Paul Ehrlich ( German: ['pa? l' e: ?? l? ÃÆ'§] Ã, ( listen ) ; March 14, 1854 - August 20, 1915 ) is a German Jewish physician and scientist working in the fields of hematology, immunology, and antimicrobial chemotherapy. He invented the precursor technique for Gram staining bacteria. The method he developed for staining tissue makes it possible to differentiate between different types of blood cells, leading to the ability to diagnose many blood diseases.
The laboratory found arsphenamine (Salvarsan), the first effective treatment for syphilis, thus starting and also naming the concept of chemotherapy. Ehrlich popularized the concept of a magic bullet. He also made a decisive contribution to the development of antiserum to combat diphtheria and devised methods for therapeutic serum standardization.
In 1908, he received the Nobel Prize in Physiology or Medicine for his contribution to immunology. He is the founder and first director of what is now known as Paul Ehrlich Institute.
Video Paul Ehrlich
Life and career
Born March 14, 1854 at Strehlen in Silesia in what is now a Polish south-western region.
Paul Ehrlich is the second child of Rosa (Weigert) and Ismar Ehrlich. His father was the innkeeper and liquor refiner and royal lottery collector at Strehelen, a town of 5,000 in Lower Lowere, now in Poland. His grandfather, Heymann Ehrlich, has become a distiller and manager of a fairly successful store. Ismar Ehrlich is the leader of the local Jewish community.
After elementary school, Paul attended a respected high school at Mary-Magdalenen-Gymnasium in Breslau, where he met Albert Neisser, who later became a professional associate. As a schoolboy (inspired by his cousin Karl Weigert who had one of the first microtomes), he became fascinated by the process of dyeing the substance of the microscopic tissue. He retained that interest during his subsequent medical studies at the universities of Breslau, Strasbourg, Freiburg im Breisgau and Leipzig. After earning a doctorate in 1882, he worked at Charità ©  © in Berlin as assistant medical director under Theodor Frerichs, founder of experimental clinical medicine, focusing on histology, hematology and color chemistry (dyes).
He married Hedwig Pinkus (then aged 19 years) in 1883. The couple had two daughters, Stephanie and Marianne.
After completing his clinical and habilitation education at the leading Charità ©  © medical school and hospital in Berlin in 1886, Ehrlich traveled to Egypt and other countries in 1888 and 1889, partially to cure the case of tuberculosis he had contracted in the laboratory. Upon his return he founded a private medical practice and a small laboratory at Berlin-Steglitz. In 1891, Robert Koch invited Ehrlich to join staff at his Berlin Institute of Infectious Diseases, where in 1896 a new branch, the Serum Research and Testing Institute ( Institut FÃÆ'¼r Serumforschung und SerumprÃÆ'¼fung ), was established for Ehrlich specialties. Ehrlich was appointed founding director.
In 1899, the institute moved to Frankfurt am Main and renamed the Institute of Experimental Therapy ( Institut fÃÆ'¼r experimentelle Therapie ). One of the important collaborators is Max Neisser. In 1904, Ehrlich received the full position of honorary professor from the University of GÃÆ'¶ttingen. In 1906 Ehrlich became director of the Speyer Georg House in Frankfurt, a private research institute affiliated with his institute. Here he discovered in 1909 the first drug targeted against specific pathogens: Salvarsan, a treatment for syphilis, which at that time was one of Europe's most deadly and infectious diseases. Among the foreign guest scientists who worked with Ehrlich were two Nobel Prize winners, Henry Hallett Dale and Paul Karrer. The institute changed its name to Paul Ehrlich Institute in honor of Ehrlich in 1947.
In 1914 Ehrlich signed the controversial Manifesto of the Ninety-Three, which was Germany's World War I political and militarist defense. On August 17, 1915 Ehrlich suffered a heart attack and died on August 20 at Bad Homburg vor der HÃÆ'¶he. Wilhelm II, the German emperor, wrote in a telegram of condolence, "I, along with the rest of the civilized world, are mourning the deaths of these meritorious researchers for their great service of medical science and human suffering, the work of his life ensuring unfailing fame and gratitude never stopped, from both his contemporaries and his descendants ".
