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 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 Nature Publishing Group Group 200 8 Nature Publishing 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.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 another challenge in its tissues, to explore how national and/or chance that vigilant people with advanced that threatens to paralyze the cultivation regional coexistence regulations might affect detection procedures will find something of GM crops in Europe: regulations on the the future adoption of Bt maize. At present, to report—regardless of real biosafety coexistence of GM and non-GM crops. Bt maize is the only GM crop planted over a issues. Therefore, if we believe this to be As a last building stone of the restyled EU significant area in the EU (Fig. 1). true, Ventria (and any other company legal framework, the adopted coexistence To ensure coexistence between cropping cultivating pharma crops in open fields) policy aims to ensure that different cropping systems, member states are currently must perform perfectly year after year to systems develop side by side without implementing or developing ex ante Nature Publishing Group Group 200 8 Nature Publishing
© avoid admixtures. In spite of the odds and excluding any agricultural option. Because coexistence regulations and ex post liability current climate, I am cautiously optimistic of the heterogeneity in farm structures, crop schemes. In ex ante coexistence regulations, that pharming rice in Kansas could be a patterns and legal environments among preventive on-farm measures are prescribed model for other companies to follow. But would they, and what issues lie 120,000 beyond admixture? There are two absolute Poland conditions to assure biosafety when pharming Slovakia crop commodities (not counting Murphy’s 100,000 Romania Law). The first requirement is extraordinary Germany physical isolation and dedicated equipment. Portugal 80,000 Still, there are limited numbers of suitably Czech Republic isolated sites that are available and conducive France
for rice production in the United States. 60,000 Spain Second, the pharma products must be safe for e plantings (ha) accidental consumption in bulk by wildlife
and humans. For the latter, accidental bulk Bt-maiz 40,000 ingestion should be part of the standard regulatory package. 20,000 The bottom line for most people is a level of discomfort with open-air pharma production of any sort, and especially when 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 it is in a grain crop that has been bred for Ye ars palatability and nutrition (that is, begging to be eaten by humans and wildlife). Figure 1 Cumulative Bt maize plantings (ha) per member state in the EU (1997–2008). In 2008, It is hard to predict when and if this France banned the cultivation of maize MON810 on its territory.
nature biotechnology volume 26 number 11 NOVEMBER 2008 1223