Paul Ehrlich 2

 

Paul Ehrlich

 

 

German medical scientist

WRITTEN BY

Heinrich Satter

Britanica Biography

 

Paul Ehrlich, (born March 14, 1854, Strehlen, Silesia, Prussia [now Strzelin, Pol.]—died Aug. 20, 1915, Bad Homburg vor der Höhe, Ger.), German medical scientist known for his pioneering work in hematology, immunology, and chemotherapy and for his discovery of the first effective treatment for syphilis. He received jointly with Élie Metchnikoff the Nobel Prize for Physiology or Medicine in 1908.

Early life

Ehrlich was born into a Jewish family prominent in business and industry. Although he lacked formal training in experimental chemistry and applied bacteriology, he was introduced by his mother’s cousin, the pathologist Carl Weigert, to the technique of staining cells with chemical dyes, a procedure used to view cells under the microscope. As a medical student at several universities, including Breslau, Strasbourg, Freiburg, and Leipzig, Ehrlich continued to experiment with cellular staining. The selective action of these dyes on different types of cells suggested to Ehrlich that chemical reactions were occurring in cells and that these reactions formed the basis of cellular processes. From this idea he reasoned that chemical agents could be used to heal diseased cells or to destroy infectious agents, a theory that revolutionized medical diagnostics and therapeutics.

After receiving his medical degree from the University of Leipzig in 1878, Ehrlich was offered a position as head physician at the prestigious Charité Hospital in Berlin. There he developed a new staining technique to identify the tuberculosis bacillus (a bacterium) that had been discovered by the German bacteriologist Robert Koch. Ehrlich also differentiated the numerous types of blood cells of the body and thereby laid the foundation for the field of hematology.

While developing new methods for the staining of live tissue, Ehrlich discovered the uses of methylene blue in the treatment of nervous disorders. In other diagnostic advances, he traced a specific chemical reaction in the urine of typhoid patients, tested various medications for reducing or removing fever, and made valuable suggestions for the treatment of eye diseases. Of the 37 scientific contributions that he published between 1879 and 1885, Ehrlich considered the last as the most important: Das Sauerstoff-Bedürfniss des Organismus (1885; “The Requirement of the Organism for Oxygen”). In it he established that oxygen consumption varies with different types of tissue and that these variations constitute a measure of the intensity of vital cell processes.

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In 1883 Ehrlich married Hedwig Pinkus, with whom he had two daughters.

Immunity and the side-chain theory

A bout with tuberculosis forced Ehrlich to interrupt his work and seek a cure in Egypt. When he returned to Berlin in 1889, the disease had been permanently arrested. After working for some time in a tiny and primitive private laboratory, he transferred to Koch’s Institute for Infectious Diseases, where he concentrated on the problem of immunity. Very little was known at the time about the precise manner in which bacteria bring about disease, and even less was known about the body’s defenses against infection or how these immune defenses could be enhanced. The hypothesis Ehrlich developed to explain immunological phenomena was the side-chain theory, which described how antibodies—the protective proteins produced by the immune system—are formed and how they react with other substances. Delivered to the Royal Society in 1900, this theory was based on an understanding of the way in which a cell was thought to absorb and assimilate nutrients. Ehrlich postulated that each cell has on its surface a series of side chains, or receptors, that function by attaching to certain food molecules. While each side chain interacts with a specific nutrient—in the same manner as a key fits into a lock—it also can interact with other molecules, such as disease-causing toxins (antigens) produced by an infectious agent. When a toxin binds to a side chain, the interaction is irreversible and blocks subsequent binding and uptake of nutrients. The body then tries to overwhelm the obstruction by producing a great number of replacement side chains—so many that they cannot fit on the surface of the cell and instead are secreted into the circulation. According to Ehrlich’s theory, these circulating side chains are the antibodies, which are all gauged to and able to neutralize the disease-causing toxin and then remain in the circulation, thus immunizing the individual against subsequent invasions by the infectious agent.

This much-debated hypothesis, although ultimately proven to be incorrect in many particulars, had a profound influence on Ehrlich’s later work and on the work of his successors. Thus Ehrlich was able to show experimentally that rabbits subjected to a slow and measured increase of toxic matter were able to survive 5,000 times the fatal dose. In the end, he established precise quantitative patterns of immunity. These findings assumed great importance in 1890, when he met Emil von Behring, who had succeeded in creating an antitoxin against diphtheria. Behring had tried to prepare a serum that could be used in clinical practice, but it was only by adopting Ehrlich’s technique of using the blood of live horses that the preparation of a serum of optimum antitoxic effectiveness became possible. Ehrlich developed a way of measuring the effectiveness of serums that was soon adopted all over the world for the standardization of diphtheria serum. He also demonstrated, in 1892, that antibodies are passed in breast milk from mother to newborn.