Paul Ehrlich is buried in the Old Jewish Cemetery, Frankfurt (Block 114 N).
Maps Paul Ehrlich
Research
Hematologic examination
In the early 1870s, Ehrlich's cousin, Karl Weigert, was the first to contaminate bacteria with dyes and introduce aniline pigments for histologic and bacterial diagnostic studies. During his studies at Strassburg under the anatomy expert Heinrich Wilhelm Waldeyer, Ehrlich continued the research initiated by his cousin in pigment and stained the tissue for microscopic studies. He spent the eighth semester of his university in Freiburg im Breisgau investigating primarily dahlia red dye (monophenylrosanilin), thus giving rise to his first publication.
In 1878 he attended Julius Friedrich Cohnheim's dissertation counselor to Leipzig, and that year obtained a doctorate with a dissertation entitled "Contribution to Histological Inheritance Theory and Practice" ( BeitrÃÆ'¤ge zur Theorie und Praxis der histologischen FÃÆ'¤rbung ).
One of the most prominent results of his dissertation investigation was the discovery of a new cell type. Ehrlich is found in plasma cell protoplasm that is thought to be a granule that can be made visible with the help of alkali dyes. He thought these granules were a good sign of food, and thus named the cells of this cell mast, (from the German word for animal fodder feed,
Beginning in 1880, Ehrlich also studied red blood cells. He showed the presence of red corpuscle blood cells, which he divided into normoblasts, megaloblasts, microblasts and poikiloblasts; he has found erythrocyte precursors. Ehrlich thus also laid the groundwork for anemi analysis, after which he created the basis for the systematization of leukemia by investigation of white blood cells.
His job at CharitÃÆ'Â © includes analyzing a patient's blood and urine specimens. In 1881 he published a new urine test that could be used to differentiate different types of typhoid from simple diarrhea cases. The intensity of the staining allows the prognosis of the disease. The pigment solution used today is known as the Ehrlich reagent. Ehrlich's remarkable achievements, but also the source of problems during his subsequent career, are that he has started a new field of interrelated study between chemistry, biology, and medicine. Much of his work was rejected by the medical profession, which lacked the necessary chemical knowledge. It also means that no teacher is suitable for Ehrlich.
Serum research
Friendship with Robert Koch
When a student at Breslau, Ehrlich was given the opportunity by the pathologist Julius Friedrich Cohnheim to conduct extensive research and was also introduced to Robert Koch, who was then a district physician in Wollstein, Posen Province. In his spare time, Koch has clarified the life cycle of anthrax pathogens and has contacted Ferdinand Cohn, who was quickly convinced by Koch's work and introduced it to his Breslau colleagues. From April 30 to May 2, 1876, Koch presented his investigation in Breslau, where student Paul Ehrlich was able to attend
On March 24, 1882, Ehrlich was present when Robert Koch, working since 1880 at the Royal Office of Public Health (Kaiserliches Gesundheitsamt ) in Berlin, presented a lecture in which he reported how he could identify pathogenic tuberculosis. Ehrlich then described this lecture as "the greatest experience in science." The day after Koch's lecture, Ehrlich had made improvements to Koch's coloring method, which Koch welcomed without hesitation. From this date, the two men were tied up in friendship.
In 1887 Ehrlich became an adjunct professor of internal medicine ( Privatdozent fÃÆ'¼r Innere Medizin ) at the University of Berlin, and in 1890 took over a tuberculosis station at a Berlin-Moabit public hospital at Koch's request. This is where Koch hopes-for tuberculosis therapeutic tuberculosis is being investigated; and Ehrlich even injected it himself. In the next tuberculin scandal, Ehrlich tried to support Koch and emphasized the value of tuberculin for diagnostic purposes. In 1891 Koch invited Ehrlich to work for the newly founded Institute of Infectious Diseases ( Institut fÃÆ'¼r Infektionskrankheiten - now Robert Koch Institute) at Friedrich-Wilhelms-UniversitÃÆ'¤t ( now the University of Humboldt) in Berlin. Koch can not give him a salary, but offers him full access to laboratory staff, patients, chemicals and laboratory animals, which Ehrlich always remembers with gratitude.
