Gene Technology in Agriculture, Environment and Biopharming: Beyond Bt-Rice and Building Better Breeding Budgets for Crops

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Gene technology in agriculture, environment and biopharming: beyond Bt-rice and building better breeding budgets for crops

ARTICLE in JOURNAL OF PLANT BIOCHEMISTRY AND BIOTECHNOLOGY · OCTOBER 2012 Impact Factor: 1.09 · DOI: 10.1007/s13562-012-0128-z

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Mohsin Abbas Zaidi Jason El Bilali Agriculture and Agri-Food Canada University of Ottawa

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Gene technology in agriculture, environment and biopharming: beyond Bt-rice and building better breeding budgets for crops

Mohsin Abbas Zaidi & Jason El Bilali & Adam Gregory Koziol & Tonya L. Ward & George Styles & Trevor J. Greenham & Whitney Michelle Faiella & Hwan Hee Son & Shen Wan & Ibrahim Taga & Illimar Altosaar

Received: 7 June 2012 /Accepted: 24 July 2012 /Published online: 11 August 2012 # Society for Plant Biochemistry and Biotechnology 2012

Abstract Applications of gene technology in agriculture, Keywords Bt . Bacillus thuringiensis . Crystalline the environment and human health fields are reviewed. This insecticidal protein . Cry1Ab . Entomocidal protein . case study of the intricate historical details of the develop- Mycotoxin reduction . Unintended effects . Material transfer ment of Bt crops like cotton and rice unveils essential agreement . Ricochet funding effect . Bt-cotton . Bikaneri elements of productive funding schemes and effective mul- Narma . Freedom to operate . Intellectual property rights . tinational collaborations. Gene technology applied to pest Kreenholm resistance traits in global cotton is analyzed using nation- specific data from India to demonstrate ‘ricochet’ results: Abbreviations Regulatory approval for one crop catalyzes an ‘Enhancer BMTA Biological materials transfer agreement Effect’ for promoting more research funding and more com- Bt Bacillus thuringiensis petitive results for other crops-in-waiting, namely rice. Just COST European Cooperation in the field of Scientific as cotton commerce promoted philanthropy in unpredictable and Technical Research situations like the Kreenholm dynasty of Ludwig Knoop, ECB European corn borer research budgets for pesticide and biocide technology have ENDURE European Network for Durable Exploitation of yielded intended effects, but several surprising unintended Crop Protection Strategies effects as well. Finally, the case is made for greater control GEAC Genetic Engineering Approval Committee of gene flow and identity preserve issues in plant biotech- GM Genetically modified nology research by invoking Appellation d’Origine Contrôlée GMT Genetically modified tree for Bt genes. ICP Insecticidal crystal protein IP Intellectual property IP Identity preserve This article is based on a paper first presented at the International IPRB International Program on Rice Biotechnology Conference on Plant Biotechnology for Food Security: New Frontiers- ISI Institute for Scientific Information 2012 New Delhi, India 21–24 February 2012 in Session IX Biotic and MTA Material transfer agreement Abiotic Stress Management, chaired by Professors S. Sopory and A. RF The Rockefeller Foundation Mattoo. SCI Science Citation Index M. A. Zaidi : J. El Bilali : A. G. Koziol : T. L. Ward : G. Styles : T. J. Greenham : W. M. Faiella : H. H. Son : S. Wan : I. Taga : I. Altosaar (*) Agricultural Biotechnology Laboratories, Introduction Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, The Rockefeller Foundation based in New York City funded 451 Smyth Road, Ottawa, ON K1H 8M5, Canada an International Program on Rice Biotechnology (IPRB) e-mail: [email protected] from 1984 through to 1999 (Normile 1999). The goal of J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9 S3 this bold 15 year long public-sector initiative was to shore articles. The landmark achievement from this period was up food security and food sustainability (Conway and from the Bose Institute in Calcutta whose article in PNAS Toenniessen 1999; Toenniessen et al. 2003). Many have has, since 1997, attracted 118 citations to date in ISI (Nayak described the 1984 sudden shift in Foundation focus, from et al. 1997). Their particle bombardment of indica rice to broad agronomic improvement efforts across many tropical produce six highly expressive independent transgenic ICP crops to focus solely on humanity’s primal sustenance, rice lines was reflected in similar efforts to produce insect resistant (Oryza sativa), as one of the single largest concerted and rice using Agrobacterium T-DNA mediated transformation long-standing scientific experiments ever undertaken methods on japonica and subtropical javanica rice varieties (Conway and Toenniessen 2003; Herdt 2006). In 1983 from the IPRB node in Canada (Cheng et al. 1998)andin the first transgenic plants expressing the kanamycin re- collaboration with China (Shu et al. 2000). sistance gene had just been reported at the Miami-Winter If one considers that such international funding of tar- Symposium (Van Montagu 2003). Thus it was logical for geted research requires gestation time, then one can consider a global organization like The Rockefeller Foundation the subsequent, equivalent ten-year window time period of (RF), one especially devoted to small-scale food pro- 1994–2003. Search terms ‘thuringiensis’ and ‘India’ yield ducers, to take note of the advent of recombinant DNA 176 ISI records. Following Nayak et al. 1997, the second techniques applied to plant science. So we are now, not most highly cited work is that from the Centre for Research only nearing the tri-decadal anniversary of genetically in Medical Entomology in Madurai on using classical Bt modified (GM) plants in 2013, but also the 30 year spray formulations for controlling mosquitoes (Rao et al. anniversary of rice biotech in 2014. Consequently it is 1995). Needless-to-say basic research on rice biotech has an appropriate