DOI: 10.3724/SP.J.1003.2012.13205

Biodiversity Science (生物多样性) 2012/20:2 PP.138-150

Assessment and management of biosafety in synthetic biology

While having developed into one of the most dynamic fields of the life sciences, synthetic biology may pose potential risks to the environment and human health. Based on current national and international risk assessment methods and current regulation of synthetic biology, we reviewed risk assessment in relation to synthetic biology’s research subfields (such as DNA-based biocircuits, minimal genome, protocells and chemical synthetic biology), its relation with biosafety engineering, its effect on ELSI (Ethics, Legal and So-cial Implications) and recent biosecurity challenges, such as biopunk (or biohackery), garage biology, do-it-yourself biology and bioterrorism. Additionally, we investigated existing strategies for management of synthetic biology research, focusing on self-regulatory or technology-focused methods and using the 5P (the principal investigator, the project, the premises, the provider of genetic material and its purchaser) strategy focusing in five different policy intervention points. Furthermore, we reviewed the current research and de-velopment of synthetic biology and its current biosafety regulations in China. Finally, we recommended management strategies to guide future research in synthetic biology with necessary amendments, including the establishment of regulations with a core of safety assessment, synthetic biology-specific good laboratory practice guidelines, and arguments for the reinforcement of internal regulation at the institution level and more active public outreach efforts for biosafety.

Key words:synthetic biology, biosafety, biosecurity, risk assessment, risk management

ReleaseDate:2014-07-21 16:28:11

Aldhous P (2008) Sunshine snuffed out. New Scientists, Febru-ary 21. ( sci-ence/2008/02/sunshine-snuffed-out.html)

Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Syn-thetic biology: new engineering rules for an emerging disci-pline. Molecular Systems Biology, 2, 1-14; doi:10.1038/ msb4100073.

Anonymous (2003) Hacking the genome. The Hacker Quar-terly, 20(4), 6-9.

Atlas RM (2005) Ensuring biosecurity and biosafety through biopolicy mechanisms: addressing threats of bioterrorism and biowarfare. Asian Biotechnology and Development Re-view, 8, 121-137.

Atlas RM (2009) Responsible conduct by life scientists in an age of terrorism. Science and Engineering Ethics, 15, 263-269.

Balmer A, Martin P (2008) Synthetic Biology: Social and Ethi-cal Challenges. Independent Review Commissioned by the Biotechnology and Biological Sciences Research Council, Institute for Science and Society, University of Nottingham.

Benner SA, Sismour AM (2005) Synthetic biology. Nature Reviews Genetics, 6, 533-543.

Bhattacharjee Y (2007) Gene-synthesis companies join forces to self-regulate. Science, 316, 1682.

Bügl H, Danner JP, Molinari RJ, Mulligan JT, Park H-O, Rei-chert B (2007) DNA synthesis and biological security. Na-ture Biotechnology, 25, 627-629.

Canton B, Labno A, Endy D (2008) Refinement and standardi-zation of synthetic biological parts and devices. Nature Bio-technology, 26, 787-793.

Carlson R (2001) Biological Technology in 2050, Published as “Open Source Biology and Its Impact on Industry,” IEEE Spectrum. ( pdf)

Cases I, de Lorenzo V (2005) Genetically modified organisms for the environment: stories of success and failure and what we have learned from them. International Microbiology, 8, 213-222.

Cello J, Paul AV, Wimmer E (2002) Chemical synthesis of poliovirus cDNA: generation of infectious virus in the ab-sence of natural template. Science, 297, 1016-1018.

Chaput JC, Ichida JK, Szostak JW (2003) DNA poly-merase-mediated DNA synthesis on a TNA template. Jour-nal of the American Chemical Society, 125, 856-857.

Check E (2006) Locals rally to combat biodefence labs. Nature, 442, 962-963.

Coleman LB (2006) Livermoore lab considers bio-defense site in Tracy. San Francisco Chronicle, May 28, 2006.

Conferees, SB2.0 (2006) Public draft of the declaration of the second international meeting on synthetic biology. (

Counsell D (2001) Hacking the genome. Linux User, 6, 26-29.

Daniels N (2008) Reflective equilibrium. In: The Standford Encyclopedia of Philosophy (Fall 2008 edition) (ed. Zalta EN). ( flectiveequilibrium/)

de Vriend H (2006) Construction life. Early Social Reflections on the Emerging Field of Synthetic Biology, Working doc-ument, Rathenau Institute, The Hague.

