In his doctoral thesis of some years earlier, Ehrlich noted that specific compounds interact with specific tissues or cells. In particular, Ehrlich's early scientific work concentrated on the use of chemical dyes for staining samples of animal tissues. These practices of staining were quite difficult and complex, and they were very important for scientists who wished to study tissues and cells with microscopes. In his investigations of staining tissues, Ehrlich was drawn into the study of how particular compounds interact with tissues and cells in particular ways. Certain cells could be stained with particular dyes but not with others. In this, Ehrlich became familiar with the type of “specific affinity” that he dreamed of for his magic bullets.

Further, Ehrlich believed that the molecular structures of compounds were important in biological processes. He envisioned the dance of molecules in and around cells as the key to the chemistry of disease and its treatment. Ehrlich believed that chemical compounds had to attach themselves to the structures of other chemical compounds of cells to have an effect upon the processes of life and disease. Specifically, he pictured the cell as surrounded by a series of chemical "side chains," structures through which the cell could capture nutrients and other needed substances and bring them into the cell. It was through these side chain molecular structures that Ehrlich believed the toxic substances produced by bacteria gained access to the cell and thereby caused disease. In turn, he viewed the immune response of the body to such an attack by a toxin through a side chain as a flood of more side chains. The body would produce scores of "side chains" with just the right structure to react with the specific bacterial toxins, would bind the toxins up, and thus prevent the toxins from reaching the side chains of cells. These responding side chains—the antibodies —would counteract the specific toxins and render the person “immune.” With both his side chain theory of immunity and his magic bullets vision of chemotherapy, Ehrlich made a key leap forward in the chemical understanding of disease and its treatment. His key insight was to think of the specific molecular structure of a substance as leading to specific biological effects.

In his quest for the discovery of magic bullets—compounds with specific structures for combating specific diseases and that would leave all else alone—Ehrlich did not always fully realize his dream. He did find compounds effective in treating diseases like malaria and sleeping sickness, which are caused by protozoan parasites (microorganisms), but these were only partially effective. He came much closer to his ideal of the magic bullet when he found compounds of arsenic effective against the bacterium that causes syphilis. These compounds, named Salvorsan and Neosalvarsan, became accepted as the standard, effective treatment for syphilis. The success of these magic bullets earned Ehrlich enduring fame as one of the central figures in the establishment of chemotherapy.

Reaching far beyond the lifetime of Ehrlich and the use of the particular drugs that he uncovered was his seminal idea that scientists could find compounds that could act against specific disease agents without harming the person with the disease. This conviction guided many subsequent scientists in their search for these magic bullets. Much of the work of Gertrude Elion and George Hitchings extended the reach of Ehrlich's belief and earned them their own Nobel Prizes in Medicine in 1988.

Bonus Page

For an in-depth look at the life of Paul Ehrlich, read this biographical sketch, reproduced from the book Pharmaceutical Achievers by Mary Ellen Bowden. Click here to read it.

For more information, at other Web sites...

Ehrlich Finds Cure for Syphilis — part of A Science Odyssey from WGBH Boston.

Paul Ehrlich — biography, part of Chemical Achievers from the Chemical Heritage Foundation.

The Nobel Prize in Physiology or Medicine 1908 — Information on the life and work of Nobel Prize winner Paul Ehrlich, from the Nobel Foundation.

The Reconstructors — be the drug discoverer in this postapocalyptic sci-fi drug development game that lets you rediscover the secrets of aspirin in a future world that has lost the knowledge of modern medicine, from Rice University.