By David N. Leff
Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.
A typical epileptic seizure leaves no visible lasting aftereffects. The subject may awaken with a headache, but usually resumes normal activities. However, neuroscientists know that the turbulent cerebral upset causes loss or damage to neurons in the brain. What they haven't known is the precise cause of this neuronal cell death.
Now a research report in the current Proceedings of the National Academy of Sciences (PNAS), dated Aug. 17, 1999, fingers one likely culprit - reactive oxidative stress (ROS). The paper is titled, "EUK-134, a synthetic superoxide dismutase and catalase mimetic, prevents oxidative stress and attenuates kainate-induced neuropathology."
The paper describes creating temporal lobe epilepsy-like seizures in rats, then treating them with EUK-134, a proprietary drug produced by Eukarion Inc., of Bedford, Mass. The compound catalytically mimics the activity of superoxide dismutase and catalase, which the body uses to ward off the toxic, tissue-savaging depredations of ROS. (See BioWorld Today, Aug. 16, 1999, p. 1.)
To render their rats epileptic, the co-authors - at the University of Southern California in Los Angeles - dosed them with kainic acid, which models seizures by activating excitatory glutamate receptors in the brain, with toxic effects on neurons. As the paper described, about 45 minutes after receiving this drug, the animals "exhibited masticatory movements and nodding," along with "numerous, intermittent 'wet-dog shakes,' [and] stereotypic movements of the forepaws, described as 'piano playing.'" Later the rodents' symptoms progressed to outright convulsions.
Neuroscientist Georges Tocco, one of two Eukarion co-authors on the PNAS paper, besides the USC contingent, told BioWorld Today the purpose of this in vivo experiment was not to test EUK-134 as an epilepsy therapeutic. "What we were testing," he explained, "is the cell death associated with seizures that occurs in the hippocampus, mainly, and in other areas of the brain. The purpose of this rat experiment was to demonstrate that in fact, even though seizures were present, we could prevent apoptosis in the brain, and also to show that the cell death associated with the seizures is in part due to oxidative stress.
"This had not been shown before," Tocco pointed out. "The real cause of cell death in the brain, caused by seizures, was not really known. I say in part because we showed that we were not protecting 100 percent of the neurons from apoptosis. The experiment that we did did not eliminate all the possible types of cell death."
The rodent cohort treated with EUK-134 had much less neuronal damage and cell death than did groups treated only with kainic acid or controls. As for using EUK-134 some day in human anti-seizure therapy, Tocco made the point, "We would need to do a lot more experiments to show that the drug could indeed be useful in humans. But at this stage, it's too early to say that."
Rebutting Monarch Butterfly Brouhaha, British Scenario Documents Benefit Of Transgenic Crops
Remember "The Butterfly That Stamped" in Kipling's Just-So Stories for children? Well, last spring a butterfly stomped all over agricultural biotechnology, and its vibes are still making waves worldwide. What started the furor was a paper in Nature, dated May 20, 1999, titled "Transgenic pollen harms monarch [butterfly] larvae."
Its three co-authors, entomologists at Cornell University collected pollen from transgenic corn plants, engineered to express the potent Bacillus thuringiensis (Bt) insecticide. Its target insect is the European corn borer (Pyrausta nubilalis), against which North American farmers spray their crops heavily with chemical insecticides.
A non-target insect, the monarch butterfly (Danaus plexippus), feeds exclusively on the common milkweed (Asclepias curassavica), which often grows adjacent to cornfields. In a laboratory experiment, the Cornell scientists allowed monarch larvae to munch on the transgenic corn pollen, which they had dusted on milkweed leaves. Larval survival was 56 percent vs. 100 percent for other insect cohorts. Ergo, the groundswell uprising against genetically engineered crop plants. (See BioWorld Today, May 24, 1999, p. 4; and June 10, 1999, p. 1.)
But that's not the end of the story. In the current issue of Nature, dated Aug. 26, 1999, a one-page "Scientific Correspondence" item, titled "Parasitoid behavior and Bt plants," recounts a different drama. Its co-authors are scientists at Britain's Institute of Arable Crops Research in Harpenden, Herts. Their laboratory experiment's cast of characters pits a transgenic Bt oilseed rape plant (Brassica napus) against two insects, one, the diamondback moth (Plutella xlostella), which feeds on rape. The other, a wasp (Cotesia plutellae), kills and eats the larvae of that moth.
When a diamondback larva chows down on a rape leaf, the plant releases volatile signals that attract the wasps. The researchers report that the parasitic insects successfully found and devoured those moths, even those target insects resistant to the Bt toxin. The wasps survived because they holed up inside their Bt-contaminated hosts.
The British scientists observed that not only do the transgenic crops survive pest damage, but so do the beneficial, non-target wasps, whereas insecticides kill both wasps and moths. The wasps, they conclude, may even help to slow the evolution and spread of Bt resistance in these plant pests by preying on them.