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The Pace and Diffusion of Synthetic Biology Building the Bio-economy Biodesic The Pace and Diffusion of Synthetic Biology Tsinghua University, Beijing, January 2013 Rob Carlson Biodesic Seattle, WA www.biodesic.com @rob_carlson [email protected] hardware wetwaremindware:: blog: www.synthesis.cc © 2011 Biodesic 1 The Past and Future Present of Biological Technologies Photosynthetic Sea Slug (Elysia chlorotica) Evolved ~100 Myr BCE PNAS © 2011 Biodesic 2 The Past and Future Present of Biological Technologies Photosynthetic Sea Slug (Elysia chlorotica) Evolved ~100 Myr BCE C. Agapakis Photosynthetic Fish (Danio rerio) Engineered 2010 +5 (?) yrs Pam Silver, Harvard Univ. PNAS © 2011 Biodesic 2 Parsing the Spread of Biological Technologies Drivers Characteristics Consequences Economic 1. International 1. Widespread access to Growth 2. Distributed tools, skills, and materials. (Beer Vs. Oil) 2. Lower environmental 3. Increasing Capabilities impact (emissions). 4. Decreasing Costs 3. Lower energy usage. Material and 5. “Open Source”? 4. Reduction in foreign Energy energy and materials Efficiencies dependency. 5. More diverse bio-economy that can withstand shocks. Carbon Load 6. More diverse technological Reduction development for rapid countermeasures. Curiosity Major Uncertainties (It’s cool, dude.) Oil Price, Petroleum Production Investment, Gov’t R&D Investment in Bio, National and Int’l Regulatory Policy, FOOD,WATER, Threat Events, EU Carbon Labeling? US Electrification? ENERGY! Chinese Renewable Investment? 3 © 2011 Biodesic A Hierarchy of Engineering and Economic Complexities Multiple Cells: Control of growth and differentiation; products are cells and structures that cells make (Tissues, Organs, Animals, Houses). Claudia Cadillo Transplant Recipient Synthetic Single Cells: Looks initially like Metabolic Engineering; products are chemicals and biologicals made by cells. J.C. Venter Multiple Genes in a Single Cell Type: Metabolic Engineering: Fuels, Plastics, Terpenoids for Drugs, US GDP ArtemisininArtemisinin pathway Flavors, and Fragrances. RFS. 2010 > 2% Single Gene in a Single Cell: Recombinant Proteins: Laundry Enzymes, HGH, EPO. 1978 ~ 0% Expression in E. coli © 2011 Biodesic 4 How Big is the Bioeconomy? © 2011 Biodesic 5 “Genetically Modified Stuff” in the US Bioeconomy (2010 est.): >$300B or Equivalent of >2% of GDP U.S. Biotech Revenues (billions) Biologics GM Crops ~$75B ~$110B Industrial ~$115B See: Robert Carlson, “Biodesic 2011 Bioeconomy Update”, August 2011, www.biodesic.com © 2011 Biodesic 6 “Genetically Modified Stuff” in the US Bioeconomy (2010 est.): >$300B or Equivalent of >2% of GDP U.S. Biotech Revenues (billions) Biologics GM revenue growth: GM Crops ~$75B Crops 10%, Biologics 10%, Industrial 20%. ~$110B (Sources: Nat Biotech, Forbes) McKinsey and E&Y estimates for industrial apps range from $70B to $140B. Industrial ~$115B See: Robert Carlson, “Biodesic 2011 Bioeconomy Update”, August 2011, www.biodesic.com © 2011 Biodesic 6 Scale and Regulation U.S. Biotech Revenues in $ Billions Highly regulated Medium regulation Long lead times to market Long lead times to market Biologics ~75B ~$1 billion ~$100s millions GM Crops ~110B Industrial ~115B + Market includes engineering tools Operate closer to consumer Could be much smaller, lower capital reqs. As low as ~$10K-100K? non-drug + non-food = not-so-regulated © 2011 Biodesic 7 U.S. Market Penetration and Pace of Major GM Crops US Market Penetration of GM Crops 100 90 80 70 60 t n e 50 c r e 40 P 30 Soy 20 Corn Cotton 10 Source: USDA Sugar beet 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Year © 2011 Biodesic 8 US Market Value of GM Crops US Farm Scale Revenues from Major GM Crops January 2013 120 GM Corn Revenues GM Cotton Revenues 100 GM Soy Revenues US GM Crop Revenues 80 Sources: USDA, Biodesic s n o i l l 60 i B D S U 40 20 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Year See: Robert Carlson, "The Market Value of GM Crops", Nature Biotechnology, 27, 984, 2009. © 2011 Biodesic 9 Average US Corn Yields: No End in Sight Average US Corn Yield, 1866-2009 200 bu/acre Open Pollinated Double Cross Single Cross Biotech/GM 180 160 U.S. Planted Area: Eight Major Crops 300 140 290 280 120 s e r 270 c A n 260 o i 100 l l i M 250 80 240 230 60 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 40 20 0 1860 1880 1900 1920 1940 1960 1980 2000 2020 Sources: USDA-NASS; Troyer, Crop Science 46.2 (2006): 528; Pioneer (Rupert and Butzen, Crop Sci, 19(2)) See: Robert Carlson, “Biodesic 2011 Bioeconomy Update”, August 2011, www.biodesic.com © 2011 Biodesic 10 Average US Corn Yields: No End in Sight Current Test Yield: Average US Corn Yield, 1866-2009 ~300 bu/acre 200 bu/acre Open Pollinated Double Cross Single Cross Biotech/GM 180 160 U.S. Planted Area: Eight Major Crops 300 140 290 280 120 s e r 270 c A n 260 o i 100 l l i M 250 80 240 230 60 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 40 20 0 1860 1880 1900 1920 1940 1960 1980 2000 2020 Sources: USDA-NASS; Troyer, Crop Science 46.2 (2006): 528; Pioneer (Rupert and Butzen, Crop Sci, 19(2)) See: Robert Carlson, “Biodesic 2011 Bioeconomy Update”, August 2011, www.biodesic.com © 2011 Biodesic 10 Economically Driven Global Adoption: Biotech Revenues as % of GDP Country 2010 Biotech Revenues 2020 Target Biotech Revenues United States > 2% NA China 2.5% (?) 