Paul Ehrlich, Chemotherapy of Infectious Disease.
Control and Cure of Host Infections, Ehrlich, Syphilis, Trypanosomes. Microbiologists first showed that specific bacteria cause specific diseases. Knowing what killed someone, did not cure them. That was next step. Dr. Paul Ehrlich took it!
A daunting list; a rogue’s gallery of horrors: plague, anthrax, tetanus, gas gangrene, syphilis, cholera, typhoid fever, boils, abscesses, only a few of the more infamous. The problem was clear, there were no cures for anything infectious. Frustrated physicians knew the disease and pathogen, and were powerless to cure. The 19th century was ending, the start of the 20th seemed hopeful. It was 1901 and Paul Ehrlich began his intensive search for chemical cures for infectious diseases
Syphilis and Spirochaetes, Metals and Poisons
Syphilitics were placed in hot steam cabinets, given toxic mercury, even exposed to malaria to fever-kill the syphilis. A simple skin sore (chancre) first, for a few weeks, then disappearance. A few months later, a second attack appearing on skin and ravaging the body within. Then, gone again. Ten to twenty years later, a third, reappearance with nervous system, heart and other organ damage.
Silver, gold, mercury,arsenic dropped onto agar plates showed zones of inhibition and killing, the “oligodynamic” effect. Lister’s phenol controlled bacteria in the environment, but it was toxic if ingested. Scientists sought ingestable antimicrobials that would inactivate, kill or destroy pathogens.
Dr. Paul Ehrlich, Adventures in Chemotherapy and Antimicrobial Cures
He was dedicated, imaginative, enthusiastic, a pack rat (hoarder) of dyes, chemicals, and science journals which he read avidly.
He liked dyes,how they behaved and what they did intrigued him. In medical school he stained and looked at all kinds of tissues and the interactions of dyes with cell parts. Membranes, nuclei, nucleoli, cytoplasm sometimes reacted differently to the same dye. This dye made the nucleus red, that one made it purple. This dye showed cytoplasmic granules, that one does not. One by one, he recorded, listed and noted all. Soon he fixed in his mind that somewhere near was a cure, a fix to diseases caused by trypanosomes or spirochaetes. A chemical that could strike the pathogen, not the host. He needed he said, a “magic bullet” to kill the pathogen, not the host. He knew that with mercury, like other chemicals, the cure can be worse than the disease.
Ehrlich read of “Atoxyl” (“not-toxic” ) used to treat some disease. Unfortunately, atoxic it was not. Sometimes it blinded, or killed. Ehrlich was intrigued by the drug. Although not a master chemist, he analyzed Atoxyl and discovered a benzene ring, with attached OH and amino group and one arsenic (see figures , click to enlarge and see several forms of 606) and a resemblance to phenol, Lister’s useful antiseptic compound. Ehrlich determined that Atoxyl could be chemically changed and modified.
He assigned his chemists the job of making new molecules to test in mice infected with trypanosomes. Everyday, they made new drugs and tested: 1, now 101,…235…,499 … ,now 601, 602, 603, 604, 605, 606. Stop! Look here, 606! It is working! It has killed all the trypanosomes and no mice! It works! It was 606 and was named Salvarsan.
Salvarsan, 606, Life Beyond Trypanosomes
Salvarsan spared the mice but not the trypanosomes. Ehrlich soon made another important connection. A scientist speculated that flexible, spiral bacteria (spirochaetes) might change into trypanosomes. Days later, back in the lab with a rabbit with a syphilitic ulcer , compound 606 was injected and the rabbit was cured. Ehrlich informed a doctor friend. Test this on your patients. I feel it will work. It worked and worked well!
It was 1909, and 8 years of intense study and work gave a “safe” drug for syphilis in this Frankfort, Germany lab. The world was only 5 years away from World War I.
Pasteur- “Chance Favors the Prepared Mind”
Salvarsan was not without fault. It cured many of syphilis, but harmed some patients over time. Strongly echoing Pasteur’s words after someone had congratulated him he said:
“You say a great work of the mind, a wonderful scientific achievement? My dear colleague…for seven years of misfortune I had one moment of good luck!” (DeKruif).
To Ehrlich’s credit his tireless and intelligent pursuit of chemical cures is not be underestimated, nor neglected.