Deplazes A (2009) Piecing together a puzzle: an exposition of synthetic biology. EMBO Reports, 10, 428-432.

DoD (Department of Defense) (2000) Standard Practice for System Safety. ( milstd882d.pdf)

Dyson F (2007) Our biotech future. The New York Review of Books, 54(12), 1-7. ( 70)

Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature, 403, 335-338.

Endy D (2007) Programing DNA: A 2-bit language for engi-neering biology. Presentation at the 24th Chaos Communi-cation Congress, December 27-30, Berliner Congress Cen-ter, Berlin, Germany.

ETC (European Trade Committee) (2007) Extreme Genetic Engineering an Introduction to Synthetic Biology. (http:// report- web.pdf)

Fischer M (2009) Synthetic Biology—the Industry’s Perspec-tive. Presentation at the Conference Applied Industrial Bi-ology in Europe—Status Quo and Perspectives, Freiburg, Germany, 17 April.

Fischer M, Maurer SM (2010) Harmonizing biosecurity oversight for gene synthesis. Nature Biotechnology, 28, 20-22.

Franco C, Deitch S (2007) Billions for biodefense: federal agency biodefense funding, FY2007-FY2008. Biosecurity and Bioterrorism: Biodefense Strategy Practice and Sci-ence, 5, 117-133.

GAO (2007) High-Containment Biosafety Laboratories. Pre-liminary Observations on the Oversight of the Prolifera- tion of BSL-3 and BSL-4 Laboratories in the United States. United States Government Accountability Office. GAO-08- 108T. (http://energycommerce. cmte_mtgs/110- oihrg)

Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature, 403, 339- 342.

Garfinkel MS, Endy D, Epstein GL, Friedman RM (2007) Synthetic Genomics, Options for Governance. (http://www.

Gibson DG, Glass JI, Lartigue C, Noskov VN, Noskov RY, Algire MA, Algire GA, Montague MG, Ma L, Moodie MM, Moodie C, Vashee S, Krishnakumar R, Assad-Garcia N, Assad-Garcia C, Denisova EA, Young L, Qi ZQ, Segall- Shapiro TH, Calvey CH, Parmar PP, Hutchison III CA, Smith HO, Venter JC (2010) Creation of a bacterial cell controlled by a chemically synthesized genome. Science, 329, 52-56.

Gold ER (2002) Merging business and ethics: new models for using biotechnological intellectual property. In: Genetically Modified Foods: Debating Biotechnology (eds Ruse M, Castle D). Prometheus Books, New York.

Greber D, Fussenegger M (2007) Mammalian synthetic biol-ogy: engineering of sophisticated gene networks. Journal of Biotechnology, 130, 329 -345.

Gu Y, Hu S, Chen J, Shao L, He H, Yang Y, Yang S, Jiang W (2009) Ammonium acetate enhances solvent production by Clostridium acetobutylicum EA 2018 using cassava as a fermentation medium. Journal Industrial Microbiology Bio-technology, 36, 1225-1232.

Hanson R (2004) Hacking the Genome—Designer Proteins, Elite Organisms, and You. Presentation at the 21st Chaos Communication Congress, December 27-29, Berlin, Ger-many. ( 21C3-2004-designer-prots-elite-organisms.pdf)

Hart Research (2009) Nanotechnology, Synthetic Biology, & Public Opinion: What Does the Public Think? (http://www. 6380/)

Hecht J, MacKenzie D (2005) Safety fears raised over biosecu- rity lapse. New Scientists, 20 January 2005. (http://www. osecurity-lapse.html)

Heinemann M, Panke S (2006) Synthetic biology-putting engi-neering into biology. Bioinformatics, 22, 2790- 2799.

Heller MA, Eisenberg RS (1998) Can patents deter innovation? The anticommons in biomedical research. Science, 280, 698-701.

Herdewijn P, Marliere P (2009) Toward safe genetically modi-fied organisms through the chemical diversification of nu-cleic acids. Chemistry and Biodiversity, 6, 791-808.

Kaiser J (2007) Synthetic biology: attempt to patent artificial organism draws a protest. Science, 316, 1557.

Kaur H, Arora A, Wengel J, Maiti S (2006) Thermodynamic, counterion, and hydration effects for the incorporation of locked nucleic acid nucleotides into DNA duplexes. Bio-chemistry, 45, 7347-7355.

Keasling JD (2008) Synthetic biology for synthetic chemistry. ACS Chemical Biology, 3, 64-76.

