Science and Engineering Ethics

, Volume 23, Issue 2, pp 365–374 | Cite as

Biological Dual-Use Research and Synthetic Biology of Yeast

  • Angela Cirigliano
  • Orlando Cenciarelli
  • Andrea Malizia
  • Carlo Bellecci
  • Pasquale Gaudio
  • Michele Lioj
  • Teresa RinaldiEmail author
Original Paper


In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related international agreements which underlines the work of the Australia Group (AG) Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials (i.e. plasmids, strains, antibodies, nucleic acids) and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals.


Synthetic Biology Biological Weapon Export Control Chemical Weapon Convention Synthetic Genome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Annaluru, N., Muller, H., Mitchell, L. A., Ramalingam, S., Stracquadanio, G., Richardson, S. M., et al. (2014). Total synthesis of a functional designer eukaryotic chromosome. Science, 344(6179), 55–58.CrossRefGoogle Scholar
  2. Atlas, R., Campbell, P., Cozzarelli, N. R., Curfman, G., Enquist, L., Fink, G., et al. (2003). Statement on the consideration of biodefense and biosecurity. Nature, 421(6925), 771.CrossRefGoogle Scholar
  3. Barash, J. R., & Arnon, S. S. (2014). A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins. Journal of Infectious Diseases, 209(2), 183–191.CrossRefGoogle Scholar
  4. Beaudoin, G. A. W. (2015). Characterization of oxidative enzymes involved in the biosynthesis of benzylisoquinoline alkaloids in opium poppy (Papaver somniferum). Ph.D thesis, University of Calgary. Available at
  5. Berns, K. I., Casadevall, A., Cohen, M. L., Ehrlich, S. A., Enquist, L. W., Fitch, J. P., et al. (2012). Adaptations of avian flu virus are a cause for concern. Science, 335(6069), 660–661.CrossRefGoogle Scholar
  6. Bügl, H., Danner, J. P., Molinari, R. J., Mulligan, J. T., Park, H. O., Reichert, B., et al. (2007). DNA synthesis and biological security. Nature Biotechnology, 25(6), 627–629.CrossRefGoogle Scholar
  7. Cameron, D. E., Bashor, C. J., & Collins, J. J. (2014). A brief history of synthetic biology. Nature Reviews Microbiology, 12(5), 381–390.CrossRefGoogle Scholar
  8. Charatsis, C. (2015). Setting the publication of ‘dual-use research’ under the export authorisation process: The H5N1 case. Strategic Trade Review, 1, 56–72.Google Scholar
  9. Collett, M. S. (2006). Impact of synthetic genomics on the threat of bioterrorism with viral agents. In Garfinkel, M.S., Endy, D., Epstein, G.L., Friedman, R.M. (Eds.), Working papers for synthetic genomics: Risks and benefits for science and society, pp. 83–103.Google Scholar
  10. DeLoache, W. C., Russ, Z. N., Narcross, L., Gonzales, A. M., Martin, V. J., & Dueber, J. E. (2015). An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nature Chemical Biology, 11, 465–471.CrossRefGoogle Scholar
  11. Dover, N., Barash, J. R., Hill, K. K., Xie, G., & Arnon, S. S. (2014). Molecular characterization of a novel botulinum neurotoxin type H gene. Journal of Infectious Diseases, 209(2), 192–202.CrossRefGoogle Scholar
  12. Dymond, J. S., Richardson, S. M., Coombes, C. E., Babatz, T., Muller, H., Annaluru, N., et al. (2011). Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature, 477(7365), 471–476.CrossRefGoogle Scholar
  13. Edwards, B., Revill, J., & Bezuidenhout, L. (2014). From cases to capacity? A critical reflection on the role of ‘ethical dilemmas’ in the development of dual-use governance. Science and Engineering Ethics, 20(2), 571–582.CrossRefGoogle Scholar