time for all plant biotechnologists, farmers only continued to intensify to this day. and food consumers to assess constraints and opportuni- Commercial agricultural biotechnology was heralded by ties that have arisen from the early days when fierce India in March 2002 when three Bt-cotton hybrids were competition among Jeff Schell, Marc van Montagu, approved for commercial cultivation. Both the Genetic Mary-Dell Chilton, Eugene Nester, Robert Fraley, Engineering Approval Committee (GEAC) and the Robert Horsch and others created the gene transfer meth- Ministry of Environment and Forests, Government of ods now available for all to use in accelerating crop India at its 32nd meeting in New Delhi approved the three improvement. Bt-cottons for release. The transgenic hybrids were developed by MAHYCO (Maharashtra Hybrid Seed Company Limited) in collaboration with Monsanto based in Saint Gene technology applied to pest resistance Louis, Missouri, and these technology partnerships were effected by other seed companies like Rasi Seeds (P) Ltd. as One of the first breeding goals for crop improvement in rice well. The Bt-cotton strains contained the lepidopteran specific was to confer insect resistance from Bacillus thuringiensis Bt gene, cry1Ac with Event MON 531 (Bollgard®). Releasing genes to elite rice varieties. From 1984 to 1993 (the first this agricultural technology was a new form of ‘green revolu- 10 years of RF funding) the Institute for Scientific tion’ in India as the new germplasm offered protection against Information (ISI) database (Thomson Reuters Web of all the major species of Indian bollworms - Helicoverpa Science) shows that for India, as an example, there were armigera (Old world bollworm), Pectinophora gossypiella 48 articles published on this topic (using ‘thuringiensis’ as a (Pink bollworm), Earias vittella (Spotted bollworm) and search-term and ‘India’ as an address term). That represents E. insulana (Spiny bollworm). an average of 4.8 papers per year of the RF-IPRB Program. In that set of studies, the most highly cited article from the first decade of infusion of funding was a report on the Regulatory approval for one crop catalyzes instability of mRNA encoding insecticidal crystal protein an ‘Enhancer Effect’ for other crops-in-waiting (ICP) genes of Bacillus thuringiensis (Bt) in electroporated carrot cells and transgenic tobacco plants (Murray et al. As a strong emerging global economy, India’s strategies and 1991). That collaboration was between Madurai Kamaraj tactics to maximize social goods are ardently analyzed. For University and Universities of Georgia and Wisconsin in the example the case of agri-chemical industries, whether they USA. With increased funding and more training of highly should enjoy a process-patent policy or a product-patent qualified personnel in plant molecular biology the produc- regulatory landscape, offers an interesting backdrop for tivity record shows that money more than tripled the amount better appreciating the future of plant biotechnology under- of results that achieved the ISI standard on international peer takings (Haley and Haley 2012). The productivity and com- review. Thus for Bt there were 108 papers from India petitiveness of plant biotechnology research in India can be between 1995–2000, representing an annual average of 18 measured by the number of research publications that made S4 J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9 it into the world’s most competitive scientific journals. More remarkable is the ricochet effect that public release Using Science Citation Index (SCI) records on rice and of GM cotton has had on plant molecular biology research cotton from India, Fig. 1 describes the effects of both re- on the model food plant, the cereal rice. The regulatory search funding and regulatory approval on national knowl- approval of Bt-cotton in 2002 coincides with a sudden spur edge outputs. The advent of international attention on rice in papers from India on rice from year 2002 onwards, so this along with the influx of new funding from The RF funding serendipity may be referred to as an ‘enhancer effect’.As clearly shows a marked boost from a pre-1984 average of seen in Fig. 1, the SCI records from India alone on rice 154 ISI articles on rice from India to a doubling of absolute numbered 266. Some short nine years later, this number had number of papers on rice from India 15 years later, 302 shot up 2.6 times to 690 records in the database. Again, the papers in year 2000 (Fig. 1). When this food crop, rice, is increases in research productivity stemming from science compared with a reference fibre crop, no such increase budget investments in India appear to be rapidly increasing. occurred with cotton: an average of 64 SCI records pre- Therefore it is encouraging to look beyond Bt-rice and 1984 compared with an average of 62 papers per year over devise even more creative research partnerships for attract- the 1996–2000 time period. However, because of the March ing healthier budgets for plant biotechnology research and 2002 approval of biotech-cotton in India, Indian articles on building better breeding programs for crops that are even cotton have started to increase dramatically. From a low of more sustainable. only 48 records in 1996, internationally competitive cotton The goal of this current article is to review some of these research from India has increased nearly five fold, reaching necessary ingredients in the research infrastructure, both 222 articles by 2011. Given the increasing focus on the role nationally and internationally, that are required for achieving of biotech cotton in India, especially on local variety food security. Seeing the power and multiplier effect that Bikaneri Narma, this rate increase in scientific productivity regulatory approval can have on plant sciences research, the is likely to continue (Jayaraman 2003; Ahuja et al. 2009). authors endeavor to analyze and underscore the importance of intellectual property and technical property issues.

