A Helminthic Tale

A HELMINTHIC TALE WILLIAM M. GOVIER* One may or may not agree that the present partnership between academicians and drug firms, with the Food and Drug Administration as watchdog/monitor, is a reasonably efficient modus operandi, even with its imperfections. There may be many, however, who do not realize that this situation has not always existed. At one time, prior to 1935 or even later in some cases, there was little drug-firm research, and great mutual suspicion existed between the university scientists and those in drug firms. Drug firms in those days sold proprietary products, galenicals, and a very few synthetics. Research in the universities was more often directed to biochemistry and physiology than to pharmacology. A scientist who worked in a drug firm was actually barred from membership in the American Society for Pharmacology and Therapeutics. The FDA did not exist, at least in present form. This communication will record a tale of these times which may be amusing to the modern researcher. At about this time the Rockefeller Foundation underwrote a huge survey of intestinal worm infestation in the southern states because of the great loss of manpower thought to be brought on by hookworm disease. This study was carried out by the Vanderbilt University Department of Preventive Medicine, and a high incidence of infestation was found. Anthelminthic studies were done in the Department of Pharmacology by Dr. Paul D. Lamson, professor and chairman, and his staff. While using a chamber to study effects of pressure gradients on intestinal absorption, Herbert Wells in the pharmacology department had shown serendipitously that hookworms cause anemia by ingesting blood, extracting the plasma, and ejecting the red cells. This finding made it obligatory to find a way of removing the worms, and the idea was attractive to the Rockefeller people. As a corollary, public health measures, ?Address: 3337 Clover Street, Pittsford, New York 14534.© 1984 by The University of Chicago. AU rights reserved. 0031-5982/85/2801-0413$01.00 104 J William M. Govier · A Helminthic Tale such as instruction on how to build and use sanitary privies, were also intensified. Anthelminthic drugs of the day were inefficient and relatively toxic. They did kill hookworms, but a most undesired side effect occurred. Many patients were bearers of ascarids (roundworms) as well as hookworms , and the drugs did not kill but merely titillated the roundworms. These animals, in trying to escape the irritation, formed balls, plugged appendices, and occasionally migrated up the esophagus and popped out of the patients's noses. This produced a certain amount of consternation , particularly in mothers of small children. Lamson undertook the problem by setting up what was probably one of the first attempts to screen a set of drugs systematically (although it was antedated by Ehrlich's arsphenamine studies, and possibly by others less well known). It was soon found that it is quite difficult to determine whether roundworms are alive or dead (the roundworms came from a local slaughterhouse) and that they need a special medium in which they can be kept for experimentation. The problem ofaliveness or deadness was solved arbitrarily by dumping them in hot water. If they wiggled, they were said to be alive. (Sometimes "dead" ones came to life later—these were perforce ignored.) The special medium turned out to be glucose in saline. At any rate, a number of chemical compounds was made and tested using this kind of a screen, the target being, of course, a compound which would kill both hookworms and roundworms. In short, it soon appeared that the alkylresorcinol series was active and that hexylresorcinol showed the best balance of anthelminthic activity and lack ofirritation to the host. An enzyme from fig tree latex, called ficin, was also fine because it dissolved the worms, but it was found also to dissolve the GI tract if the tract was irritated, such as by a snort of Kentucky moonshine, Luckily it was first tried in dogs. It was quickly forgotten. Now, hexylresorcinol was already on the market by Sharp and Dohme as the active ingredient in a mouthwash called "S.T.37" because it had a low surface tension. Lamson's approach to Sharp and Dohme produced...