Rounding up the evidence on glyphosate

We've blogged a few times (here, e.g.) about the unintended consequences of the widespread use of genetically modified Roundup-resistant plants and, consequently, Roundup (Roundup is an herbicide, and its active ingredient is glyphosate).  Not surprisingly to anyone except Monsanto--the original producers of the stuff, who said this wouldn't happen--Roundup is encouraging the growth of herbicide-resistant weeds wherever it's liberally used, and thus the need for farmers to use more, and more toxic, herbicides, or more labor-intensive horticultural practices to deal with these newly stubborn weeds.  That's evolution for ya.

But other effects are getting some attention too.  A quick check on Google and Google Scholar provides evidence that for more than a decade there have been anecdotal and scientific journal reports of neural, craniofacial, limb and other anomalies in infants born in regions with intensive Roundup use, as well as effects on amphibians and other vertebrates living in or near the fields.  Any organism exposed to water that contains glyphosate-laced runoff apparently is also at risk.

Among many other reports, a 2009 paper finds that glyphosate alone is toxic to cells, and that other chemicals added to the herbicide, supposedly inert, exacerbate the effect.

We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup (R) formulations, from 10⁵ times dilutions, on three different human cell types. This dilution level is far below agricultural recommendations and corresponds to low levels of residues in food or feed. The formulations have been compared to G alone and with its main metabolite AMPA or with one known adjuvant of R formulations, POEA. HUVEC primary neonate umbilical cord vein cells have been tested with 293 embryonic kidney and JEG3 placental cell lines. All R formulations cause total cell death within 24 h, through an inhibition of the mitochondrial succinate dehydrogenase activity, and necrosis, by release of cytosolic adenylate kinase measuring membrane damage. They also induce apoptosis via activation of enzymatic caspases 3/7 activity. 

And,

The real threshold of G toxicity must take into account the presence of adjuvants but also G metabolism and time-amplified effects or bioaccumulation. This should be discussed when analyzing the in vivo toxic actions of R. This work clearly confirms that the adjuvants in Roundup formulations are not inert. Moreover, the proprietary mixtures available on the market could cause cell damage and even death around residual levels to be expected, especially in food and feed derived from R formulation-treated crops.

Now a paper in the journal Chemical Research in Toxicology (Aug 9, 2010) reports the teratogenic effects of incubating frog and chick embryos with a 1/5000 dilution of glyphosate, and suggests a mechanism to explain the effect.

The treated embryos were highly abnormal with marked alterations in cephalic and neural crest development and shortening of the anterior−posterior (A-P) axis. Alterations on neural crest markers were later correlated with deformities in the cranial cartilages at tadpole stages. Embryos injected with pure glyphosate showed very similar phenotypes. Moreover, GBH [glyphosate based herbicides] produced similar effects in chicken embryos, showing a gradual loss of rhombomere domains, reduction of the optic vesicles, and microcephaly......  A reporter gene assay revealed that GBH treatment increased endogenous retinoic acid (RA) activity in Xenopus embryos and cotreatment with a RA antagonist rescued the teratogenic effects of the GBH. Therefore, we conclude that the phenotypes produced by GBH are mainly a consequence of the increase of endogenous retinoid activity..... The direct effect of glyphosate on early mechanisms of morphogenesis in vertebrate embryos opens concerns about the clinical findings from human offspring in populations exposed to GBH in agricultural fields.

Retinoic acid is a signaling factor that is essential for cell differentiation in the developing embryo, as a regulator of major stages in growth and patterning.  If glyphosate is confirmed to interfere with retinoic acid levels in developing vertebrate embryos, as this study suggests, it's a serious problem for farm workers, people who live in regions where glyphosate is used heavily, or who use water from sources contaminated with glyphosate runoff, as well as any other vertebrate exposed to this stuff.

The point here is not to take political sides, but to stress that evaluating the evidence independently, regardless of commercial interest (or, for that matter, tree-hugger interests) is the only way to even have a good chance of preventing major calamities--or, to become confident that they won't occur.  But what we know about evolution and development make it quite conceivable that the problems are real.

Rounded up? No, the varmints got away!

It seems there really is no free lunch....except perhaps for weeds. That's because it turns out that genetically modified crops don't defy evolution after all! The laws of Nature stand, and weren't superseded by agribusiness scientists.

A story in the New York Times this week tells about the increasing resistance of weeds to Roundup, or glyphosate, the weedkiller originally introduced by Monsanto but now sold by a number of other companies. The weedkiller was made for use with 'Roundup Ready' crops, grown from seeds genetically modified to be resistant to the herbicide. Many farmers who planted these seeds were very happy with how easily weeds could be controlled as well as the kind of no-till agriculture, and the reduction in top soil erosion that that brought, that then became possible. (Though there was, and still is, controversy over Roundup Ready crop yields, the safety of the chemical, Monsanto's legal right to insist that farmers can't save seed to plant the following year, and so on, but those issues are not for this post.)

But farmers are growing increasingly unhappy. Roundup resistant weeds -- superweeds -- were first found flexing their new-found muscles in Delaware, but now crop up all over the country (so to speak), with insidious and expensive effects.

To fight them, Mr. Anderson and farmers throughout the East, Midwest and South are being forced to spray fields with more toxic herbicides, pull weeds by hand and return to more labor-intensive methods like regular plowing.

“We’re back to where we were 20 years ago,” said Mr. Anderson, who will plow about one-third of his 3,000 acres of soybean fields this spring, more than he has in years. “We’re trying to find out what works.”

Farm experts say that such efforts could lead to higher food prices, lower crop yields, rising farm costs and more pollution of land and water.

“It is the single largest threat to production agriculture that we have ever seen,” said Andrew Wargo III, the president of the Arkansas Association of Conservation Districts.

Oddly enough, Monsanto originally promised that herbicide resistance would be insignificant. Why? They must have believed they were dealing with so fundamental a vulnerability on the weedy pests' part that they couldn't evolve a way around their assassin.

Monsanto is still saying that the problem is containable -- but they would, since they stand to lose a lot if farmers no longer have reason to buy Monsanto's Roundup resistant seeds. Did Monsanto think that, as one of the largest agricultural companies in the world, that they could make evolution stand still? And of course it's not just glyphosate resistance that's the problem. The International Survey of Herbicide Resistant Weeds lists "347 Resistant Biotypes, 195 Species (115 dicots and 80 monocots) and over 340,000 fields". The additional problem with Roundup is that farmers (and Monsanto) have become dependent on GM seeds, and the cultivation methods they've used to grow them.

The story is of course reminiscent of the increasingly widespread antibiotic resistance in bacteria, though there we had 50 good years, while with Roundup it was only several decades -- neither even a blink of the eye in evolutionary terms, of course. But, we've known for millennia that artificial selection is a fast and powerful force for change -- it was Darwin's very model for how natural selection works in the wild, after all. Farmers have chosen their best animals for breeding probably since they were first domesticated 10,000 years ago.

So, it shouldn't be surprising that in effect artificially selecting for herbicide resistant weeds, or antibiotic resistant bacteria, is fast and effective as well. The idea that we might be headed for the last roundup is naive. Nope, the truth is, pardner, that the varmints are still out there, eluding all the posses we send after them.