (Goal 1.1)

• C

ontinue to address R&D barriers to SAF production as outlined in the roadmap develope

jointly by DOE, USDA, and the Department of Transportation

by (1) conducting comparative,

sel

f-consistent analyses to understand how various technologies under development can wor

ogether to displace petroleum-derived jet fuel and (2) enabling the rapid progression from

research and innovation to scale-up and commercial deployment. (Goal 1.2)

• Explore new routes to known intermediates in SAF production and produce new bio-base

ompounds that can be used for SAF with increased GHG emissions reductions. (Goal 1.2)

• Optimize bioconversion and processing of cellulosic feedstocks by developing producti

pathways capable of using a wide variety of feedstocks while establishing fuel quality standards

nd test methods. Such systems should consider local sourcing of feedstocks and smaller-scal

ocessing options to enable distributed production systems closer to the point of use. (Goal 1.3)

Inflation Reduction Act of 2022 | U.S. Congress

The U.S. National Blueprint for Transportation Decarbonization

Industrial Heat Shot | U.S. Department of Energy

Sustainable Aviation Fuel Grand Challenge Roadmap

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Theme 2: Chemicals and Materials

Context for the Bold Goals

To achieve a net-zero emissions economy, significant changes are needed to the ways that chemicals,

materials, and products are produced in the United States. Currently, thousands of everyday products

ranging from plastics to lipstick and deodorant are manufactured from petroleum and natural gas.

Current production methods are also GHG emissions intensive, with the industrial sector accounting for

30% of gross U.S. GHG emissions.

The chemicals sector is the largest industrial GHG emitter with over

20% of industrial emissions, a significant portion of which may be eliminated using biomanufacturing

and sustainable biomass resources. Chemicals, materials, and products can be derived from more

sustainable, bio-based resources and produced in less carbon-intensive ways that promote broader reuse in

a circular bioeconomy. To reduce GHG emissions in chemicals and materials production, ongoing and

expanded R&D investments in harnessing biotechnology and biomanufacturing are needed in two areas:

developing low-carbon-intensity chemicals and materials and spurring a circular economy for materials.

Goal 2.1: Develop Low-Carbon-Intensity Chemicals and Materials. Approximately 20% of every

barrel of crude oil, and a significant fraction of natural gas, are used to make non-fuel products ranging

from plastics to paints, solvents, and asphalt. Transitioning away from fossil resources requires renewable

alternatives for all these products. Bio-based feedstocks and bioprocessing routes can reduce net GHG

emissions, stabilize commodity chemical prices, and avoid supply chain disruptions. DOE has begun to

address this need with the Industrial Heat Shot

which includes development of biomanufacturing

processes that often operate near room temperature, requiring less process heat than incumbent

petroleum-based processes.

Goal 2.2: Spur a Circular Economy for Materials. Currently, commodity polymer manufacturing

(including plastics) is responsible for GHG emissions equivalent to the global aviation sector, and

manufacturing these products is projected to represent >20% of annual global fossil fuels consumption by

2050.

Additionally, waste plastics accumulating in landfills and the broader environment is well

recognized as a planetary-scale pollution crisis. Opportunities exist to produce biobased plastics to offset

petroleum-derived plastic products, but use of biobased products must be expanded. Accordingly, an

urgent global need exists to rapidly enable a more circular economy for today’s fossil carbon-based

polymers production and to source chemical building blocks for tomorrow’s recyclable-by-design plastics

from bio-based and waste sources. DOE is addressing this transition with its Strategy for Plastics

Innovation,

a DOE-wide approach focused on GHG emissions reduction, new recycling technologies,

sustainable manufacturing, and polymers redesign for improved end-of-life properties.

R&D Needs

• Use biotechnology to identify biological pathways and biochemical processes involved in the

production of key molecules and increase the yield and process efficiency for chemicals produced

from a range of carbon sources. (Goal 2.1)

• Develop innovations at the interface of biology and chemistry to produce platform chemicals and

final products with greatest potential to reduce GHG emissions. (Goal 2.1)

• Conduct research to support regulatory efforts and safe commercialization of new products.

(Goal 2.1)

Everyday Products and Uses Fact Sheet | Colorado Oil and Gas Association

Industrial Decarbonization Roadmap | U.S. Department of Energy

Industrial Heat Shot

The New Plastics Economy: Rethinking the Future of Plastics | Ellen MacArthur Foundation

Strategy for Plastics Innovation | U.S. Department of Energy

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• Expand R&D for process development and scale-up to recycle and/or upcycle waste resources

such as plastic waste, including through selective chemical and biological methods, with an

emphasis on mixed and multi-component waste that is not recycled today. (Goal 2.2)

• Expand efforts to design or redesign materials such as plastics to improve end-of-life properties

including increased recyclability and/or compostability where appropriate. (Goal 2.2)

• Establish pilot scale-up facilities to test new technologies from synthesis, manufacturing, and

polymer processing to in-line application testing for materials and chemical synthesis and

recycling. (Goal 2.2)

Theme 3: Climate-Focused Agricultural Systems and Plants

Context for the Bold Goals

Foundational to a net-zero GHG economy, changes to agriculture and production methods for plant-based

resources will be needed to decrease the overall carbon intensity of feedstock production, a major source

of CO

emissions. Emissions from the agricultural sector comprise 9% of the U.S. total, the majority of

which are non-CO

emissions like nitrous oxide from soil and methane from enteric fermentation and

manure management.

Developing practices that retain carbon in the soil or direct it toward plant growth

are critical to transforming agriculture from a net GHG source to a net sink. These climate-focused goals

are related to ongoing efforts and goals at USDA and DOE and will require R&D investments across

government in three areas: developing measurement tools for robust feedstock production systems,

engineering better feedstock plants, and engineering circular food protein production systems.

Goal 3.1: Develop Measurement Tools for Robust Feedstock Production Systems. Agricultural soil

management practices contribute around 5% of total U.S. GHG source emissions and are a significant

source of the world’s total annual GHG production. In addition, nitrous oxide emissions from soil

management practices accounted for approximately 74% of U.S. nitrous oxide emissions in 2021.

Furthermore, emissions from ammonia production account for around 1.8% of global CO

emissions, of

which over 80% is used as fertilizer.

A focus on accurate quantification of these effects is needed to

achieve the most efficient GHG reductions in the agricultural sector. In this area, USDA leads

development of tools and data systems to measure, monitor, report, and verify carbon and nutrient fluxes

for agricultural systems. These tools are important for developing climate-focused agricultural systems

that reduce the carbon intensity of feedstock production and significantly add to the overall climate

impact by shifting to a more sustainable bioeconomy.

Goal 3.2: Engineer Better Feedstock Plants. Advanced biotechnology is providing new ways to

increase plant feedstock production and gain a much better understanding of processes that control carbon

and nutrient flux in soils among microbes and plants. Continued R&D in these areas reflects the need to

achieve parallel goals of increasing feedstock yield and resilience while lowering the overall carbon

intensity of feedstock production and improving soil health and sustainability. Scientific understanding of

plant biology is accelerating rapidly, especially as it relates to plant composition (e.g., plant cell wall),

plant regulation (e.g., carbon partition and allocation), and improved sustainability in environmental, soil

microbiome, and land-management contexts. Minimally domesticated bioenergy crops, like switchgrass,

poplar, pine, and camelina, possess great potential for improvement due to broad natural variation.

Existing crops like maize and sorghum have less variation due to decades of breeding but they have never

been bred for both current usage yield (i.e., food) and for residue yield and composition.

Goal 3.3: Engineer Circular Food Protein Production Systems. This goal is focused on protein

production-related research for climate solutions and complements a broader food production goal

Inventory of U.S. Greenhouse Gas Emissions and Sinks | U.S. Environmental Protection Agency

Ammonia: Zero-Carbon Fertiliser, Fuel, and Energy Store Policy Briefing | The Royal Society

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described in the Food and Agriculture Societal Goal Report. Greater than 25% of global anthropogenic

GHG emissions come from the global food system.

Currently, most non-aquatic food protein, whether

from plants or animals, is produced through energy-intensive land use practices. In addition, protein

production will need to be doubled by 2050 to feed the growing global population. To that end, new

biotechnologies enabling food protein production from waste substrates through microbial bioprocesses

could potentially increase production while reducing global agricultural land use. In turn, this would

improve nutrient utilization efficiency, release agricultural land for carbon sequestration, and begin to

restore global biodiversity. Microbially-produced protein is a decades-old concept with precedent in some

marketplace niches. However, there is a shortage of work ongoing in the publicly funded research and

development community related to microbial protein production from waste feedstocks. Advances in

biotechnology and precision fermentation are setting the stage for revitalization of this sector.

R&D Needs

• Improve modeling and methods for estimating, measuring, and monitoring GHG sources and

sinks and carbon cycling and sequestration in biomass and soils. (Goal 3.1)

• Develop a nationally applicable framework and associated tools for measuring and verifying

carbon and nutrient flux in agricultural systems producing bioeconomy feedstocks. (Goal 3.1)

• Conduct R&D on plants (including algae) and soil microbial communities to generate knowledge

for producing new dedicated feedstocks using less carbon-intensive practices. (Goal 3.2)

• Develop approaches to measure overall improvements in engineered plants against established

baselines based on current production crops and varieties. (Goal 3.2)

• Develop bioprocessing approaches that enable scale-up of biotechnology-based protein

production while maintaining or improving quality, and thoughtfully matching large-scale waste

feedstocks to efforts in synthetic biology and bioprocess engineering. (Goal 3.3)

• Develop rigorous and transparent process analyses relative to existing food protein production

pathways to inform development of sustainable bioprocesses. (Goal 3.3)

• Conduct research to inform regulatory efforts and safe commercialization of new products.

(Goals 3.2 and 3.3)

Theme 4: Carbon Dioxide Removal

Context for the Bold Goals

Reducing GHG emissions alone is not enough for the U.S. to reach net zero emissions by 2050 and keep a

1.5°C limit on global temperature rise within reach.

Effective approaches for CO

removal from the

atmosphere and durable sequestration are also needed to achieve net negative emissions on a massive

scale. The Intergovernmental Panel on Climate Change (IPCC) estimates that >10 gigatons of CO

per

year net negative global emissions will be required by 2100.

Biotechnology can play a large role in CO

removal through a variety of potential pathways. These advances in harnessing biotechnology and

biomanufacturing for CO

removal will require ongoing and expanded R&D investments in two areas:

developing landscape-scale biotechnology solutions and enabling biomass with carbon removal and

storage.

Goal 4.1: Develop Landscape-Scale Biotechnology Solutions. Most bio-based carbon in terrestrial

systems is stored underground in the soil system. It has been demonstrated that crops, such as perennials,

and landscape management practices, such as no-till agriculture, can steadily increase soil health and soil

Food Systems Are Responsible for a Third of Global Anthropogenic GHG Emissions | Crippa, M., et al. 2021. Nature Food

Negative Emissions Technologies and Reliable Sequestration | National Academies of Sciences, Engineering, and Medicine

Climate Change 2014: Mitigation of Climate Change. Contribution of Working Group III to the Fifth Assessment Report of the

Intergovernmental Panel on Climate Change | IPCC

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organic carbon (SOC) from year to year.

Biotechnology can further enhance these approaches through

improved plant feedstock and root microbiome design (see Goal 3.2). Additional benefits to improved

SOC, such as increased water retention and plant yields, suggest that these techniques can improve

overall agricultural system effectiveness while dramatically enhancing the system’s ability to sequester

carbon. These changes to improve SOC, along with better land management and deploying more plants in

areas not already slated for biomass feedstock or crop growth, provide landscape-scale solutions that can

be coupled with long-term, durable preservation approaches.

Goal 4.2: Enable Biomass with Carbon Removal and Storage (BiCRS). In addition to sequestering

carbon in soils (Goal 4.1), a variety of BiCRS approaches are needed to effect long-term, durable CO

removal. These approaches can utilize biomass from a variety of purpose-grown crops or wastes and

durably store biomass carbon in long-lived solid carbon materials or in appropriate geological formations.

Enabling CO

capture from the atmosphere and storage at gigaton scales for <$100 per net metric ton is a

core goal of DOE’s Carbon Negative Shot.

R&D Needs

• Develop genetic engineering and technology tools for high yield crops and forest trees with

deeper and more recalcitrant root systems to increase SOC. (Goal 4.1)

• Address knowledge gaps related to plant-soil interactions that promote SOC accumulation

without reducing nutrient mineralization and develop a predictive ecological landscape

conceptual framework for understanding soil organic matter dynamics. (Goal 4.1)

• Determine the most cost-effective BiCRS pathways and how it can complement other biomass

uses as part of a complete carbon management strategy. (Goal 4.2)

• Determine the best long-lived solid carbon materials produced through biological systems and

explore increasing capture of atmospheric CO

into materials using biomimetic or cell-free

systems, bioelectric approaches, and bioinorganic materials. (Goal 4.2)

Stakeholder Consultation

The bold goals and associated R&D needs summarized in this report build upon recent reports and

assessments related to climate change and energy solutions developed over the last several years through

workshops and with input from stakeholders across government and the private sector, as well as input

from subject matter experts at DOE national laboratories. Additionally, an industry listening session on

climate change solutions was hosted by the White House in November 2022, and public input was

collected through an Office of Science and Technology Policy-led Request for Information posted in

December 2022.

Input from this outreach informed the bold goals, R&D needs, and other sections of

this report. Additional stakeholder input included white papers, briefings, reports, and publications.

Enhancing Biosafety and Biosecurity

Effective biosafety and biosecurity throughout biotechnology development and the biomanufacturing

lifecycle are critical for maintaining a strong and resilient bioeconomy. In the area of climate change and

energy solutions, biosafety and biosecurity may be viewed through the lens of three categories for the

purposes of pinpointing vulnerabilities: (1) process input or feedstock production, (2) manufacturing and

supply, and (3) end-use and final product fate. Biosafety practices and controls reduce the risk of

unintentional exposure or release of pathogens, toxins, and harmful biological materials. Biosecurity

measures mitigate the risk of loss, theft, misuse, diversion, or intentional release of pathogens, toxins, and

Novel Technologies for Emission Reduction Complement Conservation Agriculture to Achieve Negative Emissions from Row-

Crop Production | Northrup, D. L., et al. 2021. PNAS

Carbon Negative Shot | U.S. Department of Energy

Request for Information; National Biotechnology and Biomanufacturing Initiative | Office of Science and Technology Policy

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biological materials or research-related information and technology, as well as the introduction of harmful

materials into the biotechnology and biomanufacturing ecosystem.

Existing Biosafety and Biosecurity Measures

There are ongoing and planned activities to enhance biosafety and biosecurity for biotechnology and

biomanufacturing in several critical areas, including research, workforce development, and culture

change, as will be addressed in the Biotechnology and Biomanufacturing Innovation Initiative (BBII) in

Section 9 of Executive Order 14081. Many of these activities apply across societal goals. There are also

ongoing and planned research efforts specifically relevant to biosafety and biosecurity innovation for

climate and energy solutions. For example, DOE’s Secure Biosystems Design program focuses on

building upon advances in genome science and synthetic biology to design and engineer DOE-relevant

biological systems with built-in biocontainment measures. The Biosecurity for Bioenergy Crops pilot

study under DOE’s Biopreparedness Research Virtual Environment (BRaVE) effort is developing

understanding of threats to bioenergy crops as part of a larger agnostic approach to addressing potential

biothreats, along with related mitigation strategies. In addition, ongoing research efforts not focused

solely on biosafety and biosecurity include integrated tasks and activities related to biosafety and

biosecurity innovation for a range of applications (e.g., Advanced Biofuels and Bioproducts Process

Development Unit, ecosystem testbed platforms, and algae test bed facilities at DOE national

laboratories). The National Nuclear Security Administration at DOE is also initiating a Bioassurance

program to advance U.S. capabilities to anticipate, assess, detect, and mitigate biotechnology and

biomanufacturing risks and integrate biosecurity into biotechnology development.

Recommended New Biosafety and Biosecurity Measures

Moving forward, it is critical to continue efforts and bolster recommended activities covered in BBII,

ranging from training to research to public-private partnerships. Specifically in R&D related to biosafety

and biosecurity innovation during the development of climate change solutions, it is important to consider

the molecular processes, system components, and integrated system (i.e., spanning process input or

feedstocks, manufacturing, supplies, products, and product fate) along with the pace of innovation in

biotechnology and biomanufacturing that includes technology integration.

Opportunities for Public-Private Collaboration

Existing Public-Private Partnerships

Existing public-private partnerships related to the bold goals primarily fall into the categories of

databases, user facilities, and joint funding opportunity projects. DOE encourages funded collaborations

between national laboratories and private companies to enable industry to benefit from public sector

expertise and vice versa. Open access, online basic science analysis platforms such as the DOE Systems

Biology Knowledgebase and the National Microbiome Data Collaborative and user facilities such as the

DOE Joint Genome Institute and Environmental Molecular Science Laboratory, which collect DNA

sequence and omics information, enable efficient use of new microorganisms and plants for a variety of

purposes, including production of fuels and products. Databases with information about land use,

feedstocks, and climate enable appropriate location siting and supply chain planning. Other user facilities

such as the Advanced Biofuels and Bioproducts Process Development Unit (ABPDU) and the Biomass

Feedstock National User Facility (BFNUF) enable companies to de-risk conversion technologies,

feedstock supply, and preprocessing technologies. BFNUF has worked with over 40 industry customers

across the bioenergy supply chain to address feedstock-related challenges in preprocessing and scale-up

of the bioeconomy. ABPDU, housed at Lawrence Berkeley National Laboratory since 2009, is a scale-up

facility with cutting-edge equipment and a dedicated team of experts. ABPDU has helped over 75

companies develop prototypes and scale technologies. Companies that prototyped at ABPDU have raised

over $2 billion in private funding and transitioned 17 products to market.