800

700 Cotton and philanthropy

600 John Davison Rockefeller (1839–1937) as an American 500 industrialist founded the Standard Oil Company in

Cotton Cleveland, Ohio in 1870 and ran it until he officially retired 400 Rice in 1897 (Montague 1902). Dominating the oil industry and 300 creating the first great U.S. business trust, Rockefeller rev- olutionized the petroleum industry and defined the structure 200 of modern philanthropy (Mahoney et al. 2007). 100 Historians have also called another industrialist the

Articles from India in Science Citation Index (ISI) Citation Index India in Science Articles from ‘Rockefeller’ of Europe. Johann Ludwig Knoop (1821– 0 1979 1984 1989 1994 1999 2004 2009 2014 1894), a cotton merchant from Bremen, became one of the Years richest entrepreneurs in his time (Thompstone 1984). Having learned the cotton business at Manchester with the Fig. 1 Approval of Bt cotton in India in 2002 accelerated not only cotton research in India nearly five times, but enhances research Bremen-born cotton exporter Johan Frerichs (of De Jersey productivity on the model food crop rice 2.6 times. Research produc- & Co.), Knoop went to Moscow to assist the firm’s agent tivity on the two fiber and food crops, respectively, was measured as Franz Holzhauer in 1840. That year Knoop established the number of scientific publications entered into the Science Citation first power driven cotton mill in Russia. The British ban on Index (SCI) database managed by Thomson Reuters’ Institute for Scientific Information (ISI) from an institutional address in India in a the export of cotton machinery, imposed in 1775 to protect given year. Data were extracted and are shown for the 5 years before England’s head start in technology, was lifted in 1842. the advent of The Rockefeller Foundation’s rice biotechnology pro- Knoop used English credit to establish more cotton mills – gram (1984 1999) until after year 2011 fully completed. Open arrow across Europe into Asia, with English equipment. Starting in (House) represents start time for the 15-year long RF-IPRB; closed arrow (Black down-pointing triangle) represents March 2002, point in 1857 Knoop raised, in a miraculously short 18 months, the time when India approved growth and commercial production of Bt- largest cotton spinning mill in Europe on the island of cotton varieties. Even though the total number of records in the SCI Kreenholm at Narva, Estonia, which employed 4,500 people database grew from 568,118 entries in 1980 to 1,500,767 entries in (Fig. 2). By 1894 it employed 5,300 employees and over 2011, the absolute numbers of publications issuing from India increased in response to budgetary, regulatory and intellectual property 10,000 workers by 1911 (Thompstone 2003). Ginned cotton considerations surrounding cotton and rice fibre bales were imported into Estonia from India, the J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9 S5

property (IP) management practices adhered to by all will ensure progress, productivity and promulgation of food security not only in India but globally as well (Kowalski et al. 2002; Chi-Ham et al. 2012).

