Medical Microbiology

Semester III
Hematology, immunology, and antimicrobial
chemotherapy. Among his foremost achievements
were finding a cure for syphilis in 1909 and inventing
the precursor technique to Gram staining bacteria. The
methods he developed for staining tissue made it
possible to distinguish between different types of
blood cells, which led to the ability to diagnose
numerous blood diseases.
 Hematological staining

• He accustomed mice to the poisons ricin and abrin. After feeding them with small but
increasing dosages of ricin he ascertained that they had become "ricin-proof

• Ehrlich also researched autoimmunity, but he specifically rejected the possibility that
an organism's immune system could attack the organism's own tissue calling it
"horror autotoxicus"

• Ehrlich was the first to propose that regulatory mechanisms existed to protect an
organism from autoimmunity, saying in 1906 that "the organism possesses certain
contrivances by means of which the immunity reaction, so easily produced by all
kinds of cells, is prevented from acting against the organism's own elements".

• Ehrlich proceeded to show that feeding laboratory animals low doses of a toxin
protected them against an otherwise lethal dose of the same toxin, and he formulated
the concept of active and passive immunization.
 First work on immunity
• Ehrlich was one of the early founders of immunology and studied immune and hemolytic
reactions. Building on the work of others, Ehrlich developed the “Side Chain Theory” of
immunology where cells have receptor sites or side chains, much like dye molecules have
reactive sites.

He imagined that harmful

compounds (toxins) could mimic
nutrients for which cells express side
chains that he called ‘nutriceptors’.
Each cell would express multiple
types of side chains to allow the
specific uptake of essential nutrients.

Ehrlich’s side-chain theory

 Cancer research

• Insight: when tumors are cultivated by transplanting tumor cells, their malignancy
increases from generation to generation. If the primary tumor is removed, then
metastasis precipitously increases. He recommended studies to control tumors by
immunological methods.

• In analogy to vaccination, he attempted to generate immunity to cancer by injecting

weakened cancer cells.

He introduced the new technology of in vivo staining. One of his findings was that
pigments can only be easily assimilated by living organisms if they are in granular form. He
injected the dyes Alizarin blue and Indophenol blue into laboratory animals and
established after their death that various organs had been colored to different degrees. In
organs with high oxygen saturation, indophenol was retained; in organs with medium
saturation, indophenol was reduced, but not alizarin blue, in areas with low oxygen
saturation, both pigments were reduced.

With this work, Ehrlich also formulated the conviction which guided his research: that all
life processes can be traced to processes of physical chemistry occurring in the cell.
 "Therapia sterilisans magna",

• As a model for experimental therapy Ehrlich used a guinea pig disease trypanosoma and
tested out various chemical substances on laboratory animals- Dye trypan red.

• Atoxyl-Ehrlich elaborated the systematic testing of chemical compounds in the sense of

screening as now practiced in the pharmaceutical industry.

• With the support of his assistant Sahachiro Hata Ehrlich discovered in 1909 that
Compound 606, Arsphenamine, effectively combatted "spirillum" spirochaetes bacteria,
one of whose subspecies causes syphilis.

• Salvarsan was the first agent with a specific therapeutic effect to be created on the basis
of theoretical considerations
 Chemotherapy

• “Chemicals must not adversely affect the host but destroy the organism, and that the
agent bind to selective sites on the organism/cell”

• He devised a therapeutic index related to dosage and recognized organisms can build a
resistance to therapeutic agents.

• Ehrlich is recognized as the “Father of Chemotherapy.”

 Magic bullet

• Ehrlich reasoned that if a compound could be made that selectively targeted a disease-
causing organism, then a toxin for that organism could be delivered along with the agent
of selectivity

• The concept of a "magic bullet" has to some extent been realized by the development of
antibody-drug conjugates (a monoclonal antibody linked to a cytotoxic biologically active
drug), as they enable cytotoxic drugs to be selectively delivered to their designated
targets (e.g. cancer cells).
 Ehrlich's reagent

• In 1881 he published a new urine test which could be used to distinguish various types
of typhoid from simple cases of diarrhea. The intensity of staining made possible a
disease prognosis. The pigment solution he used is known today as Ehrlich's reagent.

• Ehrlich's reagent or Ehrlich reagent is a reagent containing p-dimethylaminobenzaldehyde

(DMAB) and thus can act as an indicator to presumptively identify indoles and urobilinogen.

• Ehrlich reagent can be used to detect urobilinogen, which can indicate

jaundice or other liver-related issues.

• A very common Ehrlich test is a simple spot test to identify possible

psychoactive compounds such as tryptamines (e.g. DMT) and
lysergamides (e.g. LSD).

p-DMAB
 Legacy

• In 1908, he received the Nobel Prize in Physiology or Medicine for his

contributions to immunology