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Opportunities for U.S. Government Incentivization of Private Sector

Compelling opportunities exist for the U.S. government to build additional databases, develop standards,

increase R&D funding opportunities, and expand user facilities for scale-up. Investments in workforce

development and direct incentives, as well as private industry participation and feedback, are critical to

the success of the goals outlined in this report.

Collecting information and making it available in databases should be prioritized to support the private

sector, underpinned by the Data Initiative described in Section 4(a) of Executive Order 14081. All

varieties of omics data, in addition to phenotype and imaging data, should be made publicly accessible in

a Findable, Accessible, Interoperable, and Reusable (FAIR) manner whenever possible, while providing

appropriate data security to protect personal identifiable and sensitive information. In addition, applied

R&D process data, such as life-cycle assessments, technoeconomic analyses, and standards, should be

made broadly available to help industry use best practices to understand, demonstrate, and improve their

sustainability impacts and attract investment.

The private sector can play a key role in populating these databases. For example, through public-private

partnerships, a labeling and quantification system could be developed for consumers to make informed

choices about the products they purchase. Quality standards for different feedstocks and bio-based

products should be developed to support robust supply chain development and market entry, and

standards for new industrial microbes and plants would also aid adoption. The private sector, along with

government agencies like National Institute of Standards and Technology, USDA, DOE, NSF, and others,

should play an integral role in developing these standards and validating the test methods.

New public-private partnerships and research consortia with shared precompetitive goals for commodity

fuel and chemical production that benefit climate outcomes can help address key industry challenges

preventing market entry and expansion. The DOE Agile Biofoundry and the Department of Defense

BioMADE are successful examples of this type of consortium. Expanding similar efforts would help

propel the bioeconomy. Ongoing private sector input on the most critical research challenges would help

direct these efforts and enable industry growth. Interdisciplinary and international collaborations should

be greatly expanded to leverage expertise across fields and spur innovation globally.

New and expanded user facilities and incentives for the private sector to develop scale-up capacity are

needed to de-risk new technologies. Field trials for new plant feedstocks and shared, common gardens for

experimentation, phenotyping, and validation should be established to enable new feedstocks and develop

feedstock standards. Expanded shared, fit-for-purpose fermentation and downstream processing scale-up

facilities with state-of-the-art process monitoring and control capabilities are needed to help companies

develop process understanding and control strategies for production scale. A network of these facilities is

also needed so companies can create batches large enough for product testing to confirm performance and

attract investors and customers. The current network of facilities in the United States does not meet

demand and lags overseas networks, driving some companies to conduct scale-up efforts abroad.

A trained workforce is critical to carry out the efforts described in this report. The U.S. government can

support this through expanded STEM workforce development programs and other activities that support

implementation of Section 7 of Executive Order 14081 on promoting bioeconomy workforce

development. In addition, while the incentives created by the Inflation Reduction Act provide a good

foundation, they may not be sufficient to overcome the capital risks faced by developers or to fully

incentivize farmers to produce sustainable biomass, absent further policy support. For example, incentives

for production of low-carbon-intensity feedstocks and products produced and manufactured in the United

States would help overcome the high capital risk of needed advancements, along with creating or

expanding incentives that encourage companies to use raw materials and products with lower carbon

intensity. Furthermore, incentives could support farmers to produce sustainable biomass; these could

include tax incentives and subsidies for inputs, equipment, and facilities that lead to lower carbon

intensity feedstock production.

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Opportunities for Public Participation

Public participation and input will be essential as R&D programs are developed and implemented to

harness biotechnology and biomanufacturing to achieve the climate solution goals outlined in this report.

For example, opportunities for public participation may include R&D funding opportunities related to the

specific goals in this report, as well as input at workshops, sessions at meetings, listening sessions, and

requests for information. Furthermore, public trust, public education, and public acceptance are critical

for widespread adoption of biotechnologies. Therefore, the public must be engaged at many points

throughout the technology development process. Full transparency and strong national regulatory

oversight, including technology-specific risk assessments, are critical to ensuring public trust,

understanding, and acceptance.

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Biotechnology and Biomanufacturing R&D to

Further Food and Agriculture Innovation

In collaboration with other U.S. Federal Government departments and agencies,

this report was authored by the U.S. Department of Agriculture

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Executive Summary

Biotechnology and biomanufacturing are providing transformative solutions to many of the greatest

challenges facing U.S. agriculture and food production, including climate change, food and nutrition

insecurity, and pests and diseases in agricultural plants and animals. Naturally occurring genetic variation

offers tremendous promise for improvements in agricultural plants, animals, and microorganisms,

particularly when paired with accelerated breeding strategies and biotechnology, including genome

editing. Biotechnology and biomanufacturing can provide needed value-added income streams to

America’s farmers, ranchers, producers, and forest landowners in the bioeconomy.

Applying biomanufacturing and biotechnology in food and agriculture requires strategic and sustained

investment in technology platforms. Such investment can shorten the time to commercialization and

reduce risk for new product development, so innovators can successfully manage the costs of innovation

prior to marketing and revenue generation. Investment and support are also needed to expand the

availability and deployment of currently available solutions. Additional needs include support to research

and build marketplace demand, expand the workforce, ensure abundant feedstock supplies, build or

repurpose physical infrastructure, and develop other partnerships and processes necessary to grow the

bioeconomy.

The U.S. Department of Agriculture (USDA) has a critical role in advancing the bioeconomy by

providing leadership and scientific research to enable American farmers and foresters to remain globally

competitive and to enable American businesses to produce innovative products. USDA has outlined an

ambitious vision for bioeconomy research and development (R&D) that fits into three themes: (1)

improving sustainability and resource conservation while increasing agricultural productivity; (2)

improving food nutrition, quality, and consumer choice; and (3) protecting plants and animals against

environmental stressors.

In Theme 1, we describe goals for increasing agricultural productivity, increasing climate-smart

feedstock production and biofuel usage, reducing nitrogen and methane emissions, and reducing food

waste. The future of U.S. agriculture depends on improvements in production capacity, efficiency, and

environmental stewardship. To spur economic growth and meet the demands of a growing global

population, agricultural lands need to be more productive and use both inputs and outputs efficiently.

In Theme 2, we describe goals for developing new food and feed sources, enhancing nutrient density in

foods, and reducing foodborne illness. Innovations in food and feed can boost both dairy and cultivated

protein companies, for example, sustainably expanding the range of available protein options. Improving

nutritional quality and reducing foodborne illness are essential for increasing food security.

In Theme 3, we describe goals for detecting and mitigating pests and pathogens as well as improving

resilience to biotic and abiotic stress. Climate change is contributing to increased incidences of pest and

disease outbreaks. Unprecedented droughts and floods, unseasonably warm winters, late frosts, and wet

springs are changing farmers’ needs and how they manage agricultural production.

Achieving these bold goals will require actions from the private sector, public-private partnerships, and

effective coordination with domestic and international partners. The United States has long been a global

leader in agricultural research and development to improve productivity and promote more efficient use

of natural resources in agriculture. By leveraging innovation in biotechnology and biomanufacturing, we

can expand the toolbox for farmers, ranchers, and other producers to meet the many challenges in food

and agriculture.

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Bold Goals for Harnessing Biotechnology and Biomanufacturing

The following goals are transformative solutions for food and agriculture intended to provide a broad

vision for the U.S. bioeconomy. These should not be read as commitments by USDA to undertake specific

activities. Achieving these bold goals will require significant prioritization of R&D investments and

efforts across the U.S. government, as well as actions from the private sector, and state, local, and tribal

governments.

Theme 1: Improving Sustainability and Resource Conservation While Increasing

Agricultural Productivity

Goal 1.1 Increase Agricultural Productivity – Over the next 10 years, increase agricultural total factor

productivity growth to meet global food and nutrition security needs while improving natural resource use

efficiency and conservation, toward the global goal of increasing agricultural productivity by 28% in the next

decade.

Goal 1.2: Increase Climate-Smart Feedstock Production and Biofuel Usage – By 2030, increase

climate-smart production of conventional and alternative agricultural and forestry feedstocks for

biomanufacturing, biobased products, and biofuels; reduce the lifecycle greenhouse gas intensity of biofuels

by 50%; and expand overall biofuel blend rates in U.S. liquid transportation fuels by 50%.

Goal 1.3: Reduce Nitrogen Emissions – Within the next 5 years, develop technologies to reduce nitrogen

emissions from agriculture, including by decreasing the need for applied nitrogen by increasing nitrogen use

efficiency in plants and improving fertilizer products and practices.

Goal 1.4: Reduce Methane Emissions – By 2030, reduce methane emissions from agriculture, including by

increasing biogas capture and utilization from manure management systems, reducing methane from ruminant

livestock, and reducing methane emissions from food waste in landfills, to support the U.S. goal of reducing

greenhouse gas emissions by 50%

and the global goal of reducing methane emissions by 30%

Goal 1.5: Reduce Food Loss and Waste – By 2030, reduce food loss and waste by 50%

, including by

developing and commercializing new technologies and encouraging adoption of new and existing technologies.

Theme 2: Improving Food Nutrition, Quality, and Consumer Choice

Goal 2.1: Develop New Food and Feed Sources – Develop new food and feed sources, including

production of novel or enhanced protein and fat sources at scale, to support the United Nations Sustainable

Development Goal to eliminate global hunger by 2030

Goal 2.2: Enhance Nutrient Density in Foods – Within the next 20 years, enhance nutrient density in

agricultural plants and animals, develop underutilized plants and animals that have enhanced nutrient density,

and build on traditional ecological knowledge to better utilize and conserve culturally important and

nutritionally relevant plants and animals.

Goal 2.3: Reduce Foodborne Illness – Reduce incidence of foodborne illness, including with new and

improved screening tools, toward meeting goals set in Healthy People 2030,

such as a 25% reduction in

Salmonella illnesses.

OECD-FAO Agricultural Outlook 2022-2031 | Organisation for Economic Co-operation and Development and the United

Nations Food and Agriculture Organization

Fact Sheet: President Biden Sets 2030 Greenhouse Gas Pollution Reduction Target | White House

U.S. Methane Emissions Reduction Action Plan | White House

Food Waste FAQs | U.S. Department of Agriculture

U.N. Sustainable Development Goals: Goal 2 – Zero Hunger | United Nations

Foodborne Illness | U.S. Department of Health and Human Services

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Theme 3: Protecting Plants and Animals Against Environmental Stressors

Goal 3.1: Increase Capacity to Detect and Mitigate Pests and Pathogens – Within the next 5 years,

improve capacity to detect and mitigate high-consequence existing and emerging animal and plant pathogens

and pests, especially disease-vectoring and damaging pests.

Goal 3.2: Improve Resilience to Biotic and Abiotic Stress – Within the next 20 years, increase resilience

of agriculture and forestry and develop tools that increase resilience to biotic stress (disease and pest threats)

and abiotic stresses (including extremes in drought, heat, cold, and precipitation).

Bold Goals Explored

Theme 1: Improving Sustainability and Resource Conservation While Increasing

Agricultural Productivity

Context for the Bold Goals

Innovations in agriculture—including plant and animal breeding, agricultural inputs, and equipment—

have enabled continuing growth in agricultural output. These innovations can help tackle multiple

challenges at once, allowing producers to conserve resources and improve environmental outcomes while

meeting the world’s food, fiber, and renewable needs. Biotechnology and biomanufacturing present major

opportunities to improve sustainability and resource conservation and to increase yields while decreasing

inputs and related costs. An estimated 30 to 40% of food is wasted in the United States; reducing food

loss and waste can improve food security, reduce agricultural inputs, and reduce greenhouse gas

emissions

. In addition, expanding markets for bioenergy and biobased products can help achieve

greenhouse gas mitigation goals. Supporting the bioeconomy and reducing costs and barriers to entry can

bring new economic growth opportunities across the United States, including rural areas where feedstocks

are grown and urban areas where tree maintenance provides residual biomass. Forest thinning in areas

between homes and forests can provide additional feedstocks while helping to reduce wildfire risk and

protect vulnerable habitats and communities.

R&D Needs

To support increases in agricultural productivity (Goal 1.1):

• Better understand genetic, physiological, environmental, and biochemical constraints on yield to

develop plants and livestock with higher production potential.

• Use accelerated breeding strategies and biotechnology to improve plants, animals, and

microorganisms to enhance productivity and reduce environmental impacts of agriculture.

• Bolster research in innovative approaches and technologies—including precision agriculture and

circular and nature-based solutions—that improve sustainability; reduce inputs; and rebuild soil

health, carbon, and organic matter.

To support climate-smart feedstock production and biofuel usage (Goal 1.2):

• Accelerate research into climate-smart feedstocks with reduced carbon intensity, learning from

relevant Partnerships for Climate-Smart Commodities projects, including emerging feedstocks

such as hemp and camelina, and feedstocks that are derived from agricultural waste, tree removal

and wildfire fuel reductions, and coproducts to support the circular economy.

Food Waste FAQs | U.S. Department of Agriculture

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• Develop tools that rapidly assess and track feedstock qualities to evolve markets that reward

producers for product quality in addition to yield

• Develop biochemical and biomanufacturing processes, including enzymatic and microbial

ocesses, for efficiently converting feedstocks into intermediates and products at scale.

• Develop technologies to economically move, store, and process biomass prior to its use as

feedstocks for biomanufacturing or conversion into biobased products

• E

xpand upon biorefinery technologies to efficiently break down biomass into its components

(e.g., lignin, hemicellulose, and cellulose); to convert lignin and hemicellulose into plastics

dhesives, and low-energy building materials; and to convert cellulose fiber into nanomaterials

and cellulose derivatives for fibers, coatings, renewable packaging, and other products.

To support reduction of nitrogen emissions (Goal 1.3):

• Continue research into efficient nutrient management practices, such as precision application,

more efficient delivery systems, and sustainable fertilizer formulations that enable more efficient

nutrient cycling with reduced environmental impact.

• Improve methods to reclaim nitrogen in wastewater by growing crops such as algae a

duc

kweed for fertilizer and feedstocks for the bioeconomy.

• Bolster research into biostimulants that increase nitrogen use efficiency and replenish nitrogen

stores in soil as part of an integrated approach to reducing fertilizer use, such as genome-edited

soil microorganisms to enhance biological nitrogen fixation.

• Use accelerated breeding strategies and biotechnology to develop plants with reduced reliance

nputs and that increase uptake, storage, and recycling of soil nitrogen and phosphorus.

• Characterize materials that improve soil nitrogen balance and soil health, particularly materials

that may be considered waste, such as biochar.

To support reduction of methane emissions (Goal 1.4):

• Develop new and improve existing tools and models to accurately assess methane fluxes from

agricultural systems.

• Develop affordable and efficient tools to capture biogas from manure management systems; us

ethane for power generation and other purposes.

• Bolster research into feed sources, new feed additives, and feed ingredients that reduce enteric

methane emissions from ruminants and from aquaculture.

• Develop new technologies and innovative production systems that do not require rice production

n paddies that generate methane-producing anaerobic bacteria.

To support reduction of food loss and waste (Goal 1.5):

• Use accelerated breeding strategies and biotechnology to develop plants with traits that exte

shelf life, such as reduced browning from bruising or resistance to mold growth.

• Improve or develop strategies to measure food waste, including both edible food and non-edible

waste such as banana peels, bones, and eggshells, anywhere along the food chain.

• Bolster research into methods, products, and tools that prevent or reduce food loss from spoilage,

pests, mold, and inadequate climate control, including sustainable, user-friendly, and

odegradable packaging and biobased coatings that extend product freshness and shelf life.

• Develop and expand strategies to increase food recovery or recycling programs at scale, includi

dvanced biochemical and microbial systems for efficient conversion of food waste into fee

ertilizers, materials, bioproducts, and fuels.

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Theme 2: Improving Food Nutrition, Quality, and Consumer Choice

Context for the Bold Goals

The United Nations Food and Agriculture Organization (FAO) estimates that by 2050 we will need to

produce 60% more food to feed a world population of 9.3 billion

. Food must be nutritious as well as

abundant. In the United States, poor nutrition is a leading cause of illness, associated with 600,000 deaths

per year and linked with increased risk of obesity, diabetes, and heart disease as well as broader impacts

including higher healthcare costs and decreased productivity

. Foodborne illness causes an estimated 48

million illnesses and 3,000 deaths each year in the United States

. In addition to increasing productivity,

biotechnology and biomanufacturing can spur development of novel food sources with improved

sustainability, including new crops and protein sources, which can augment our current food system and

help provide equitable access to nutritious foods. Such innovation can also equip farmers and food

manufacturers to reduce foodborne illness and meet changing consumer demand. Traditional ecological

knowledge is an essential and powerful resource for improving nutrition. Many native plants and animals

play vital roles in the cultures and economies of the people of the United States, particularly Indigenous

communities with long-standing connections to native forests and grasslands.

