two main classes of cells that either stained purple (“Gram-positive”) or
red (“Gram-negative”) in response to a series of staining steps with crystal
violet and safranin stains.
Paul Ehrlich was intrigued by why different dyes were attracted to
particular species of bacteria, but handicapped by primitive research tools,
had no way of formulating a scientific response. However, demonstrating
the type of keen insight that geniuses possess, Ehrlich skipped several
steps ahead and wondered if the dye materials could be manipulated not to
just embellish a slide but to kill bacteria. If a staining material could be
identified that targets and binds with a particular class of bacteria, it made
sense to the pioneering scientist that a dye could be used as a weapon.
Ehrlich traveled to London in 1907 to lecture to Britain’s Royal
Institute of Public Health, delivering a lecture for the ages. He dreamed
that one day there could be a “targeted drug, one that would attack a
disease-causing microbe without harming the host suffering from the
disease.”^2 Ehrlich conceived of chemical compounds that would serve as
magic bullets, just decades after researchers had finally proven the germ
theory. Barely fifty years removed from John Snow’s revolutionary
epidemiological research during the cholera outbreak of 1854, Ehrlich
returned to the very London neighborhood that had been (literally) awash
in diarrhea, stumping for magic bullets.
By the time Paul Ehrlich had traveled to London, he was already well
on his way in the quest for the magic bullet. Modern chemistry was in full
bloom, with Dmitri Mendeleev’s periodic table coming into focus and a
developing appreciation of how atoms bind together to form complex
molecules. For an extremely insightful researcher like Ehrlich, the
mysteries of simple chemical compounds were beginning to dissolve at
the turn of the 20th century, and as one of the fathers of histological
staining, it’s not a surprise that he turned to azo dyes like methylene blue,
congo red, and alizarin yellow in the search for a chemical breakthrough.
Since the mid-1880s, Ehrlich had experimented with the azo dyes as
potential therapeutic agents, and although he was inadvertently turning his
patients’ eyes and urine various colors of the rainbow, he and his lab
partners were able to show a response to malaria.
Azo dyes—aniline derivatives like the mauveine discovered by William
Perkin in 1856—are chemically stable and not very changeable; Ehrlich
and his cohorts were hoping to find another substance that acted like a dye