COrrespOndence Pharming in crop commodities To the editor: the time of admixture. These events might pharma product in food or feed? What On October 6th, the US Department of be construed as an unfortunate mistake of about nontarget exposure and hazards to Agriculture (USDA) proposed new rules little practical consequence that was blown arthropods and vertebrates in the field? governing the regulations and oversight of out of context. The questions of biosafety and risks are genetically engineered crops1. Although One can argue, as Henry Miller of the handled by regulators on a case-by-case some of the changes represent steps in Hoover Institute (Stanford, CA, USA) has basis. Toxicology from various exposure the right direction by making regulatory done so eloquently, that overly cautious rates to appropriate organisms are done for oversight more coherent, the new biotech food manufacturers and regulators have each overexpressed protein or metabolite regulations would allow fallen into the hands of interest. This procedure is no different the outdoor cultivation of of Luddites in that from that for dozens of transgenic events pharma food crops, in stark insignificant amounts deregulated in the United States and has contrast to the editorial of DNA and protein proven to be effective because no negative stance of your journal, ‘contaminants’ could human health or environmental effects have which calls for food plants not have any biological been noted as trillions of transgenic plants to no longer be used for effects—that is, no harm, have been grown in the United States5. producing drugs2. Indeed, no foul4. But I do not see Pharming crosses paradigms of Jane Rissler, senior scientist Miller changing many agriculture and pharmaceutical & deputy director, Food & minds in food industry production, yielding economies of Environment Program at and regulation. Thus, we scale, and also transcends the nature of the Union of Concerned are left with the brute fact agriculture6. Even proponents of agbiotech http://www.nature.com/naturebiotechnology Scientists (Washington, that transgenic pharma like me are cautious about pharming DC) has denounced the seeds of commodities applications, especially in commodities. proposed USDA changes, will inevitably get mixed Why? The issue is not that risk assessments saying, “If these proposals are enacted into unless extreme measures are taken to are not performed or performed law, American consumers must accept segregate types. Even then, there is the improperly. As noted above, US regulators the possibility of drugs in their breakfast issue of biosafety of ingestion by wildlife have performed admirably in protecting cereal or other common foods. Moreover, and accidental bulk ingestion by humans. the environment and food supply in the these rules likely will lead to contamination In many ways, pharming in food and feed past 13 years of commercial transgenic scares, which will hurt the food industry.” commodities are bad company. crop production in the United States. The History has repeated itself several times Interspecific mixing has occurred USDA Animal and Plant Health Inspection when it comes to adventitious presence already with a pharmaceutical transgene— Service (APHIS) risk assessment concluded Nature Publishing Group Group Nature Publishing 8 of transgenes in crop commodities. the Prodigene (College Station, TX, USA) that the lysozyme, lactoferrin and human Adventitious presence or admixture refers debacle of 2001–2002, in which volunteer serum albumin being produced by Ventria 200 7 © to the accidental mixing of transgenic transgenic corn was found growing in a rice are not toxic to nontarget organisms . plants or plant parts in nontransgenics. soybean field3. Now, SemBioSys (Calgary, The main issue here is not about Thus far, admixture has resulted in no Alberta, Canada) is growing safflower in pharmaceutical or food purity. Transgenic documented negative health effects, but is Washington state to produce a carp growth DNA or proteins are the only ‘contaminant’ that situation due to change as more and hormone and Ventria is planting hundreds I am aware of where the adventitious more therapeutic proteins are ‘pharmed’ of hectares of rice around Junction City, presence doctrine is invoked at all—Miller in recombinant grain crop commodities? Kansas, for the production of several is correct about misplaced fears4. The Corn, wheat, rice and soybean are four human proteins3. determination of adventitious presence of the largest crop commodities that Transgene adventitious presence can is basically a product of the sensitivity are shipped by the boxcar load from occur by pollination of nontransgenic of detection equipment and frightened farms hundreds of kilometers to massive plants