I NEWS OF THE WEEK I MOSQUITO INSECTICIDE

New pesticide blocks protein digestion A n astute observation on mos-

/ % quitoes by a technician at a JL J L University of Florida ento­mology lab in 1986 has led to discov­ery of a new type of pesticide: a fam­ily of environmentally benign, natu­rally occurring hormones that stops insects from reproducing by pre­venting them from digesting protein.

Several papers on the Florida team's findings have been published in specialized journals, three patents on the technology have been issued during the past two years, and a bio­technology company has begun ef­forts to commercialize it. But so far, this advance has been little known outside a narrow group of special­ists, and development of the pesti­cides has languished because of lack of funding.

That situation may now change, thanks to an enterprising university media relations specialist who inter­viewed the somewhat reticent re­searchers and issued a press release about their work on July 14. The release has aroused extensive media coverage, including articles in the Boston Globe and San Francisco Chronicle, radio reports on the BBC and NBC networks, and even a joke on a late-night television show.

The focus of this newfound attention is a natural mosquito hormone that in­hibits biosynthesis of trypsin, the insect's main digestive enzyme. When the hor­mone is given to an adult mosquito by injection or in its food, the mosquito can­not reproduce because it cannot produce trypsin, which is needed to digest blood for egg maturation. Larval mosquitoes are directly killed by the hormone, be­cause they cannot digest protein needed for growth and maturation.

The Florida researchers find this new mechanism of action to be applicable to other insect species as well. The devel­opers of the pesticide—biochemistry professor Dov Borovsky of the Florida Medical Entomology Laboratory, Vero Beach (a unit of the University of Flori-

Borovsky (left) and technician pursue research in lab at University of Flonda

da), organic analytical chemist David A. Carlson of the Department of Agricul­ture's Agricultural Research Service lab in Gainesville, Fla., and coworkers—call the pesticide a "diet pill" for insects.

The researchers discovered the new mechanism serendipitously when they found that a particular fraction of mos­quito ovary extract inhibits egg matura­tion, making the mosquitoes sterile. "Ini­tially we thought it was a birth-control pill," Borovsky tells C&EN.

However, a technician in the lab— Carol Smoyer, now a junior high school math teacher—noticed that treated mos­quitoes had an unusually large amount of undigested blood in their gut. "Carol started bugging me all the time about it," Borovsky explains. Upon further study, he found that the extract was turn­ing off trypsin biosynthesis. As Smoyer had suggested, it was interfering with digestion, not egg development. "It wasn't a birth-control pill, but was in­stead a diet pill," Borovsky notes.

The team found the active ingredient

in the extract to be a hormone, trypsin-modulating oostatic factor (TMOF), a peptide with 10 amino acid units. The researchers discov­ered that TMOF was, in fact, the nat­ural signal that terminates trypsin biosynthesis after a mosquito's meal has been digested.

Borovsky was excited about these findings, "but nobody else was for many years," he says. "Every time we tried to get a grant from federal granting agencies, they always said the work was premature. Our funds are just drying out."

But the potential implications "are tremendous," Borovsky stresses. "A lot of agricultural pests use trypsin, which means a similar signal might inhibit digestion in other insects."

TMOF retains its activity after be­ing eaten by mosquitoes—an advan­tage for use as a pesticide. "It is not readily digested because of the unique structure of the hormone," Borovsky

explains. "We have shown that it very rapidly goes from the gut into the h e molymph [circulatory fluid]." And be­cause it is produced endogenously by insects, the researchers believe it would be hard for them to develop resistance toit.

For use as a pesticide, the team be­lieves the hormone could be sprayed on plants or applied in an encapsulated form to bodies of water in which insects breed. Potentially, microorganisms that serve as an insect food source could be genetically engineered to produce the hormone. Genes for the hormone might also be introduced into corn and other major crops by genetic engineering, en­abling the plants to produce the hor­mone internally and thus resist insect at­tack.

Insect Biotechnology, Redwood City, Calif., has exclusive licenses to patents on the technology and is actively seek­ing investment partners to participate in commercialization. Alan E. Brandt, founder and chief executive officer of

JULY 26,1993 C&EN 3

NEWS OF THE WEEK

Monsanto plant flooded in south St. Louis The chemical industry has been man­aging fairly well in the face of the rains and floods in Midwest states (C&EN, July 19, page 7). However, last week saw the first flooding of a chemical plant.

Monsanto's Carondelet plant in south St. Louis was partly flooded July 18 after a levee break on the Des Peres River, a small and usually plac­id Mississippi tributary. A dike around the plant failed, sending 3 feet of water into the administration building and flooding part of an en­gineering building. However, all em­ployees were reporting to work and striving to contain damage. Monsan­to is supplying customers with food-grade phosphates and surfactants from inventory recently moved to a warehouse on higher ground.