Budgets for pesticides and biocide technology: intended and unintended effects

Strategists of food security may learn much from the European Network for Durable Exploitation of Crop Protection Strategies, ENDURE. From 2007 to end of 2010 the European Union funded over three hundred European researchers who are committed to defining more sustainable crop protection strategies and developing research priorities to reduce pesticide use. The ENDURE NoE (Network of Excellence) enjoyed the financial support of the European Commission’s Sixth Framework Programme, priority 5: ‘Food Quality and Security’ to the tune of €11.2 million. One of the key ‘Intended Effects’ of Fig. 2 The Kreenholm cotton factory still standing in Narva, Estonia. www.endure-network.eu was to reduce pesticide use against Europe’s largest textile plant built in 1857 by the “Rockefeller of stalk and ear rots plaguing many European agri-systems, ” Europe Ludwig Knoop, and by employing over 10,000 Estonian namely and very specifically Fusarium graminearum and Russian workers, Kreenholm has provided broad historical moments in the development of industrial labor relations world-wide. Schwabe, F. verticillioides (Sacc.) Nirenberg, F. prolifera- The Kreenholm strike was a crucial event in the history of Czarist tum (Matsush.) Nirenberg, and F. culmorum (Wm. G. Sm.) Russia and recent historical research sheds new light on local power Sacc. This food security program focused on the pests’ relations at play on this assembly-line factory-island (Zelnik 1995). metabolites, the mycotoxins - fumonisins, trichothecenes Coupled inextricably with high-level politics in St. Petersburg of the times and with controversies over the rule of law, Kreenholm is now (deoxynivalenol, nivalenol, T-2), and zearalenone - assess- viewed as the central ‘thread’ leading to a better understanding of the ing their acute and chronic toxic effects in humans and origins of the Russian labor movement (Altosaar 1991). Photo credit: livestock. ENDURE focused on the toxic effects in animals Madis Tuuder, taken 26.04.2011, with permission, Cultural Heritage that eat pest-ridden vegetation, i.e. damaged reproductive Monument of Estonia number 14037 organs, digestive organs, and animal death. Such grain maize contamination via silage maize had been recently southern USA, Egypt and later from Central-Asia. The targeted by the European Commission when it issued strict Narva factory had nearly half a million spindles driven by maximum levels for Fusarium-mycotoxins (deoxynivale- water-power. Knoop took the responsibilities to his work- nol, zearalenone and fumonisins) in foodstuffs (EC 2007), force seriously, introducing a health insurance scheme and and guidance values for animal feed (EC 2006). supplying workers with dwellings, kindergartens and ENDURE’s assessment of Europe’s options to reduce schools (Zelnik 1995; Kaiser 2001). insecticides noted that Cry1Ab protein controls European Given the powerful industrial history of cotton, from Sir corn borers (ECB) in seven EU countries, where at least Richard Arkwright (1732–1792)’s invention and patenting 107,000 hectares of GM crops were produced in 2008 of the spinning frame in Cromford in 1769, to current disputes (Meissle et al. 2010). Most Bt maize is produced in Spain over freedom to operate with Bt-cotton (Jayaraman 2012), it is (79 Kha) where dramatic increases in adoption of GMO’s paramount that all stakeholders in plant biotechnology adhere has occurred, e.g. in the Ebro Valley: 15 % of corn acreage to and observe not only good labour practices but also good in 2002 was GM, shooting up to 65 % in 2007 (Meissle et laboratory practices when manipulating plant breeders’ germ- al. 2010). This EU network also noted that new GM lines plasm and recombinant DNA technical materials (Krattiger have been developed, such as Cry3 Bt maize hybrids, but 2010). For example, first authorship position on a scientific their deployment has been held up by “the authorization publication, being senior author and the ethical responsi- process in the EU”. ENDURE stated “Because of the high bilities it entails, or one’s journal impact factor are of efficacy of the Bt proteins expressed in Bt maize hybrids, critical importance to the international reputation of any insecticides against the target pests are no longer needed” scientist. These principles are internationally recognized and this has been interpreted as a clear endorsement of and generally observed. Similarly, good intellectual transgenic crops by those hopeful that more EU Member S6 J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9

