GC Open #55
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Paul Ehrlich (14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology and antimicrobial chemotherapy. Among his foremost achievements were finding a cure for syphilis in 1909 and inventing an important modification of the technique for 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.
His laboratory discovered arsphenamine (Salvarsan), the first antibiotic and first effective medicinal treatment for syphilis, thereby initiating and also naming the concept of chemotherapy. Ehrlich introduced the concept of a magic bullet. He also made a decisive contribution to the development of an antiserum to combat diphtheria and conceived a method for standardising therapeutic serums.
In 1908, he received the Nobel Prize in Physiology or Medicine for his contributions to immunology. He was the founder and first director of the Paul Ehrlich Institute, a German research institution and medical regulatory body named for him in 1947, that is the nation's federal institute for vaccines and biomedicines. A genus of Rickettsiales bacteria, Ehrlichia, is named after him.
Ehrlich has been called "father of immunology".
Hematological staining
In the early 1870s, Ehrlich's cousin Karl Weigert was the first person to stain bacteria with dyes and to introduce aniline pigments for histological studies and bacterial diagnostics. During his studies in Strassburg under the anatomist Heinrich Wilhelm Waldeyer, Ehrlich continued the research started by his cousin in dyes and staining tissues for microscopic study. He spent his eighth university semester in Freiburg im Breisgau investigating primarily the red dye dahlia (monophenylrosanilin), giving rise to his first publication.
In 1878 he followed his dissertation supervisor Julius Friedrich Cohnheim to Leipzig, and obtained a doctorate with a dissertation entitled "Contributions to the Theory and Practice of Histological Staining" (Beiträge zur Theorie und Praxis der histologischen Färbung).
One of the most outstanding results of his dissertation investigations was the discovery of a new cell type. Ehrlich discovered in the protoplasm of supposed plasma cells a granulate which could be made visible with the help of an alkaline dye. He thought this granulate was a sign of good nourishment, and accordingly named these cells mast cells, (from the German word for an animal-fattening feed, Mast). This focus on chemistry was unusual for a medical dissertation. In it, Ehrlich presented the entire spectrum of known staining techniques and the chemistry of the pigments employed. While he was at the Charité, Ehrlich elaborated upon the differentiation of white blood cells according to their different granules. A precondition was a dry specimen technique, which he also developed. A drop of blood placed between two glass slides and heated over a Bunsen burner fixed the blood cells while still allowing them to be stained. Ehrlich used both alkaline and acid dyes, and also created new "neutral" dyes. For the first time this made it possible to differentiate the lymphocytes among the leucocytes (white blood cells). By studying their granulation he could distinguish between nongranular lymphocytes, mono- and poly-nuclear leucocytes, eosinophil granulocytes and mast cells.
Starting in 1880, Ehrlich also studied red blood cells. He demonstrated the existence of nucleated red blood cells, which he subdivided into normoblasts, megaloblasts, microblasts and poikiloblasts; he had discovered the precursors of erythrocytes. Ehrlich thus also laid the basis for the analysis of anemias, after he had created the basis for systematising leukemias with his investigation of white blood cells.
His duties at the Charité included analysing patients' blood and urine specimens. In 1881 he published a new urine test which could be used to distinguish different types of typhoid from simple cases of diarrhea. The intensity of staining made possible a disease prognosis. The pigment solution he used became known as Ehrlich's reagent. Ehrlich's great achievement, but also a source of problems during his further career, was that he had initiated a new field of study interrelating chemistry, biology and medicine. Much of his work was rejected by the medical profession, which lacked the requisite chemical knowledge. It also meant that there was no suitable professorship in sight for Ehrlich.
Ehrlich's side-chain theory
Ehrlich postulated that cell protoplasm contains structures which have chemical side chains (macromolecules) to which the toxin binds, affecting function. If the organism survives the effects of the toxin, the blocked side-chains are replaced by new ones. This regeneration can be trained, the name for this phenomenon being immunisation. If the cell produces a surplus of side chains, these might also be released into the blood as antibodies.
In the following years Ehrlich expanded his side chain theory using concepts ("amboceptors", "receptors of the first, second and third order", etc.) which are no longer customary. Between the antigen and the antibody he assumed there was an additional immune molecule, which he called an "additive" or a "complement". For him, the side chain contained at least two functional groups.
For providing a theoretical basis for immunology as well as for his work on serum valency, Ehrlich was awarded the Nobel Prize for Physiology or Medicine in 1908 together with Élie Metchnikoff. Metchnikoff, who had researched the cellular branch of immunity, Phagocytosis, at the Pasteur Institute had previously sharply attacked Ehrlich.
Cancer research
In 1901, the Prussian Ministry of Finance criticised Ehrlich for exceeding his budget and as a consequence reduced his income. In this situation Althoff arranged a contact with Georg Speyer, a Jewish philanthropist and joint owner of the bank house Lazard Speyer-Ellissen. The cancerous disease of Princess Victoria, the widow of the German Emperor Friedrich III, had received much public attention and prompted a collection among wealthy Frankfurt citizens, including Speyer, in support of cancer research. Ehrlich had also received from the German Emperor Wilhelm II a personal request to devote all his energy to cancer research. Such efforts led to the founding of a department for cancer research affiliated with the Institute of Experimental Therapy. The chemist Gustav Embden, among others, worked there. Ehrlich informed his sponsors that cancer research meant basic research, and that a cure could not be expected soon.
Among the results achieved by Ehrlich and his research colleagues was the insight that 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. Ehrlich applied bacteriological methods to cancer research. In analogy to vaccination, he attempted to generate immunity to cancer by injecting weakened cancer cells. Both in cancer research and chemotherapy research (see below) he introduced the methodologies of Big Science.
Source: Wikipedia
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