R&D Needs

To support development of new food and feed sources (Goal 2.1):

• Expand research into food components that make novel foods more palatable, affordable, easier

to prepare, and more easily incorporated into manufactured foods.

• Research the structural design and food architecture of alternative protein (e.g., plant-based,

fermentation-derived, and cell-cultured) products, including how plant and microbial materials

compare to animal-based products.

• Identify and conduct feasibility studies for high-volume, low-cost protein and fat sources that

could be used in food or feed, including products resulting from precision fermentation and co-

products or waste streams from other industries.

• Develop and validate science- and risk-based processes for crop segregation, grain management

and processing, and other controls to safely enable production of animal proteins in crops while

mitigating potential commingling and allergen cross-contact in food supply chains.

• Bolster research into animal diets with improved digestibility and enhanced amino acid profiles,

including integration of amino acids in animal diets, that improve conversion of feeds into food.

• Bolster research into alternative feed ingredients for livestock and aquaculture, including plants,

algae, or seaweeds, that can enhance or replace feed ingredients.

To support enhancement of nutrient density in foods (Goal 2.2):

• Use accelerated breeding strategies and biotechnology to develop plants and animals with

enhanced nutrient density, including enhanced levels of micronutrients and nutraceuticals.

• Expand the range of organisms that can be used for nutritional purposes and enhance the nutrient

density of plant and animal species that are currently used in agriculture.

• Expand joint research with tribes and other guardians of traditional ecological knowledge

regarding cultivation of culturally important foods.

• Identify niche markets and opportunities for expanding production of culturally important

nontimber forest products and wetland and grassland food species.

Feeding the World Sustainably | United Nations

Food and Nutrition Security | U.S. Department of Agriculture

Foodborne Illness and Disease | U.S. Department of Agriculture

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To support reduction of foodborne illness (Goal 2.3):

• Use accelerated breeding strategies and biotechnology to develop plants and animals that are less

likely to carry pathogens that cause food-related infections.

• Develop risk-based tools to identify virulence factors and antimicrobial resistance in pathogens.

• Research methods to reduce occurrence of and mitigate pathogens that cause food-borne illness in

food systems, including in both production settings and processing facilities.

• Develop rapid screening, detection, and quantification technologies and a national network for

pathogens, chemical contaminants, and physical hazards.

Theme 3: Protecting Plants and Animals Against Environmental Stressors

Context for the Bold Goals

U.S. agricultural production is under increasing pressure from biotic and abiotic stressors. Climate change

is driving more frequent and severe weather events, such as unprecedented droughts in California and

floods in the Mississippi River basin. The changing climate is also contributing to pest and disease

outbreaks as increased travel and trade lead to additional pest and pathogen invasions. These effects

compound: pests and disease may have greater impacts on weather-stressed plants and animals. Globally,

up to 40% of crop production is lost to pests, with costs to the global economy estimated at over $70

billion for invasive insects and $220 billion for plant diseases annually

, with additional losses due to

abiotic stresses like drought and floods. Each year, an estimated $300 billion is lost to animal diseases in

livestock, globally

. In the United States, for example, from December 2022 through March 2023, over

58 million chickens, turkeys, ducks, and other poultry were affected by highly pathogenic avian

influenza

. Livestock losses due to heat stress are expected to increase with climate change, reaching $40

billion annually by the end of the century

. Innovation in biotechnology and biomanufacturing can

improve resiliency of crops and livestock, protect yields, improve animal health, and reduce emergence of

zoonotic disease.

R&D Needs

To support capacity to detect and mitigate pests and pathogens (Goal 3.1):

• Develop and validate rapid screening, detection, and quantification methods for pathogens, with

accessible, timely, and accurate laboratory services nationwide.

• Develop commercially viable countermeasures for high-consequence diseases in plants and

animals, including animal vaccines and antivirals.

• Begin research into molecular technologies to induce plant and animal defense responses,

including plants that can detect, report, signal, and self-treat infection.

• Expand research on integrated pest management of pathogen-carrying pests, such as biocontrol

agents, sterility, gene drives, pheromones, biorationals, and plant-incorporated protectants.

• Use genome sequencing to characterize new plant and animal pathogen isolates and identify their

potential to acquire novel host ranges, including the potential to become a zoonosis.

Climate Change Fans Spread of Pests and Threatens Plants and Crops, New FAO Study | United Nations Food and Agriculture

Organization

Animal Health Through an Economic Lens | World Organisation for Animal Health

2022–2023 Confirmations of Highly Pathogenic Avian Influenza in Commercial and Backyard Flocks | U.S. Department of

Agriculture

Heat Stress for Cattle May Cost Billions by Century's End | Cornell Chronicle

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• Expand screening for and sequence the genomes of agricultural plants and animals and their wild

relatives that are resistant to pests and disease; use accelerated breeding strategies and

biotechnology to develop plants and animals with improved disease resistance.

To support resilience to biotic and abiotic stress (Goal 3.2):

• Use accelerated breeding strategies and biotechnology to develop plants and animals, including

beneficial insects, that are adapted to present and predicted climates, with increased production

under abiotic stress.

• Improve resistance screening and use accelerated breeding strategies and biotechnology in native

tree species to improve resistance to pests and pathogens; develop assisted migration protocols to

find, breed, and promote resilient trees.

• Increase understanding of agricultural and forest ecosystem dynamics in the face of stressors

across scales to enhance resiliency and improve landscape health.

Overarching R&D Needs

To support biotechnology and biomanufacturing innovation throughout food and agricultural systems,

USDA has identified four overarching R&D needs: (1) scale-up, standardization, and regulatory science;

(2) plant, animal, and microorganism genome to phenome; (3) data analytics, infrastructure, and sharing;

and (4) affordability, equitable access, and consumer perception. Partnerships across all sectors will be

key to success in all of these R&D needs, especially in scaling the bioeconomy.

Scale-Up, Standardization, and Regulatory Science

• Build sufficient shared pilot facilities and intermediate-scale infrastructure that could be used by

multiple organizations, reducing the time and cost to scale-up new technologies and products.

• Develop an ecosystem of biomanufacturing facilities (including for precision fermentation) close

to feedstocks and workforce development opportunities; co-locate and coordinate food and fuel

production facilities and processes so that co-products and waste can support circular economies.

• Develop new public research infrastructure and a matching skilled workforce to support the scale-

up of biomanufacturing processes.

• Train the next-generation biomanufacturing workforce at pilot facilities, including operators for

fermentation processes, who do not require formal education but do need specialized training.

• Develop standardized biomanufacturing methods, tools, and equipment.

• Develop standardized systems for measuring nutritional characteristics of different ingredients as

well as sensory properties such as olfactory components, mouthfeel, taste, and texture.

• Develop standardized methods for measuring sustainability and conducting related assessments

such as lifecycle analyses (LCAs).

• For all areas of innovation, increase investments in regulatory science to support regulatory

review and safe commercialization of new products, such as through the USDA Biotechnology

Risk Assessment Research Grants (BRAG) Program

Plant, Animal, and Microorganism Genome to Phenome

• Support public plant and animal breeding infrastructure to identify beneficial genes, pathways,

and regulatory controls that perform in varying production environments.

• Increase capacity to screen species for relevant agricultural traits and enable data collection with

advanced imagery, spectra, and sensors to better describe phenotypes.

Biotechnology Risk Assessment Research Grants (BRAG) Program | U.S. Department of Agriculture

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• Improve access to sequencing, bioinformatics, genomics-based breeding, genome editing, and

other innovative techniques for improving diverse plants, animals, and microorganisms; identify

and alleviate bottlenecks in crop transformation and regeneration methods.

• Sequence and annotate genomes of agriculturally relevant plants, animals, and microorganisms,

including domesticated plants and animals and their wild relatives, pest and beneficial arthropods,

weeds, plant and animal pathogens, and key ecosystem microbiomes.

• Expand, curate, phenotype, and sequence germplasm and genetic resource collections, including

the USDA National Plant Germplasm System, Animal Germplasm Collection, and U.S. National

Culture Collection.

Data Analytics, Infrastructure, and Sharing

• Forge partnerships to improve data collection, analytics, infrastructure, and sharing, including

improvement of syntactic and semantic data and leverage Findability, Accessibility,

Interoperability, and Reusability (FAIR) principles, while respecting intellectual property rights.

• Develop customizable digital twins to mimic major agriculture, forestry, or food systems,

including plants, animals, and microorganisms.

• Integrate digital tools into agriculture and forestry operations by promoting precision agriculture,

screening, and sensing technologies that support site-specific management systems.

• Use artificial intelligence (AI) and machine learning to enhance diagnostic applications, genome

sequence analysis, and functional genomic annotation.

• Combine AI and autonomous robotic systems in programmable, large-scale, data-driven farming

and forestry practices.

• Develop tools to better forecast production of resources from agriculture and forestry.

• Develop an open-access “Food Data Web” integrating production, consumer, environmental, and

health data related to food.

Affordability, Equitable Access, and Consumer Perception

• Expand research into consumer perception, preference, acceptance, and adoption of alternative

packaging, biobased products, biofuels, and foods developed with biotechnology and

biomanufacturing.

• Understand how labeling for production practices (e.g., climate-smart, organic), sustainability

(e.g., water usage, carbon footprint, biodiversity), food safety, nutritional content, and other

attributes influence consumer behavior and purchasing of products and how effects vary across

settings (e.g., restaurants, online, on-site grocery).

• Research the efficacy of education and engagement methods for informing consumers about

innovative products to inform methods to increase awareness and expand the demand.

Stakeholder Consultation

In November 2022, the White House convened a roundtable on food and agriculture, in which USDA’s

Chief Scientist and other USDA staff heard from stakeholders about sustainability, nutrient density in

foods, data sharing, standardization of methods, consumer acceptance, regulatory and trade concerns,

biomanufacturing infrastructure, bioeconomy workforce, and other topics. The White House Office of

Science and Technology Policy published a Request for Information and held a virtual public listening

session on January 9, 2023; many commenters were from the agricultural sector. Additional R&D-

focused listening sessions were hosted by the Good Food Institute and by land grant institutions at Iowa

State University; regulation-focused listening sessions were hosted by the American Seed Trade

Association, Biological Products Industry Association, and Biotechnology Industry Organization.

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All stakeholders discussed the need for biomanufacturing scale-up infrastructure and a trained workforce

to fill jobs across the bioeconomy. Many stakeholders described having to go outside of the United States

to find fermentation capacity. Facilities and processes are needed within the United States for scaling up

proof-of-concept or small-scale biomanufacturing to commercial scale. Stakeholders also described the

need for risk-proportionate regulation of biotechnology, international alignment of regulation, and

communication across the value chain about innovations in food and agriculture.

Enhancing Biosafety and Biosecurity

Existing Biosafety and Biosecurity Measures

USDA has many efforts to advance biosafety and biosecurity on farms and in agricultural R&D. USDA

maintains a comprehensive, systematic surveillance system to detect threats to plant health

and animal

health

. USDA invests in development of veterinary biologics, vaccines, and other countermeasures. The

USDA National Bio and Agro-Defense Facility

(NBAF) for large animals in Manhattan, Kansas,

conducts foreign animal disease research, training, and diagnostics. NBAF is essential for research on

diseases that can devastate animal agriculture, research that cannot safely take place elsewhere.

Recommended New Biosafety and Biosecurity Measures

The Biosafety and Biosecurity Innovation Initiative (BBII) will identify key areas for investment across

the bioeconomy. In agriculture, these investments can improve identification of emerging pathogens. For

example, a plant health defense facility analogous to NBAF would allow for advancement of research to

protect U.S. crops from emerging pathogens and pests.

Opportunities for Public-Private Collaboration

Partnerships between private companies and academic institutions allow them to use a portion of their

infrastructure for R&D and enable them to take advantage of existing knowledge to scale up new

products. Such collaborations are critical in incentivizing investments, creating new jobs and market

opportunities, and boosting sustainability.

Existing Public-Private Partnerships

Long-standing partnerships between USDA and Land Grant Universities (LGUs) and the Cooperative

Extension System bring discoveries from laboratories to producers who can put knowledge into practice.

The Foundation for Food and Agriculture Research (FFAR) matches public and private-sector

investments to address agricultural challenges. USDA is advancing climate-smart agriculture and food

systems through the Agriculture Innovation Mission for Climate (AIM4C), enabling global investments

of over $8 billion with more than 300 partners. Domestically, USDA’s Partnerships for Climate-Smart

Commodities will provide $3.1 billion for public-private partnerships that provide technical and financial

assistance to producers to implement climate-smart production practices.

Public-private partnerships also support targeted innovation. For example, the USDA Bioproducts Pilot

Program

supports scale-up of bioproduct manufacturing through collaboration between academic

institutions and private enterprises. The Germplasm Enhancement of Maize

(GEM) Project brings

together LGUs and corn breeding companies to increase the diversity of U.S. maize germplasm. The

Wheat Genetics Resource Center (WGRC) aims to unlock the genetic potential of wheat’s ancient

Crop Biosecurity and Emergency Management | U.S. Department of Agriculture

Animal Health Surveillance in the United States | U.S. Department of Agriculture

National Bio and Agro-Defense Facility | U.S. Department of Agriculture

Bioproduct Pilot Program | U.S. Department of Agriculture

Germplasm Enhancement of Maize | U.S. Department of Agriculture

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ancestors with input from an extensive advisory council. The Meat Animal Research Center

is a

cooperative effort to solve high-priority problems for the beef, sheep, and swine industries. The P3Nano

partnership promotes use of cellulose nanomaterials derived from wood to reduce our dependence on

greenhouse-gas-intensive materials like cement, plastic, and oil.

Opportunities for U.S. Government Incentivization of Private Sector

Strengthening existing and creating new partnerships will promote translation of research into products

that meet challenges in food and agriculture. For example, USDA could establish an extramural program

based on the Industry-University Cooperative Research Centers

program, which facilitates public-

private collaborations for precompetitive R&D. Participating companies contribute $50,000 annually,

participate in setting research priorities, can access information and intellectual property, and can license

technologies either exclusively or well ahead of nonparticipating companies.

Stakeholders from the plant-breeding sector suggest that collaborations like GEM and WGRC could be

initiated for other species, in which the private sector provides germplasm and in-kind support and the

public sector leads “pre-breeding” efforts to diversify the species, with input from producers and

manufacturers. Stakeholders from the alternative proteins sector suggest new Centers of Excellence that

would innovate new products and processes, train the next-generation workforce, and enable information

exchange between academia and the private sector through Industry Advisory Boards.

Opportunities for Public Participation

There will be opportunities for public participation as R&D programs are developed, such as R&D

funding opportunities related to the goals in this report, as well as input at workshops, sessions at

meetings, listening sessions, and Requests for Information.

U.S. Meat Animal Research Center | U.S. Department of Agriculture

P3Nano – Advancing Commercialization of Cellulosic Nanomaterials | U.S. Endowment for Forestry and Communities

Accelerating Impact Through Partnerships: Industry-University Cooperative Research Centers | National Science Foundation

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Biotechnology and Biomanufacturing R&D to

Further Supply Chain Resilience

In collaboration with other U.S. Federal Government departments and agencies,

this report was authored by the U.S. Department of Commerce

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Executive Summary

Recent global disruptions, geopolitical conflicts, and weather events exposed the vulnerability of U.S.

supply chains critical for industrial production. Some companies were forced to overhaul operations and

rethink their sourcing strategies for raw materials needed for essential goods including vehicles, airplanes,

medical equipment, power generation, batteries, and catalytic converters.

New biotechnologies and

biomanufacturing processes have the potential to help mitigate the risks and effects of supply chain

disruptions. Synthetic biology can be used to replace existing production processes, such as for precursor

materials, and to create new products, resulting in new opportunities for diversifying production pathways

and alleviating supply chain chokepoints. For example, realizing biomanufacturing breakthroughs for

active pharmaceutical ingredients (APIs) has the potential to create environmentally sustainable, domestic

alternatives to API production, which is currently heavily concentrated abroad. Biotechnology and

biomanufacturing can transform production of food, fuels, materials, and chemicals more broadly,

creating flexible and adaptive platforms that not only mitigate disruption risks, but also enable producers

to address disruptions more quickly. In the near-term, new developments in biotechnology platforms and

advanced data analytics could enable manufacturers to pivot more efficiently and deliver multiple needed

goods at scale compared to current production pathways. Industry analysis suggests that biological

production applications could have direct economic impact of up to $4 trillion a year over the next 10 to

20 years.

This report provides a vision for harnessing research and development (R&D) advances in biotechnology

and biomanufacturing to build supply chain resilience. This vision is comprised of nine near- and long-

term bold goals, and associated R&D needs, within three major themes. If this vision is achieved, the

United States can bring innovative biotechnologies and products to markets faster while building a more

robust supply chain ecosystem.

