Skip to main content

Biosafety of Molecular Farming in Genetically Modified Plants

  • Chapter
  • First Online:
Molecular Farming in Plants: Recent Advances and Future Prospects

Abstract

The use of genetically modified plants for large-scale production of recombinant compounds for pharmaceutical or industrial use, known as plant molecular farming, holds several promises. However, any development in this field must be counterbalanced by a thorough evaluation of risks to human health and the environment. The possible impact of accidental contamination of the food and feed chain or of transgene spread in the environment, in particular when major food/feed crops grown in open fields are involved, highlights the need to carefully address some important issues during the safety assessment of genetically modified farming plants, such as the choice of the production platform, the implementation of containment or confinement measures and the adoption of other relevant management strategies. In this chapter, we report on the applicability of the current risk assessment methodology and principles, outline some important issues linked to the assessment of environmental and health risks, and comment in more detail general management strategies that could be applied to limit potential environmental and human health impacts linked to plant molecular farming.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahmad A, Pereira EO, Conley AJ, Richman AS, Menassa R (2010) Green biofactories: recombinant protein production in plants. Recent Pat Biotechnol 4(3):242–259

    Article  CAS  Google Scholar 

  • Alderborn A, Sundström J, Soeria-Atmadja D, Sandberg M, Andersson HC, Hammerling U (2010) Genetically modified plants for non-food or non-feed purposes: straightforward screening for their appearance in food and feed. Food Chem Toxicol 48(2):453–464

    Article  CAS  Google Scholar 

  • Basaran P, Rodríguez-Cerezo E (2008) Plant molecular farming: opportunities and challenges. Crit Rev Biotechnol 28(3):153–172

    Article  Google Scholar 

  • Becker G, Vogt D (2005) Regulation of plant-based pharmaceuticals. CRS report for congress. Order Code RS21418, March 8

    Google Scholar 

  • Breyer D, Goossens M, Herman P, Sneyers M (2009) Biosafety considerations associated with molecular farming in genetically modified plants. J Med Plant Res 3(11):825–838

    Google Scholar 

  • CFIA (2004a) Directive 94–08. Assessment criteria for determining environmental safety of plants with novel traits. http://www.inspection.gc.ca/english/plaveg/bio/dir/dir9408e.shtml. Accessed 28 Feb 2011

  • CFIA (2004b) Directive Dir2000-07: conducting confined research field trials of plant with novel traits in Canada. http://www.inspection.gc.ca/english/plaveg/bio/dir/dir0007e.shtml. Accessed 28 Feb 2011

  • Codex (2003) Codex Alimentarius Commission 2003 (ALINORM 03/34A). Guideline for the conduct of food safety assessment of foods derived from recombinant DNA plants. Annex on the assessment of possible allergenicity, Rome, Italy. Codex Alimentarius Commission, Yokohama

    Google Scholar 

  • Commandeur U, Twyman RM, Fischer R (2003) The biosafety of molecular farming in plants. AgBiotechNet 5:1–9

    Google Scholar 

  • Corrado G, Karali M (2009) Inducible gene expression systems and plant biotechnology. Biotechnol Adv 27:733–743

    Article  Google Scholar 

  • Daniell H (2002) Molecular strategies for gene containment in transgenic corps. Nat Biotechnol 20:581–586

    Article  CAS  Google Scholar 

  • de Maagd RA, Boutilier K (2009) Efficacy of strategies for biological containment of transgenic crops. Plant Research International B.V., Wageningen

    Google Scholar 

  • Dunwell JM, Ford CS (2005) Technologies for biological containment of GM and non-GM crops. Defra contract CPEC 47. Final report. http://www.gmo-safety.eu/pdf/biosafenet/Defra_2005.pdf. Accessed 28 Feb 2011

  • EC (2001) Council Directive 2001/18/EC of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC. Off J Eur Union L106:1–38

    Google Scholar 

  • EC (2003) Regulation (EC) No 1829/2003 of the European Parliament and of the Council of 22 September 2003 on genetically modified food and feed. Off J Eur Union L268:1–23

    Google Scholar 

  • EC (2004) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Off J Eur Union L136:1–33

    Google Scholar 

  • EC (2006) Commission Regulation (EC) No 2023/2006 of 22 December 2006 on good manufacturing practice for materials and articles intended to come into contact with food. Off J Eur Union L384:75–78

    Google Scholar 

  • EC (2009) Directive 2009/41/EC of the European Parliament and of the Council of 6 May 2009 on the contained use of genetically modified micro-organisms. Off J Eur Union L125:75–97

    Google Scholar 

  • EFSA (2006) Guidance document of the scientific panel on genetically modified organisms for the risk assessment of genetically modified plants and derived food and feed. EFSA J 99:1–100

    Google Scholar 

  • EFSA (2009) EFSA scientific panel on Genetically Modified Organisms (GMO); Scientific opinion on guidance for the risk assessment of genetically modified plants used for non-food or non-feed purposes, on request of EFSA. EFSA Journal 1164. [42 pp.]. Available online http://www.efsa.europa.eu