by transgenic plants resulting in people. Quantitative PCR can detect processors, and three of these, especially seeds with the transgene in the hemizygous transgene presence in very low titers8 and corn, rice and soybeans, have fallen prey state, or from inadvertent seeding. with immediate potential of detecting to admixtures. The adventitious presence Pollination can be averted by physical transgenes in the range of 1:50,000– in most cases has involved transgenes isolation and using crops that do not 1:200,000 genomic equivalent range (Yuan, coding for agronomic traits, such as a have sexually compatible relatives nearby. J. & Stewart C.N.; unpublished data) with Bacillus thuringiensis (Bt) toxin transgene Limiting seed flow is more problematic robust statistical procedures9. The issue for insect control (e.g., StarLink event in because it can occur by movement of of concern is one of perception. Reports 2000 in corn) or glufosinate-resistance seeds from adjacent fields by wildlife of adventitious presence, no matter how gene encoding better weed control in rice3. and farm machinery or further afield benign, are bad publicity for plant biotech The transgenes and proteins underlying by transportation of seeds that escape as a whole. Not only will biotechnologists these traits are undoubtedly safe for from containers. Of course, exposure is suffer from guilt by association, but consumption as food and feed, but the only half of the risk equation. The other farmers and other agriculturalists are hurt transgenic events in question were not half is hazard. What would be the effects when their state or region is found to have deregulated for human consumption at of miniscule amounts of transgenic adventitious presence of transgenes. 1222 VOLUME 26 NUMBER 11 NOVEMBER 2008 NATURE BIOTECHNOLOGY COrrespOndence That said, Ventria, at least, seems to circumstance will change. In the meantime, (2004). have learned from the mistakes of others. the proposed rules are available for public 3. Fox, J.L. Nat. Biotechnol. 25, 367–368 (2007). 4. Stewart, C.N., Jr. Genetically Modified Planet: They are now growing transgenic pharma comment for 45 days until November 24. Environmental Impacts of Genetically Engineered rice in a state (Kansas) where little-to-no Plants (Oxford University Press, New York; 2004). rice is produced, which is also outside its 5. Miller, H.I. Nat. Biotechnol. 21, 480–481 (2003). C Neal Stewart Jr 6. Ramessar, K. et al. Phytochem. Rev. 7, 579–592 traditional production area. No other rice is Department of Plant Sciences, University of (2008). grown within nearly 500 km of their fields7. 7. <http://www.aphis.usda.gov/brs/aphisdocs/06_27801r_ Tennessee, Knoxville, TN 37996, USA. ea.pdf> They use dedicated farm machinery and e-mail: [email protected] 8. Pla, M. et al. Transgenic Res. 15, 219–228 (2006). take inordinate care in transporting their 9. Yuan, J. et al. BMC Bioinformatics 8 Suppl 7, S6 transgenic rice to processing. Processing 1. <http://federalregister.gov/OFRUpload/OFRData/2008- (2007). 23584_PI.pdf> 10. Stewart, C.N., Jr. Nat. Rev. Genet. 4, 806–817 and storage of rice is in a dedicated facility 2. Anonymous. Editorial. Nat. Biotechnol. 22, 133 (2003). as well. Weedy red rice is the same species as cultivated rice, but it has not been reported to grow in the area of cultivation, therefore hybridization and introgression is not of concern and introgression rates are very low Coexistence in the EU—return of anyway in this species10. So why worry? Scientifically, I have the moratorium on GM crops? very few worries with regards to biosafety in this particular case. Ventria is indeed To the editor: member states, the European Commission taking extraordinary measures to ensure The decision of European Union (EU; (EC; Brussels) follows the subsidiarity transgene containment. USDA APHIS Brussels) commissioner for environment, principle for the implementation of legal continues to evolve and has improved Stavros Dimas, to defer market approvals coexistence frames1. According to this http://www.nature.com/naturebiotechnology inspection frequency and procedures. I do of maize Bt11 and 1507 against the principle, coexistence should be handled worry that, until we devalue the doctrine of recommendation of his scientific advisers by the lowest authority possible. In the adventitious presence, any slight detection is an indication that Europe remains in a following text, we use the example of Bt of transgenes outside of their intended state of quasi-moratorium regarding the maize, a crop that expresses the insecticidal locales will be overblown beyond reason. cultivation of genetically modified (GM) protein Cry1Ab from Bacillus thuringiensis In spite of Ventria’s care, there is still a crops. Here, we outline