In Theme 1, we provide bold goals for alternative supply chain pathways via biotechnologies and

biomanufacturing to promote economic security. We identify R&D opportunities to promote the

development of innovative biomanufacturing pathways that could address supply chain bottlenecks for

critical drugs, chemicals, and other materials.

In Theme 2, we explore biomanufacturing innovation to enhance supply chain resilience. We identify

R&D efforts required to advance flexible and adaptive biomanufacturing platforms to mitigate the effects

of supply chain disruptions.

In Theme 3, we address standards and data infrastructure to support biotechnology and biomanufacturing

commercialization and trade. We identify standards and data R&D needed to enable biotechnology and

biomanufacturing scale-up and global competitiveness of U.S. companies.

Achieving these bold goals will require public-private partnerships, effective coordination with domestic

and international partners, and integration of key biosafety and biosecurity considerations. Realization of

these bold goals can also enable the United States to maintain its global leadership in the emerging

bioeconomy and create quality jobs while addressing some of society’s greatest challenges.

OECD Policy Responses on the Impacts of the War in Ukraine | Organisation for Economic Co-operation and Development

The Bio Revolution: Innovations Transforming Economies, Societies, and Our Lives | McKinsey & Company

Building Resilient Supply Chains, Revitalizing American Manufacturing, and Fostering Broad-Based Growth: 100-Day

Reviews under Executive Order 14017 | White House

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Bold Goals for Harnessing Biotechnology and Biomanufacturing

The following goals are intended to provide a broad vision to build supply chain resilience for the

U.S. bioeconomy. These should not be read as commitments by the U.S. Department of Commerce (DOC)

to undertake specific activities. Achieving these bold goals will require significant prioritization of R&D

investments and efforts across the U.S. government, as well as actions from the private sector and state,

local, and tribal governments.

Theme 1: Alternative Supply Chain Pathways via Biotechnologies

and Biomanufacturing to Promote Economic Security

Goal 1.1: Improving Supply Chains for Critical Drugs – In 5 years, deploy broad synthetic biology

and biomanufacturing capabilities to produce at least 25% of all active pharmaceutical ingredients (APIs)

for small molecule drugs.

Goal 1.2: More Sustainable Chemical Production – In 20 years, produce at least 30% of the U.S.

chemical demand via sustainable and cost-effective biomanufacturing pathways.

Goal 1.3: Accelerating Development of Biomanufactured Products – In 20 years, implement new

biotechnologies into biomanufacturing workflows to produce ten new biomanufactured products in each of

at least 3 sectors with identified supply chain bottlenecks.

Theme 2: Biomanufacturing Innovation to Enhance Supply Chain Resilience

Goal 2.1: Predictive Capabilities – In 5 years, enable prediction of at least 50% of supply chain

weaknesses and direction of real-time biomanufacturing adjustments to address bottlenecks.

Goal 2.2: Real-time Biomanufacturing Process Adjustments – In 5 years, operationalize monitoring

systems to measure and adjust biomanufacturing parameters in real time.

Goal 2.3: Adaptive Supply Chains – In 20 years, deploy a suite of advanced biomanufacturing

platforms and capabilities to respond to supply chain bottlenecks within one week of identification.

Goal 2.4: Supply Chain Flexibility – In 20 years, implement 80% of viable biomanufacturing

technologies to address domestic production capability needs.

Theme 3: Standards and Data Infrastructure to Support Biotechnology and

Biomanufacturing Commercialization and Trade

Goal 3.1: Data Infrastructure – In 5 years, launch a data infrastructure, including effective and secure

data sharing mechanisms, via advances and integration of data standards, tools, and capabilities.

Goal 3.2: Standards Infrastructure – In 20 years, establish a robust standards infrastructure to enable

the rapid development and deployment of biomanufactured products and processes.

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Bold Goals Explored

Theme 1: Alternative Supply Chain Pathways via Biotechnologies and

Biomanufacturing to Promote Economic Security

Context for the Bold Goals

Biomanufacturing, part of the Administration’s priority in advanced manufacturing, can be utilized to

make products to mitigate existing and future supply chain bottlenecks.

Biotechnology innovations can

create new processes to make products ranging from active pharmaceutical ingredients to biofuels,

chemicals, plastics, enzymes, critical materials, and beyond. State-of-the-art biomanufacturing facilities

can lead to long-term production cost savings and transform domestic manufacturing to be more

sustainable and reduce environmental impacts compared to traditional production pathways. For some

products, the biotechnologies already exist to address high-risk bottlenecks, and public-private

partnerships must focus on de-risking technology deployment and expansion. Other biotechnologies are

more nascent, and public investment must focus on translating them from R&D to biomanufacturing

practice. Doing so will help enable a more secure, sustainable, diversified, and resilient supply chain—

from locally sourced feedstocks at the beginning, through manufacturing processes, to market-viable

goods. Goals 1.1 through 1.3 aim both to replace at-risk products with biomanufactured goods where the

technology has already demonstrated potential viability and to develop new biomanufactured products to

diversify and replace supply chain inputs, including in sectors where biomanufacturing is not currently

utilized or is underutilized.

Goal 1.1: Improving Supply Chains for Critical Drugs. Biomanufacturing can help address the risk of

domestic dependence on concentrated geographies for active pharmaceutical ingredients (APIs).

Currently, most APIs of small molecule drugs are synthesized through a chemical process abroad,

including in China and India, which poses supply chain risks.

There have been relatively low financial

incentives for reshoring these chemical manufacturing processes, especially for production of molecules

with low profit margins. Biomanufacturing pathways would create opportunities for cost-effective

domestic API production. For example, advances in synthetic biology, including in precision fermentation

and the use of cell-free systems, could enable firms to produce multiple APIs in the same facility, with a

reduced need for retooling. Additional proof of concept at scale is needed to help overcome private sector

hesitancy to invest in adaptive and flexible technologies with long-term potential.

Goal 1.2: More Sustainable Chemical Production. Biomanufacturing has the potential to transform

U.S. chemical manufacturing by reducing reliance on fossil fuels and advancing domestic production.

Biomanufacturing production, extraction, recycling, and upcycling are already replacing supply chain

staples such as fuels, solvents, enzymes, and plastics; however, there is opportunity to expand. The

biobased products industry directly added $150 billion to the U.S. economy in 2017, while biobased

chemicals and enzymes contributed an additional $6.2 and $21.7 billion, respectively.

A well-developed

bioeconomy could use more than one billion tons of sustainable biomass and biogenic carbon in the

United States within the next 20 years.

Bulk chemicals produced from biomass can help the United

States avoid both the carbon impacts of traditional feedstocks and the price volatility of commodity

feedstocks. To produce 30% of U.S. demand of chemicals with biomass, R&D must be expanded beyond

current capabilities and focused on production, transportation, and pre-processing of biomass, and on

improving downstream processing and precision fermentation capabilities.

National Strategy for Advanced Manufacturing | National Science and Technology Council

Building Resilient Supply Chains, Revitalizing American Manufacturing, and Fostering Broad-Based Growth: 100-Day

Reviews under Executive Order 14017 | White House

Indicators of the U.S. Biobased Economy, 2018 | U.S. Department of Agriculture

2016 Billion-Ton Report | U.S. Department of Energy

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Goal 1.3: Accelerating Development of Biomanufactured Products. Recent advances in synthetic

biology and artificial intelligence (AI) are leading to new breakthroughs for the bioeconomy.

Biotechnology innovation can provide access to new classes of molecules currently inaccessible using

traditional chemistry, driving new applications and opportunities for economic growth. For example,

biotechnologies could enhance the domestic supply chain for critical minerals, which is currently

insufficient to support reshoring and expansion of the semiconductor industry. Additionally, biomass can

serve as a dynamic feedstock for drop-in fuels in hard-to-abate sectors such as aviation and marine

shipping. Strategic investments must be made to translate these biotechnology breakthroughs into large-

scale production, including developing methods to help recover valuable commodity chemicals and

materials from discarded devices and other waste streams for transitioning back into the supply chain. If

successful, this will reduce the dependence on fossil fuels and non-domestic sources of critical chemicals

and materials while helping to meet the Administration’s climate and sustainability goals.

R&D Needs

• Develop cost-competitive alternative biomanufacturing pathways, such as cell-based processes

and cell-free systems, to produce key APIs, chemicals, and other materials. (Goals 1.1, 1.2, 1.3)

• Design and test sustainable and cost-effective manufacturing capabilities and capacities to

support large-scale biomanufacturing for commodity material production. (Goals 1.2, 1.3)

• Advance synthetic biology tools and innovative bioprocessing means to reclaim/harvest critical

minerals, including, but not limited to, lithium and cobalt. (Goal 1.3)

• Conduct lifecycle cost analyses to determine the most economically viable model(s) for

biomanufacturing while ensuring biosafety, biosecurity, and biocontainment. (Goals 1.1, 1.2, 1.3)

• Develop lifecycle management practices to enable more sustainable biomanufacturing and

develop biomanufacturing solutions for advancing the circular (bio)economy via recycling or

upcycling of existing products and other wastes or byproducts. (Goals 1.2, 1.3)

• Develop models to predict the most promising chemical production processes where

biomanufacturing alternatives can produce equal or greater scale or quality while maximizing

sustainability. (Goals 1.1, 1.2, 1.3)

• Improve accessibility to platform technologies for engineering biology with AI to speed and

optimize R&D and scaling of new processes and products. (Goals 1.1, 1.2, 1.3)

• Address current scale-up challenges and regulatory science needs. (Goals 1.1, 1.2, 1.3)

Theme 2: Biomanufacturing Innovation to Enhance Supply Chain Resilience

Context for the Bold Goals

An advanced biomanufacturing ecosystem has the potential to mitigate disruptions, but also to adapt

when inevitable shortages occur. U.S. stakeholders have emphasized the need for increased data and

models to predict potential bottlenecks, such as disruptions in shipping routes or shortages of materials. A

more advanced supply chain predictive capability could provide manufacturers with enough time to shift

or pre-position assets and inventories to prevent bottlenecks. Further, biomanufacturing can offer agile

platforms and workflows that can be used to quickly shift from the production of one good to another

without major infrastructure changes. Goals 2.1 through 2.4 lay the foundation for this resilient

production ecosystem, so that the United States and international partners can expand advanced

biomanufacturing capabilities, including more regional biomanufacturing close to feedstocks.

Goal 2.1: Predictive Capabilities. Some supply chain disruptions are unavoidable, whether due to

geopolitical conflict, transportation delays, public health emergencies, weather-related disasters, or

production errors. Regardless of the disruption type, both the private and public sectors must better

understand supply chain sources and feedstocks, as well as their relationships on interconnected supply

chains. A data-driven understanding of supply chain dependencies will help enable stakeholders to

prepare for and mitigate the effects of shocks. Technological tools, including access to data and deploying

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machine learning and AI, can enable government and firms to map supply chains, identify risks, and

invest in biomanufacturing capabilities to address those risks. In the long-term, real-time data could be

used to flag emergent risks, enabling manufacturers to maintain their economic viability while pivoting

production for continued delivery of necessary goods to consumers.

Goal 2.2: Real-Time Biomanufacturing Process Adjustments. Biomanufacturing using living cells

may be more variable than traditional chemical manufacturing, requiring advanced monitoring systems to

better control quality and yield. Real-time monitoring and process control of bioreactor processes, such as

fully enclosed fermentation systems, are needed to enable real-time quality control. To provide real-time

monitoring of living organisms at scale, emerging biotechnology-based solutions should be considered.

For example, reporter cell lines and organisms containing genetic sensors that can provide readouts on

specific biological responses could address current analytical bottlenecks. Such monitoring and process

control innovations can help manufacturers understand production problems and adjust relevant

parameters more quickly, resulting in added biomanufacturing efficiencies toward achieving resilient

supply chains.

Goal 2.3: Adaptive Supply Chains. Advanced biomanufacturing platforms and capabilities fueled by

biotechnology innovation and increased connectivity, automation, and data analytic capabilities have the

potential to create more agile and sustainable products faster. In the face of supply chain disruptions,

manufacturers could shift production more efficiently, including in coordination with international

partners, rather than undergoing capital-intensive retooling. These developments would also provide

customizable options to make different products as demand shifts while building supply chain redundancy

and flexibility. However, limited investments have been made toward the development of advanced

biomanufacturing technologies. A robust set of biotechnologies, including bioreactors, raw materials and

reagents, and measurement capabilities would enable the United States to quickly address supply chain

bottlenecks using a diversified set of technology solutions, including better access and utilization of raw

materials.

Goal 2.4: Supply Chain Flexibility. Large-scale production of new biotechnology products requires a

robust global manufacturing ecosystem and infrastructure. The most functional and economical way to

expand the biomass-to-chemicals industry is to locate biomass processing facilities close to feedstock

production. Such co-localization can promote economic growth across the Nation, strengthen resilience to

domestic supply chains, and address the policy goal of revitalizing the economies of rural communities,

as well as those facing hardships associated with the loss of traditional manufacturing jobs. To promote a

robust biomanufacturing ecosystem, investments are needed to develop and implement fit-for-purpose

manufacturing platforms, including modular and/or mobile platforms, for converting biomass, enzymes,

metabolites, and other sources into viable products. Importantly, biomanufacturing technologies must

keep pace with rapid biotechnology innovations to produce a diverse product portfolio for multiple

sectors. Additionally, continued improvement in biomanufacturing technologies is necessary to make

processes cheaper, more efficient, and more sustainable.

R&D Needs

• Develop predictive models to identify the supply chain bottlenecks that would benefit most from

biomanufacturing alternatives (such as high-demand commodity chemicals or materials) and

models to forecast market trends and workforce needs (such as skills, geography, and permanent

and surge capacity) to address biomanufacturing and supply chain bottlenecks. (Goal 2.1)

• Develop accurate models to integrate a decentralized or distributed biomanufacturing ecosystem

and supporting information technology infrastructure, including a map of domestic capacities,

and to predict the availability and use impacts of biological feedstocks to enable on-demand local

production. (Goals 2.1, 2.3, 2.4)

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• Develop innovative in-line, at-line, and in-process measurement technologies, including

engineered reporter cell lines and living measurement systems, to enable real-time evaluation of

and adjustments to quality attributes. (Goal 2.2)

• Develop datasets, standards, and predictive capabilities (including use of AI, machine learning,

and digital twins) to enable real-time feedback loops and analysis of process control and supply

chain data with appropriate access controls and data security. (Goal 2.2)

• Advance smart biomanufacturing that can seamlessly integrate automation, software, equipment,

and people to increase process speed, reliability, and efficiency. (Goals 2.2, 2.3)

• Develop platform technologies and standards to accelerate the development, production, and

interoperability of biomanufacturing equipment, components, and consumables and improve the

characterization and testing of biomanufacturing processes and products. (Goals 2.3, 2.4)

• Develop standard sets of microbial strains, cell free systems, key reagents, sequences of known

function and performance, and supply chain precursor molecules and compounds that can be

rapidly produced, distributed, and scaled up on demand. (Goals 2.3, 2.4)

• Develop standardized quality metrics for raw materials and reagents to enable interoperability

from multiple vendors, and advanced algorithms to enable adaptive stockpiling capable of using

alternative feedstocks or processes when supply chains are limited or disrupted. (Goals 2.3, 2.4)

• Develop innovative design, robust quality management systems, and standards to enable more

efficient use of biomanufacturing facilities. (Goals 2.3, 2.4)

• Develop technologies and related strategies that can be used to effectively retrofit existing

facilities for biomanufacturing in urban and rural areas. (Goals 2.3, 2.4)

• Develop modular biomanufacturing capabilities to be scaled up, down, or out. (Goals 2.3, 2.4)

• Develop single-use technologies and both fit-for-purpose and end-to-end biomanufacturing

platforms that can quickly switch between organisms and processes. (Goals 2.3, 2.4)

Theme 3: Standards and Data Infrastructure to Support Biotechnology and

Biomanufacturing Commercialization and Trade

Context for the Bold Goals

Stakeholder reports and global bioeconomy strategies recognize that a sustainable, safe, and secure

bioeconomy is built upon standards and the availability of high-quality data.

53,54

Data, particularly from

genomics and multiomics, underpins advances in biotechnology, for example, by enabling the rapid

design of systems to produce needed medicines, food, and materials. Standards,

particularly

international standards, can help accelerate

R&D and commercialization of new, safe, and effective

medicines and therapeutics; contribute to food product safety, quality, and consistency; promote

international trade; and instill confidence among consumers for products in all sectors of the economy.

For industry, standards can promote research and manufacturing innovation, streamline regulatory review,

and enable international alignment, interoperability, and coordination. As biotechnology converges with

automation, connected devices, and AI, a robust data infrastructure can also accelerate R&D and

commercialization of emerging technology.

4,5

The Administration’s Data for the Bioeconomy Initiative

(Data Initiative) under Section 4 of the Executive Order will help inform these efforts.

Goal 3.1: Data Infrastructure. A standardized data infrastructure to connect and integrate various

biological data types, including those associated with biomanufacturing, can accelerate biotechnology and

biomanufacturing innovations, such as understanding the efficacy and toxicity of a drug and how each can

be affected by the manufacturing process. To better leverage the large amount of data generated from

The U.S. Bioeconomy: Charting a Course for a Resilient and Competitive Future

European Bioeconomy Policy: Stocktaking and Future Developments | European Commission, Directorate-General for

Research and Innovation

Standards can include documentary standards, reference materials, and reference data.