States will be approving GM crops as well (Schroder et al. Gene flow and identity preserve: invoking Appellation 2007). It has long been recognized that due to the high d’Origine Contrôlée for Bt genes specificity of Bt, non-target herbivores remain uncontrolled, thus the ecosystem’s complex of natural enemies also The business of biotechnology like any business, be it remains unharmed, securing Bt’s pivotal place in integrated cotton farming or fibre weaving, progresses more produc- pest management history (Andow et al. 2001). The biolog- tively when contract laws are made meaningful and are ical control functions of Bt entomocidal proteins are often readily abided by. Identity preservation usually refers to sufficient to keep secondary pest populations below eco- supply chain logistics for managing crop growth and har- nomic injury levels (Romeis et al. 2008). Recognizing that vesting to avoid comingling of conventional germplasm only 14–25 % of the potential environmental benefit (re- with biotech lines, be they potatoes (Guenthner et al. duced insecticide use) has been realized to date in the EU 2012), tomatoes (Juarez et al. 2012; TTGC 2012)orGM (Brookes 2009), it has been warned that the much-needed rice (Mulvaney et al. 2011). Intellectual property laws alike increase of adoption rates is unfortunately limited by other govern ownership of patents and dictate freedom to operate, national bans of Bt maize (Meissle et al. 2010). as mentioned above (Krattiger 2010). When various labora- Unintended effects of Bt gene deployment include reduced tories discovered that prokaryotic mRNA of various contaminants from stalk and ear rot in the food chain. F. Bacillus thuringiensis genes from the wild type, upon being verticillioides was more likely to be isolated from ECB- transformed into eukaryotic hosts effecting widely different injured tissue and the overall species diversity of stalk rot codon preferences, did not translate efficiently into desired complex was observed to be lower in Bt hybrids (Gatch et protein product, codon-optimized coding sequences of Bt al. 2002; Gatch and Munkvold 2002). In addition, the Bt event genes were synthesized and contemplated as being neces- MON810 was observed to have reduced fumonisins B1+B2 sary for Bt crop development (Perlak et al. 1991; Kumar and with an efficacy over 90 %. This has led to a wider appreci- Sharma 1995; Sardana et al. 1996). Such constructs synthe- ation of GM biocide technology: transgenic maize as an sized in our hands proved effective not only in maize for ecological tool is very useful because it indicates that ecosys- deterring insect damage but in rice (Cheng et al. 1998) and tem relationships among Lepidoptera, Fusarium spp, ear rot many other crops ranging from coffee trees (Leroy et al. disease and mycotoxins have multivariate interactions 2000) to spruce trees (Lachance et al. 2007). Thanks to the (Folcher et al. 2009). power of the RF-IRBP network our lab enabled national Given these startling and unintended benefits of Bt crop crop development programs to test such synthetic gene protection, it is indeed heartening that the EU has recently constructs in their local plant transformation programs. funded a new network to study similar benefits of plant Having collaborated earlier with Indian labs on cloning biotechnology, not in annual crops but in woody perennials, repeated DNA sequences for genetic purposes in the the trees (Fladung et al. 2012). European Cooperation in the Triticeae (Gupta et al. 1992), it was therefore much easier field of Scientific and Technical Research (COST) is one of in the late 1990’s to extend our technology transfer efforts the longest-running European efforts funding cooperation into GM crop programs like 1Ac-tomato (Mandaokar et al. among scientists and researchers across Europe as well as 2000; Mandaokar et al. 2012), 1Ac-sorghum (Girijashankar with international specialists, for example with Canada, et al. 2005), and cry1Ac-chickpea (Mehrotra et al. 2011). given its