Trends in Biotechnology Investment

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1 Trends in Biotechnology Investment National Academies Workshop Future Biotechnology Products and Opportunities to Enhance Capabilities of Biotechnology Regulatory System June 1, 2016 Theresa Good, Deputy Division Director, Molecular and Cellular Biosciences National Science Foundation 1

2 NSF Mission (from 1950 Act) To promote the progress of science; to advance the national health, prosperity, and welfare; and to secure the national defense; and for all other purposes. NSF Vision [to enable the USA to become a] nation that creates and exploits new concepts in science and engineering and provides global leadership in research and education. Core Values Scientific Excellence Organizational Excellence Learning Inclusiveness Accountability for Public Benefit Strategic Goals Transform the frontiers of science and engineering Stimulate innovation and address societal needs through research and education Excel as a Federal Science Agency

3 NSF is unique among federal research funding agencies Mandate to fund both research and education Focus on basic research in all areas of science All areas of science, engineering and computer science are housed in one agency Funding decisions based on advisory peer review to program directors who have discretion to set direction/ balance portfolio

4 NSF at a glance

5 NSF Investments in Engineering Biology The ability to predict the behavior and design complex biological systems, Biological systems (i.e., cells) rely on exquisitely complex, high fidelity, self-replicating, adaptive, and responsive machines that utilize a wide range of starting materials, and that are refined via evolution. The challenge in engineering biology is to harness the intrinsic capabilities of biological systems to manufacture products that are of benefit to mankind. Contributing biological disciplines: synthetic biology, systems biology, metabolic engineering, protein engineering, and Supporting disciplines that enable the systematic and predictable design or redesign of biological systems, including mathematics, high performance computing, and computer science The research needs are to: Understand the physical, chemical and biological principles that govern life Improve tools, techniques and methodologies for prediction and design Enable scaling-up, usability, interoperation, safety, security, ethics Develop a future workforce Interdisciplinary education and training Address challenges in advanced manufacturing to ensure future US competitiveness

6 History of Funding in Engineering Biology UK names synthetic biology one of 8 great technologies, invests 60 M GBP SynBERC funded DARPA announces Living Foundries NSF participates in ERASynBio DARPA 1000 molecules $110M Directed Evolution CBiRC funded SBIR synbio STTR synbio First igem competition DARPA convenes first synbio meetings Metabolic Engineering DOE funds 3 Bioenergy Centers at $25M/year ea Synthetic biology sandpit w/ EPSRC Enhancing photosynthesis sandpit w/ BBSRC Systems & Synthetic Biology Program in MCB Nitrogen fixation ideas lab w/bbsrc Synthetic Biology part of NSF budget request for 1 st time

7 Biotechnology is funded throughout the NSF Engineering: Engineering Research Centers, Biotechnology and Biochemical Engineering, SBIR/STTR, I/UCRCs in Biomanufacturing, Advanced Cellular Biomanufacturing initiatives to create the new technologies and products that could potentially lead to growth in US economy, train a workforce, in areas of health, consumer products, food, energy and environment Biological Sciences: Molecular and Cellular Biosciences, Environmental Biology, Organismal Biology, Plant Genome developing new technologies; using tools of synthetic biology, advanced biology to address basic biological questions around origins of life, evolution, epistasis, fitness, pattern formation and development: asking the questions why does biology do it this way, and why not this other way? Mathematics and Physical Sciences: Chemistry of Life Processes, Physics of Living Systems application of theory to understand basic biological phenomena, development of new catalysts, materials from biological systems, bioinspired design Computer and Information Science and Engineering: Development of computational tools to enable advances in biotechology Social, Behavioral and Economic Sciences: Science, Technology and Society, Risk Assessment understanding impact of science on public, tolerance for risk