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R&D investments, the United States and international partners can work to develop tools, capabilities,

and standards in accordance with Findable, Accessible, Interoperable, and Reusable (FAIR) principles.

An open data infrastructure would enable R&D data to be aggregated and analyzed to drive innovation.

For example, combining data related to genomics, protein structures, and biological functions has

expedited the development of SARS-CoV-2 vaccines. Synergy from interdisciplinary collaborations,

enabled by an open data architecture, could accelerate R&D, scale-up, and biomanufacturing processes.

Goal 3.2: Standards Infrastructure. As the United States expands its manufacturing capacities, there is

an increasing need to develop pre-competitive technologies, ensure a level playing field for both domestic

and multinational companies, and reduce barriers to market access. The United States can support growth

of a bioeconomy through continued leadership in and development of international standards, including in

emerging biotechnologies (e.g., synthetic biology) and biomanufacturing. For example, standard

manufacturing processes, testing methods, raw materials, and data can support agile manufacturing to

mitigate the effects of supply chain bottlenecks and ensure quality production. A holistic, global approach

to a sustained standards infrastructure that keeps pace with rapidly evolving biotechnology will catalyze

innovations and accelerate bioeconomy growth. Continued investment is needed to develop dissemination

and educational tools are needed to drive industry adoption of the latest standards.

R&D Needs

• Support development and integration data standards, tools, and capabilities to create a data

infrastructure consistent with the Administration’s Open Science efforts

while respecting

intellectual property rights, data security, and other needs in continuous coordination with

domestic and international stakeholders. (Goal 3.1)

• Create data standards (e.g., ontology, schema, and metadata structure) to enable development,

integration, and utilization of advanced data analytics, including AI and machine learning, and for

operationalizing digital twin approaches. (Goals 3.1, 3.2)

• Establish benchmarks and tools for validating or verifying materials, systems, processes,

equipment, software, and data for both lab-based and field-based technologies. (Goal 3.2)

• Develop analytical method standards and the underpinning measurement infrastructure to enable

greater comparability of complex biological systems. (Goal 3.2)

• Develop bioprocessing standards to support emerging biomanufacturing capabilities, including

for raw materials, unit operations, bioreactors, and related interoperability. (Goal 3.2)

• Translate industry benchmarks, tools, capabilities, and best practices into international standards

in collaboration with Manufacturing USA institutes and other open forums to ensure that

standards promote, and do not inadvertently stifle, innovation. (Goal 3.2)

Stakeholder Consultation

To develop this report, DOC leveraged existing industry and government analyses and consulted with

public and private sector stakeholders. This included participation in listening sessions organized by the

White House and workshops such as the National Academies of Sciences, Engineering, and Medicine’s

“Successes and Challenges in Biomanufacturing.”

DOC also reviewed responses to the Request for

Information on the National Biotechnology and Biomanufacturing Initiative and collaborated with experts

from multiple Federal agencies.

Fact Sheet: Biden-⁠Harris Administration Announces New Actions to Advance Open and Equitable Research | White House

Successes and Challenges in Biomanufacturing – A Workshop | National Academies of Sciences, Engineering, and Medicine

Request for Information on the National Biotechnology and Biomanufacturing Initiative | Office of Science and Technology

Policy

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Enhancing Biosafety and Biosecurity

To realize the potential of biotechnology and biomanufacturing to promote U.S. economic growth and

enhance supply chain resilience, it is imperative that biosafety and biosecurity are integrated into both

biotechnology R&D and implementation strategies for newly adopted biomanufacturing processes.

Existing Biosafety and Biosecurity Measures

The United States has decades of experience in implementing biosafety and biosecurity measures, as will

be outlined in the forthcoming plan for the Biosafety and Biosecurity Innovation Initiative established

through the Bioeconomy Executive Order. Although most evident in the health sector and at laboratories

with biological materials at the highest biosafety levels, systems and cultures throughout the bioeconomy

R&D enterprise have been developed and cultivated through training and education provided by the U.S.

government, universities, and professional societies such as ABSA International. Several Federal agencies

engage in outreach domestically and internationally to propagate biosafety and biosecurity best practices.

Expanding upon this robust foundation is critical as biotechnology and biomanufacturing are used to

enhance supply chain resilience across sectors that do not have the same historical biosafety and

biosecurity standards.

Recommended New Biosafety and Biosecurity Measures

Themes 1 and 2 involve developing, implementing, and scaling up new biotechnologies and

biomanufacturing processes to serve as alternatives to more conventional production pathways. By

default, the implication is that biological materials and systems will be utilized in new ways while being

engineered to make both new and familiar products. Biosafety and biosecurity should be included in these

new technologies and processes early in the design phase (including for living systems and their

interactions with more traditional manufacturing equipment), during hardware and software integration,

and through intentional assessments to monitor for new risks, gaps, or challenges.

Themes 2 and 3 emphasize the importance of data for supply chain resilience. Best practices for data

management and protection should be enacted, including concepts such as those within the National

Institute of Standards and Technology (NIST) Research Data Framework and the NIST Cybersecurity

Framework. These practical guides can help end users work through the balance of utilizing open or

shared supply chain data while securing the more vulnerable data results from predictive modeling that

indicate specific supply chain risks and opportunities.

Theme 3 centers on standards development to help increase the use of promising biotechnology and

biomanufacturing developments to improve supply chain resilience. Each of the referenced standard types

(documentary standards, data standards, and reference materials) should be developed to ensure the

integration of biosafety and biosecurity best practices. This includes for administrative, engineering, and

access controls; handling of potential dual-use biological materials; and critical infrastructure hardening.

Doing so will help realize the economic benefits possible through increased adoption of biotechnologies

and biomanufacturing innovations while minimizing risks as the biotechnology workforce expands.

Opportunities for Public-Private Collaboration

Achieving this vision for supply chains requires a coordinated and concerted effort to overcome shared

challenges between Federal, state, local, and tribal governments, and the private sector. A key barrier that

stakeholders have emphasized is a severe lack of domestic biomanufacturing infrastructure for the pilot

and commercial scales. To test or to manufacture products at scale, many companies must seek options

abroad, which still pose long wait periods, or invest in the infrastructure themselves. This is an onerous

endeavor for a startup with limited capital and production know-how. If these hurdles persist, the United

States may miss a rare opportunity to innovate while strengthening its supply chains. Public-private

partnerships (PPPs) have the potential to drive commercialization and enhance broader supply chain

resilience, including if coupled with policymaking and investment incentives at the local, state, and/or

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Federal level. Such efforts can drive the translation of emerging biotechnologies into practical

applications; promote technology development, support, and deployment; increase access to pilot and test

capabilities; build capacity; and develop and train a robust workforce.

The President’s Council of Advisors on Science and Technology has recommended the development of

biomanufacturing infrastructure hubs across America to advance manufacturing methods for complex

new bioproducts and provide workforce development opportunities.

The power of PPPs lies in the

cohesive network of stakeholders, coming together to enable tangible demonstrations of technology,

capabilities, and concepts with collective effort. Pilot biotechnology demonstrations require substantial

supply chain considerations, such as raw materials, infrastructure needs, circular production

considerations, and market fit. Shared facilities operated in the pre-competitive space may improve or

expand laboratory infrastructure, including state-of-the-art piloting and scale-up facilities, to enable the

demonstration of engineering biology metrology and bioeconomy standards, demonstrate pre-competitive

technologies, pressure-test supply chain considerations in an industry-representative environment, and

provide a platform for training opportunities and workforce development. These types of hubs and

collaborations can significantly de-risk the investments needed to develop and integrate new

biotechnologies and biomanufacturing processes, including through decreased costs for capitalized

equipment, increased use of common platform technologies to scale up new pathways, and improved

clarity on the viability of biomanufactured products in one or more economic sectors.

Existing Public-Private Partnerships

DOC is well-poised to lead and participate in such PPPs. Intended to boost economic recovery from the

pandemic and rebuild American communities, the Economic Development Administration’s (EDA) Build

Back Better Regional Challenge led in part to investments in biomanufacturing research centers across the

country. EDA’s Regional Technology and Innovation Hubs program is intended to drive technology- and

innovation-centric growth that leverages existing R&D strengths and technology demonstration and

deployment capacities within a region to catalyze the creation of good jobs for American workers

equitably and inclusively. The Small Business Innovation Research and Small Business Technology

Transfer programs encourage technology commercialization by domestic small businesses. The national

network of Manufacturing USA institutes was created to secure U.S. global leadership in advanced

manufacturing through large-scale public-private collaboration to overcome technical hurdles, share state-

of-the-art facilities and equipment, and train tomorrow’s workforce. The National Institute for Innovation

in Manufacturing Biopharmaceuticals (NIIMBL), BioFabUSA, and BioMADE target biomanufacturing,

while other institutes can also drive relevant advancements. The network of Manufacturing Extension

Partnership centers in every state and Puerto Rico serves small and medium-sized manufacturers to

optimize supply chains, deploy new technologies, and train and recruit talent, among other services. Via

consortia like Rapid Microbial Testing Methods, Genome Editing, Flow Cytometry Standards, and

Genome in a Bottle, NIST works with industry and international partners to lay the foundation for

developing research, standards, capacities, and expertise for supporting biotechnology and

biomanufacturing.

Opportunities for U.S. Government Incentivization of Private Sector and Public

Participation

The Federal Government can support biotechnology and biomanufacturing commercialization via unique

lab-to-market incentive mechanisms. Proven tools to address market failure and applied technologies gaps

include prize and challenge competitions, market shaping procurement or loan programs, and streamlined

funding of open, cross-disciplinary research. A new PPP could coordinate across multiple efforts to

ensure they drive toward rapid technology assimilation and execution. Under Themes 1 and 2, PPPs can

Biomanufacturing to Advance the Bioeconomy | President’s Council of Advisors on Science and Technology

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help address challenges in technology demonstration, process development, and continuous optimization

by seeding a bioproduction R&D shared facility network. As a starting point, this could occur across at

least four geographical locations to offer bioprocess optimization capabilities to the greater bioeconomy

and execute pilot and scale-up challenges wherein participating facilities would compete in areas such as

workflow optimization, scaling, and transfer. Generated data could be captured in an open data

infrastructure (Theme 3) and support generation of supply chain predictive models (Theme 2). PPPs

could provide participants access to neutral forums for addressing pre-competitive needs through (1)

public workshops; (2) participation in development of experimental benchmarks, guidelines, standards,

technologies, manufacturing platforms, equipment, and facilities to build competence; (3) access to co-

developed tools, capabilities, and expertise; and (4) institutional representation on consortia committees.

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Biotechnology and Biomanufacturing R&D

to Further Human Health

In collaboration with other U.S. Federal Government departments and agencies,

this report was authored by the U.S. Department of Health and Human Services

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Executive Summary

Improvements in human health outcomes have benefited from advances in biotechnology and

biomanufacturing over the last two centuries, from the discovery of genetics and the development of early

vaccines to modern robotic limbs and engineered cell therapy. To prevail in the fight against disease and

strive toward healthy living, several emerging fields in biotechnology and biomanufacturing need to be

strengthened and developed further. In taking these key steps, the U.S. government, in collaboration with

the private sector, can advance areas throughout the full health continuum—from prevention to diagnosis

and monitoring, to more efficient therapeutic manufacturing, to therapy and ultimately healthy

survivorship. This report describes ten aspirational bold goals under five broad themes that will accelerate

medical breakthroughs and advance human health. The report also details important research and

development necessary to work toward the bold goals.

Theme 1, accessible health monitoring, includes bold goals to identify indicators of health and develop

and distribute a simple-to-use home diagnostic assay kit to report health across the lifespan and meet the

needs of diverse populations. This theme focuses on prevention, monitoring, and survivorship.

Theme 2, precision multi-omic medicine, includes bold goals to collect multi-omic measures in large

cohorts with diverse populations, as well as to develop molecular classifications for diagnosis and/or

treatment and make these actionable with development of the $1,000 multi-ome. This theme focuses on

enabling diagnosis and monitoring as well as survivorship.

Theme 3, biomanufacturing of cell-based therapies, includes bold goals to expand the toolset of

technologies used to create cell-based therapies to achieve high viability and targeted delivery at the time

of patient administration, as well as expand access to cell-based therapies to decrease health inequities.

This theme focuses on equitable access to next-generation therapy.

Theme 4, AI-driven bioproduction of therapeutics, includes bold goals to increase the speed and

diversity of therapeutic manufacturing, including manufacture of current therapeutics as well as design of

novel ones. This theme focuses on enabling broad access to advanced therapeutics.

Theme 5, advanced techniques in gene editing, includes bold goals to assess current gene-editing

systems and emerging technologies for therapeutic gene editing as well as to strengthen the

biomanufacturing ecosystem to produce millions of doses of therapeutic gene-editing systems annually.

This theme focuses on enabling new therapeutics.

All these topic areas and their component bold goals require continued support for R&D and

establishment of public-private partnerships as well as consideration of biosafety and biosecurity. The

goals require innovation across the biotechnology development spectrum, from basic science and

prototyping to validation, clinical studies, manufacturing, and commercialization, culminating in

regulatory approval and health insurance authorization and reimbursement. Also, building in sound

biosafety and biosecurity practices that preserve critical discovery and innovation is a key component of

the development of all referenced biotechnologies. This enables safe solutions to human health challenges

and is a critical factor that must be considered in the design and implementation of programs that might

be pursued to achieve these goals. In summary, these bold goals are designed to accelerate emerging

fields in biomedicine for the benefit of Americans by increasing the quality of life of people across their

lifespans through advancements in biotechnology and biomanufacturing.

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Bold Goals for Harnessing Biotechnology and Biomanufacturing

The following goals in the advancement of human health are intended to provide a broad vision for the

U.S. bioeconomy. These should not be read as commitments by the U.S. Department of Health and

Human Services to undertake specific activities. Achieving these bold goals will require significant

prioritization of R&D investments and efforts across the U.S. government as well as actions from the

private sector and state, local, and tribal governments.

Theme 1: Accessible Health Monitoring

Goal 1.1: Identify Bio-Indicators of Health – In 5 years, leverage novel sensors to identify at least ten

next-generation bio-indicators of health that can be monitored as part of standard healthy living and

preventative medicine practice, such as immune competency or microbiome composition.

Goal 1.2: Integrated Health Diagnostics – In 20 years, develop and distribute a simple-to-use,

affordable home diagnostic assay kit (“Health Kit”) leveraging novel bio-indicators of health, useful in the

clinic and community, and meeting the needs of diverse populations to decrease disparities in health

outcomes by 50%.

Theme 2: Precision Multi-Omic Medicine

Goal 2.1: Collect Multi-Omic Data – In 5 years, collect multi-omic measures in large cohorts with

participants from diverse populations and identify which measures are most relevant to the diagnosis and

management of at least 50 diseases with high incidence and impact.

Goal 2.2: Enable Personal Multi-Ome – In 20 years, develop molecular classifications for diagnosis,

prevention, and treatment to address leading causes of disease-related mortality in the U.S. and make these

actionable with development of the $1,000 multi-ome.

Theme 3: Biomanufacturing of Cell-Based Therapies

Goal 3.1: Increase Therapeutic Efficacy – In 5 years, expand the technologies used to develop cell-

based therapies to achieve at least 75% cell viability in patients.

Goal 3.2: Enable Scale-Up – In 20 years, increase the manufacturing scale of cell-based therapies to expand

access, decrease health inequities, and decrease the manufacturing cost of cell-based therapies 10-fold.

Theme 4: AI-Driven Bioproduction of Therapeutics

Goal 4.1: Increase Manufacturing Speed – In 5 years, leverage a national network of resource labs to

address barriers in autonomous production and bioproduction of existing biotherapeutics, increasing

manufacturing speed of ten commonly prescribed therapeutics by 10-fold.

Goal 4.2: Increase Manufacturing Diversity – In 20 years, integrate artificial intelligence and machine

learning (AI/ML) into the national network of resource labs to design novel biotherapeutics, increasing the

speed of novel drug discovery and production by 10-fold.

Theme 5: Advanced Techniques in Gene Editing

Goal 5.1: Increase Editing Efficiency – In 5 years, further develop gene-editing systems for clinical use

to enable, with little to no side effects, cures for ten diseases with known genetic causes.

Goal 5.2: Enable Scale-Up – In 20 years, strengthen the biomanufacturing ecosystem to produce at least

5 million doses of therapeutic gene-editing systems annually.

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Bold Goals Explored

Theme 1: Accessible Health Monitoring

Context for the Bold Goals

A major healthcare challenge is detecting and monitoring disease early so prevention, progression, and

treatment are manageable. This is especially true in areas with difficult access to healthcare and

populations underrepresented in clinical studies. Identification of next-generation indicators of health in

diverse populations that can be simply monitored at home or in community clinic settings could help

address this issue, giving clinicians and patients a way to assess and monitor health and disease more

effectively and affordably. These indicators can include known biomarkers with currently unknown

clinical implications, as well as new biomarkers relevant to the function of human systems that are still

difficult to monitor or measure, such as the immune system or the microbiome. Under this paradigm,

healthcare providers and patients could use a new set of tools to organize, track, personalize, and

prioritize patient care, enabling earlier diagnosis no matter the distance from a healthcare provider via

telemedicine integration, testing of developmental therapeutics, and identification of ways to improve

health across diverse populations. The bold goals for achieving this include a need to identify novel next-

generation bioindicators of health as well as a need to enable integrated health diagnostics in a variety of

care settings.