On the basis of these achievements, Ehrlich was made director of a government-supported institute near Berlin, which was transferred to Frankfurt am Main in 1899 as the Royal Institute for Experimental Therapy. No restrictions of any kind were placed upon the direction of his research. While this corresponded to Ehrlich’s own talents and inclinations, it did not please Behring, who endeavoured to have his colleague specialize in immunology and serum therapy. The strained relationship between the two men was exacerbated by personality differences. Ehrlich, utterly indifferent to monetary rewards, had no ambition to become an industrialist like Behring; he was content to carry out his research.

He had by then recognized the limitations of serum therapy. Many infectious disorders, in particular those caused by protozoa rather than bacteria, failed to respond to serum treatment. The recognition of this fact marks the birth of chemotherapy. Ehrlich started experimenting with the identification and synthesis of substances, not necessarily found in nature, that could kill parasites or inhibit their growth without damaging the organism. He began with trypanosomes, a species of protozoa that he unsuccessfully attempted to control by means of coal tar dyes. There followed compounds of arsenic and benzene; other compounds proved to be too toxic. Instead of declaring himself vanquished by these difficulties, Ehrlich turned his attention to the spirochete Treponema pallidum, the causal organism of syphilis.

Syphilis studies

Ehrlich had at this time several institutes at his disposal as well as sizable research funds. He also had a staff of highly competent collaborators; in fact, his colleague Hata Sahachirō contributed much to his eventual success in combating syphilis. His preparation 606, later called Salvarsan, was extraordinarily effective and harmless despite its large arsenic content. The first tests, announced in the spring of 1910, proved to be surprisingly successful in the treatment of a whole spectrum of diseases; in the case of yaws, a tropical disease akin to syphilis, a single injection was sufficient. It seemed as if a “magic bullet,” to use a favourite expression of Ehrlich’s, had been found.

 

 

With affection,

Ruben

 

Paul Ehrlich 1

 

Paul Ehrlich

 

Biographical

Source:Nobel Price

Paul Ehrlich was born on March 14, 1854 at Strehlen, in Upper Silesia*, Germany. He was the son of Ismar Ehrlich and his wife Rosa Weigert, whose nephew was the great bacteriologist Karl Weigert.

Ehrlich was educated at the Gymnasium at Breslau and subsequently at the Universities of Breslau, Strassburg, Freiburg-im-Breisgau and Leipzig. In 1878 he obtained his doctorate of medicine by means of a dissertation on the theory and practice of staining animal tissues. This work was one of the results of his great interest in the aniline dyes discovered by W. H. Perkin in 1853.

In 1878 he was appointed assistant to Professor Frerichs at the Berlin Medical Clinic, who gave him every facility to continue his work with these dyes and the staining of tissues with them. Ehrlich showed that all the dyes used could be classified as being basic, acid or neutral and his work on the staining of granules in blood cells laid the foundations of future work on haematology and the staining of tissues.

In 1882 Ehrlich published his method of staining the tubercle bacillus that Koch had discovered and this method was the basis of the subsequent modifications introduced by Ziehl and Neelson, which are still used today. From it was also derived the Gram method of staining bacteria so much used by modern bacteriologists.

In 1882 Ehrlich became Titular Professor and in 1887 he qualified, as a result of his thesis Das Sauerstoffbedürfnis des Organismus (The need of the organism for oxygen) as a Privatdozent (unpaid lecturer or instructor) in the Faculty of Medicine in the University of Berlin. Later he became an Associate Professor there and Senior House Physician to the Charité Hospital in Berlin.

In 1890 Robert Koch, Director of the newly established Institute for Infectious Diseases, appointed Ehrlich as one of his assistants and Ehrlich then began the immunological studies with which his name will always be associated.

At the end of 1896 an Institute for the control of therapeutic sera was established at Steglitz in Berlin and Ehrlich was appointed its Director. Here he did further important work on immunology, especially on haemolysins. He also showed that the toxin-antitoxin reaction is, as chemical reactions are, accelerated by heat and retarded by cold and that the content of antitoxin in antitoxic sera varied so much for various reasons that it was necessary to establish a standard by which their antitoxin content could be exactly measured. This he accomplished with von Behring‘s antidiphtheritic serum and thus made it possible to standardize this serum in units related to a fixed and invariable standard. The methods of doing this that Ehrlich then established formed the basis of all future standardization of sera. This work and his other immunological studies led Ehrlich to formulate his famous side-chain theory of immunity.

In 1897 Ehrlich was appointed Public Health Officer at Frankfurt-am-Main and when, in 1899, the Royal Institute of Experimental Therapy was established at Frankfurt, Ehrlich became its Director. He also became Director of the Georg Speyerhaus, which was founded by Frau Franziska Speyer and was built next-door to Ehrlich’s Institute. These appointments marked the beginning of the third phase of Ehrlich’s many and varied researches. He now devoted himself to chemotherapy, basing his work on the idea, which had been implicit in his doctorate thesis written when he was a young man, that the chemical constitution of drugs used must be studied in relation to their mode of action and their affinity for the cells of the organisms against which they were directed. His aim was, as he put it, to find chemical substances which have special affinities for pathogenic organisms, to which they would go, as antitoxins go to the toxins to which they are specifically related, and would be, as Ehrlich expressed it, «magic bullets» which would go straight to the organisms at which they were aimed.

