By David N. Leff

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Why do weather forecasters come within 10 percent of pure chance? Aficionados of Chaos Theory might adduce their "butterfly effect" to explain this frustrating phenomenon. It goes like this: "When a butterfly in Tokyo flaps its wings, the result may be a hurricane in Florida a month later."

Last year, monarch butterfly caterpillars dying in a Cornell University laboratory set off chaos in the agricultural biotechnology movement that still is resonating. The flap it caused began with a paper in Nature dated May 20, 1999, titled: "Transgenic pollen harms monarch [butterfly] larvae." Its entomologist co-authors collected pollen from corn plants genetically engineered to express the powerful Bacillus thuringiensis (Bt) organic insecticide. Its target insect is the European corn borer (Pyrausta nubilalis), against which farmers in the U.S. and Canada spray their crops heavily with conventional chemical bug killers - more than 80 million pounds in a recent year.

At their Cornell laboratory in Ithaca, N.Y., the researchers allowed the larvae of a nontarget insect, the monarch butterfly, to feed on pollen from the transgenic corn, which they had dusted on milkweed leaves, the monarch's provender of choice. Result: Only 56 percent of the larvae survived.

The bright orange and black monarch butterfly quickly became the poster bug for opponents of biotech. But in April of this year, a report from the National Research Council proposed, "This is a prime example of an issue that needs to be researched further, with rigorous field evaluations."

The nerve that statement struck was criticism that the Cornell finding relied entirely on artificial laboratory conditions. And this month came a report in the current Proceedings of the National Academy of Sciences (PNAS) online edition, dated June 6, 2000. Its title: "Absence of toxicity of Bacillus thuringiensis pollen to black swallowtails under field conditions." Its authors are entomologists at the University of Illinois, Urbana.

Black swallowtails (Papilio polyxenes), despite their evocative name, are not birds but butterflies. Like monarchs (Danaus plexippus), swallowtails feed on plants that grow in close proximity to cornfields. To gauge the impact of transgenic pollen ingestion in the field, the Illinois researchers placed plants infested with larval swallowtails at varying distances from a field of corn harboring the Bt gene. They report that while many of the swallowtail caterpillars died during the seven-day field trial, there was no evidence that pollen from the transgenic corn contributed to that mortality.

As Monoclonal Antibody Clinical Trials Against Septic Shock Lick Their Wounds, A Different Agent Emerges

A very recent appeal from the World Health Organization urges the medical profession to cool its over-prescription of antibiotics, which only encourage bacteria to develop drug resistance. Even scrub-up antibacterial soaps are fingered for their role in promoting this hazard.

But in hospital intensive care units, surgical recovery rooms and ERs, patients justifiably receive antibiotics against the lethal gram-negative bacteria that proliferate in these nosocomial environments. However, here of all places the cards are stacked in favor of the pathogens.

Most antibiotics work by penetrating and disrupting a bacterium's cell wall, causing the germ's death. But that very mechanism backfires: The cell-wall fragments consist largely of the very endotoxic lipopolysaccharides (LPS) that cause septic shock. Statistics vary, but an estimated 300,000 cases of septic shock occur in the U.S. each year, and a million worldwide. From 40 percent to 70 percent of them die.

Ironically, they die of their immune systems' efforts to neutralize the LPS toxin. It floods the body with cytokines, such as tumor necrosis factor (TNF) and interleukins. Since the 1980s, these molecules looked like tempting targets for monoclonal antibodies, and the biotech woods are littered with the whitened skeletons of failed clinical trials, those pitting monoclonals against the proinflammatory toxic TNF in particular.

As molecular biologist Sunil David, at the University of Kansas in Kansas City puts it: "Numerous clinical trials designed to test the therapeutic efficacy of monoclonal antibodies have, to date, failed to establish that the use of such antibodies is of clinical value." He is senior author of a paper in the April 1999 issue of the journal Antimicrobial Agents and Chemotherapy, which describes an alternative anti-sepsis strategy. Its title: "Lipopolyamines: Novel antiendotoxin compounds that reduce mortality in experimental sepsis caused by gram-negative bacteria."

David describes his innovative agents as "sequestrants" rather than antibiotics, because they "sequester LPS, thereby blocking downstream cellular activation events that lead to the production of proinflammatory mediators." He is first inventor of U.S. patent No. 5,998,482, dated Dec. 7, 1999, and headed: "Use of synthetic polycationic amphiphilic substances with fatty acid or hydrocarbon substituents as anti-sepsis agents."

After Decades Of No-Knock Genes, GeneticistsMake `Knock-In' And `Knockout' Fruit Flies

Scientific genetics began with the garden peas cultivated by Gregor Mendel (1822-1884), which propounded Mendelian inheritance. Then, early in the 20th century, geneticists at Columbia University adopted the common fruit fly (Drosophila melanogaster) as their in vivo model for studying chromosomes, the engines of inheritance. That modest brownish-black insect has held top billing ever since, with one major irony.

As other animal models came along - nematodes, frogs, mice and so on - these newcomers enjoyed one capability that escaped D. melanogaster, namely the ability to become knockouts. For decades, the fly geneticists have cross-bred strains of the insects in order to study their 13,601 genes. But they couldn't disable or "mutate" a particular gene of interest. Now they can, thanks to a report in the current issue of Science, dated June 16, 2000. Its title: "Gene targeting by homologous recombination in Drosophila."

Its authors, drosophilosophers at the University of Utah in Salt Lake City, took for starters a yellowish strain of fly, which had a visible error in its natural brown-color gene. Their technique, to "knock in" a correct version of the body-color gene, hinged on the common knowledge that broken bits of DNA don't hang around long, but are rapidly recombined back into the genome. Science tells how they did it.

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