Treatments of Tuberculosis

At this time, disinfectants or antiseptics such as phenol and cresol were known. These are both very effective germicides but are (general protoplasmic) poisons equally dangerous to human tissues. On the other hand, true chemotherapeutic drugs can be absorbed into the human body without too much danger.

Chemotherapy really started in 1905 with Paul Ehrlich’s deliberate search for a synthetic substance which would cure syphilis. The German organic chemists had had great success in developing synthetic dyes which stain animal tissues in a selective manner. That is, they stain certain cells and not others, or certain parts of a cell. Ehrlich thought that if this were possible it should also be possible to find or make substances which would selectively stick onto and kill the syphilis parasite and leave the patient’s tissues unharmed. Two dyes, trypan red and trypan blue, which stain parasitic protozoa called trypanosomes were found effective in treating African sleeping sickness or trypanosomiasis. Eventually Ehrlich’s researches were crowned with success with the production of arsphenamine, an organic arsenic compound, which was effective in both syphilis and trypanosomiasis. It is also effective in treating various other diseases caused by spiral shaped bacteria like the syphilis spirochaete. Until the introduction of penicillin, arsphenamine or similar compounds remained the standard treatment of syphilis. Many of the dyes long used for staining bacteria for microscopic examination can be used to kill bacteria and can be used on the skin or in the mouth to treat surface infections, but they are too poisonous to be injected into the tissues. Gentian Violet is an example of such a bactericidal dye. It is often used on the skin and can even be swallowed to treat thread worm infestations of the intestine, since it is not absorbed to any great extent from the intestines into the tissues of the body.

No drug has yet been found effective against all bacteria. In fact, this selectivity is probably unavoidable since an essential feature of a drug used in treatment is that it must "select" between the cells of the human tissues and the bacterial cells, leaving the former as far as possible unharmed. It is not surprising therefore that these drugs will also be choosy about which sort of bacteria they attack.

From Ehrlich’s success with arsphenamine in 1905 there was little practical progress in chemotherapy until 1935 when Domagk, another German, produced a compound, sulfonamido-crysoidin, effective against streptococcal infections. This compound was given the trade name "prontosil." Streptococci cause many common acute and serious diseases, notably scarlet fever, septic tonsillitis, child-birth fever, and sepsis in wounds. These bacteria were, and still are sometimes, the most serious and rapidly spreading killers to which man is subject, and their exclusion was a constant headache in surgical and maternity wards of hospitals. The discovery of a drug such as prontosil which could cure these infections was an enormous step forward in medical practice.

Prontosil was interesting in that it did not kill streptococci when added to them in a test-tube but only in the body of an infected human or animal. It is a very complicated chemical compound and it was soon discovered by British and French scientists that in the body it was broken down to a simpler compound, sulfanilamide, which was responsible for its effect, – and is much cheaper and easier to make.

Sulfanilamide is effective not only in streptococcal infections but also in epidemic meningitis, gonorrhea, and several less common parasitic diseases. Modifications of this compound were soon discovered which were effective against more and more bacteria, beginning with the discovery of sulfapyridine in Britain in 1938 which cured pneumonia and pneumococcal meningitis, a hitherto fatal condition, and soon followed by several American discoveries such as sulfadiazine, one of the most effective and least toxic of the sulfonamide series of drugs. Sulfaguanidine is another interesting American discovery in that it is not absorbed to any great extent from the intestine, so that it can be given in very large doses to treat infections such as dysentery where the responsible bacteria are largely confined to the intestine. After penicillin, it was probably the next most important factor in maintaining military manpower in the final stages of the war against Naziism. In a round-about manner thus Domagk’s discovery of the first of the sulfonamide series helped to cleanse his country of at least one scourge. He was privileged to make one of the most far-reaching discoveries in modern medicine, although others were hot on his heels.