far larger surface area. As the first and widest In each case where identified genes have been trans- European intergovernmental network for coordination of ferred, their identity has been preserved by both Provider nationally funded research activities, it is encouraging to and User of the said biological materials (i.e. Bt gene con- see that the lessons learned from the ‘Rockefellers’ of sci- structs and expression cassettes). Standard legal practice in ence, from the 16 years of biotech crops grown globally in at technology transfer is to cover the jurisprudence aspects of least 29 regulated countries, and from the wisdom promul- any exchange of materials, technical or biological, by sign- gated by ENDURE is now being applied by COST to plants ing a material transfer agreement (MTA) or in the cases with longer lifespans. The main objective of this FP0905 involving DNA fragments of cloned genes, by a Biological Action is to evaluate and substantiate the scientific knowl- Materials Transfer Agreement (BMTA) (Staley et al. 2010). edge relevant for genetically modified trees (GMT) espe- In each case of the Ottawa Bt gene constructs being shared cially concerning their biosafety protocols, given that GMTs for research or commercial purposes, a complete BMTA was have been grown out in the open in field trials there for first signed in duplicate and invoked by both parties before about 20 years. This existing information generated in var- any gene(s) was couriered to collaborators, at minimum ious European countries provides a science-based platform consisting of a Recipient (responsible Director of borrowing for future EU policy and regulation for the environmental institution) and Recipient Scientist, i.e. User. More valuable impact assessment and the safe development and practical than expensive brand names of French wines or fine use of GMTs (Fladung et al. 2012). cheeses, provenance of genetic material is paramount. It is J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9 S7 just as important to have traceability of genes in plant Table 1 Identity preservation of promiscuous plasmids still governed science as it is to have traceability of plant products for by contract law. An example of a key clause (#8) in any critical Biological Materials Transfer and Collaboration Agreement plant quarantine purposes. Therefore the BMTA covering (BMTCA) between Provider and Recipient. Specific phrasing is from each transfer of a Bt gene contained explicit clauses, not- BMTCA governing use of Ottawa Bt genes. Stating IPR and FTO withstanding which Cry protein encoding DNA sequence issues by the Provider confers sense of due diligence upon Recipient to was being distributed, be it for Cry1A, 1C or 2A (Riaz et al. investigate and understand any IPR issues in their own national jurisdiction 2006; Gulbitti-Onarici et al. 2009; Zaidi et al. 2009). Every BMTA legal contract contained clauses stating “The mate- 8. PROVIDER hereby advises RECIPIENT and RECIPIENT rial shall not be provided, transferred, released or distributed SCIENTIST that the PROVIDER has no patent rights in the MATERIALS. to anyone other than individuals working under the direct ” Furthermore, the MATERIALS may be subject to intellectual property supervision of recipient scientist in recipient institution and rights belonging to third parties. “ Recipient and recipient scientist recognize that the sample One or more patents or pending patent applications may exist, the of the material provided hereunder is the sole property of the claims of which, if granted, may be infringed by the use of provider and on written request of the provider, unused MATERIALS by RECIPIENT and RECIPIENT SCIENTIST. material including all its copies, samples and replications, In particular, the PROVIDER draws RECIPIENT and RECIPIENT ” SCIENTIST’s attention to the following publications describing the will be returned to the provider or destroyed. Just as na- a tional patent acts and legislation governing intellectual prop- origin and