Sulfa; Yesterday's Hero Is Still Taking Bows

Article excerpt

Before penicillin, there were the sulfa drugs. The sulfonamides, as they are more corectly called, were the first effective chemotherapeutic agent for the prevention and treatment of bacterial infections in humans. Their introduction into the world of medicine in 1935 opened up the "golden age of drugs."

Initially the sulfonamides were greeted with enthusisasm as "wonder drugs." Their popularity, however, has diminished over the years. The introduction of more effective and lesstoxic antibiotics and the development of bacterial resistance to sulfonamides have limited their usefulness; yet sulfonamides continue to have an important place in medicine and are, in fact, the drugs of choice against certain infections. Further, they have led to the discovery of treatments for a variety of other diseases, including high blood pressure and glaucoma.

The story of the sulfonamides began in Vienna near the turn of the century. Medicine was not what chemistry student Paul Gelmo had in mind when he synthesized paraaminobenzenesulfonamide from coal tar in 1906. His interest was in dyes. Gelmo published a paper on his work in a German chemical journal in 1908 and offered it as a thesis in his candidacy for a doctoral degree.

The following year, scientists at I.G. Farbenindustrie, the German chemical giant, experimented with sulfonamides as dyes for textiles. While some studies of the medical uses of these dyes were made in the following years, intensive investigations in this area probably did not begin until sometime in 1930.

On Dec. 25, 1932, the German Patent Office issued to Drs. Fritz Mietzsch and Joseph Klarer of I.G. Farbenindustrie a patent covering a sulfonamide-containing dye called Prontosil. In the same year Gerhard Domagk, a research director of the same company, observed that mice with streptococal and other infections could be protected by Prontosil. Domagk is also said to h ave given the new compound to his own daughter after she pricked her finger and developed blood poisoning.

In May 1933 the first clinical report about Prontosil was made in Dusseldorf, Germany, by a Dr. Foester who described the dramatic cure of a 10-month-old child suffering from staphylococal septicemia.

Domagk did not publish his findings until 1935. Three other clinical reports on Prontosil appeared in the same German medical journal, inducating that other German scientists were studying the new drug in the early 1930s. Domagk was awarded the Nobel Prize in 1938, although the Nazi regime prevented him from accepting it and actually imprisoned him. In 1947 the scientist did go to Sweden to deliver the Nobel lecture and received the gold medal and diploma.

Chemistry student Gelmo was never heard of again.

Once the news was out, the rest of the world took notice. In 1935 scientists at France's Pasteur Instituute reported that para-aminobenzenesulfonamide was the active part of the molecule. In England, other investigators reported favorable clinical results with Prontosil and sulfanilamide in puerperal sepsis (blood poisoning following childbirth) and meningococal infections.

Although the first reference to the new chemotherapy in the Journal of the American Medical Association was an abstract from a French journal and did not appear until June 1936, there was no lack of interest in the new drug in the United States. Scientific investigations began in earnest in a number of institutions, including the National Institutes of Health and Johns Hopkins University. Scientists at Johns Hopkins proved that sulfonamides are bacteriostatic and not bacterioicidal--that is, they slow down, rather than kill, bacteria.

What really put the sulfas in the headlines in 1936 was the dramatic cure of Franklin Roosevelt Jr., who was suffering from a severe streptococcal infection. The new drug had been flown to Boston after an appeal from the president's wife. …