Chemical Machinery or Metabolism. Chemotherapy

The drive against the bacterial diseases is in some ways simpler than that against the virus diseases. As explained in the previous chapter, bacteria are easier to culture. In addition, bacteria are more vulnerable. Living as they do outside cells, they are capable of doing damage by successfully competing for food or by liberating toxic substances. However, their chemical machinery, or metabolism, is generally different from that of the cells of the host in at least some respects. There is always the chance, therefore, that they might be vulnerable to chemicals that would disorder their metabolism without seriously affecting the metabolism of the host cells.

The use of chemical remedies against disease dates back into prehistory. Down to modern times, the "herbwoman" and her concoctions, handed down empirically over the generations, have on occasion done some good. The use of quinine against the malaria parasite is the best-known example of a chemical that began as a folk remedy and was later accepted by the medical profession.

With the coming of synthetic organic chemicals that did not occur in nature, however, the possibility arose that many more such specifics might be found; that every disease might have its particular chemical remedy. The great early protagonist of this view was Ehrlich, who spoke of such chemical remedies as "magic bullets" that sought out the germ and slew it while leaving the body cells in peace.

He had worked with dyes that stained bacteria and, since these dyes specifically combined with some constituent of the bacterial cell, they ought to damage the bacterial cell's working mechanism. He hoped to find one that would do this without harming ordinary cells too badly. Indeed, he did discover a dye, "trypan red," which helped destroy the trypanosomes (a protozoan, rather than a bacterium, but the principle was the same) that caused such diseases as sleeping sickness.

Ehrlich kept looking for something better. He decided that the action of trypan red was caused by the nitrogen-atom combinations it contained. Arsenic atoms resemble nitrogen atoms in chemical properties but, in general, introduce a more poisonous quality into compounds. Ehrlich was led by that into a consideration of arsenicals. He began to try all the arsenic-containing organic compounds he could find or synthesize, hundreds of them, one after the other.

In 1909, one of his assistants discovered that the compound numbered 606, tried against the trypanosome and found wanting, was very effective on the causative agent of syphilis. Ehrlich named the chemical "Salvarsan" (though a more frequently used synonym, nowadays, is "arsphenamine") and spent the remainder of his life improving the technique for using it to cure syphilis.

Trypan red and Salvarsan marked the beginning of modern chemotherapy (the treatment of disease by chemicals, a word coined by Ehrlich) and for a while hopes were high that other diseases would be treated in similar fashion. Unfortunately, for twenty-five years after the discovery of arsphenamine's effect, the vast list of synthetic organic chemicals seemed to offer nothing more.

But then came another stroke of good fortune. A German biochemist and physician, Gerhard Domagk (1895- ), working for a dye firm, began a systematic survey of new dyes with a view to finding possible medical applications for some of them. One of the dyes was a newly synthesized orange-red compound with the trademark "Prontosil." In 1932, Domagk found that injections of the dye had a powerful effect on streptococcus infections in mice.

He quickly had a chance to try it on humans. His young daughter had been infected by streptococci following the prick of a needle. No treatment did any good until Domagk in desperation injected large quantities of Prontosil. She recovered dramatically and, by 1935, the world had learned of the new drug.

It was not long before it was recognized by a group of French bacteriologists, that not all of the molecule of Prontosil was needed for the antibacterial effect to be evident. A mere portion of it, called "sulfanilamide" (a compound known to chemists since 1908) was the effective principle. The use of sulfanilamide and related "sulfa" compounds inaugurated the era of the "wonder drugs." A number of infectious diseases, notably some varieties of pneumonia, suddenly lost their terrors.