Bases of Controls

How Fungicides Have Been Developed

John C. Dunegan, S. P. Doolittle.

How to keep school boys from pilfering their grapes had been a problem of French peasants in the Medoc region for a long time.

For the pilferers they found the answer, a poisonous-looking mixture of lime and copper sulfate that stuck tenaciously to the leaves when sprinkled on vines near the roadsides.

Pilfering was not the peasants' only worry, for mildew mildiou, they called it every year defoliated the vines in early fall. Professor P. M. A. Millardet,of the University of Bordeaux, was commissioned to study this disease recently introduced from America.

One day, in 1882, as he walked through the Medoc countryside, he noticed that there was less mildew on the sprinkled vines.

The professor put two and two together: The cure for pilfering might be the cure for the mildew. The next year he started tests that confirmed his guess. He and his colleague, U. Gayon, in 1885 published illustrations of treated and untreated vines. By 1887 they claimed unqualified success.

The mixture became famous as "Bouillie Bordelaise" bordeaux mixture and was applied with fiber brooms or, later, with sprayers in vineyards ravaged by vine mildew and also in blighted fields of potatoes and tomatoes.

Thus only 70-odd years ago chemical weapons came into use to control blights, rusts, mildews, and fungus diseases that for countless centuries have robbed men of the fruits of their labor.

Chemicals used to control fungus diseases are called fungicides, a word derived from the Latin fungus, a microscopic plant, and caedo, "I kill."

Originally the term was restricted to any substance applied to higher living plants in active growth to kill parasitic fungi or prevent the development of fungus diseases without seriously injuring the host plant. The meaning has been further broadened and as currently used denotes any substance or mixture of substances used for controlling fungi present in any environment. Thus, materials used to prevent molds from destroying the insulation of electrical equipment or etching camera lenses are properly called fungicides.

In agriculture, fungicides by and large are used to prevent infection, because once the fungus has caused any extensive alteration of the part attacked little is to be gained by killing the fungus. To do so will not repair the damage already done, although it may prevent the further spread of the fungus.

The virtues of bordeaux mixture were soon demonstrated, but so were its faults. On certain plants the mixture produced injury. Attention was turned to other materials. In 1905 A. B. Cordley introduced lime-sulfur solution, a mixture of calcium poly-sulfides formed by boiling sulfur and lime together in water. The material proved to be exceptionally efficient against the apple scab fungus and eliminated the russeting of the fruit that followed the use of bordeaux mixture early in the season.

Lime-sulfur solution, however, proved to be too caustic to use on peaches. In 1907 W. M. Scott and T. W. Ayers introduced another sulfur mixture they called "self-boiled lime-sulfur." They made it by adding sulfur to stone lime slaking in water. Enough heat was produced by the slaking of the stone lime to cause a mild chemical reaction. The mixture turned out to be too mild to control the apple scab fungus, but it proved to be effective against the peach brown rot and scab fungi, the cause of two serious peach diseases. It did not injure peach trees and it made the commercial production of peaches practical in humid sections of the East.

Bordeaux mixture proved to be good for most vegetable diseases and for such midseason apple diseases as blotch and bitter rot. With it and lime-sulfur solution for early use on apples and pears for scab control and self-boiled lime-sulfur for use on peaches, pathologists felt they were well equipped to prevent fungus diseases on fruits and vegetables.

Indeed, from 1907 until about 1930, the three preparations were standard. Experiments were concerned largely with tests of the proper timing of sprays, the number of applications, and the amounts to be used, rather than with the development of new materials.

But as time went on, people noticed that in seasons when the fungi did not develop extensively the yield from unsprayed tomato plants frequently was better than from those protected by the bordeaux mixture. Probably it was the result of physiological changes induced by the residue of copper and lime on the plants. Also, they found that the lime-sulfur solution affected the leaf and shoot growth early in the season and had an adverse effect on the setting of the fruit of certain apple varieties. Bordeaux mixture too frequently caused a russeting of the fruit, severe injury to the leaves, and a premature defoliation. The main objection to self-boiled lime-sulfur was the need of stone, or unslaked, lime, which was cumbersome to handle and had to be stored in sealed containers.

Those defects led to the development of entirely new compounds as technicians began to explore the fungicidal properties of other inorganic compounds such as the fixed (relatively insoluble) copper compounds and the organic compounds. The latter compounds exist in almost countless numbers. Some 25,000 have already been tested as possible fungicides and new compounds are constantly being synthesized in the research laboratories.

Obviously, with such a multitude of compounds available, some orderly testing or screening procedure is necessary to expedite the big task. It would be physically and financially impossible to test each compound by actual spraying tests in the fields.

In these screening tests, spores of certain disease-producing fungi are suspended in solutions or suspensions of the chemical. They are removed at stated intervals, and their viability is tested. An alternate method is to expose spore suspensions of the test organisms to the chemical on glass slides and later determine whether the spores have been killed by contact with the chemical.

The test can be further improved by determining the effect of environment upon the dried deposits of the chemicals exposed on glass slides outdoors for varying periods. Tests are made at fixed intervals, frequently at the end of 7, 14, and 21 days and are compared with the effects of freshly prepared residues on the fungus spores. The tests tell whether the exposure outdoors has affected the fungicidal activity of the chemical and have eliminated unstable compounds that appear promising when freshly prepared. Other phases of the screening procedure deal with the physical Properties (particle size, solubility, tenacity) of the material. As the result of these various laboratory studies it is now possible to compare the effectiveness of various compounds at different dosage rates and even to determine the portion of the complex organic molecule that actually kills the fungus.

Special types of spraying and dusting equipment have been devised for laboratory use that deliver known amounts of material with great precision. These machines make it possible to duplicate in the laboratory or greenhouse many of the factors that occur in the normal use of the compound and are an important part of the screening procedure.

Compounds that have passed through the various screening tests must still surmount the final barrier of actual field usage. They must control the fungus diseases, must be compatible with compounds added for the control of insects, and must not, either alone or in combination, produce injury to the treated plants. Furthermore, the new compounds must not be so toxic that their widespread use presents dangerous hazards either to the user or the consumer and finally their price must be such that they can compete with other compounds currently in use.

The development of a new compound therefore is a tedious and expensive process. On the average this development involves an investment between 250,000 and 350,000 dollars and may even exceed a million dollars.

"Many are tested but few are chosen," to modify an old adage, aptly applies to the development of new fungicide materials. Less than 0.1 percent of the many thousands of compounds tested are in general use.