Prof. Joe Cummins lifts the lid on a new wave of genetically engineered products that claim to offer "healthier foods" and "direct consumer benefits".
In September 2004, Monsanto announced a "Vistive soybean" with reduced linolenic (low linolenic or LL) acid content that will be available for planting in the 2005 season. Although promoted as "produced through conventional breeding" [1] because it includes natural genes reducing the oil content of linolenic acid, Vistive also has transgenes conferring the Roundup Ready trait.
Vistive soybean does not appear to have been approved under the usual procedure for transgenic crops because the reduced linolenic acid content was achieved using traditional selection and breeding. Instead, government regulators assumed that the Roundup Ready trait acts independently of the LL trait and for that reason the two kinds of traits could be joined by crossing two strains.
Certainly, there is no precedent for reviewing and approving novel crops produced by conventional breeding, but if the LL trait interacts with the Roundup Ready (glyphosate tolerance) trait, Vistive soybeans should be re-evaluated as an alteration to the original Roundup Ready trait. There is a clear indication that the use of glyphosate on the soybean crop will result in an impact on fatty acid metabolism through the breakdown products of the herbicide (see later).
Vistive soybeans with the Roundup Ready trait are claimed to contain less than 3% linolenic oil, in contrast to the 8% linolenic content for conventional soy oil. Low linolenic oil is more stable, with a better flavour and requires less hydrogenation. Trans fatty acids are produced in the hydrogenation process; and trans fatty acids are linked to heart disease because they lower HDL (good) cholesterol while raising LDL (bad) cholesterol [1]. Ironically, trans-fats labelling is to begin in 2006 in the United States, even though industry and regulators in the United States resist labelling of products containing transgenes.
In plants, fatty acids are produced in the chloroplasts. Two molecules are crucial for fatty acid synthesis: acetyl-CoA and malonly-CoA (acetyl-CoA with an added carbon dioxide molecule). The number of carbon atoms in the long fatty acid chain is always even, and the carbon molecules are added two at a time. The newly synthesized fatty acids may be altered in mitochondria, or the endoplasmic reticulum, or stored in membrane bound lipid vesicles.
Catabolism of the fats is undertaken in organelles called glyoxysomes where the fatty acids are degraded two carbon atoms at a time, by a process called beta-oxidation [2]. Fatty acids are modified in organelles and the endoplasmic reticulum by the lipoxygenase pathway to produce plant defence and signalling compounds such as jasmonates [3]. Glyoxysomes carry out the glyoxylate cycle - a modification of the tricarboxylic acid cycle found in plants and microbes - as well as beta-oxidation [4]. Fatty acid metabolism is crucial to energy transformation in plants, but also contributes to cell structure and to signalling and defence.
The transgenic parent of Vistive soybean is the soybean line GTS40-3-2 (event MON-04032-6), tolerant to glyphosate. The strain was released commercially in the United States in 1994, then Canada (1995), Japan (1996), Argentina (1996), Uruguay (1997), Mexico (1998), Brazil (1998) and South Africa (2001) [5]. The transgenic construct includes a synthetic approximation of the EPSPS gene from Agrobacterium for tolerance to glyphosate, adjusted for the codon preference of the crop. The EPSPS gene was driven by the enhanced 35s cauliflower mosaic virus promoter, and the sequence included a chloroplast transit protein from petunia and a nopaline synthesis terminator from Agrobacterium [5, 6].
Six years after Roundup Ready soy was released to the environment, Monsanto acknowledged that an "inactive" 75 base pair fragment and a 250 base pair fragment of the EPSPS gene were inserted outside the open reading frame of the EPSPS protein (those inserts were over 20% the size of the EPSPS gene) [7]. The origin of the gene fragments and their possible activity was curtly dismissed without fuller explanation. The evident instability of these and other crop transgenes has been discussed by Mae-Wan Ho [8, 9], and raises many biosafety concerns.
Possible interactions between the LL and Roundup Ready genes of Vistive soy cannot be dismissed, as the crop will certainly be sprayed with glyphosate. The herbicide will accumulate to levels toxic to animals and humans if it is not broken down in the plant cell. In plants, glyphosate is normally broken down by glyphosate oxidase (GOX) enzyme (presumably an enzyme present to digest natural products). GOX enzyme accelerates the breakdown of the herbicide glyphosate into two compounds, aminomethylphosphonic acid (AMPA) and glyoxylate. Glyoxylate is commonly found in plant cells and is further broken down by the glyoxylic pathway for lipid metabolism. The increased concentration of glyoxylate due to glyphosate breakdown would certainly disturb the metabolism of fatty acids.
Glyphosate exposure of herbicide tolerant groundnut was observed to increase glyoxylase enzyme [10]. Presently, it is not possible to predict the nature and extent of disturbance of fatty acid metabolism, nor the impact on LL function. The point is that there is a clear link between Roundup Ready and LL traits, which should be explored fully before the Vistive crop reaches general distribution. Every transgenic crop should be reassessed after it has been crossed with a variety derived from conventional selection, especially one that has a clear metabolic association with the transgene, before any release of the crop. There should be a rule to ensure that careful reassessment is done.
The burden of proving that releases such as Vistive are safe rests with the proponent. Experiments must be done to ensure that the Roundup Ready genes and the LL genes are independent of each other, and that any interactions are fully risk assessed. In addition, Roundup Ready soybean itself should be reassessed in light of new scientific evidence raising questions about transgenic instability.
Article first published 25/11/04
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