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means that, at least some of the says more government-sponsored re time,ribozymescan evolve new search is needed to speed the develop capabilities without first acquir ment of alternative pesticides and eco nomical synthetic chemical pesticides ing mutations that change their that pose less risk to humans and the RNA environment. Bartel and Schultes study how, in the course of evolution, "Chemical pesticides should remain new RNA folds develop and part of a larger toolbox of diverse pestthereby new functions develop. management tactics for the foreseeable future," says May Berenbaum, profes Both theoretical arguments and sor of entomology, University of Illinois, an examination of the sequences Urbana-Champaign, who chaired the of naturally occurring ribozymes committee that wrote the report. show that a wide variety of very different sequences can all pro Plants genetically engineered to resist duce the same basic fold. That pests are probably safer for the environ means that RNA sequences can ment than traditional synthetic pesti accumulate a lot of changes that cides, the committee says. However, not do not affect their folding or cat enough is known about how fast pests be Ligase HDV alytic function. "Sequences can come resistant to transgenic plants; how the plants affect nontarget species, such drift very, very far," Bartel says, as the monarch butterfly; and how readi "so far that they approach the se ly pest-resistant transgenes move to quences of otherribozymeswith weedy relatives. Until these questions are A single RNA sequence (at top) represent other folds and other fonctions." ed as beads on a string, is capable of fold answered, chemical pesticides will be The researchers wanted to test ing into active ligase and HDV conforma needed, the report says. whether these regions of drift tions. The beads (nucleotides) are color could actually overlap, so that Among its recommendations on re coded to reflect regions of hydrogen bond the same sequence could fold in search, the report says that the National ing in the ligase conformation, which do two different ways to become, in Science Foundation and the Environ not carry over into the HDV structure. effect, two different ribozymes. mental Protection Agency should fund research on pest behavior on actual To test this possibility, they chose tworibozymesof the same size but professor of chemistry at Scripps Re farms so that farmers might know each with different structures and catalytic search Institute, La Jolla, Calif., in a com year which crops would likely be at functions. One is the hepatitis delta virus mentary accompanying publication of the tacked by particular pests and rotate (HDV)ribozyme,a naturally occurring ri- MIT work. "Imagine generating a string their crops accordingly. It also recom bozyme that catalyzes a reaction that of text that, without changing the order of mends that the government fund more cleaves RNA The other is a class ΙΠ li- a single letter, could be grouped into dif research on organic farming methods, gase generated in the laboratory by "test- ferent words so as to provide two para which now consumes only 0.1% of agri tube" evolution that catalyzes formation graphs that have entirely different mean culture research dollars. ings," he writes. Such a task would be "The crop protection industry whole of a phosphodiester bond. "When you know the sequence re nearly impossible using the standard 26- heartedly agrees with the [NRC] com quirements for bothribozymes,you can letter alphabet or the 20-letter amino acid mittee that an array of pest management write down sequences that you think "alphabet" used to construct proteins. It technologies, including biotech plants might be able to fold into one or the oth can be done with RNA, however, because and chemical pesticides, can help make er ribozyme and catalyze the two reac it is constructed from a four-letter alpha agriculture more productive and profit able," says Jay J. Vroom, president of tions," Bartel says. "We've done that, bet of nucleic acids. the American Crop Protection Associa and in the couple that we have tested, Rebecca Rawls tion. "Farmers must have a broad range they do have a little bit of the activity for of pest-control options available to re both enzymes." spond to pest pressures and outbreaks." The resulting sequence is more likely Synthetic Pesticides Jay Feldman, executive director of to fold into the shape of the ligase ri Beyond Pesticides/National Coalition bozyme, where it produces a 460-fold im Still Useful, Needed Against the Misuse of Pesticides, had a provement over the uncatalyzed rate of reaction. But sometimes it folds into the Synthetic chemical pesticides will con mixed reaction to the report. Although HDVribozymeshape, where it improves tinue to play an important role in U.S. the NRC committee's advocacy of the RNA cleavage rates about 70-fold. By agriculture for at least the next decade, development of safer pesticides is a pos making one or two key changes to the concludes a report from the National itive step, "it erred on the side of [pro moting] continued reliance on pesti RNA sequences, the researchers can Research Council (NRC). There is no justification for com cides in agricultural systems that are greatly improve theribozyme'scatalytic ability for either reaction, but when they pletely abandoning chemical pesticides, increasingly avoiding dependency on do so, they lose all crossover capability. the report says, because in many situa pesticides," he says. The report can be read at http://www. Although Bartel makes finding the tions, the benefits of pesticides are high right sequence seem a simple matter, it is relative to their risks. In other cases, al nationalacademies.org. Bette Hileman "no mean feat," writes Gerald F. Joyce, ternatives do not exist. Still, the report 12 JULY 24,2000 C&EN