First job on immunity
Ehrlich has started his first experiment on immunization in his private laboratory. He accustomed rats with rinin and abrin toxins. After feeding them with small doses but increasing the risin he ensures that they have become "ricin-proof." Ehrlich interprets this as immunization and observes that it suddenly begins after a few days and persists after a few months, but mice immunized against the risin are as sensitive to abrin as untreated animals.
This was followed by an investigation of the "inheritance" of acquired immunity. It is well known that in some cases after smallpox or syphilis infection, specific immunity is transmitted from parents to their offspring. Ehrlich refused inheritance in a genetic sense because the male rats were immunized against abrin and untreated female mice were not immune to abrin. He concluded that the fetus is administered with antibodies through the maternal lung circulation. This idea is supported by the fact that this "inherited immunity" declines after a few months. In another experiment, he exchanged untreated and untreated female rats. Rats treated by treated females are protected from toxins, providing evidence that antibodies may also be delivered in milk.
Ehrlich also examined autoimmunity, but he specifically rejected the possibility that the immune system of organisms could invade the tissue of the organism itself which calls it "autotoxicus horror." Ironically, Ehrlich's student Ernest Witebsky, who points out that autoimmunity can cause disease in humans.
Working with Behring on serum diphtheria
Emil Behring had worked at the Berlin Institute of Infectious Diseases until 1893 in developing an antiserum to treat diphtheria and tetanus but with inconsistent results. Koch suggested that Behring and Ehrlich work together on this project. This joint work was successful as far as Ehrlich was able to rapidly increase the immune level of laboratory animals based on his experience with mice. Clinical trials with diphtheria serum at the beginning of 1894 succeeded and in August the chemical company Hoechst began marketing Behring's "Diphtheria Remedy synthesized by Behring-Ehrlich." The two inventors initially agreed to split earnings after Hoechst's shares were reduced. Their contracts changed several times and eventually Ehrlich was finally pressured to accept a profit share of just eight percent. Ehrlich hated what he regarded as unfair treatment, and his relationship with Behring after it was problematic, a situation that later increased over the tetanus serum valence problem. Ehrlich acknowledges that the principle of serum therapy has been developed by Behring and Kitasato. But he argues that he is the first person to develop serum that can also be used in humans, and his role in developing serum diphtheria has not been adequately recognized. Behring, for his part, conspired against Ehrlich at the Prussian Ministry of Culture, and from 1900 at Ehrlich refused to collaborate with him. von Behring was the sole recipient of the first Nobel Prize in Medicine, in 1901, for research contributions to diphtheria.
Serum Valence
Since antiserum is an entirely new type of drug whose quality varies greatly, the system of governance is established to ensure its safety and effectiveness. Beginning April 1, 1895, only government-approved serums could be sold in the German Reich. The testing station for serum diphtheria is temporarily placed at the Institute of Infectious Diseases. On the initiative of Friedrich Althoff, the Serum Research and Testing Institute ( Institut fÃÆ'¼r Serumforschung und SerumprÃÆ'¼fung ) was founded in 1896 at Berlin-Steglitz, with Paul Ehrlich as director (which required him to cancel all contracts with Hoechst). In this function and as an honorary professor at Berliner University, he has an annual income of 6,000 marks, roughly the salary of a university professor. In addition to the testing department, the institute also has a research department.
To determine the effectiveness of diphtheria antiserum, a stable diphtheria toxin concentration is required. Ehrlich found that the toxin used was durable, unlike what he had assumed, which for him caused two consequences: He did not use toxins as a standard, but the powder serum developed by Behring, which had to be dissolved. in the liquid shortly before use. The strength of the test venom is first determined in comparison with this standard. The toxin test can then be used as a reference to test other serum. For the test itself, the toxins and serum are mixed in ratios so that the effect is only canceled off each other when injected into the guinea pig. But since there is a large margin in determining whether the symptoms of the disease are present, Ehrlich sets an unambiguous target: animal death. The mixture should be such that the test animal will die after four days. If die earlier, the serum is too weak and rejected. Ehrlich claims to have made the determination of serum valency as accurate as chemical titration. This again shows his tendency to measure life sciences.