R&D Needs

The following aspects of R&D could be pursued in consultation with the National Institutes of Health

(NIH), the Biomedical Advanced Research and Development Authority (BARDA), the Food and Drug

Administration (FDA), the Centers for Medicare and Medicaid Services (CMS), and other government

stakeholders.

To discover next-generation bioindicators of health (Goal 1.1):

• Develop innovative sensors and sensor arrays for detection of novel bioindicator types.

• Combine longitudinal studies with studies of basic human biology to identify markers of health

and healthy aging, requiring development of relevant AI/ML models to integrate data types.

• Integrate social and clinical studies on diverse population sets, including race, gender, and

geographic area, into biomarker discovery to understand inequities, gaps in accessibility and

affordability to health technologies, and biomarker diversity.

• Work closely with decentralized clinical studies and industry partners to design and launch new

models for large-scale studies that can enable next-generation biomarker discovery and

validation.

• Harmonize, integrate, and analyze Electronic Health Record (EHR) data across the many existing

platforms to identify health biomarkers and enable interoperability. Other sections of this report

refer to the challenges of data collection, curation, and storage within data infrastructures, but for

this theme a specific infrastructure is required to handle mixed patient data from multiple sources

while ensuring the security and protection of sensitive biological data and considering issues of

privacy and deidentification.

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To develop integrated health diagnostics (Goal 1.2):

• Develop miniature detectors and sensors as well as advanced yet simple-to-use multiplexed

detection panels, building on existing studies including those against cancer (part of the Cancer

Moonshot

initiative

) and COVID-19 (part of the RADx® program

and BARDA DRIVe).

• Coordinate and consult with FDA and CMS for guidance in development and clinical use of

Health Kits.

• Create specific partnerships with experts in public health, nursing, patient advocacy, and many

others to ensure Health Kits are designed for accessible and affordable use by all Americans.

Many partnerships are already in place to inform other efforts (such as RADx Tech for

Accessible Tests

) as well as a coordinated distribution infrastructure. This could be informed by

the infrastructure built to distribute home tests during the COVID-19 pandemic.

• Advance the validation and commercialization of novel wearable remote sensors, electronic

health records (EHRs), and other sources of physiological data, potentially building on existing

programs, such as those established by BARDA DRIVe, to predict vulnerability to disease and

monitor for long term consequences.

• Consider data infrastructure for Health Kits, including how the data could be used to enable

health improvement and be shared with a primary care provider or other clinician while still

emphasizing protection of patient privacy and data security.

Theme 2: Precision Multi-Omic Medicine

Context for the Bold Goals

Precision medicine is an approach for disease prevention, diagnosis, and treatment that considers people’s

individual variations in genes, environment, and lifestyle.

Reductions in the cost of sequencing a human

genome to <$1,000

has enabled DNA sequences to be incorporated into large-scale precision medicine

initiatives (e.g., UK Biobank, All of Us

Research Program, 100+ Cohort Consortium), studies of rare

disorders (e.g., UDN, GREGoR, IRDIC), and studies of cancer in a rapid and cost-effective manner. This

ability to directly measure, annotate, and interpret DNA sequence variation has transformed the approach

to disease biology. Similarly, the addition of multi-omics technologies (e.g., epigenomics,

transcriptomics, proteomics, metabolomics) into large cohorts with participants from diverse populations

is poised to have similar transformational impacts on understanding and managing human health and

disease. Major efforts such as The Cancer Genome Atlas

have used multi-omic data to characterize the

molecular basis of cancer and demonstrate how that information can change the way patients are treated

in the clinic—an approach also taken by programs supported by the Cancer Moonshot initiative.

multi-omics approach could allow improved diagnosis and therapy options for patients, enabling

classification of disease on a molecular basis combined with environment and lifestyle factors within a

precision medicine paradigm. Achieving this medical paradigm at a large and equitable scale requires

biotechnologies and biomanufacturing innovations to integrate multi-omic information in standard

clinical practice. The bold goals for achieving this include collection of multi-omic data, as well as

enabling of the personal multi-ome, with a focus on representation of diverse populations.

Cancer Moonshot℠ | National Cancer Institute

Rapid Acceleration of Diagnostics (RADx) | National Institutes of Health

RADx® Tech Accessible At-Home COVID-19 Tests | National Institutes of Health

The Precision Medicine Initiative | National Institutes of Health

The Cost of Sequencing a Human Genome | National Human Genome Research Institute

Outcomes and Impact of The Cancer Genome Atlas | National Cancer Institute

Generation of Human Tumor Atlases | National Cancer Institute

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R&D Needs

To collect multi-omic data (Goal 2.1):

• Develop novel sensors, such as in vivo DNA-based recorders, that allow for more passive

longitudinal collection of data to enhance the widespread adoption of multi-omics approaches.

• Drive down costs through targeted investment in novel high-throughput technologies, including

synthetic biology and cell-free approaches, with emphasis on enabling multi-omics

characterization with spatial resolution throughout tissues for <$1000 per sample.

To enable the personal multi-ome (Goal 2.2):

• Develop robust standards and benchmarks for multi-omics in consultation with agencies that

support the development of diagnostic tools (e.g., NIH and BARDA) and those that approve and

support diagnostic assays for use (e.g., FDA and CMS).

• Develop multi-omic data security and use covenants to protect patient privacy.

• Develop transformational approaches for assimilating, sharing, and analyzing complex multi-

omic data types from lab values to EHR data, including improved methods for data visualization

while ensuring data protection and security.

• Create standardized multi-omic data-collection and analytical approaches that enable predictive

models.

• Develop clinical research methods integrating multi-omics with environmental, lifestyle, and

other phenotypic data to enable clinically actionable patient classification, diagnosis, and therapy.

Theme 3: Biomanufacturing of Cell-Based Therapies

Context for the Bold Goals

Engineered cell-based therapy represents a new and exciting paradigm in therapeutic design, presenting

new options to patients with severe diseases (such as cancer) who, in some cases, can be limited to

traditional types of therapies with little hope of success. Perhaps the best-known cell-based therapies that

have reached widespread clinical use are for cancer, including chimeric antigen receptor T (CAR-T) cells

for certain hematological malignancies. CAR-T cells

have received six FDA approvals and have

reached greater accessibility, enabling 40% durable remissions in patients with certain cancers. To reach

its full potential, the method of manufacturing must be shortened, since the manufacturing time for certain

CAR-T cell products average around 2 weeks. Also, the current manufacturing method incurs low

availability, difficult harvesting of cells from each patient, shipping challenges, and difficulty in

identifying patients who are likely to benefit from the treatment, which results in extremely high costs.

All these challenges, coupled with the high potential for therapeutic efficacy in patients with few options,

point to the need for a concerted effort to change the manufacturing of cell-based therapies. The bold

goals for achieving this include focusing on increasing therapeutic efficacy of cell-based therapies as well

as increasing manufacturing capability and efficiency to enable a larger scale of cell-based therapeutic

production.

R&D Needs

Harmonization and advancement toward these bold goals could be pursued in consultation with the

agencies that support research into cell-based therapies (e.g., NIH), support biomanufacturing-capacity

CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers | National Cancer Institute

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investments (e.g., BARDA), and approve cell-based therapies for clinical use (e.g., FDA) and reimburse

patients for their use (e.g., CMS).

To increase therapeutic efficacy (Goal 3.1):

• Develop novel gene-editing techniques and genetic programming that can be leveraged to create

next-generation cell-therapies.

• Pair synthetic biology innovations with novel non-viral delivery vehicles, such as lipid or

polymeric nanoparticles, to further increase their utility and effectiveness. The fields of synthetic

biology and nanotechnology are already working in this space but require further specific effort

toward this goal.

• Investigate shipping protocols and storage technologies to keep source and engineered cells at

high viability without the use of toxic preservatives, such as dimethyl sulfoxide.

• Develop robust clinical and genomic indicators to identify patients who may be a good candidate

for cell-based therapies as well as computational models to identify and predict the therapeutic

impact of important engineered qualities of the cell-based therapies.

• Continue support for clinical team science approaches, bringing together clinicians, biologists,

engineers, and synthetic biologists.

To increase manufacturing scale (Goal 3.2):

• Identify and develop new source cells that may be more reproducible and less costly than patient

cells, such as allogeneic cells or minimal synthetic cells.

• Harmonize methods and standards across cell-based therapy manufacturing facilities by cell

types, reducing cost and wait time. The clinical-scale manufacturing of certain cell-based

therapeutics is already in place but could benefit from coordination and regulatory insight.

• Develop modular, platform-engineered cell-based technologies alongside patient-specific

formulations.

• Provide access to clinical-scale, cell-based manufacturing expertise as a national resource.

• Test and de-risk new biomanufacturing practices for next-generation biotechnology products in

commercial-quality manufacturing facilities.

• Partner with clinicians and other hospital staff to create training materials to ensure equity of care

across facilities and to consider equipment needs and assignment of clinical staff to patients

receiving cell-based therapies.

• Enhance public engagement for the acceptance of cell-based therapies, leveraging experience

with existing cell-based therapies such as CAR-T cells.

Theme 4: AI-Driven Bioproduction of Therapeutics

Context for the Bold Goals

While traditional forms of manufacturing therapeutics, such as small molecules, biologics, peptides, and

cell-based therapies, can be considered sufficient to meet the demands of patients with common diseases,

certain cases require new ways to produce therapeutics quickly and at a large scale, such as occurred

during the recent COVID-19 pandemic. New capabilities should be developed to meet the demands of

scalability, flexibility, and reliability for the on-demand manufacturing and biomanufacturing of

therapeutics. Novel forms of biomanufacturing, such as those involving microbes instead of mammalian

cells, have the potential to enable large increases in scale, but a concerted effort is required to identify

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opportunities to leverage systems of next-generation forms of manufacturing. Artificial intelligence may

provide the potential of enabling more distributed manufacturing of therapeutics by optimizing distributed

manufacturing and linking physically separated laboratories to act in a cohesive fashion. This potential

could be especially useful to respond to large-scale manufacturing needs for biotherapeutics, and this

approach could also enable faster design and production of new therapeutics utilizing AI/ML approaches

in combination with laboratory automation. The bold goals for achieving this include using automation

and AI/ML-enabled therapeutic design and testing techniques to increase manufacturing speed and

diversity.

R&D Needs

These efforts could be pursued in consultation with the agencies that support R&D AI/ML methods in

biomedicine (e.g., NIH and BARDA) and those that approve biotherapies for clinical use (e.g., FDA).

To increase manufacturing speed: (Goal 4.1):

• Develop a national network of biomanufacturing resources including three core components:

o A set of distributed, modular, and next-generation autonomous laboratories that focus on

capabilities, such as high-throughput screening, sensitive online sensors of relevant

metabolites, next-generation sequencing, high-content imaging, polymerase chain

reaction diagnostics, and others.

o A cloud-based virtual research organization to which each distributed automated

laboratory is directly connected.

o A federated model to integrate the physical laboratories with the virtual cloud

environment, such that AI methods can be utilized to generate hypotheses based on

previous experiments that could then be tested in a physical laboratory environment (i.e.,

a pre-competitive global lab of experimental data).

• Establish a training program and curriculum for a technical workforce to operate these

laboratories.

• Consider biosafety and biosecurity implications.

To increase manufacturing diversity through AI-driven therapeutic design (Goal 4.2):

• Create harmonized and standardized experimental data accessible to researchers anywhere in the

country in near real-time to help expedite biotherapeutic development.

• Develop novel AI/ML methods to design therapeutics of every class (e.g., small molecules,

biologics, peptides, and cell-based therapies).

• Develop technologies with 10-fold lower limits of detection, accuracy, and precision compared to

traditional techniques. In conjunction with quantum computing capabilities, quantum sensors are

emerging as technologies for detecting minute amounts of biologics in small samples, enabling

analysis of data to diagnose and address complex conditions.

• Develop and operationalize the use of novel technologies for the online sensing of metabolites,

physical parameters, and biologics during biomanufacturing.

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Theme 5: Advanced Techniques in Gene Editing

Context for the Bold Goals

Millions of Americans every year struggle with diseases caused by genetic mutations, many of which

cannot be cured using existing therapies. Recent cures have entered the pharmaceutical marketplace based

on gene therapy, including a recent therapy

announced that claims to cure beta-thalassemia with only a

single injection. Significant progress has been made in the development of gene-editing systems, from

novel delivery vehicles, such as viral vectors and lipid nanoparticles, to paradigm-shifting gene editors

like CRISPR-Cas9. With further advancement in gene therapy techniques, more cures like these could be

applied to other diseases including cystic fibrosis, sickle cell anemia, Tay Sachs, and many rare diseases.

Cures can be difficult to develop because of the need for safe and reliable delivery of the gene therapy as

well as the financial impracticality of creating specific, complex therapeutics for diseases that affect few

patients (in the case of rare diseases). The development of advanced platform technologies to edit

problematic genes would immediately enable the development and rollout of therapies toward these

diseases. The U.S. can look forward to a future including more cures, but the consistency, reliability,

long-term safety profiles, and efficacy of these cures must be addressed through strategic

biomanufacturing considerations. The bold goals for achieving this include increasing efficacy of

therapeutic gene editors as well as increasing manufacturing capability to meet rising demand.

R&D Needs

These efforts could be pursued in consultation with the agencies that support research into gene therapies

(e.g., NIH), work with industry on advanced development and commercialization (e.g., BARDA), and

approve gene therapies for clinical use (e.g., FDA) and reimburse patients for their use (e.g., CMS).

To increase efficacy (Goal 5.1):

• Develop gene delivery vehicles, gene editors, and editing systems, building on the success of

programs, such as the Somatic Cell Genome Editing program

• Develop standard assays in partnership with the research community (bioengineers; experts in

nanotechnology, biomaterials, and synthetic biology; clinicians, and more) to assess editing

efficacy in vitro and in vivo as well as create standard approaches to pair gene editors and

delivery vehicles leveraging AI/ML techniques.

• Develop methods to use AI/ML with clinical studies to establish short- and long-term gene editor

safety.

• Coordinate stakeholders around unified gene-editing standards through a dedicated stakeholder

group composed of expertise in standards development, regulatory considerations (including

consultation with FDA), industry and manufacturing capabilities, and academic research.

To increase manufacturing capacity (Goal 5.2):

• Address gaps in the current landscape of contract research organizations (CROs) and contract

manufacturing organizations.

o Create in chemico, in silico, in vitro, and in vivo core characterization facilities for

evaluating the safety and efficacy of gene editors and their delivery vehicles.

o Engage CROs to assess current capabilities and potentially add new ones.

o Address clinical infrastructure by installing necessary equipment to receive, store, and

prepare gene therapies.

FDA Approves First Cell-Based Gene Therapy to Treat Adult and Pediatric Patients with Beta-thalassemia Who Require

Regular Blood Transfusions | U.S. Food and Drug Administration

Somatic Cell Genome Editing | National Institutes of Health

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• Develop gene-editing platform technologies that can be produced at scale and then applied to

multiple diseases with little customization.

• Engage the clinical and patient communities to address financial hardship because of the high

cost of gene therapies.

• Assess the clinical workflow and pricing for the use of gene therapy.

• Create training materials for clinical staff, patient coordinators, and navigators and assign gene

therapy champions at major hospitals to serve as local experts in the application of gene therapy

and enable public engagement.

Stakeholder Consultation

These bold goals were identified through a variety of relevant stakeholder workshops and analysis of

relevant trends in biotechnology (particularly those funded by NIH) and consideration of feedback from a

White House Office of Science and Technology Policy Request for Information and accompanying

listening session for the bioeconomy.

Enhancing Biosafety and Biosecurity

Advancement in biotechnology R&D and biomanufacturing drives medical breakthroughs and has made

immeasurable positive impacts on American life. Alongside these advancements is a potential risk of

laboratory or manufacturing accidents or misuse of medical technologies for harmful purposes, which in

turn may cause harm to human health, public trust, or the environment. Such potential risks require the

U.S. government, in collaboration with the biomedical community, to continue taking protective actions

to appropriately mitigate these risks

without placing roadblocks on the discovery and innovation that

distinguish the U.S. biomedical enterprise. Implementing appropriate biosafety and biosecurity practices

ensures public safety, promotes trust, strengthens integrity in the bioeconomy, and ultimately benefits the

public.

The Bioeconomy Executive Order establishes the Biosafety and Biosecurity Innovation Initiative (BBII),

charged with reducing biological risks associated with advances in biotechnology, biomanufacturing, and

the bioeconomy. BBII will coordinate with key related Administration initiatives, and a forthcoming plan

for BBII will outline recommendations for increased Federal investments in several critical areas,

including research, workforce development, and culture change. These investments are an important step

to enable agencies to adequately manage potential risks throughout the R&D of this report’s bold goals.