  • EFSA (2010) EFSA scientific panel on Genetically Modified Organisms (GMO); guidance on the environmental risk assessment of genetically modified plants. EFSA Journal 8(11):1879. [111 pp.]. doi:10.2903/j.efsa.2010.1879. Available online http://www.efsa.europa.eu/efsajournal.htm

    Google Scholar 

  • FDA (2002) Draft guidance for industry. Drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124811.pdf. Accessed 28 Feb 2011

  • Federal Register Notice (2003) 68 FR 11337–11340. http://www.aphis.usda.gov/brs/pdf/7cfr.pdf. Accessed 28 Feb 2011

  • Fox JL (2003) Puzzling industry response to prodigene fiasco. Nat Biotechnol 21:3–4

    Article  CAS  Google Scholar 

  • Franconi R, Costantina O, Demurtas OC, Massa S (2010) Plant-derived vaccines and other therapeutics produced in contained systems. Expert Rev Vaccines 9(8):877–892

    Article  CAS  Google Scholar 

  • Goldstein DA, Thomas JA (2004) Biopharmaceuticals derived from genetically modified plants. QJM 97:705–716

    Article  CAS  Google Scholar 

  • Gressel J, Valverde BE (2009) A strategy to provide long-term control of weedy rice while mitigating herbicide resistance transgene flow, and its potential use for other crops with related weeds. Pest Manag Sci 65:723–731

    Article  CAS  Google Scholar 

  • Hennegan K, Yang DC, Nguyen D, Wu LY, Goding J, Huang JM, Guo FL, Huang N, Watkins S (2005) Improvement of human lysozyme expression in transgenic rice grain by combining wheat (Triticum aestivum) puroindoline b and rice (Oryza sativa) Gt1 promoters and signal peptides. Transgenic Res 14:583–592

    Article  CAS  Google Scholar 

  • Hills MJ, Hall L, Arnison PG, Good AG (2007) Genetic use restriction technologies (GURTs): strategies to impede transgene movement. Trends Plant Sci 12:177–183

    Article  CAS  Google Scholar 

  • Howard JA, Hood EE (2007) Methods for growing nonfood products in transgenic plants. Crop Sci 47:1255–1262

    Article  Google Scholar 

  • Hüsken A, Prescher S, Schiemann J (2010) Evaluating biological containment strategies for pollen-mediated gene flow. Environ Biosafety Res. doi:10.1051/ebr/2010009

  • Kobayashi K, Munemura I, Hinata K, Yamamura S (2006) Bisexual sterility conferred by the differential expression of barnase and barstar: a simple and efficient method of transgene containment. Plant Cell Rep 25:1347–1354

    Article  CAS  Google Scholar 

  • Komarova TV, Baschieri S, Donini M, Marusic C, Benvenuto E, Dorokhov YL (2010) Transient expression systems for plant-derived biopharmaceuticals. Expert Rev Vaccines 9(8):859–876

    Article  CAS  Google Scholar 

  • Lau OS, Sun SS (2009) Plant seeds as bioreactors for recombinant protein production. Biotechnol Adv 27(6):1015–1022

    Article  CAS  Google Scholar 

  • Liénard D, Sourrouille C, Gomord V, Faye L (2007) Pharming and transgenic plants. Biotechnol Annu Rev 13:115–147

    Article  Google Scholar 

  • Mascia PN, Flavell RB (2004) Safe and acceptable strategies for producing foreign molecules in plants. Curr Opin Plant Biol 7:189–195

    Article  CAS  Google Scholar 

  • Meyers B, Zaltsman A, Lacroix B, Kozlovsky SV, Krichevsky A (2010) Nuclear and plastid genetic engineering of plants: comparison of opportunities and challenges. Biotechnol Adv 28:747–756. doi:10.1016/j.biotechadv.2010.05.022

    Article  CAS  Google Scholar 

  • Moon HS, Li Y, Stewart CN Jr (2010) Keeping the genie in the bottle: transgene biocontainment by excision in pollen. Trends Biotechnol 28(1):3–8

    Article  CAS  Google Scholar 

  • Moschini G (2006) Pharmaceutical and industrial traits in genetically modified crops: co-existence with conventional agriculture. Working paper 06-WP 429. Center for Agricultural and Rural Development

    Google Scholar 

  • Murphy DJ (2007) Improving containment strategies in biopharming. Plant Biotechnol J 5:555–569

    Article  CAS  Google Scholar 

  • NARA (2005) Introductions of plants genetically engineered to produce industrial compounds. Fed Regist USA 70(85):23009–23011

    Google Scholar 

  • Obembe OO, Popoola JO, Leelavathi S, Reddy SV (2010) Advances in plant molecular farming. Biotechnol Adv. doi:10.1016/j.biotechadv.2010.11.004

  • Peterson RKD, Arntzen CJ (2004) On risk and plant-based biopharmaceuticals. Trends Biotechnol 22:64–66