Kelle A (2007) Synthetic biology and biosecurity awareness in Europe, Vienna, IDC. ( /uploads/// pdf/Synbiosafe-Biosecurity_awareness_in_Europe_Kelle.pdf)

Kelle A (2009a) Ensuring the security of synthetic biology- towards a 5P governance strategy. Systems and Synthetic Biology, 3, 85-90.

Kelle A (2009b) Security issues related to synthetic biology between threat perceptions and governance options. In: Synthetic Biology: The Technoscience and Its Societal Con-sequences (eds Schmidt M, Kelle A, Ganguli A, de Vriend H), pp. 101-119. Springer Academic Publishing.

Klotz L (2007) Casting a wider net for countermeasure R&D funding decisions. Biosecurity and Bioterrorism: Biodefense Strategy Practice and Science, 5, 313-318.

Kurzweil R, Joy B (2005) Recipe for destruction. New York Times: A23. (October 17, 2005)

Liu W, Brock A, Chen S, Chen S, Schultz PG (2007) Genetic incorporation of unnatural amino acids into proteins in mammalian cells. Nature Methods, 4, 239-244.

Luisi PL (2003) Autopoiesis: a review and a reappraisal. Die Naturwissenschaften, 90, 49-59.

Luisi PL, Chiarabelli C, Stano P (2006) From never born pro-teins to minimal living cells: two projects in synthetic biol-ogy. Origins of Life and Evolution Biospheres, 36, 605-616.

MacKenzie D (2007) Plague of bioweapons accidents afflicts the US. New Scientists, 5 July. (http://www.newscientist. com/channel/health/dn12197-plague-of-bioweapons-accidentsafflicts-the-us.html). Accessed 3 June 2008.

Marchant GE, Pope LL (2009) The problems with forbidding science. Science and Engineering Ethics, 15, 375- 394.

Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD, (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotechnoogy, 21, 796-802.

Maurer SM, Zoloth L (2007) Synthesising biosecurity. Bulletin of the Atomic Scientist, 63, 16-18.

National Institutes of Health (2011) NIH Guidelines for Re-search Involving Recombinant DNA Molecules. (http://

NSABB (2007) Roundtable on Synthetic Biology. October 11, 2007. National Science Advisory Board for Biosecurity. ( 20Website.pdf). Accessed 3 June 2008.

O’Malley M, Powell A, Davies JF, Calvert J (2008) Know- ledgemaking distinctions in synthetic biology. BioEssays, 30, 57-65.

OECD (2001) Understanding the Digital Divide. (http://www. pdf)

Oye K, Yeddanapudi N (2008) Synthetic biology chassis de-sign and demonstration for safety and security, a preliminary blueprint for research and policy. Poster presented at the SB 4.0 Conference in Hong Kong, China, 10-12 October, 2008

Pauwels E (2009) Review of quantitative and qualitative stud-ies on U.S. public perceptions of synthetic biology. Systems and Synthetic Biology, 3, 37-46.

Pauwels E, Ifrim I (2008) Trends in American and European Press Coverage of Synthetic Biology. (http://www.synbiopr- ld_care/, accessed 31 March, 2010)

Pei L, Markus S, Wei W (2011a) Synthetic biology: an emerg-ing research field in China. Biotechnology Advances, 29, 804-814.

Pei L, Markus S, Wei W (2011b) Can synthetic biology bring sustainable development to China? Biochemist, 33, 14-18.

POST (Parliamentary Office of Science and Technology) (2008) Synthetic Biology, Postnote 298, London. (http://

Ro D-K, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MCY, Withers ST, Shiba Y, Sarpong R, Keasling JD(2006) Production of the antimalarial drug precursor ar-temisinic acid in engineered yeast. Nature, 440, 940-943.

Royal Society (2004) Social and ethical issues. In: Nanoscience and Nanotechnologies: Opportunities and Uncertainties. (

Schmidt M (2006) Public will fear biological accidents, not just attacks. Nature, 441, 1048.

Schmidt M (2008) Diffusion of synthetic biology: a challenge to biosafety. Systems and Synthetic Biology, 2, 1-6

Schmidt M, Torgersen H, Ganguli-Mitra A, Kelle A, Deplazes A, Biller-Andorno N (2008) SYNBIOSAFE e-conference: online community discussion on the societal aspects of syn-thetic biology. Systems and Synthetic Biology, 2, 7-17.

Schmidt M (2009) Do I undestand what I can create? Biosafety issues in synthetic biology. In: Synthetic Biology: The Technoscience and Its Societal Consequences (eds Schmidt M, Kelle A, Ganguli A, de Vriend H), pp. 81-100. Springer Academic Publishing.