Existing Biomedical Biosafety and Biosecurity Measures

Federal agencies invest significantly in safety and security throughout the biomedical enterprise. The U.S.

has a comprehensive biosafety and biosecurity oversight system driven by Federal regulations, guidelines,

and policies. This system is based on identifying and assessing benefits and risks and appropriately

mitigating the risks. Also, the U.S. continues to invest in applied biosafety research and biosecurity

innovation, training researchers and professionals in biosafety and biosecurity, and infrastructure in

support of good biosafety and biosecurity practices. It is critical that, as the biomedical field evolves, we

continue to assess and, as needed, update biosafety and biosecurity investments to reduce risk throughout

the bioeconomy.

Federal Select Agent Program | Centers for Disease Control and Prevention, U.S. Department of Agriculture; Dual Use

Research of Concern | National Institutes of Health; Research Review Under the HHS P3CO Framework | U.S. Department

of Health and Human Services

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Recommended Actions to Enhance Biosafety and Biosecurity in the Biomedical

Enterprise

Using investments proposed through BBII, the following actions will help ensure proper assessment and

management of biorisks throughout R&D of the bold goals outlined in this report.

• Assess and manage risks throughout the entire biomedical lifecycle—from conception to

product—in a manner that continues to preserve critical discovery and innovation.

• Use evidence-based and iterative approaches to develop metrics that quantify success of biosafety

and biosecurity practices and understand where improvement is needed.

• Continue investments in training biomedical professionals, biocontainment and biomedical

facility infrastructure, oversight, and applied biosafety research and biosecurity innovation.

• Strengthen the culture of good biosafety and biosecurity practices, in collaboration with

government, academia, industry, and the public, that can serve as a model globally.

• Support R&D to enhance cybersecurity and other data protection measures as medical devices

and smart manufacturing facilities hold more sensitive information, such as genomic data, disease

risk factors, and intellectual property.

• Engage in interagency coordination through BBII to ensure that biosafety and biosecurity

information, lessons learned, and good practices are shared by and with the biomedical

community.

Opportunities for Public-Private Collaboration

Pursuing opportunities for collaboration across government and in partnership with the domestic and

international public and private sectors will be critical to advancing foundational scientific capabilities in

biotechnology and biomanufacturing and translating that knowledge into products that improve human

health and strengthen the U.S. bioeconomy. A variety of public-private partnerships already exist in the

health space; they provide models and lessons learned for future partnerships and could be extended to

meet new goals or involve new partners. Such partnerships enable alignment on strategic objectives and

coordination of activities across Federal agencies and dozens of stakeholders from academia,

philanthropic organizations, and industry to achieve medical breakthroughs.

Existing Public-Private Partnerships

One example is the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL

), a

public-private partnership (part of Manufacturing USA®) focused on accelerating biopharmaceutical

innovation, supporting development of manufacturing standards, and education and training of the

biopharmaceutical manufacturing workforce, fundamentally advancing U.S. competitiveness in this

industry. Another example is BARDA Ventures, a public-private partnership with private investors using

venture capital practices to invest in transformative technologies to advance commercialization of

technologies, including in biotechnology and biomanufacturing. The Accelerating Medicines

Partnership® (AMP®) program

is another example of a public-private partnership between NIH, FDA,

the Foundation for the National Institutes of Health, and multiple public and private organizations,

including biotechnology and pharmaceutical companies. One project in AMP®, the AMP® Bespoke

Gene Therapy Consortium (BGTC),

aims to develop platforms and standards that will speed the

development and delivery of customized gene therapies.

National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) | National Institute of Standards and

Technology, Manufacturing USA®

Accelerating Medicines Partnership® program | National Institutes of Health

Bespoke Gene Therapy Consortium | National Institutes of Health

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Opportunities for U.S. Government Incentivization of Private Sector

Public-private partnerships enable incorporation of industry expertise and promote cooperation between

the private sector and the U.S. government. For example, Operation Warp Speed, which transitioned to

the Countermeasures Acceleration Group and is now known as H-CORE, and the Accelerating COVID-

19 Therapeutic Interventions and Vaccines (ACTIV)

partnership drove important aspects of the

Nation’s response to the COVID-19 pandemic by accelerating advancements in biotechnology, the

conduct of clinical trials, streamlining regulatory pathways, and rapidly sharing data. The AMP® projects

have partial funding from the private sector, and private-sector members are partners in governance,

stimulating private investment through programs such as the AMP® BGTC. Each of the themes proposed

involves significant needs for partners in the private sector, listed in the R&D needs for each theme. The

private sector may also benefit from harmonizing safety and quality standards for manufacturing and from

the creation of workforce development programs for training to bolster domestic capacity, such as for AI-

driven bioproduction of therapeutics (Theme 4).

Opportunities for Public Participation

Several of the themes identified require development of broadly applicable technologies that should be

enjoyed equitably by all Americans. Public participation, particularly focused on engagement with diverse

populations, will be critical in the development of these tools such that the needs of patient groups as well

as clinicians at every level are recognized and considered in the design, manufacture, and application of

these technologies. It will be important to seek patient and patient advocate perspectives through public-

private partnerships on the awareness and acceptance of novel cell-based therapies to develop

implementation strategies that increase equity of access, relevant to Theme 3. The same kind of input will

be important for all themes, with a special emphasis on the development of advanced gene therapies,

multiplexed diagnostic assays, and Health Kits, described in Themes 5, 2, and 1, respectively.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) | National Institutes of Health

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Biotechnology and Biomanufacturing R&D

to Further Cross-Cutting Advances

In collaboration with other U.S. Federal Government departments and agencies,

this report was authored by the U.S. National Science Foundation

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Executive Summary

We are on the cusp of a biotechnology revolution. Societal problems are increasingly being solved by

combinations of fundamental biological discovery and advances in science and engineering fields as

disparate as biomaterials and artificial intelligence. New and re-imagined tools like DNA-based

diagnostics, whole genome sequencing, and genome editing, which originated through curiosity-driven

research, are now commonplace for creating real-world solutions to previously insurmountable challenges

in fields from medicine to agriculture to clean energy. For example, COVID-19 tests and mRNA

vaccines, developed and deployed within the first year of the SARS-CoV-2 pandemic, saved over 3

million lives. These products of biotechnology would not have been possible without the foundational

research that was conducted decades earlier.

To ensure continued rapid advances in biotechnology and biomanufacturing to create the bioeconomy of

our future, we must boost innovation along multiple dimensions to protect our climate, improve the health

of Americans, support developments in food and agriculture, and build resilient supply chains. This report

describes six cross-cutting research and development themes which, if fully funded, would provide the

foundational discoveries, innovations, and infrastructure essential to advance all sectors of the

bioeconomy.

We must work to discover and understand the diversity of life (Theme 1) and how it has adapted to

harsh conditions and hard problems. The knowledge gained by tapping into Earth’s biodiversity must be

coupled with improved capabilities to predict the function and behavior of complex biological systems

and to use that information for new bio-inspired design (Theme 2). We have tools to automate the design

and manufacture of biological systems, but they work best for idealized systems like single-celled

organisms, not the complex systems of our future needs such as those needed to safely capture rare earth

elements by harnessing microbes capable of biomining. In addition, our ability to measure performance

lags our ability to design and build new systems; we need new measurement tools to accelerate discovery

and innovation (Theme 3). Scale-up of engineered biological processes from the laboratory to successful

commercialization remains dependent on trial and error, and we need new solutions for understanding

and controlling the performance and quality of bioconstructs in scaled biomanufacturing

environments (Theme 4). Existing bioreactor environments barely tap into the potential for

biomanufacturing innovation (Theme 5), which is crucially important for accelerating the scope and

pace of the bioeconomy revolution. Further, to ensure that new biotechnologies are widely adopted and

used by the public, we must engage end-users early in the ideation and creation (Theme 6) of such

advances.

We highlight bold goals that align with the needs described in the six themes above. Achieving the bold

goals within these areas and harnessing the potential power of biotechnology will require investments in

basic multidisciplinary R&D, new infrastructure, and public and private collaborations. To fully realize

the potential of the U.S. bioeconomy, these investments must be distributed across the nation, expanding

the geography of innovation and ensuring equitable access to and benefits from biotechnology and

biomanufacturing R&D.

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Bold Goals for Harnessing Biotechnology and Biomanufacturing

The following bold goals in cross-cutting R&D are intended to provide a broad vision for the U.S.

bioeconomy. These should not be read as commitments by the National Science Foundation (NSF) to

undertake specific activities. Achieving these bold goals require significant prioritization of R&D

investments and efforts across the U.S. government, as well as actions from the private sector and state,

local, and tribal governments.

Theme 1: Leverage Biodiversity Across the Tree of Life to Power the Bioeconomy

Goal 1.1: In 5 years, sequence the genomes of one million microbial species and understand the function

of at least 80% of the newly discovered genes.

Goal 1.2: In 20 years, speed discovery of new gene sequences, metabolisms, and functions by 100-fold

over current practice across all types of organisms.

Theme 2: Enhance Predictive Modeling and Engineering Design of Biological

Systems

Goal 2.1: In 5 years, increase the ability to predictably design small molecules or enzymes capable of

binding selectively to any desired target, and reduce the time needed for this process to 3 weeks.

Goal 2.2: In 20 years, leverage multidisciplinary advances in theory to enable high-confidence (90%)

design of purposeful engineered biological systems at all scales, from molecular to ecosystem level.

Theme 3: Expand Capabilities to Build and Measure Performance and Quality

of Biological Systems

Goal 3.1: In 5 years, develop the capabilities to read and write any genome, epigenome, transcriptome, and

expressed proteome to enable the construction and measurement of any single cell within 30 days.

Goal 3.2: In 20 years, build a synthetic minimal plant that can be used as a chassis for food, feedstock,

chemical, or pharmaceutical production.

Theme 4: Advance Scale-Up and Control of Biological Systems

Goal 4.1: In 5 years, advance bioprocess design, optimization, and control tools to enable predictable

scale-up to commercial production of any bioprocess within 3 months with a 90% success rate.

Goal 4.2: In 20 years, advance integration of all aspects of feedstock use, organism design, process design,

and end-of-use disposal with technoeconomic analysis such that sustainability and commercial goals can be

achieved for more than 85% of new bioprocesses within the first year of deployment.

Theme 5: Innovate Biomanufacturing Approaches

Goal 5.1: In 5 years, reproducibly manufacture devices that integrate living and non-living components

such as organ-chip or human-robotic interfaces that maintain over 90% viability and connectivity of

components, paving the way for innovations in biomanufacturing including the development of human-

assistive devices that will enable healthier aging.

Theme 6: Enable Ethical, Safe, and Equitable Co-Generation and Translation of

Biotechnology Products

Goal 6.1: In 5 years, include broad public and end-user participation; technology co-generation; rigorous

assessment; integration of social, behavioral, economic, and socio-technical sciences; and formal

evaluations in all biotechnological and biomanufacturing projects from their beginning.

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Bold Goals Explored

Theme 1. Leverage Biodiversity Across the Tree of Life to Power the Bioeconomy

Context for the Bold Goals

Unleashing the amazing promise of biotechnology relies on using the diverse capabilities found in living

organisms to produce new products and processes with the potential to diagnose and treat disease,

develop resilient crops, create clean forms of energy, and more. For example, many of the antibiotics and

anticancer drugs we use today were found by exploring the chemicals produced by different microbes and

plants. Many enzymes found in laundry detergents came from organisms that live at high temperatures.

We are discovering how to make strong glues and even stronger fibers by mimicking processes in

barnacles and spiders. We are identifying organisms capable of capturing greenhouse gases and

leveraging the power of biotechnology to convert organisms to textiles. These innovations and others like

them have sprung out of knowledge of a tiny fraction of the ways that life on Earth has evolved. Imagine

what more could be revealed from the estimated millions of species of plants, animals, fungi, and

potentially one trillion species of microbes on the planet.

Tapping into this huge reservoir of undiscovered and uncategorized species will provide knowledge of

new genes and how those genes create different physical traits, a connection known as genotype-to-

phenotype. Moreover, research on all manner of organisms—from microbes to plants to animals—and

comparisons among them will be required to identify similarities and differences that can be harnessed in

novel biotechnologies and biomanufacturing processes. Achieving the bold goals of sequencing diverse

species and learning the functions of their genes will rely on new tools and methods of understanding

gene function to accelerate the process and reduce costs. Storing and analyzing huge amounts of genome

and phenotype data will require innovations in computing, including artificial intelligence (AI). Using

those data to create new products for the bioeconomy will require innovations in bioengineering and

biodesign as well as sustained support for needed infrastructure.

R&D Needs

Enhance discovery of novel function from diverse organisms across the tree of life:

• Connect private genome sequencing capabilities with new and existing public capacity to

accelerate sequencing output and reduce time and costs.

• Develop a national strategy for selecting organisms to sequence so that comparative analyses are

likely to reveal functional variation that can be used for biological design. (Theme 2)

• Accelerate development of computational and experimental tools to enhance comparative

discovery of sequence and functional elements (e.g., regulatory networks, metabolic pathways,

and traits) that define genotype-to-phenotype relationships from evolutionarily diverse organisms

and provide the basis for new biotechnology innovations.

Put biodiversity to use in new biotechnology applications:

• Create new and improved technologies to move genes from one organism to another.

• Use outcomes of functional discovery to expand the number of organisms that can be used as

hosts (chassis) in engineered biological systems.

• Combine innovations from chemistry and materials science with outcomes of sequencing and

functional analyses to expand the repository of “parts” for so-called “plug-and-play” design-build

capabilities that incorporate biotic-abiotic interfaces as control elements.

• Create innovation laboratories to leverage learnings from biodiversity studies for bioinspired

design of new materials, devices, and products for the bioeconomy.

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Enable a robust ecosystem of multiagency, secured data infrastructure for the bioeconomy:

• Collaborate to enhance nationwide capacity for data handling and analysis, including

cyberinfrastructure and bioinformatics, to enable equitable, wide-spread access to data from

biodiversity studies.

• Align with the open data initiative by encouraging biological data (and biological parts) to be

Findable, Accessible, Interoperable, and Reusable (FAIR), and to include standardized metadata

and enhance support for cyberinfrastructure and data architectures which permit computation and

integration for discovery across diverse datasets. At the same time, balance the need for open data

with respect for intellectual property rights to maintain innovation incentives and appropriate data

protection and security measures for sensitive data.

• Sustain and enhance living and digitized collections to ensure they remain a resource for diverse

downstream applications.

• Support synthesis activities through center-scale investments that enable community-driven use

and analysis of data to foster innovations in discovery from across the tree of life.

Theme 2. Enhance Predictive Modeling and Engineering Design of Biological

Systems

Context for the Bold Goals

The ability to reliably design biological systems with specified function at all scales has been, and

continues to be, a holy grail of engineering biology. Achieving reliable and predictable design would

enable creation of drugs from scratch, proteins for enhanced agricultural output, and nature-based climate

change mitigation. A key step to rapid progress toward this goal is the use of predictive power to inform

and speed the design process.

Great strides in prediction have been made to date by combining fundamental evolutionary and

biophysical theory with AI-enabled deep learning. For example, we can now predict the function of a

protein from just its genetic sequence. However, this understanding relies on an approach that is only

possible on small and simple biological systems. New advances are needed to predict and design

biological functions in more complex systems, such as engineered plants that would be more drought

tolerant, engineered collections of microbes that could target and capture rare minerals in the soil, or a

natural ecosystem more capable of reducing wildfire risks associated with climate change.

Achieving the bold goals for rapid and accurate prediction and design of new biological systems at all

scales—from molecules to ecosystems—will require us to incorporate emerging data and new knowledge

of biological mechanisms at multiple scales and to leverage new design elements, or parts, gleaned from

biodiversity studies (Theme 1). Advances can build on current methods of automation and design that

have already been applied to gene circuit construction, and will leverage measurement capacity (Theme

3) as well as data from existing ecological observatories. Coupling these advances with learning from

iterative prediction and design cycles and the growing power of AI offers unprecedented opportunities to

advance engineering of biological systems with desired functions.

R&D Needs

Advance prediction at biomolecular, cellular, organismal, and ecosystem levels:

• Expand the ability to predict the often weak or transient biomolecular interactions that control

important functions of small biomolecules and enzymes, including those relevant to drug

discovery.

• Leverage advances in signal processing and information theory to predict modes of

communication among cells, organisms, and communities for incorporation into biological

designs.

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• Combine mathematical and computational modeling with knowledge of key steps in development

to inform design of artificial tissues and organs or to test human avatars on a dish.

• Use advanced computing and AI to analyze ecosystem data from long-term ecological sites and

from continental-scale and ocean observatories to predict ways to design natural systems and

mixed human/natural systems that are resilient to the effects of climate change.

• Advance theoretical, computational, and experimental tools at all levels to understand the

mechanisms of evolution and adaptation that drive change in biological systems and predict how

evolutionary change might be leveraged to positively impact biological design.

Exploit the powers of prediction and AI to advance biological design:

• Develop novel computational algorithms and automation workflows to combine logic and rules

enabling prediction of possible constructs with predictive models and libraries of biological parts

and their associated functions (Theme 1) to enable design of constructable complex cells,

organisms, and other complex biological systems.