provenance of the Materials encoding Cry1Ab and Cry1Ac proteins: erty laws always entails the quid pro quo “to teach” the a. Cheng X, Sardana R, Kaplan H, Altosaar I. Agrobacterium- public, in a similar manner the BMTA also teaches the transformed rice plants expressing synthetic Cry1A(b) and Cry1A(c) Recipient about the Identity Preserve (IP) of the plasmids genes are highly toxic to yellow stem borer and striped stem borer. themselves: “Provider hereby advises recipient and recipient Proc. Natl. Acad. Sci. USA, 95: 2767–2772 (1998). scientist that the provider has no patent rights in the materi- b. Perlak FJ et al. Modification of the coding sequence enhances plant als. Furthermore, the materials may be subject to intellectual expression of insect control protein genes. Proc. Natl. Acad. Sci. USA 88: 3324–3328 (1991). property rights belonging to third parties. One or more c. Perlak FJ et al. Insect resistant cotton plants. Bio/Tech 8: 939–943 patents or pending patent applications may exist, the claims (1990). of which, if granted, may be infringed by the use of materi- d. Sardana R, Dukiandjiev S, Giband M, Cheng X, Cowan K, Sauder als by recipient and recipient scientist. In particular, the C, Altosaar I. Construction and rapid testing of synthetic and Provider draws Recipient and Recipient Scientist’s attention modified toxin gene sequences Cry1A (b&c) by expression in maize – to the following publications describing the origin and prov- endosperm culture. Plant Cell Reports 15: 677 681 (1996). enance of the materials encoding cry1ab and cry1ac pro- a N.B. emphasis on “origin and provenance” is authors’ emphasis teins:” As emphasized in Table 1, this advisory was always followed by four foundational articles describing the origins of optimized Bt genes (Cheng et al. 1998; Perlak et al. 1991; agricultural production zones may take advantage of another Sardana et al. 1996; Perlak et al. 1990). Better budgets for soil bacterium, Pseudomonas stutzeri, whose nitrous oxide bigger and more robust biotech cropping systems will de- reductase encoding gene, nosZ, has been expressed in trans- mand even more fastidious attention be devoted to the fine genic tobacco (Wan et al. 2012b). With excessive fertilizer details of record keeping, maintaining meticulous laboratory applications leaving more run-off of urea and ammonia in notebooks, geneflow containment and gene confinement in the soils and streams (generating increasing levels of nitrous plant biotechnology collaborations in the future as this type oxide from dissassimilative denitrification), it is encourag- of research can only intensify. ing to observe that the nosZ gene can be targeted by tissue specific expression in plant roots with the aim of creating a catalytic complex of stable nitrous oxide reductase complex Future prospects: detoxifying our atmospheric in the soil matrix for long-term and sustainable detoxifica- environment, bolstering our immune systems tion of the air (Wan et al. 2012a). The past 25 years has also seen an increasing interest in molecular biopharming: the In addition to reducing the use of chemicals in food produc- production of human pharmaceutical proteins, vaccines, tion (e.g. fungicides) through use of the soil bacterium monoclonal antibodies and industrial enzymes in transgenic Bacillus thuringiensis, now GM crops are starting to be plant parts for direct oral delivery and for downstream explored for their potential to reverse global warming purification of the gene products (Sardana et al. 2007; (Wan et al. 2012c). Adoption of GM crops should become Tackaberry et al. 2008). Such plant protein production plat- more universal if it can be demonstrated in field trials that forms using GM crops are also a logical manifestation of the the application of plant biotechnology can mitigate climate environmental sustainable way forward for producing valu- change. Such phytoremediation of the air surrounding able proteins. S8 J. Plant Biochem. Biotechnol. (October 2012) 21 (Suppl 1):S2–S9

