He described the process as being similar to key fitting a lock that, in modern terms, would involve cells having receptors for antigens. Upon contact with the antigen, the receptors are shed into the bloodstream as antitoxins. The proposition was ridiculed by many contemporary scientists, and Ehrlich had to wait several years before being awarded the Nobel Prize for this work.
Even in spite of the award, the theory did not become a cornerstone of immunology for almost 60 years. Many modern scientists believe that it was simply too advanced for its time. The ridicule and denial of the Nobel Prize appears not to have fazed Ehrlich. He continued with his research and eventually turned his attention to other endeavors. This opportunity provided him the resources to conduct more rigorous research.
The strength of his reputation gave him access to the best products of the synthetic chemical industry and a multidisciplinary team of scientists. It was here that he reapplied the magic bullet theory in pursuit of a treatment for syphilis. Ehrlich continued to defy conventional thought with the belief that it was possible to synthesize a compound that negatively impacted the parasite with little damage to healthy body tissue.
August Wasserman discovered the reaction for the diagnosis of syphilis in It took four years and failed attempts for Ehrlich and his colleagues to arrive at arsphenamine, a form of organic arsenic. It was initially called compound , but then marketed under the name Salvarsan. In fact, the compound had been dismissed and shelved after an evident failure in Their primary function was to absorb nutrients for the cell, but they also allowed toxic substances to enter.
Ehrlich thought the body defended itself against these toxins by producing excess side-chains matching the toxin, which flooded the body and neutralised free toxins by attaching to them. It was also known as , because the successful compound, the main therapeutic ingredient of which was arsenic, was the th tested by the researchers. Ehrlich, who reportedly eschewed physical exercise and smoked 20 cigars a day, suffered a heart attack and died on 20 August Cosmos is published by The Royal Institution of Australia, a charity dedicated to connecting people with the world of science.
Salvarsan was used to treat syphilis until the s. The researchers, now including an organic chemist, Alfred Bertheim, and a bacteriologist, Sahashiro Hata, broadened the targeted microorganisms to include spirochetes, which had recently been identified as the cause of syphilis.
Salvarsan was first tried on rabbits that had been infected with syphilis and then on patients with the dementia associated with the final stages of the disease. More testing revealed that Salvarsan was actually more successful if administered during the early stages of the disease. Salvarsan and Neosalvarsan retained their role as the most effective drugs for treating syphilis until the advent of antibiotics in the s.
In Michaelis and Menten published their seminal work on enzymes—almost all of which are proteins. Their research cast new light on these complex compounds that make possible the chemical reactions of life.
Skip to main content. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. This year marks the th anniversary of the award of the Nobel Prize for Physiology or Medicine to Paul Ehrlich, in recognition of his contribution to immunology.
His impact, however, extended far beyond this — for example, in his pioneering research in discovering new anti-infectives, which are once again in urgent demand.
A century ago, syphilis was a major public health threat in Europe. But by the s, this situation was improved dramatically by the successful introduction of the first antibacterial drugs to combat the disease.
These therapies resulted from the research of Paul Ehrlich Supplementary information S1 box , who also received the Nobel Prize with Elie Metchnikoff years ago in recognition of his work on immunity. In view of this centennial, and the current stagnation in antibacterial pipelines, it seems timely to reflect on the ground-breaking contributions of Ehrlich to the birth of chemotherapy see Ref. Ehrlich's research career began with selective cell staining with dyes, which allowed him to identify mast cells and the different types of granulocytes.
Such studies led him to formulate the concept of molecules that specifically bind to cell receptors; like a key that can only open the lock it was made for. In Ehrlich's beloved Latin terminology: Corpora non agunt nisi fixata agents only work when they are bound.
The key—lock principle led to the side-chain theory of antibody formation, which became a cornerstone of the newly emerging discipline of immunology, as recognized by the Nobel Prize. Then, Ehrlich decided to revisit small molecules, now with the aim of finding a magic bullet or therapia sterilisans magna great sterilizing therapy to kill microbial pathogens. During his work with dyes, Ehrlich had tested the effects of methylene blue on malaria plasmodia, and so he first searched for drugs against parasites.
Together with his postdoc, Shiga, he chose African trypanosomes as a target and trypan red as the drug, and soon established proof of principle in He also noted the first example of the emergence of resistance to chemotherapy. Ehrlich next turned his attention to atoxyl, an arsenic compound that had already been used for treatment of sleeping sickness in Africa, which unfortunately had blindness as an intolerable side effect.
Ehrlich, however, recognized the potential of chemical modifications of atoxyl to improve its safety. Schaudinn and Hoffmann had identified the aetiological agent of syphilis, now known as Treponema pallidum , in , and, importantly, Uhlenhuth and Salmon had earlier reported that atoxyl is not only active against trypanosomes, but also against fowl spirochetes.
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