  14. Enia, J., & Fields, J. (2014). The relative efficacy of the biological and chemical weapon regimes. The Nonproliferation Review, 21(1), 43–64.CrossRefGoogle Scholar
  15. Enserink, M. (2012). Will dutch allow ‘export’ of controversial flu study? Science, 336(6079), 285.CrossRefGoogle Scholar
  16. Enserink, M. (2013). Dutch H5N1 ruling raises new questions. Science, 342(6155), 178.CrossRefGoogle Scholar
  17. Enserink, M. (2015). As new botulism threat implodes, more questions. Science, 347(6225), 934–935.CrossRefGoogle Scholar
  18. Evans, S. A., & Valdivia, W. D. (2012). Export controls and the tensions between academic freedom and national security. Minerva, 50(2), 169–190.CrossRefGoogle Scholar
  19. Fossati, E., Narcross, L., Ekins, A., Falgueyret, J. P., & Martin, V. J. (2015). Synthesis of morphinan alkaloids in Saccharomyces cerevisiae. PLoS ONE, 10(4), e0124459.CrossRefGoogle Scholar
  20. Galanie, S., Thodey, K., Trenchard, I. J., Interrante, M. F., & Smolke, C. D. (2015). Complete biosynthesis of opioids in yeast. Science, 349, 1095–1100.CrossRefGoogle Scholar
  21. Gibson, D. G., Glass, J. I., Lartigue, C., Noskov, V. N., Chuang, R. Y., Algire, M. A., et al. (2010). Creation of a bacterial cell controlled by a chemically synthesized genome. Science, 329(5987), 52–56.CrossRefGoogle Scholar
  22. Gibson, D. G., & Venter, J. C. (2014). Synthetic biology: Construction of a yeast chromosome. Nature, 509(7499), 168–169.CrossRefGoogle Scholar
  23. Gronvall, G. K. (2013). H5N1: A case study for dual-use research. New York, NY: Council on Foreign Relations.Google Scholar
  24. Gurkan, C., & Ellar, D. J. (2005). Recombinant production of bacterial toxins and their derivatives in the methylotrophic yeast Pichia pastoris. Microbial Cell Factories, 4(1), 1.CrossRefGoogle Scholar
  25. Herfst, S., Schrauwen, E. J., Linster, M., Chutinimitkul, S., de Wit, E., Munster, V. J., et al. (2012). Airborne transmission of influenza A/H5N1 virus between ferrets. Science, 336(6088), 1534–1541.CrossRefGoogle Scholar
  26. Herrlich, P. (2013). The responsibility of the scientist. EMBO Reports, 14(9), 759–764.CrossRefGoogle Scholar
  27. Hooper, D. C., & Hirsch, M. S. (2014). Novel Clostridium botulinum toxin and dual use research of concern issues. Journal of Infectious Diseases, 209(2), 167.CrossRefGoogle Scholar
  28. Hunter, P. (2012). H5N1 infects the biosecurity debate. EMBO Reports, 13(7), 604–607.CrossRefGoogle Scholar
  29. Imai, M., Watanabe, T., Hatta, M., Das, S. C., Ozawa, M., Shinya, K., et al. (2012). Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature, 486(7403), 420–428.Google Scholar
  30. Jackson, R. J., Ramsay, A. J., Christensen, C. D., Beaton, S., Hall, D. F., & Ramshaw, I. A. (2001). Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. Journal of Virology, 75(3), 1205–1210.CrossRefGoogle Scholar
  31. Kalb, S. R., Baudys, J., Raphael, B. H., Dykes, J. K., Luquez, C., Maslanka, S. E., & Barr, J. R. (2015). Functional characterization of botulinum neurotoxin serotype H as a hybrid of known serotypes F and A (BoNT F/A). Analytical Chemistry, 87(7), 3911–3917.Google Scholar
  32. Kelle, A. (2009). Synthetic biology and biosecurity. EMBO Reports, 10(1S), S23–S27.CrossRefGoogle Scholar
  33. Kelle, A. (2013). Beyond patchwork precaution in the dual-use governance of synthetic biology. Science and Engineering Ethics, 19(3), 1121–1139.CrossRefGoogle Scholar
  34. Kelle, A. (2014). Prohibiting chemical and biological weapons: Multilateral regimes and their evolution. Incorporated: Lynne Rienner Publishers.Google Scholar