Influenced by the mayor of Frankfurt am Main, Franz Adickes, who sought to establish a science institution in Frankfurt in preparation for university establishment, the Ehrlich institute moved to Frankfurt In 1899 and renamed the Institute for Experimental Therapy of the Kingdom of Prussia ( KÃÆ'¶niglich PreuÃÆ'Ÿisches Institut fÃÆ'¼r Experimentelle Therapie ). The German quality control methodology was copied by governmental serum agencies around the world, and they also obtained standard serum from Frankfurt. After diphtheria antiserum, tetanus serum and various bactericidal serum for use in veterinary medicine are developed in rapid sequence. It is also evaluated at institutes, such as tuberculin and then on various vaccines. Ehrlich's most important partner at the institute was Jewish physician and biologist Julius Morgenroth.
Ehrlich side chain theory
He postulates that cell protoplasm contains a special structure that has a chemical chain (the current term is macromolecule) that binds toxins, affects function. If the organism survives the toxic effects, blocked side chains are replaced with new ones. This regeneration can be trained, the name for this phenomenon is immunization. If a cell produces a side chain surplus, it can also be released into the blood as an antibody.
In the following years Ehrlich expanded his side-chain theory using concepts ("amboceptors," "first, second and third order receptors," etc.) that were no longer customary. Between the antigens and antibodies it assumes there is an additional immune molecule, which he calls "additive" or "complementary". To him, the side chain contains at least two functional groups.
To provide a theoretical basis for immunology as well as for his work on serum valence, Ehrlich was awarded the Nobel Prize for Physiology or Medicine in 1908 along with ÃÆ' â € ° lie Metchnikoff. Metchnikoff, who has studied the cellular branch of immunity, Phagocytosis, at the Pasteur Institute earlier attacked Ehrlich sharply.
Cancer research
In 1901, the Russian Finance Ministry criticized Ehrlich for exceeding his budget and consequently reduced his income. In this situation, Althoff arranges contacts with Georg Speyer, a Jewish philanthropist and co-owner of Lazard's home bank Speyer-Ellissen. The cancer of Princess Victoria, the widow of the German Emperor Friedrich II, has received much public attention and encouraged collections among wealthy Frankfurters, including Speyer, to support cancer research. Ehrlich also received a request from the German Emperor Wilhelm II, a personal request to devote all his energies to cancer research. These efforts led to the establishment of a department for cancer research affiliated with the Institute of Experimental Therapy. Chemist Gustav Embden, among others, works there. Ehrlich told his sponsor that cancer research meant basic research, and that the cure could not be expected immediately.
Among the results achieved by Ehrlich and his research colleagues is the insight that when tumors are cultivated by tumor cell transplants, their malignancy increases from generation to generation. If the primary tumor is removed, the metastasis will increase dramatically. Ehrlich applied bacteriological methods for cancer research. In analogy with vaccination, he seeks to produce immunity to cancer by injecting weakened cancer cells. Both in cancer research and chemotherapy research (see below) he introduced the Big Science methodology.
Chemotherapy
In in vivo coloring
In 1885 Ehrlich's monograph "The Need for Organisms for Oxygen," ( Das SauerstoffbedÃÆ'¼rfnis des Organismus-Eine farbenanalytische Studie ) appeared, which he also proposed as a habilitation thesis. In it he introduces new in vivo coloring technology. One finding is that pigments can only be easily assimilated by living organisms if they are in granular form. He injects blue and blue indophenol alizarin dyes into laboratory animals and was established after their death that the various organs have been colored with different degrees. In organs with high oxygen saturation, indophenol is maintained; in organs with moderate saturation, indophenol is reduced, but not alizarin blue. And in areas with low oxygen saturation, both pigments are reduced. With this work, Ehrlich also formulates the beliefs that guide his research: that all life processes can be traced to the physical chemical processes occurring within the cell.
