Tuesday, October 01, 2002

David Schubert of the Salk Institute in Nature Biotechnology
insufficient attention has been paid to three important issues: first, introduction of the same gene into two different types of cells can produce two very distinct protein molecules; second, the introduction of any gene, whether from a different or the same species, usually significantly changes overall gene expression and therefore the phenotype of the recipient cell; and third, enzymatic pathways introduced to synthesize small molecules, such as vitamins, could interact with endogenous pathways to produce novel molecules. The potential consequence of all of these perturbations could be the biosynthesis of molecules that are toxic, allergenic, or carcinogenic. And there is no a priori way of predicting the outcome. In what follows I outline these concerns and argue that GM food is not a safe option, given our current lack of understanding of the consequences of recombinant technology.

Given that GM plants will sometimes produce different amounts of proteins, and perhaps totally new proteins, as compared with the parental species, what are the possible results? A worst-case scenario would be that an introduced bacterial toxin is modified to make it toxic to humans. Prompt toxicity might be rapidly detected once the product entered the marketplace if it caused a unique disease, and if the food were labeled for traceability, as were the GM batches of tryptophan. However, cancer or other common diseases with delayed onset would take decades to detect, and might never be traced to their cause. Conversely, plant flavonoids and related molecules have great health benefits, and there is evidence that these can be depleted in GM crops.

These points were raised to some extent by Jane Rissler of UCS on CSPAN yesterday [Washington Journal, 9/30/02]. I have to say I felt sorry for her interlocutor, who seemed like a decent guy forced to hew to untenable positions by his industry paymasters. Of course it is in the interest of such industries to hire people who seem decent.

Meanwhile, a study in Science shows that a single gene confers DDT resistance in Drosophilia:

The results reinforce the hypothesis that resistance genes need not arise de novo to cause problems in a particular region. Through natural migration or human-mediated transport, resistant pests have the capacity to disperse and transfer genes over large areas in very short periods of time. This phenomenon has previously been described for mosquitoes that resist insecticides by amplification of insecticide-detoxifying carboxylesterase genes. Sequencing of DNA surrounding these genes implied a common origin and spread, probably through passive migration on ships or airplanes (3). Similar geographic spread has been confirmed for crop pests such as aphids and whiteflies, no doubt facilitated by the extensive global trade in plant produce [e.g., (4)]. The ease with which resistance genes can be transferred over large areas, both nationally and internationally, emphasizes that strategies for resistance management need to be implemented on an area-wide, even global, basis. A recent outbreak of malaria in South Africa was correlated with the spread of resistant mosquitoes from neighboring Mozambique (5).

Cyp6g1 is reported to have an unusually broad substrate specificity. It appears to resist not only DDT but also a range of other insecticide groups, including organophosphates, neonicotinoids (recently developed analogs of nicotine), and benzoylphenylureas (compounds interfering with insect development). These groups encompass strikingly different modes of action and might be considered ideal candidates for rotation strategies aimed at avoiding continuous selection for the same resistance mechanism. Patterns of cross-resistance are, however, very difficult to predict, particularly for detoxification mechanisms, where specificity may depend on subtle features of the chemical structure of insecticides. One important practical consequence is that as such broad-spectrum mechanisms accumulate in pest populations, the risk of resistance extending to new agents increases.

Science is "excited" by the prospects for "managing resistance". In unrelated news, Bell Labs had to fire a physicist for fabricating his data:
Scientists in the field are likewise saddened, although unsurprised, by the panel's findings. "I'm sorry that so many people were working on [replicating Sch´┐Żn's results] and couldn't get it to work," says physicist Lydia Sohn of Princeton University, one of the first to notice the duplicate graphs. "But hopefully people will learn something and move forward."

Bell Labs is the research arm of the communications giant Lucent Technology. Its chastening experience has raised questions about peer review, co-author responsibility and career progression in science.


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