8 Engineering Biology Success Stories artemisinin, cosmetics, fragrances, fuels 8

9 Ginkgo founded (MIT & SynBERC spinout) IP development contract ($4.1M) ARPA-E electrofuels organism contract ($6.67M) CLIO Gene Guard contract ($3.5M) Expanded to 11,000 sq ft facility Venture Funding ($54M); producing 20 different organisms for 10 different facility clients CAE software SBIR Phase I launch ($100K) SBIR Phase IB ($50K) 1 st automated build run DNA assembly tech PoC completed TIP ($1M) Test pipeline development initiated Fragrance company organism contract SBIR Phase I ($150K) Build pipeline doubles capacity The organism is the product

10 Engineering Biology Success Stories

11 Current Basic Research at NSF Research Focus: Explore the fundamental principles of biology (the rules of life) using the tools of Synthetic biology. EXPLORING THE DESIGN SPACE THAT CAN SUPPORT LIFE , Chaput , Guo , Chang , Dawson Leading Edge: Uncovering rules of life by modeling and building life-mimicking systems; systems approaches to examine mechanisms of regulation and control of biological processes; development of new paradigms at intersection of biology, mathematics, physics, chemistry and engineering to explore the Rules of Life.

12 Mission Driven Research Infrastructure Basic Agency Investment in Engineering Biology NSF: Basic science & engineering, education, societal impact; 2 centers SynBERC, CBiRC focused on developing technology and biorenewable chemicals, SBIR NIH: Basic research, discovery of new antibiotics, understanding cancer, stem cells, cellular aging, tools for biopharmaceutical manufacture USDA-NIFA: Basic research in crops and livestock; risk assessment; industrial feedstocks from agriculture DARPA: Living Foundries & 1000 molecules to build foundries/ infrastructure for biomanufacture; Attribution, Gene Guard and Memory: Biosafey and Biosecurity, genetic labeling of organisms such that we can track origin (for IP protection or identification of where a biological warfare agent came from); to build safety features into organisms; BRICS to build in robustness to evolution NIST: Standards development to facilitate commerce; metrology; data resources for predictive modeling NASA: understanding other forms of life; capacity to sustain life away from earth ONR: organisms for sensing, material production, bio-inspired robotics NSRDEC: materials synthesis, sensors DOE: Biofuels, bioelectricity and biologically produced products, large centers, pilot scale facilities, TRL

13 TRL of current investments needs to achieving TRL 9 Current investments Research/ Technology Development Needs Operate at Scale DuPont Susterra Lanza, Genomatica - butadiene Amyris Ginkgo DOE BTO DARPA Bio-MOD DOE ARPA-E DARPA BRICS ONR Bolt DARPA Foundries NSF CBiRC NSF SynBERC NSF ENG NSF BIO Integrate Process Components biocatalysis and chemical catalysis upstream and downstream processes design/ engineering of feedstocks to enhance fermentation continuous bioprocessing/ integration of reactor design w/ organism productivity Grow Organism at Scale control behavior of organism in process environment control relationship between cell concentration, nutrient concentration, mass transfer, and physiology control mutation rate/ evolution over process time control environment model/ predict/ control behavior of communities Design Organism discover enzymes evolve/ design new biocataysis control expression optimize pathway model/ predict performance standardize/ automate assembly high-throughput testing

14 Effort Engineering biology today is a time and money intensive process but with future investments it doesn t have to be. 1.00E+11 virus minimal bacterium yeast humans 1.00E E E E E+06 GEVO isobutanol 2012 JBEI/Amyris artemisinin 2009 C. Voigt bacterial edge detector DuPont 1,3 propanediol 2002 Amyris Product 1 (biofuels/chemicals) Amyris Product 2 (biofuels/chemicals) With improvements in: Design, build & test cycle Understanding biological complexity. J. Boeke Yeast chromosome synthesis C. Voigt Nitrogen Fixation Ginkgo Bioworks What might be possible with future investments 1.00E+05 C. Voigt bacterial photograph 1.00E E+03 metabolic engineering complex genetic circuits genome rewrite ,000 10, ,000 Complexity