The word “antibiotic” comes from the Greek words meaning “against life.” Early folk medicine relied on some natural compounds that cured certain diseases, the ground bark of a tree, certain cheese molds, certain fungi. Doctors knew that these natural compounds worked, but had no idea of how or why they worked.
Paul Ehrlich conducted the first modern chemical investigation of antibiotics and discovered the first antibiotic chemical compounds. His work opened a new era for medical and pharmacological research and founded the field of chemotherapy. Antibiotics (penicillin, discovered in 1928, is the most famous) have saved many millions of lives and trace their modern origin to Paul Ehrlich’s work.
Paul Ehrlich was born in Germany in 1854. A gifted student, he entered graduate school to study for a medical degree. There he became deeply involved in the process of staining microscopic tissue samples so that they would show up better under the microscope. The problem was that most dyes destroyed the tissue samples before they could be viewed. Ehrlich struggled to find new dyes that wouldn’t harm or kill delicate microscopic organisms. This work showed Ehrlich that some chemical compounds killed some types of tissue and made him wonder if the process could be controlled.
By 1885 it had become clear that the causative agent for many illnesses was microorganisms. Many scientists made a great effort to study these bacteria under the microscope. Again Ehrlich found that many of the available dyes and stains killed the organisms before they could be studied. This finding inspired Ehrlich to propose that chemical compounds may exist that could kill these organisms without harming the human patient, thus curing an illness by killing only its causative agent.
In the mid-1890s, Ehrlich shifted his focus to studies of the immune system and how to control the reaction between chemical toxins and antitoxins. Again it occurred to Ehrlich that, just as antitoxins specifically sought a toxin molecule to which they were related and destroyed it, so, too, he might be able to create a chemical substance that would go straight to some disease-causing organism and destroy it. Ehrlich called such a chemical substance a “magic bullet.” It seemed that 25 years of work had led him directly to this idea.
During this same period, many specific disease-causing bacteria were being identified and studied. This gave Ehrlich well-understood targets to attack as he sought ways to create magic bullets. He chose to start with spirochaete, the microorganism that caused syphilis. Ehrlich began testing different chemicals using an arsenic base for his compounds. Arsenic had been effective in destroying a number of other microorganisms.
By 1907, Ehrlich had reached the 606th compound to be tested. He tested this compound on rabbits infected with syphilis. It cured the rabbits. Ehrlich named it salvarsan and conducted over 100 additional tests to be sure it worked and that it wouldn’t harm human patients. He then worked for two more years to develop a form of this drug that was easier to manufacture and that was easier to administer. Of the thousand variations he tried, version number 914 was the best. He named it neosalvarsan.
Ehrlich’s final test of neosalvarsan was to give it to terminal patients suffering from the dementia that was the final stage of syphilis. While neosalvarsan helped all of these patients, remarkably, several completely recovered.
Neosalvarsan was the first man-made chemical that would specifically destroy a target organism and not affect the human patient. This discovery founded the field of chemotherapy.
Resistance to antibiotics works by the ordinary rules of natural selection: that segment of the bacteria population that has a natural ability to counter the drug’s effect will survive, so that their genes eventually are shared by the entire population. Many disease-causing viruses and bacteria have developed virtual immunity to many antibiotics, making medical planners fear massive disease outbreaks in the near future.