Blue methylene
In the course of his investigation, Ehrlich finds methylene blue, which he considers very suitable for bacterial staining. Later, Robert Koch also used methylene blue as a dye in his research on tuberculosis pathogens. In Ehrlich's view, an added benefit is that blue methylene also stains the long complement of nerve cells, axons. He started his doctoral dissertation on the subject, but did not follow up on the topic itself. It was the opinion of neurologist Ludwig Edinger that Ehrlich thus has opened a great new topic in the field of neurology.
After mid-1889, when Ehrlich was unemployed, he personally continued his research on methylene blue. His work on in vivo staining gave him the idea of ​​using it therapeutically. Since the parasite family Plasmodiidae - which includes a malaria pathogen - can be stained with methylene blue, he thinks it may be used in the treatment of malaria. In the case of two patients who were admitted to a city hospital in Berlin-Moabit, their fever indeed subsided and the malaria plasmodia disappeared from their blood. Ehrlich obtained the blue methylene from Meister Lucius & amp; BrÃÆ'¼ning AG (later renamed Hoechst AG), which started a long collaboration with this company.
Search for chemotherapia specifica
Before the Institute of Experimental Therapy moved to Frankfurt, Ehrlich was back at work on methylene blue. After the death of Georg Speyer, Franziska Speyer's widow blessed the Georg-Speyer House in her memories erected next to Ehrlich's agency. As director of the Georg-Speyer House, Ehrlich shifted his chemotherapy research there. He seeks agents that are as effective as methylene blue, but without side effects. The model on the one hand is the impact of quinine on malaria, and on the other hand, in analogy with serum therapy, he thinks there must be chemical drugs that have specific effects on individual diseases. The goal is to find "Therapia sterilisans magna," in other words a treatment that can kill all pathogens of the disease.
As a model for experimental therapy Ehrlich used trypanosoma rabbit disease and tested various chemicals in laboratory animals. The trypanosomes can indeed be successfully killed with a trypan red dye. Beginning in 1906, he intensively investigated atoxyl and was tested by Robert Koch along with other arsenic compounds during the exposure of Koch's sleeping sickness of 1906/07. Although the name literally means "nonpoisonous," atoxyl does not cause damage, especially in the optic nerve. Ehrlich outlines the systematic testing of chemical compounds in the sense of screening as is now practiced in the pharmaceutical industry. He found that Compound 418 - Arsenophenylglycine - had an impressive therapeutic effect and was tested in Africa.
With the support of his assistant Sahachiro Hata Ehrlich discovered in 1909 that Compound 606, Arsphenamine effectively combat spirochaetes "spirillum" bacteria, one of the subspecies that cause syphilis. The compounds proved to have some side effects in human trials, and spirochetes disappeared in seven syphilis patients after this treatment.
After extensive clinical testing (all study participants had a negative example of tuberculosis) the Hoechst company began marketing the compound towards the end of 1910 under the name Salvarsan. This is the first agent with special therapeutic effects to be made on the basis of theoretical considerations. Salvarsan proved to be extremely effective, especially when compared with conventional mercury salt therapy. Produced by Hoechst AG, Salvarsan became the most widely prescribed drug in the world. It was the most effective drug to treat syphilis until penicillin was available in the 1940s. Salvarsan needed improvements for side effects and solubility and was replaced in 1911 with Neosalvarsan. Ehrlich's work illuminates the existence of a blood-brain barrier.
The drug triggered the so-called "war of Salvarsan." On the one hand there is hostility on the part of those who are afraid of moral damage due to sexual barriers. Ehrlich was also accused, with a clear anti-Semitic tone, enriching himself excessively. In addition, Ehrlich's associate, Paul Uhlenhuth claimed priority in finding the drug.
Since some people died during clinical trials, Ehrlich was accused of "stopping at nothing." In 1914, one of the most famous accusers was convicted of criminal defamation in court that Ehrlich was summoned to testify. Although Ehrlich was thus freed, the trials made him a depression that never fully recovered.