8% Malaysia 2.5% 10% India 0.24% NA Pakistan 1.4% NA Europe ~1% NA Source: Biodesic Main source of uncertainty is definition of “biotechnology”; i.e., all biology or only products of genetic modification. See: Robert Carlson, “Causes and Consequences of Bioeconomic Proliferation”, 2012 Biodefense Net Assessment, Homeland Security Institute, http://bit.ly/Qm3fxi © 2011 Biodesic 11 How Fast Is The World Changing? © 2011 Biodesic 12 1 • Executive Summary Looking ahead, ongoing improvements in the performance of key enabling technologies, includ- ing DNA sequencing and synthesis, are likely to deliver significant further increases in prod u c t i v - ity and reductions in cost over the next decade. Intensifying global competition among companies and countries providing sequencing and synthesis services, coupled with abundant technological in n o vation, is driving the rapid diffusion of new technology. In turn, the overall market for these se r vices is growing rapidly and is likely to continue to expand at rates as high as 10—20% annu- al l y . These trends will have significant direct economic impacts within the biotechnology industry itself and across the economy at large. The implications of these trends for the U.S. economy are explored in Section 3. The combinato- rial engineering approaches that have transformed the fields of electrical engineering and software design are now being leveraged to accelerate biological engineering. Alrea d y , these techniques are being utilized to produce high value products for a variety of commercial purposes, and the range of potential applications is huge. Howeve r , the continuing “buildout” of these technologies will be shaped in large measure by an array of outstanding legal, ethical, economic, social, reg u l a t o r y and political questions and issues that have yet to be res o l v ed. The ways in which these perplexing questions are addressed by governments and societies arou n d the world will haveAn a significant Inflection affect on thePoint future impactin Biotech of biological Capabilities?engineering on the econ- omy and the earth ’s living systems. Figure 1-2: An Inflection Point for Biological Technology New enabling tech- nologies, especially in sequencing and synthesis, coupled with the development of new approaches to bio- logical engineering, have defined an inflection point in advance of biotech- nological capabilities, and could mark the “Genome Synthesis and Design Futures: Implications for the U.S. Economy” beginning of a new Bio Economic Research Associates, 2007. www.bio-era.net technology revolution in 13 the economy at large. © 2011 Biodesic 2 Genome Synthesis and Design Futures: Implications for the U.S. Economy • © 2006 bio-era Oligo Synthesis and Gene Assembly double stranded DNA A T G C T C T A A A G single stranded DNA © 2011 Biodesic 14 Enabling Technologies Are Improving Rapidly Productivity in DNA Synthesis and Sequencing Updated Spring 2008 1.00E+10 1.00E+09 Number of transistors per chip 1.00E+08 Commercially Available Sequencers Commercially Available 1.00E+07 Synthesizers 1.00E+06 1.00E+05 1.00E+04 1.00E+03 Number of transistors per chip. per transistors of Number 1.00E+02 Productivity [bases per person per day] per person per [bases Productivity 1.00E+01 1.00E+00 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 Year © 2011 Biodesic 15 What is Moore’s Law? Moore’s Law is about vision, it's about what you're allowed to believe. Because people are really limited by their beliefs, they limit themselves by what they allow themselves to believe what is possible. So here's an example where Gordon [Moore], when he made this observation early on, he really gave us permission to believe that it would keep going. - Carver Mead Also about finance and planning in a multi-billion dollar industry. Finally, Moore’s Law is about exponential markets that, for some time period, grow faster than transistor costs fall. Potentially very different than biology. © 2011 Biodesic 16 Cost c. 2011 Cost Per Base of DNA Sequencing and Synthesis Rob Carlson, June 2011, www.synthesis.cc 1.0E+02 1.0E+01 1.0E+00 1.0E-01 s r 1.0E-02 a l l Sanger/Capillary o D 1.0E-03 S U 1.0E-04 1.0E-05 Cost: Sequencing 1.0E-06 Cost: Short Oligo Cost: Gene Synthesis Pyro, Beads 1.0E-07 1988 1993 1998 2003 2008 2013 © 2011 Biodesic Years 17 The Future? Oxford Nanopore © 2011 Biodesic 18 Constructing Genes and Genomes !"#$%&'()*+,-&.%/(&012 !(&)*&# !(&)*&- D<EF0345'&!&6 Bacteria D<EF0345'&&%6 F 9 !(&)*&$ F 2 I 4 F .08C?2A45'&&,6 C 0 C B<2345'&&,6 Viruses H < > !(&)*&, 3 @9AA045'&&'6 0 @ =>9??9145!""$6 72389:;<45!""&6 !(&)*&+ Genes ./0123245!"#"6 Oligos !(&)*&' !"#$ !"%& !"%$ !""& !""$ '&&& '&&$ '&!& '&!$ G921 Sources: see http://www.synthesis.cc/2010/05/booting-up-a-synthetic-genome-1.html © 2012 Biodesic 19 “Synthetic Cells” “What we are doing with the synthetic chromosome is going to be the design process of the future.” J.
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