From Pioneering Invention to Sustained Innovation: Herbicides at DuPont

George Levitt with a model of Glean. Courtesy of the Hagley Museum and Library

By Gaurab Bhardwaj

The oil shocks of the 1970s hit hard in the United States. Americans felt the effects in their daily lives as they formed lines at gas stations and feared for their jobs. While families struggled to adapt, chemical companies scrambled to find new niches that would allow them to retain their relevance in the new economy. Supply problems and high feedstock prices forced chemical industry leaders to dramatically cut costs and move into new product lines. At DuPont, one of the most venerable names in American chemistry, managers looked for ways to develop areas that required less dependence on oil. The company’s new corporate plan emphasized the life sciences: agrochemicals, pharmaceuticals, and medical products. And with its executive committee averse to the idea of major acquisitions, DuPont turned to its own researchers for ideas.

Agriculture was not an entirely new direction for DuPont; the company had researched and produced herbicides, pesticides, and fungicides on a small scale for nearly 50 years. In 1975, however, one of their researchers, George Levitt, discovered sulfonylurea herbicides, a class of chemicals that would revolutionize the market and DuPont’s place in it. By 2001 DuPont’s crop protection division was producing 40 products and maintaining operations in 40 countries. But while sulfonylurea herbicides are now widely used in the global weed-control market, DuPont nearly canceled the research program in its infancy. The story of its survival offers a telling example of how one company turned a pioneering invention into a sustained program of innovation.

The Origins of an Herbicide

George Levitt joined agrochemicals research at DuPont in 1956. Early in his tenure there he synthesized several compounds derived from various arylsulfonyl isocyanates. (A sulfonyl group consists of a highly oxidized sulfur atom double bonded to two oxygen atoms and single bonded to two other organic groups.) These derivatives showed no biological activity in primary response screenings for plant growth regulators, insecticides, and fungicides, but they were nevertheless added to DuPont’s chemical library. Levitt moved on to other projects. Almost 16 years later a DuPont entomologist working on a new screen for mite chemosterilants found some activity in one of these derivatives, a sulfonylurea. Intrigued, Levitt began making analogs of the sulfonylurea molecule and had them screened for various responses. Most of the analogs showed little promise, but one demonstrated a weak ability to slow plant growth at a rate of two kilograms per hectare. Levitt did not think this finding was particularly promising and did not bother to include it in a report to management on his activities, but it was of mild-enough interest that he mentioned it to his supervisor, Raymond W. Luckenbaugh, in August 1974.

Luckenbaugh agreed that it was a mere “wiggle of activity.” But he too had been interested in sulfonylurea compounds and encouraged Levitt to continue his work. Luckenbaugh believed in having his chemists “scout around” and pursue any wiggles of activity they found. He gave Levitt a list of 90 sulfonylurea molecules in DuPont’s chemicals library. Of these only 2 showed promise; coincidentally, Levitt had synthesized both of them in 1962.

Levitt noticed that these 2 molecules shared an interesting characteristic. Each had a heterocyclic group attached to the nitrogen end of the sulfonylurea chain; in fact, they were the only 2 among the 90 to have heterocyclic compounds in their structure. Remembering that many heterocyclic compounds are biologically active, he realized that this might be a fruitful area of research. A widely selling corn herbicide contained a heterocycle, as did some DuPont products. Heterocyclic derivatives were also found in some fungicides and pharmacological agents. Perhaps, thought Levitt, different heterocyclic compounds could lead to greater biological activity. This insight proved crucial.

Levitt began making structural changes to the heterocyclic compound with the hope of developing molecules with greater herbicidal activity. One of these, named R4321, showed an astonishingly high level of plant-growth retardation when it was tested in July 1975. R4321 was so potent that minor residues remaining in the spray system damaged plants that were later being treated with other compounds. Levitt recalls, “I knew we were on to something with R4321, but I felt there was a lot more we had to do to upgrade that kind of activity. . . . I didn’t think that that was the end of the story . . . it was the beginning.” The research program grew. In February 1976 Levitt created the molecule chlorsulfuron, whose field tests that summer surpassed even that of R4321.