To achieve this, Ehrlich tested, with the help of his assistants, hundreds of chemical substances selected from the even larger number of these that he had collected. He studied, among other subjects, the treatment of trypanosomiasis and other protozoal diseases and produced trypan red, which was, as his Japanese assistant Shiga showed, effective against trypanosomes. He also established, with A. Bertheim, the correct structural formula of atoxyl, the efficiency of which against certain experimental trypanosomiases was known. This work opened a way of obtaining numerous new organic compounds with trivalent arsenic which Ehrlich tested.

At this time, the spirochaete that causes syphilis was discovered by Schaudinn and Hoffmann in Berlin, and Ehrlich decided to seek a drug that would be effective especially against this spirochaete. Among the arsenical drugs already tested for other purposes was one, the 606th of the series tested, which had been set aside in 1907 as being ineffective. But when Ehrlich’s former colleague Kitasato sent a pupil of his, named Hata, to work at Ehrlich’s Institute, Ehrlich, learning that Hata had succeeded in infecting rabbits with syphilis, asked him to test this discarded drug on these rabbits. Hata did so and found that it was very effective.

When hundreds of experiments had repeatedly proved its efficacy against syphilis, Ehrlich announced it under the name «Salvarsan». Subsequently, further work on this subject was done and eventually it turned out that the 914th arsenical substance to which the name «Neosalvarsan» was given, was, although its curative effect was less, more easily manufactured and, being more soluble, became more easily administered. Ehrlich had, like so many other discoverers before him, to battle with much opposition before Salvarsan or Neosalvarsan were accepted for the treatment of human syphilis; but ultimately the practical experience prevailed and Ehrlich became famous as one of the main founders of chemotherapy.

During the later years of his life, Ehrlich was concerned with experimental work on tumours and on his view that sarcoma may develop from carcinoma, also on his theory of athreptic immunity to cancer.

The indefatigable industry shown by Ehrlich throughout his life, his kindness and modesty, his lifelong habit of eating little and smoking incessantly 25 strong cigars a day, a box of which he frequently carried under one arm, his invariable insistence on the repeated proof by many experiments of the results he published, and the veneration and devotion shown to him by all his assistants have been vividly described by his former secretary, Martha Marquardt, whose biography of him has given us a detailed picture of his life in Frankfurt. In Frankfurt the street in which his Institute was situated was named Paul Ehrlichstrasse after him, but later, when the Jewish persecution began, this name was removed because Ehrlich was a Jew. After the Second World War, however, when his birth-place, Strehlen, came under the jurisdiction of the Polish authorities, they renamed it Ehrlichstadt, in honour of its great son.

Ehrlich was an ordinary, foreign, corresponding or honorary member of no less than 81 academies and other learned bodies in Austria, Belgium, Brazil, Denmark, Egypt, Finland, France, Germany, Great Britain, Greece, Hungary, ltaly, The Netherlands, Norway, Roumania, Russia, Serbia, Sweden, Turkey, the U.S.A. and Venezuela. He held honorary doctorates of the Universities of Chicago, Göttingen, Oxford, Athens and Breslau, and was also honoured by Orders in Germany, Russia, Japan, Spain, Roumania, Serbia, Venezuela, Denmark (Commander Cross of the Danebrog Order), and Norway (Commander Cross of the Royal St. Olaf Order).

In 1887 he received the Tiedemann Prize of the Senckenberg Naturforschende Gesellschaft at Frankfurt/Main, in 1906 the Prize of Honour at the XVth International Congress of Medicine at Lisbon, in 1911 the Liebig Medal of the German Chemical Society, and in 1914 the Cameron Prize of Edinburgh. In 1908 he shared with Metchnikoff the highest scientific distinction, the Nobel Prize.

The Prussian Government elected him Privy Medical Counsel in 1897, promoted him to a higher rank of this Counsel in 1907 and, in 1911, raised him to the highest rank, Real Privy Counsel with the title of Excellency.

Ehrlich married, in 1883, Hedwig Pinkus, who was then aged 19. They had two daughters, Stephanie (Mrs. Ernst Schwerin) and Marianne (Mrs. Edmund Landau).

When the First World War broke out in 1914 he was much distressed by it and at Christmas of that year he had a slight stroke. He recovered quickly from this, but his health which had never, apart from a tuberculous infection in early life which had made it necessary for him to spend two years in Egypt, failed him, now began to decline and when, in 1915, he went to Bad Homburg for a holiday, he had, on August 20 of that year, a second stroke which ended his life.

 

With affection,

Ruben