In summary, plants will continue to attract more attention Gatch E, Munkvold G (2002) Fungal species composition in maize and bigger breeding budgets as more economic and sustain- stalks in relation to European corn borer injury and transgenic insect protection. Plant Dis 86:1156–1162 able means are required to meet the demands for feed, food, Gatch E, Hellmich R, Munkvold G (2002) A comparison of maize and fibre by an ever growing world population. Plant bio- stalk rot occurrence in Bt and non-Bt hybrids. Plant Dis 86:1149– technology research programs themselves need to be culti- 1155 vated in a new culture of accountability, traceability and Girijashankar V, Sharma H, Sharma K, Swathisree V, Prasad L, Bhat B, ‘ ’ Royer M, San Secundo B, Narasu M, Altosaar I, Seetharama N transparency. For both the input process of basic research (2005) Development of transgenic sorghum for insect resistance to be secured and for the ‘output’ product to be secure and against the spotted stem borer (Chilo partellus). Plant Cell Rep sustained, each thread in the fabric of multilateral collabo- 24:513–522 rations must be tested and strengthened as much as possible. Guenthner JF, Johnson AJ, McIntosh CS (2012) Seed variety mix: an indicator for GM potato identity preservation. Am J Potato Res 89:172–174 Acknowledgments The research productivity of The Altosaar Lab- Gulbitti-Onarici S, Zaidi MA, Taga I, Ozcan S, Altosaar I (2009) oratory would not have been possible without the generous support of Expression of Cry1Ac in transgenic tobacco plants under the several funding agencies: Syngenta Foundation for Sustainable Ag- control of a wound-inducible promoter (AoPR1) isolated from riculture, The Rockefeller Foundation, Rasi Seeds (P) Ltd. (Attur, Asparagus officinalis to control Heliothis virescens and Manduca Tamil Nadu, India), Natural Sciences and Engineering Research sexta. Mol Biotechnol 42:341–349 Council of Canada, Canadian Institutes of Health Research (Institute Gupta P, Giband M, Altosaar I (1992) Two molecular probes charac- of Nutrition Metabolism and Diabetes Grant 82816), Monsanto Canada terizing the A and C genomes in the genus Avena (Oats). Genome Inc., and Intellectual Ventures Canada (IV). IT is the grateful recipient of a 35:916–920 postdoctoral fellowship from L’Agence universitaire de la Francophonie Haley GT, Haley UCV (2012) The effects of patent-law changes on (AUF), MAZ of an UNESCO Biotech Fellowship, HHS is an uOttawa innovation: the case of India’s pharmaceutical industry. Technol Undergraduate Research Scholar, WMF and JTEB were UROP awar- Forecast Soc Chang 79:607–619 dees, and TLW is an NSERC Canada Graduate Scholar. Herdt RW (2006) Biotechnology in agriculture. 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