Schmidt M, Ganguli-Mitra A, Torgersen H, Kelle A, Deplazes A, Biller-Andorno N (2009) A priority paper for the societal and ethical aspects of synthetic biology. Systems and Synth- etic Biology, 3, 3-7.

Schmidt M, Dando M, Deplazes A (2011) Dealing with the outer reaches of synthetic biology. Biosafety, biosecurity, IPR and ethical challenges of chemical synthetic biology. In: Chemical Synthetic Biology (eds Luisi PL, Chiarabelli C), pp. 321-342. John Wiley & Sons, Hoboken.

Schmidt M (2010) Xenobiology: a new form of life as the ulti-mate biosafety tool. BioEssays, 32, 322-331.

Smith HO, Hutchison CA, Pfannkoch C, Venter JC (2003) Generating a synthetic genome by whole genome assembly: ΦX174 bacteriophage from synthetic oligonucleotides. Proceedings of the National Academy of Sciences, USA, 100, 15440-15445.

Sole RV, Munteanu A, Rodriguez-Caso C, Macia J (2007) Synthetic protocell biology: from reproduction to computa- tion. Philosophical Transactions of the Royal Society Bio- logical Sciences, 362, 1727-1739.

Sunshine Project (2007) Texas A&M Bioweapons Accidents More the Norm than an Exception. (http://www.sunshine project. org/publications/pr/pr030707.html)

Szostak JW, Bartel DP, Luisi PL (2001) Synthesizing life. Na-ture, 409, 387-390.

Tucker JB, Zilinskas RA (2006) The promise and perils of synthetic biology. The New Atlantis. (http://www.thenewat htm)

Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A (2005) Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science, 310, 77- 80.

UNODC (United Nations Office on Drugs and Crime) (2005) World Drug Report 2005. United Nations Office for Drugs and Crime. Volume 1. United Nations Publication. Sales No. E.05.XI.10. ISBN 92-1-148200-3.

van Est R, de Vriend H, Walhout B (2007) Constructing Life, The World of Synthetic Biology. ( loadfile.asp?ID=1331)

Wang HH, Zhou XR, Liu Q, Chen GQ (2011) Biosynthesis of polyhydroxyalkanoate homopolymers by Pseudomonas putida. Applied Microbiology and Biotechnology, 89, 1497- 1507.

Wang JC (王冀川), Zhang ZW (张志文) (2011) A new area in biology—synthetic biology. Bulletin of Biology (生物学通报), 46, 1-4. (in Chinese with English abstract)

Weiss R (2007) Synthetic biology: from bacteria to stem cells. In: Annual ACM IEEE Design Automation Conference: Proceedings of the 44th Annual Conference on Design Au-tomation. (

Wilson J (2001) Biotechnology intellectual property-bioethical issues. In: Encyclopedia of Life Science. John Wiley & Sons, Ltd. Published Online: 25 APR 2001. (

Wimmer E (2006) The test-tube synthesis of a chemical called poliovirus. EMBO Reports, 7, S3-S9.

Xiong Y (熊燕), Chen DM (陈大明), Yang C (杨琛), Zhao GP (赵国屏) (2011) Progress and perspective of synthetic biol-ogy. Chinese Bulletin of Life Sciences (生命科学), 23, 826-837. (in Chinese with English abstract)

Yang C, Freudl R, Qiao C, Mulchandani A (2010) Cotransloca-tion of methyl parathion hydrolase to the periplasm and of organophosphorus hydrolase to the cell surface of Es-cherichia coli by the Tat pathway and ice nucleation protein display system. Applied Environmental Microbiology, 76, 434-440.

Yu H, Yao Y, Liu Y, Jiao R, Jiang W, Zhao GP (2007) A com-plex role of Amycolatopsis mediterranei GlnR in nitrogen metabolism and related antibiotics production. Archives of Microbiology, 188, 89-96.

Zhang CT (张春霆) (2009) The research progress of synthetic biology. Bulletin of National Natural Science Foundation of China (中国科学基金), 2, 65-69. (in Chinese with English abstract)

Zhang L, Peritz A, Meggers E (2005) A simple glycol nucleic acid. Journal of the American Chemical Society, 127, 4174-4175.

Zilinskas R (2006) Technical Barriers to Successful Biological Attacks with Synthetic Organisms, Security and Regulation of Experiments of Concern. ( topics/synbio101/bibliography/govern- ance/)