Editing Paul Ehrlich (section)

===Chemotherapy===
====In vivo staining====
In 1885 Ehrlich's monograph "The Need of the Organism for Oxygen" (''Das Sauerstoffbedürfnis des Organismus – Eine farbenanalytische Studie'') appeared, which he also submitted as a [[habilitation]] thesis. In it 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 coloured to different degrees. In organs with high oxygen saturation, indophenol was retained; in organs with medium saturation, indophenol was reduced, but not alizarin blue. And 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.

====Methylene blue====
[[File:Mundschleimhautzelle.jpg|thumb|Staining ''in vivo'' with [[methylene blue]] of a cell from the mucous membrane of a human mouth]]

In the course of his investigations Ehrlich came across [[methylene blue]], which he regarded as particularly suitable for staining bacteria. Later, Robert Koch also used methylene blue as a dye in his research on the tuberculosis pathogen. In Ehrlich's view, an added benefit was that methylene blue also stained the long appendages of nerve cells, the [[axon]]s. He initiated a doctoral dissertation on the subject, but did not follow up the topic himself. It was the opinion of the neurologist [[Ludwig Edinger]] that Ehrlich had thereby opened up a major new topic in the field of [[neurology]].

After mid-1889, when Ehrlich was unemployed, he privately continued his research on methylene blue. His work on in vivo staining gave him the idea of using it therapeutically. Since the parasite family of ''[[Plasmodiidae]]'' – which includes the [[malaria]] pathogen – can be stained with methylene blue, he thought it could possibly be used in the treatment of malaria. In the case of two patients so treated at the city hospital in Berlin-Moabit, their fever indeed subsided and the malaria plasmodia disappeared from their blood. Ehrlich obtained methylene blue from the company Meister Lucius & Brüning AG (later renamed Hoechst AG), which started a long collaboration with this company.

====The search for a ''chemotherapia specifica''====
Before the Institute of Experimental Therapy had moved to Frankfurt, Ehrlich had already resumed work on methylene blue. After the death of Georg Speyer, his widow Franziska Speyer endowed the Georg-Speyer House in his memory<ref>[http://www.georg-speyer-haus.de/aboutus_history.php?sprache=en History of the Georg-Speyer-Haus] {{webarchive|url=https://web.archive.org/web/20121201125635/http://www.georg-speyer-haus.de/aboutus_history.php?sprache=en |date=1 December 2012 }}. georg-speyer-haus.de</ref> which was erected next door to Ehrlich's institute. As director of the Georg-Speyer House, Ehrlich transferred his chemotherapeutic research there. He was looking for an agent which was as effective as methylene blue, but without its side effects. His model was on the one hand the impact of [[quinine]] on malaria, and on the other hand, in analogy to serum therapy, he thought there must also be chemical pharmaceuticals which would have just as specific an effect on individual diseases. His goal was to find a ''Therapia sterilisans magna'', in other words a treatment that could kill all disease pathogens.

[[File:Paul Ehrlich and Sahachiro Hata.jpg|thumb|left|Ehrlich and [[Sahachiro Hata]]]]

As a model for experimental therapy Ehrlich used a guinea pig disease [[trypanosoma]] and tested out various chemical substances on laboratory animals. The trypanosomes could indeed be successfully killed with the dye trypan red. Beginning in 1906, he intensively investigated [[Arsanilic acid|atoxyl]] and had it tested by Robert Koch along with other arsenic compounds during Koch's sleeping sickness expedition of 1906/07. Although the name literally means "nonpoisonous", atoxyl does cause damage, especially to the optic nerve. Ehrlich elaborated the systematic testing of chemical compounds in the sense of screening as later practiced in the pharmaceutical industry. He discovered that Compound 418 - Arsenophenylglycine - had an impressive therapeutic effect and had it tested in Africa.

With the support of his assistant [[Sahachiro Hata]] Ehrlich discovered in 1909 that Compound 606, [[Arsphenamine]], effectively combatted "[[Spiral bacteria|spirillum]]" [[spirochaete]]s bacteria, one of whose [[subspecies]] causes [[syphilis]].<ref>{{cite book |quote=Ironically, financial restrictions which apparently caused Ehrlich to forego the testing of a similar compound in 1907 against mal de Caderas, where it might well have proven ineffective and been forever discarded, may have played a positive role in 1909 in the (re)discovery and testing of "606" against syphilis, where it proved to be highly effective |first=Frank |last=Heynick |year=2002 |title=Jews and Medicine: An Epic Saga |publisher=Ktav |location=Hoboken |pages=354–355 |isbn=978-0881257731 }}</ref> The compound proved to have few side effects in human trials, and the spirochetes disappeared in seven syphilis patients after this treatment.

After extensive clinical testing (all the research participants had the negative example of tuberculin in mind) the Hoechst company began to market the compound toward the end of 1910 under the name [[Salvarsan]]. This was the first agent with a specific therapeutic effect to be created on the basis of theoretical considerations. Salvarsan proved to be amazingly effective, particularly when compared with the conventional therapy of mercury salts. Manufactured by Hoechst AG, Salvarsan became the most widely prescribed drug in the world. It was the most effective drug for treating syphilis until penicillin became available in the 1940s.<ref>{{cite magazine |url=http://pubs.acs.org/cen/coverstory/83/8325/8325salvarsan.html |title=Salvarsan |access-date=1 February 2010 |magazine=[[Chemical & Engineering News]] }}</ref> Salvarsan required improvement as to side effects and solubility and was replaced in 1911 with [[Neosalvarsan]]. Ehrlich's work illuminated the existence of the [[Blood–brain barrier#History|blood-brain barrier]], although he himself never believed in such a barrier, with [[Lina Stern]] later coining the phrase.

The medication triggered the so-called "Salvarsan war". On one side there was hostility on the part of those who feared a resulting moral breakdown of sexual inhibitions. Ehrlich was also accused, with clearly [[Antisemitism|anti-Semitic]] undertones, of excessively enriching himself. In addition, Ehrlich's associate, [[Paul Uhlenhuth]] claimed priority in discovering the drug.

Because some people died during the clinical testing, Ehrlich was accused of "stopping at nothing." In 1914, one of the most prominent accusers was convicted of criminal libel at a trial for which Ehrlich was called to testify. Though Ehrlich was thereby exonerated, the ordeal threw him into a depression from which he never fully recovered.<ref>Lehrer, Steven (1979) ''Explorers of the Body: Dramatic Breakthroughs in Medicine from Ancient Times to Modern Science''. Doubleday. {{ISBN|0595407315}}. p. 295.</ref>