Magical bullet
Ehrlich reasoned that if a compound can be made that selectively targets the disease-causing organism, then the toxins for the organism may be sent together with the selectivity agent. Therefore, the "magic bullet" ( magische Kugel , the term for the ideal therapeutic agent) will be created that kills only the targeted organism. The concept of "magic bullets" to some extent has been realized by the development of drug-antibody conjugates (monoclonal antibodies associated with biologically active cytotoxic drugs), because they allow cytotoxic drugs to be selectively sent to a prescribed target (eg cancer cells).
Legacy
In 1910, a street was named after Ehrlich in Frankfurt-Sachsenhausen. During the Third Reich, Ehrlich's achievement was ignored while Emil Adolf von Behring was considered the ideal Aryan scholar, and the path named after Ehrlich was given a different name. Shortly after the end of the war, Paul-Ehrlich-Strasse's name was restored, and now many German cities have a street named Paul Ehrlich.
West Germany issued a stamp in 1954 on the anniversary of the 100th birth of Paul Ehrlich (March 14, 1854) and Emil von Behring (March 15, 1854).
The Deutsche Mark 200 note shows Paul Ehrlich.
The Paul Ehrlich Institute of Germany, the successor of the Steglitz Institute for Serum Research and Serum Testing as well as the Frankfurt Experimental Therapy Institute, was named in 1947 after its first director, Paul Ehrlich.
His name is also borne by many schools and pharmacies, by Paul-Ehrlich-Gesellschaft fÃÆ'¼r Chemotherapie e. V. (PEG) in Frankfurt am Main, and Paul-Ehrlich-Clinic in Bad Homburg vor der HÃÆ'¶he. The Paul Ehrlich and Ludwig Darmstaedter Prize are the most prominent German awards for biomedical research. A network of European PhD studies in Drug Chemistry has been named after him (Paul Ehrlich MedChem Euro PhD Network).
The Anti-Polling League honors Paul Ehrlich-Günther K. Schwerin Human Rights.
The moon cemetery is named after Paul Ehrlich in 1970.
The life and work of Ehrlich is featured in the US film of 1940. Ehrlich's Magic Bullet with Edward G. Robinson in the title role. It focuses on Salvarsan (arsphenamine, "compound 606"), the cure for syphilis. Because the Nazi government opposed this respect to a Jewish scientist, efforts were made to keep the film secret in Germany.
Awards and titles
- 1882 Gained a Professorship
- 1890 Appointing Extraordinary Professor at Friedrich-Wilhelms-UniversitÃÆ'¤t (now Humboldt University)
- 1896 Given the non-Academic Prussian degree from the Medical Advisor ( Geheimer Medizinalrat )
- 1903 Received the highest Prussia award in science, the Great Gold Science Medal (previously only given to Rudolf Virchow)
- 1904 Honorary teacher at GÃÆ'¶ttingen; honorary doctorate from the University of Chicago
- 1907 Spokes a title rarely given Senior Medical Adviser ( Geheimer Obermedizinalrat ); awarded an honorary doctorate from Oxford University
- 1908 Delivering the Nobel Prize in Physiology or Medicine for "the work of his immunity"
- 1911 Prussia's highest civilian pronouncement, Personal Advisor ( Wirklicher Geheimer Rat with the title of "Your Excellency")
- 1912 Became a citizen of honor of Frankfurt a.M. and the birthplace of Strehlen
- 1914 Appointed full Professor of Pharmacology at the newly established University of Frankfurt.
See also
- Ehrlich reagent
- German inventor and inventor
- List of Jewish Nobel laureates
References
External links
- Nobel Museum: Biography of Paul Ehrlich
- Paul Ehrlich's publication (ordered chronologically, as a full-text PDF)
- Film Annotations Dr. Ehrlich's Magic Bullet
- Paul Ehrlich and the Hebrew University of Jerusalem; Chemistry in Israel. Bob Weintraub.
- Paul Ehrlich's Work at Project Gutenberg
- Works by or about Paul Ehrlich in the Internet Archive
- Paul Ehrlich's work on LibriVox (public domain audiobook)
Source of the article : Wikipedia
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