A Monsanto insecticide plant at

Muscatine, Iowa, has had flooding on its grounds, but water has not en­tered production facilities. Limited shipments in and out are proceeding.

Farther up river, levees in besieged Quincy, 111., still held as the Missis­sippi reached its crest last week. The J. M. Huber calcium carbonate plant in town remained safe.

To aid flood victims, the Monsanto Fund, a company philanthropic founda­tion, has given $100,000 to the American Red Cross. The company's agriculture group will match employee, retiree, and area business donations to the Red Cross up to $1 million, as will the Mon­santo Fund. And Olin has donated $50,000 to the Alton-Wood River, 111., chapter of the Red Cross. The com­pany's Brass & Winchester Division is based in East Alton, ΠΙ.

Marc Reisch

the company, says: "We want to do the testing for EPA registration, get the ma­terial registered, and start formulating products for use as insecticidal agents for mosquitoes and other agricultural pests. . . . We anticipate we could get registration within a 12- to 15-month time frame/'

Brandt adds that TMOF, used alone or in combination with chemical pesti­cides, could "reduce the total amount of toxic pesticides used and the resistance that develops in insects. This will pro­vide a significant benefit.,,

Asked to comment on the signifi­cance of the findings, biochemistry pro­fessor Roger G. H. Downer of the Uni­versity of Waterloo, Ontario, Canada, who specializes in the development of novel insecticides, says: "Borovsky and Carlson have developed an interesting, exciting concept that has considerable potential. . . . The proposal to clone the gene and express it in an appropriate microorganism, or incorporate it into a plant genome, is eminently feasible and should be pursued/'

However, says Downer, "Much work remains to be done before the product is ready for market/' Potential obstacles he cites include problems that could arise in field-testing, cost of the compound (if it needs to be sprayed at fairly high concentrations), questions about stability in the environment and takeup by other organisms, and the

complexities of microencapsulation technology.

A more skeptical view of the devel­opment was taken by comedian Jay Leno on his July 16 "Tonight Show": "Science at work . . . Scientists say they've discovered a hormone that when injected into a mosquito interferes with the mosquito's ability to digest food and it causes the mosquito to starve to death. Now think about this. First you got to anesthetize the mosquito. Then you got to inject it with a hormone. Then the mosquito has to recover from the opera­tion. Then the mosquito starves to death. Wouldn't it be a lot simpler just to go [slap]?"

Stu Borman

Vista Chemical protests Quebec plant subsidies Vista Chemical has petitioned U.S. trade representative Mickey Kantor to intercede against plans by Quebec's government to subsidize new Canadi­an production of linear alkylbenzene (LAB). The International Chemical Workers Union has joined Vista in this action.

Filed under section 409 (b) of the U.S.-Canada Free Trade Agreement Implementation Act, Vista's petition asks Kantor to find that the U.S. LAB

industry will face "likely harm" from subsidized Canadian LAB exports. Vis­ta and Monsanto are the only major U.S. LAB producers.

Vista's request is only the second such petition ever filed under the U.S.­Canada free trade pact, and the first during the Clinton Administration. The nonferrous metal industry filed the first petition.

At issue is Canada's first LAB plant, a 220 million-lb-per-year plant in Becan-cour, Quebec, near Montreal; it is sched­uled to come on stream in 1995. The Spanish company Petroquimica Espano-la (Petresa), a major LAB producer, will own 51% of the venture, and Société Générale de Financement du Québec (SGF), a corporation wholly owned by the Quebec government, will own 49%.

Vista contends Canada cannot absorb this new LAB supply, because its market is about 68 million lb per year, with little or no prospect for growth. Vista charges that the project is designed to take ad­vantage of elimination of tariffs on LAB trade under the U.S.-Canada free trade pact. Before the pact, the effective U.S. tariff on LAB from Canada—had there been any—would have been 18.1%, as it is on LAB imports from other countries.

However, tariffs are not the issue. Vis­ta says the excess Canadian output will move into U.S. markets "at predatory price levels," made possible by subsidies enjoyed by SGF and other government-owned corporations. Advantages in­clude favorable financing, partial tax-free status, and nonmarket pricing for goods and services. Even government ownership, says Vista, is itself a subsidy.

Based on an Arthur D. Little (ADL) study it commissioned, Vista says the Quebec LAB plant makes no economic sense without subsidy. The project's probable financial returns are below what private-sector investments typical­ly require. In fact, ADL says, the project will generate negative cumulative cash flows beyond 2005 under two different scenarios.

Like the Canadian market, the U.S. LAB market is not growing, but it is much larger at 590 million lb a year. Mexico's market is growing, with an estimated current demand of 290 mil­lion lb per year; however, it does not now produce LAB. Both Canadian and U.S. LAB will be able to enter Mexico duty-free if the North American Free Trade Agreement is ratified by the three countries.

4 JULY 26,1993 C&EN