• Combine AI with knowledge of evolutionary processes to move beyond protein design and

accelerate biological design at all scales of biological organization.

• Incorporate knowledge of thermodynamic, biophysical, mechanistic, physiological, and

phylogenetic factors to define and constrain the possible design space.

• Develop benchmarking approaches and standards for testing and validating AI-based and other

computational models to ensure reliability and trustworthiness of the resulting designs.

• Explore the limits of biological design via both top-down (i.e., breaking down a complex system

into component parts) and bottom-up (i.e., piecing together simple parts to make a more complex

system) approaches to build cell-free systems, synthetic cells, minimal cell, or organism systems.

Theme 3. Expand Capabilities to Build and Measure Performance and Quality of

Biological Systems

Context for the Bold Goals

Moving engineered biological systems from the proverbial drawing board to reality proceeds through the

“design-build-test-learn” cycle. Designed systems (Theme 2) are built from parts (Theme 1) and then

tested by measuring their performance. Learning from these tests, powered by AI, completes the cycle by

providing information to inform the next generation of design and build steps.

Building and testing new biological systems both face significant hurdles. Building requires specialized

technologies for assembling the designed system from component parts so that it functions in the desired

fashion. Testing relies on the ability to measure performance of the built system and often takes

advantage of components that have been incorporated specifically to report on performance. Of these two

steps, testing presents the more substantial bottleneck because the pace at which we can design and build

new systems far exceeds our ability to test their performance.

To address these challenges in biological technologies, we need to adopt advances from multiple fields to

generate new platforms for manipulating and assembling new systems that not only yield the designed

functions but also enable facile testing of performance. Providing broad access to such tools and

platforms via public infrastructure will help ensure that we can achieve bold goals. Examples include

accelerating the rate of building and testing, or producing engineered whole organisms such as a synthetic

plant chassis for food, feedstock, chemical, or pharmaceutical production.

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R&D Needs

Expand capabilities for building novel forms and functions:

• Develop advanced technologies for precisely manipulating genomes, transcriptomes, proteomes,

and metabolomes of organisms—from microbes to animals and plants—to enable highly

predictable spatial and temporal control of complex phenotypes.

• Expand biomaterial design by developing and deploying multi-faceted capabilities, including

non-natural biopolymers and their building blocks, chemical functionality across the periodic

table, living materials (e.g., abiotic-biotic systems) that can sense and respond to the environment,

and biocompatible materials for biomedical components.

• Build platforms for precise high-throughput chemical modification of biomolecules and cells by

leveraging knowledge of diverse regulatory pathways and on-off controllers.

• Develop novel modalities for precise assembly of cells into organs, organisms, or ecosystems that

incorporate abiotic components as key control or sensing elements.

Expand capabilities for measuring, sensing, actuating, and controlling biological systems:

• Develop biological and non-biological sensors and transducers that do not interfere with cellular

function and that take advantage of quantum, optical, magnetic, and other sensing modalities

which can receive exogenous signals and interface with biological systems.

• Develop platform technologies to fully read the expressed genome, proteome, and metabolome to

enable high-throughput precision phenotyping of any organism.

• Develop platforms and tools for rapid, multimodal measurement of complex signals from cellular

and multicellular systems in the context of their interconnected natural and built environments.

• Develop sensor/transducer systems which can both measure and transmit signals that actuate a

calculated response, thus enabling open or closed loop control of biological systems. Examples

include conversion of undifferentiated cells into mature, functional cells or organoids; assembly

of natural or synthetic communities of cells for environmental remediation; and engineering of

whole organisms to signal and control a change in nutrient conditions.

Accelerate design-build-test-learn capabilities via public infrastructure:

• Build a national network of biofoundries to enable democratized access to facilities, both virtual

and physical, for modern biotechnology associated with design-build-test-learn cycles in cell-free,

cellular, organoid, and whole-organism systems.

• Connect biofoundries with expanded publicly accessible repositories of “parts” and sensors.

Theme 4. Advance Scale-Up and Control of Biological Systems

Context for the Bold Goals

Over the past 20 years, the U.S. has been a world leader in biological design and innovation, yet our

ability to predictably scale-up and control biological systems has not kept pace. This methodological gap

leads to lengthy process development and wasted R&D investment.

A key challenge in the scale-up of biological systems compared to more traditional industries such as

petrochemicals is that, unlike chemicals, biological systems behave differently depending upon the

environment. For example, a cell engineered to produce a commodity chemical might deliver high yields

when grown in the lab in a 100-milliliter flask, but that performance can change dramatically when scaled

up to a commercial scale of 10,000 liters. Another complication in commercial-scale production is that

organisms are frequently designed to produce a biochemical without considering how the chemical will

be purified after production or be disposed of at the end of its use. This lack of integration at the outset

leads to high costs and unneeded waste, impeding successful commercialization. Thus, to achieve bold

goals of speeding scale-up for simple bioprocesses as well as integrated industrial-scale operations, a

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compelling need exists to integrate new developments in predictive modeling of biological processes

(Theme 2) and measurement (Theme 3) with advances in process engineering to advance the science of

scale-up and control of biological systems.

R&D Needs

Accelerate scale-up via robust process modeling, optimization, and design:

• Develop the ability to predict performance and behavior (including evolution) of cells, organisms,

systems of organisms, and the molecules they use and produce in complex production and

processing environments.

• Advance theory-driven and AI-enabled multiscale modeling using data from biofoundries to

couple models of biological system performance with models of bioprocess performance.

• Integrate optimization parameters across all aspects of the bioprocess, including design, upstream

and downstream processes, product end-of-life, and non-conventional bioprocess environments.

• Improve bioproduct supply chain resiliency by advancing process design methods to transition

from (semi)-batch to continuous and intensified processes, including through the use of modular,

geographically distributed, and potentially reconfigurable processes or facilities.

• Advance capabilities in digital twins across a broad range of application spaces, including both

in-fermenter and outside the fermenter applications.

• Leverage existing Manufacturing USA institutes and other public and private infrastructure to

support model validation via prototypes and scaled-up or scaled-down systems.

• Develop robust tools for technoeconomic analysis and life cycle assessment that can be integrated

within the design process.

Advance biological process control:

• Advance the capacity to develop process control strategies that include control at the cellular

level (e.g., embedded sensors/actuators within cells, Theme 3) and at the whole-system level.

• Advance model-based process optimization and control that can explicitly account for biological

uncertainty, stochasticity, and variation in biological as well as physical systems.

• Advance estimation techniques to predict the many states (e.g., cell phenotype, protein

expression, or enzyme activity) of biomanufacturing processes that cannot be measured directly.

Theme 5. Innovate Biomanufacturing Approaches

Context for the Bold Goals

New biotechnologies and bio-inspired designs hold the potential to extend human capability, increase

health, and enable forms of data storage and computation requiring far less space and energy than

conventional systems. However, to realize these and other potential applications, new forms of

biomanufacturing are required.

Innovations in biomanufacturing modalities will need to leverage all the advances in R&D envisioned in

Themes 1 through 4, together with advances in multi-materials processing, robotics, and cyber-

manufacturing. To achieve the bold goal of producing devices that integrate living and non-living

components and pave the way for assistive devices to benefit human health, advances will be needed in

sensors, the internet of things, autonomy, human-machine teaming, and computation at the human-

technology frontier. Moreover, new methods and processes are necessary to develop new application-

specific uses (e.g., human-machine interfaces, wearable devices, and biotechnologies that augment human

capabilities) and provide alternative fuels and infrastructure materials. Again, realizing new methods and

processes proceeds through the “design-build-test-learn” cycle.

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R&D Needs

Innovate in biomaterials manufacturing:

• Advance capabilities in nanomanufacturing that leverage biobased nanomachines and designs.

• Develop engineered biological and biomanufacturing systems to produce biopolymers and

process them in situ and at scale, thereby enabling manufacture of biomaterials which mimic

those found in nature such as insect silks or exoskeletons.

Advance integration of cells and tissues with devices and the creation of multi-materials:

• Advance development of bio-enabled processes using DNA, viruses, and bacteria, including

DNA-enabled self-assembly for data storage applications.

• Advance capabilities for bioprinting cell scaffolds, bone or cartilage replacements, and multi-

material structures to mimic or replace living tissues. Advance capabilities for bioprinting in

applications including fuels, electronics, and materials.

• Incorporate the potential for new cells and tissues to participate in sensing, actuating, data

capture, feedback, repair, and scale-up of manufacturing printed living materials reproducibly.

• Advance capabilities for manufacturing functional neuron or brain organoid devices, both for

neuronal stimulation and repair and for potential biological computing applications.

Create innovations at the human-technology frontier:

• Develop manufacturing of wearable and ubiquitous technology to provide enhanced mobility and

assist with communication and everyday needs.

• Create appropriate technologies to improve worker productivity and quality of life, including

collaborative physical and cognitive assistance, seamless augmented reality and telepresence, and

private and secure health and wellness monitoring.

Theme 6. Enable Ethical, Safe, and Equitable Co-Generation and Translation of

Biotechnology Products

Context for the Bold Goals

New discoveries from across the tree of life (Theme 1), advancements throughout the design-build-test-

learn cycle (Themes 2 and 3), new scale-up capabilities (Theme 4), and innovative biomanufacturing

approaches (Theme 5) will provide a wealth of foundational, technical, and practical know-how for

advancing biotechnology and biomanufacturing. However, the promise of these advances to positively

impact the bioeconomy will depend largely on public willingness to adopt and use these new innovations.

This cannot be taken for granted. For example, recent research suggests many people and nations still

doubt the safety of genetically modified foods. To help ensure that the biotechnology advances proposed

in this report will be embraced, we must engage stakeholders and end users early and often as the

technology is designed, implemented, and deployed.

Achieving the bold goal of involving the public from the outset will require evidence-based, collaborative

new approaches and methods of engagement, changes in practice, and coordination across the product

lifecycle from discovery through design and disposal. We also will need to develop the evidentiary basis

of the science of science, social and behavioral research, and economics. This will ensure use of rigorous,

data-driven approaches to inform best practices enabling ethical, safe, and equitable translation of

biotechnology products.

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R&D Needs

Develop biotechnology foci within the social sciences:

• Develop new research opportunities within the social sciences with a focus on biotechnology and

biomanufacturing.

• Advance the science of public engagement and public participation, as applied to biotechnology

and biomanufacturing, to develop an evidentiary basis for meaningful public involvement in

considerations of biotechnology.

• Invest in programs and efforts that incorporate social scientists within research teams working in

fields related to biotechnology and biomanufacturing.

• Conduct research on ethical issues related to biotechnology and biomanufacturing to develop new

understanding of how ethical concerns can inform public policies around biotechnology and

biomanufacturing.

• Develop new methods and processes to incorporate ethical, societal, decision-making, and

economic research into decisions at all phases of biotechnology development.

Enhance the evidentiary basis to ensure the safety of products and processes of the bioeconomy:

• Develop the capability to assess the health and environmental risks of products and processes of

the bioeconomy.

• Expand investments in research to enable science-based regulation of products and processes.

Enhance diversity and equity within biotechnology and biomanufacturing R&D:

• Expand investments in equity-focused science, including social justice, environmental justice,

and equity-advancing efforts, such as the Analytics for Equity Initiative led by NSF in partnership

with the Office of Science and Technology Policy (OSTP) and other research-backed efforts, to

advance better, more equitable outcomes for all of America.

• Develop educational and training pathways to broaden participation of underrepresented groups

to ensure diverse perspectives are included in future biotechnology and biomanufacturing R&D.

• Expand investments in accessibility to enable all individuals to participate in the bioeconomy and

benefit from biotechnology and the bioeconomy regardless of disability.

Stakeholder Consultation

This report was informed by community input gathered from a recent workshop series on Innovation in

the Bioeconomy, sponsored by NSF and facilitated by the University Industry Demonstration Partnership.

Valuable perspectives were also provided by policy papers from the Engineering Biology Research

Consortium (EBRC) and the Engineering Research Visioning Alliance, as well as input via OSTP-

sponsored listening sessions and a Request for Information from the National Biotechnology and

Manufacturing Initiative.

Enhancing Biosafety and Biosecurity

Foundational R&D in biotechnology and biomanufacturing can create immense benefits in fields such as

agriculture, medicine, energy, and climate science. It can also raise questions and highlight gaps related to

safety and security, both in the R&D process and in resulting products. Alleviating these concerns

requires public-private collaboration, community engagement, and development of best practices that can

be applied across sectors to ensure safety, enhance security, and promote trust.

Current concerns in biosafety and biosecurity associated with foundational R&D and the cross-cutting

advances meant to enable the whole bioeconomy include a lack of critical infrastructure in the U.S. and

vulnerabilities within existing infrastructure; lack of scientific, technological, and engineering expertise

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within the American biotechnology and biomanufacturing workforce; and potential for accidental or

purposeful creation and/or release of organisms or systems that could harm the environment or the public.

Lack of infrastructure, including sequencing and synthesis capabilities, open data repositories and

computational capabilities, biological parts collections, and biofoundries, creates the potential for stalled

development and offshoring of R&D to the detriment of the U.S. bioeconomy. Similarly, a lack of needed

expertise within the workforce, detailed in a separate report, increases the possibility of critical

technologies not making it to market.

Existing infrastructure requires increased investment to alleviate concerns around cybersecurity attacks,

introduction of contaminants into the supply chain, and physical breakdown of or attack on critical

repositories or parts of the supply chain. Such incidents could be purposeful or malicious, but they may

also result from accidents or aging systems; either cause can result in potential harm to the environment

or the public.

Mitigating the risks of accidental or purposeful design or release of harmful organisms requires an

expanded evidentiary basis to enable the prediction of biosafety risks of any synthetic sequence, part, or

organism. Technological innovations at sequencing, foundry, and scale-up facilities are also needed to

prevent accidental manufacture and release of potentially harmful agents.

Recommended New Biosafety and Biosecurity Measures

The Bioeconomy Executive Order calls for creation of a government-wide Biosafety and Biosecurity

Innovation Initiative (BBII) to enhance biosafety and biosecurity across the bioeconomy while

maximizing its benefits. In alignment with BBII plan recommendations, reducing biorisks associated with

foundational R&D, which cut across all sectors, will require support for critical infrastructure, workforce

development, cybersecurity as described above, and enhanced R&D on biocontainment, organismal

digital identifiers, and sequences of concern.

Opportunities for Public-Private Collaboration

Public-private partnerships represent a key component of the investments necessary to spur advances

across all sectors of the bioeconomy. These collaborations, both domestic and international, will enable

and support the necessary physical and cyberinfrastructure required to conduct fundamental R&D, ensure

connections between researchers and end-users, and translate new discoveries to the market at speed and

scale. They also provide an opportunity to advance equity and broaden participation through intentional

efforts to ensure involvement of underrepresented racial and ethnic groups and communities.

Existing Public-Private Partnerships

Existing public-private partnerships include industry-academia consortia such as EBRC, Manufacturing

USA institutes, and efforts connecting academia with industry. Leveraging these extant connections will

enable development of critical pipelines from academia through small business to industry at scale

(Themes 1-5), support crucial engagement of stakeholders (Theme 6), and inform policy development

with respect to biosecurity and biosafety risks.

Opportunities for U.S. Government Incentivization of Private Sector

Additional public-private interfaces can build consensus for strategic sequencing and data for bioeconomy

initiatives and consolidate efforts to maximize bioeconomy impacts. Sequencing capabilities developed

during the SARS-CoV-2 pandemic can be leveraged to address data for bioeconomy needs. Leveraging

existing biofoundries and pilot or production capacity, as well as repurposing existing infrastructure,

provides government-supported small businesses and researchers with low-cost or subsidized access to

critical design-build-test-learn capabilities needed to develop new biotechnologies (Themes 2 and 3) or

advance biomanufacturing (Theme 5), and access to needed scale-up infrastructure (Theme 4).

Partnerships with companies with sizeable computing power will help build the data fabric and systems

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needed to support the large amounts of existing and to-be-created biological data from large-scale

biodiversity studies (Theme 1).

Opportunities for Public Participation

In addition to engaging with the public sector in the partnerships and connections outlined above, the

private sector can provide in-kind support for any of the R&D needs listed in this report; collaborate with

academia on development of critical technology, tools, and infrastructure; provide novel educational and

internship opportunities to enhance the future workforce; and collaborate with foundations in such efforts.

Public engagement and participation are critical to the success of biotechnology and biomanufacturing

efforts (Theme 6). Pilot programs can identify best practices in community engagement and knowledge

co-generation as research on the science of science advances. These practices can increase interest in

biotechnology and biomanufacturing among diverse individuals across education levels.

Building on the successes of crowdfunding in the private sector, the U.S. government could invest in pilot

projects to facilitate crowdfunding of translational activity. The public could also engage through citizen

science programs. Similarly, research can benefit from public interest such as through efforts to leverage

idle computational capacity like Folding@Home, which utilizes volunteered computing power to run

protein folding simulations that have assisted in developing therapeutics to fight disease.

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Appendix A. Agency Research and

Development Efforts

Ongoing R&D activities from Federal departments and agencies related to bold goal themes are listed

in the table below.