    Article  CAS  Google Scholar 

  • Plasson C, Michel R, Lienard D, Saint-Jore-Dupas C, Sourrouille C, de March GG, Gomord V (2009) Production of recombinant proteins in suspension-cultured plant cells. Methods Mol Biol 483:145–161

    Article  CAS  Google Scholar 

  • Pogue GP, Vojdani F, Palmer KE, Hiatt E et al (2010) Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J 8(5):638–654

    Article  CAS  Google Scholar 

  • Ramessar K, Sabalza M, Capell T, Christou P (2008) Maize plants: an ideal production platform for effective and safe molecular pharming. Plant Sci 174:409–419

    Article  CAS  Google Scholar 

  • Rehbinder E, Engelhard M, Hagen K, Jørgensen RB, Pardo Avellaneda R, Schnieke A, Thiele F (2009) Pharming. Promises and risks of biopharmaceuticals derived from genetically modified plants and animals. Ethics of science and technology assessment, Vol 35. Springer, p 334. ISBN: 978-3-540-85792-1

    Google Scholar 

  • Ruf S, Karcher D, Bock R (2007) Determining the transgene containment level provided by chloroplast transformation. Proc Natl Acad Sci USA 104(17):6998–7002

    Article  CAS  Google Scholar 

  • SCBD (2000) Secretariat of the convention on biological diversity. Cartagena protocol on biosafety to the convention on biological diversity: text and annexes. Secretariat of the Convention on Biological Diversity, Montreal

    Google Scholar 

  • Shama LM, Peterson RKD (2008a) Assessing risks of plant-based pharmaceuticals: I. Human dietary exposure. Hum Ecol Risk Assess 14:179–193

    Article  CAS  Google Scholar 

  • Shama LM, Peterson RKD (2008b) Assessing risks of plant-based pharmaceuticals: II. Non-target organism exposure. Hum Ecol Risk Assess 14:194–204

    Article  CAS  Google Scholar 

  • Sparrow PA, Twyman RM (2009) Biosafety, risk assessment and regulation of plant-made pharmaceuticals. Methods Mol Biol 483:341–353

    Article  Google Scholar 

  • Sparrow PA, Irwin JA, Dale PJ, Twyman RM, Ma JK (2007) Pharma-Planta: road testing the develo­ping regulatory guidelines for plant-made pharmaceuticals. Transgenic Res 16(2):147–161

    Article  CAS  Google Scholar 

  • Spök A (2007) Molecular farming on the rise – GMO regulators still walking a tightrope. Trends Biotechnol 25:74–82

    Article  Google Scholar 

  • Spök A, Karner S (2008) Plant molecular farming: opportunities and challenges. European commission, joint research centre, institute for prospective technological studies

    Google Scholar 

  • Spök A, Twyman RM, Fischer R, Ma JKC, Sparrow PAC (2008) Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol 646:1–12

    Google Scholar 

  • Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, Lamphear BJ, Drees CF, Jilka JM, Hood EE, Howard JA (2003) Corn as a production system for human and animal vaccines. Vaccine 21:812–815

    Article  CAS  Google Scholar 

  • Union of Concerned Scientists (2006) UCS position paper: pharmaceutical and industrial crops. UCS. http://www.ucsusa.org/food_and_environment/genetic_engineering/ucs-position-paper.html. Accessed 28 Feb 2011

  • USDA (2006) Permitting genetically engineered plants that produce pharmaceutical compounds. BRS factsheet. http://www.aphis.usda.gov/publications/biotechnology/content/printable_version/BRS_FS_pharmaceutical_02-06.pdf. Accessed 28 Feb 2011

  • USDA (2008) Guidance for APHIS permits for field testing or movement of organisms intended for pharmaceutical or industrial use. http://www.aphis.usda.gov/brs/pdf/Pharma_Guidance.pdf. Accessed 28 Feb 2011

  • Vancanneyt G, Dubald M, Schröder W, Peters J, Botterman J (2009) A case study for plant-made pharmaceuticals comparing different plant expression and production systems. Methods Mol Biol 483:209–221

    Article  CAS  Google Scholar 

  • Verma D, Daniell H (2007) Chloroplast vector systems for biotechnology applications. Plant Physiol 145:1129–1143

    Article  CAS  Google Scholar 

  • WHO (2003) WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. http://whqlibdoc.who.int/publications/2003/9241546271.pdf. Accessed 28 Feb 2011

  • Wolt JD, Karaman S, Wang K (2007) Risk assessment for plant-made pharmaceuticals. CAB Rev Perspect Agric Vet Sci Nutr Nat Resour 2(12):1–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Didier Breyer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Breyer, D., De Schrijver, A., Goossens, M., Pauwels, K., Herman, P. (2012). Biosafety of Molecular Farming in Genetically Modified Plants. In: Wang, A., Ma, S. (eds) Molecular Farming in Plants: Recent Advances and Future Prospects. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2217-0_12

Download citation

Publish with us

Policies and ethics