Drought Resistant GM Rice Toxic?

Prof. Joe Cummins explains why one method to genetically engineer drought resistant rice could be perilous for human and animal health

Commercial genetic engineering has been based on inserting a single transgene along with control elements into a crop plant. Traits such as herbicide tolerance, insect resistance and virus resistance have been commercialized without much understanding of the metabolic consequences of the alterations.

To deal with more complex and agriculturally significant traits, a technique called metabolic engineering has been developed [1] to retune endogenous metabolic pathways.

Recently, transgenic rice modulated in the polyamine biosynthetic pathway has been found to be drought tolerant [2, 3]. Polyamines are carbon chains containing two or more amine (NH 2 ) groups. Polyamines are essential compounds found in all living cells. They increase as bacteria putrefy animal flesh, producing a strong rotting odor. Polyamines are given names such as putrescine and cadaverine or spermine and spermidine. Even though the polyamines are essential for cell growth, they may also cause disease in animals.

In animals and fungi, putrescine is the precursor of spermidine and spermine ; it is synthesized from the amino acid ornithine. Plants have an alternative pathway that converts the amino acid arginine to putrescine, using the enzyme arginine decarboxylase (ADC) , the product of the adc gene. This is followed by additional reactions to form spermidine and spermine using S-adenosylmethionine and the action of the enzyme S-adenosylmethionine carboxylase (SAMDC), the product of the Samdc gene.

Rice plants were transformed with the ADC gene from Datura (Jimson weed, a traditional and commercial source of drugs), driven by the maize ubiquitin promoter and the first intron; and transcription was terminated with the Agrobacterium nos transcription terminator. The transgenic rice plants had elevated basal levels of putrescine, that were further elevated during drought stress, leading to enhanced production of spermidine and spermine by increased SAMDC enzyme.

The exact mechanism by which increased putrescine increases drought resistance is not fully understood but it is clear that elevated putrescine levels activate spermidine and spermine synthesis that, in turn, regulate putrescine production and sets in motion the resistance to stress [2, 3]. The transgenic rice is designed to provide sustainable rice production under stress conditions.

Stress resistant rice has been reported without reference to the potential impact of the metabolic alteration – such as increase in polyamines - on mammals consuming the transgenic rice. Polyamines are known to be elevated in the cells and body fluids of cancer patients. Drugs inhibiting the synthesis of polyamines can prevent cancer and have been used in cancer treatment [4].

Moreover, polyamines can give rise to toxic products. Spermidine and spermine can be metabolized to hydrogen peroxide, ammonium and acrolein, which are toxic to cells . Polyamines can contribute to the suppression of immunologic reactions in the lung [5]. Polyamines are implicated as uremic toxins leading to renal failure [6]. Chicken feed containing elevated amines, such as putrescine, performed poorly and caused a condition called “necrotic cellular debris” [7]. Wines may contain elevated polyamines from grape must and fermentation. It is believed that spermidine and spermine may be beneficial in wine while putrescine and cadaverine are linked to symptoms such as nausea, sweating and difficult breathing [8].

The good-news message that transgenic rice may be grown under drought conditions should be tempered by the bad-news that eating the transgenic rice may make one quite ill. The promotion of this transgenic crop along with others in the scientific journals seems invariably to neglect the potential adverse effects of the crop on humans and wild life. Open field trials should not be undertaken in the absence of proper risk assessment and toxicity tests.

Article first published 24/09/04

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References

1. Capell T and Christou P. Progress in plant metabolic engineering Current Opinion in Plant Biotechnology 2004, 15, 148-54.
2. Capell T, Bassie L and Christou P. Modulation of the polyamine biosynthetic pathway in transgenic rice confers tolerance to drought stress Proc. Nat. Acad. Sci. USA 2004, 101, 9909-14.
3. Capell T. Enhanced drought tolerance in transgenic rice, August 2004, http://www.isb.vt.edu/news/2004/news04.aug.html#aug0402
4. Bachrach U. Polyamines and cancer: Minireview article Amino Acids 2004, 26, 307-9.
5. Hoet P and Nemery B. Polyamines in the lung: polyamine uptake and polyamine linked pathological or toxicological conditions Am. J. Physiol. Lung Cell Mol. Biol. 2000, 278, L417-33.
6. Sakat K, Kashiwagi K, Sharmin S, Ueda S, Irie Y, Murotani N and Igarashia K. Increase in putrescine, amine oxidase, and acrolein in plasma of renal failure patients Biochemical and Biophysical Research Communications 2003, 305, 143-9.
7. Tamim N, Bennett L, Shellem T and Doer J. High-performance l iquid chromatographic determination of biogenic amines in poultry carcasses J. Agric. Food Chem. 2002, 50, 5012-15.
8. Herberger K, Csomos E and Simon-Sarkadi L. Principal component and linear discriminant analyses of free amino acids and biogenic amines in Hungarian wines J.Agric. Food Chem. 2003, 51, 8055-60.