  35. Kuhlau, F., Eriksson, S., Evers, K., & Höglund, A. T. (2008). Taking due care: Moral obligations in dual use research. Bioethics, 22(9), 477–487.CrossRefGoogle Scholar
  36. Kumar Singh, M., Kumar Dhaked, R., Singh, P., Gupta, P., & Singh, L. (2011). Characterization of LC-HCC fusion protein of botulinum neurotoxin type A. Protein and Peptide Letters, 18(3), 295–304.CrossRefGoogle Scholar
  37. Lartigue, C., Vashee, S., Algire, M. A., Chuang, R. Y., Benders, G. A., Ma, L., et al. (2009). Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science, 325(5948), 1693–1696.CrossRefGoogle Scholar
  38. Liu, B., Shi, D., Chang, S., Gong, X., Yu, Y., Sun, Z., & Wu, J. (2015). Characterization and immunological activity of different forms of recombinant secreted Hc of botulinum neurotoxin serotype B products expressed in yeast. Scientific Reports, 5, 7678. doi: 10.1038/srep07678.
  39. Miller, S., & Selgelid, M. J. (2007). Ethical and philosophical consideration of the dual-use dilemma in the biological sciences. Science and Engineering Ethics, 13(4), 523–580.CrossRefGoogle Scholar
  40. National Research Council (2004). Biotechnology research in an age of terrorism. Committee on research standards and practices to prevent the destructive application of biotechnology. Washington, D.C.: National Academies Press.Google Scholar
  41. Oye, K. A., Lawson, J. C., & Bubela, T. (2015). Drugs: Regulate ‘home-brew’ opiates. Nature, 521(7552), 281.CrossRefGoogle Scholar
  42. Paddon, C. J., Westfall, P. J., Pitera, D. J., Benjamin, K., Fisher, K., McPhee, D., et al. (2013). High-level semi-synthetic production of the potent antimalarial artemisinin. Nature, 496(7446), 528–532.CrossRefGoogle Scholar
  43. Rath, J., Ischi, M., & Perkins, D. (2014). Evolution of different dual-use concepts in international and national law and its implications on research ethics and governance. Science and Engineering Ethics, 20(3), 769–790.CrossRefGoogle Scholar
  44. Relman, D. A. (2013). The increasingly compelling moral responsibilities of life scientists. Hastings Center Report, 43(2), 34–35.CrossRefGoogle Scholar
  45. Suk, J. E., Zmorzynska, A., Hunger, I., Biederbick, W., Sasse, J., Maidhof, H., & Semenza, J. C. (2011). Dual-use research and technological diffusion: Reconsidering the bioterrorism threat spectrum. PLoS Pathogens, 7(1), e1001253.CrossRefGoogle Scholar
  46. Thodey, K., Galanie, S., & Smolke, C. D. (2014). A microbial biomanufacturing platform for natural and semisynthetic opioids. Nature Chemical Biology, 10, 837–844.CrossRefGoogle Scholar
  47. Tucker, J. B. (Ed.). (2012). Innovation, dual use, and security: Managing the risks of emerging biological and chemical technologies. Cambridge, MA: MIT Press.Google Scholar
  48. Uhlenhaut, C., Burger, R., & Schaade, L. (2013). Protecting society. EMBO Reports, 14(1), 25–30.CrossRefGoogle Scholar
  49. van der Bruggen, K. (2012). Possibilities, intentions and threats: Dual use in the life sciences reconsidered. Science and Engineering Ethics, 18(4), 741–756.CrossRefGoogle Scholar
  50. Webster, R. G. (2012). Mammalian-transmissible H5N1 influenza: The dilemma of dual-use research. MBio, 3(1), e00005-12.13.Google Scholar
  51. Yong, E. (2012). Mutant-flu paper published. Nature, 485, 13–14.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Biology and BiotechnologyLa Sapienza University of RomeRomeItaly
  2. 2.Department of Industrial Engineering, School of Medicine and SurgeryUniversity of Rome Tor VergataRomeItaly
  3. 3.Ministry of DefenseRomeItaly

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