- Person
- Paul Ehrlich
- Lived
- 1854–1915
- Field
- Immunology & chemotherapy
- From
- German
The story
Trypanosomes are single-celled parasites that cause serious diseases in people and animals, among them African sleeping sickness in humans and the animal diseases nagana and mal de caderas. At the start of the twentieth century Paul Ehrlich, director of the Royal Prussian Institute of Experimental Therapy in Frankfurt since 1899, made them one of the first targets of his new science of chemotherapy. His aim was to find chemicals with a special affinity for these organisms, which would strike them while sparing their host.
Rather than wait for a lucky discovery, Ehrlich tested compounds systematically. In 1901 his team tried more than 100 synthetic dyes against trypanosome infections in laboratory animals. Only one, a red dye called Nagana red, showed any activity, and it worked poorly, probably because it dissolved badly in water. At Ehrlich's request, the chemist Ludwig Benda of the Cassella dye works made a more soluble version in 1903 by adding an extra sulphonic acid group. The new dye, trypan red, was shown by Ehrlich's Japanese assistant Shiga to be effective against trypanosomes.
Trypan red was not a perfect drug. It was effective against the parasite of mal de caderas but not against other trypanosomes. Yet it proved that Ehrlich's method worked: by changing a molecule step by step and testing each version, a team could improve a drug deliberately.
From 1906 the team turned to arsenic compounds, beginning with atoxyl, which Robert Koch tested against human sleeping sickness during his expedition to Africa in 1906 and 1907. Atoxyl damaged the optic nerve, so Ehrlich and the chemist Alfred Bertheim worked out its structure and made many new derivatives. One of them, compound 606, became Salvarsan in 1909, the first effective drug against syphilis and also a treatment for African trypanosomiasis.
The trypan red project was an early example of the systematic screening of chemical compounds against disease, a method that the pharmaceutical industry would later adopt as standard practice.
Why it matters
The trypan red project established the systematic screening and step-by-step improvement of chemical compounds against disease, the method still at the heart of pharmaceutical research.
About Paul Ehrlich
Nobel-winning German Jewish physician who imagined the “magic bullet”, founded chemotherapy and, with Salvarsan in 1909, produced the first effective drug against syphilis.
More about Paul Ehrlich
- Paul Ehrlich named and characterised the mast cellWhile still a young scientist, Paul Ehrlich named and characterised the mast cell, the immune cell now known to drive allergic reactions.
- Paul Ehrlich's maxim is the first rule of drug designPaul Ehrlich summed up a basic law of pharmacology in four Latin words, corpora non agunt nisi fixata: a drug acts only when it is bound to its target.
- Paul Ehrlich's dyes revealed the blood-brain barrierPaul Ehrlich noticed that dyes injected into the bloodstream coloured nearly every organ except the brain, an early clue to the blood-brain barrier that protects our nervous system.
- Paul Ehrlich's dyes founded modern haematologyUsing the new synthetic dyes of the 1870s and 1880s, Paul Ehrlich learned to tell the different kinds of white blood cells apart, laying the foundations of modern blood science.
- Paul Ehrlich improved the tuberculosis test overnightThe day after Robert Koch announced the tuberculosis bacterium in March 1882, Paul Ehrlich improved Koch's method of staining it, making the deadly germ far easier to detect.
- Paul Ehrlich's "magic bullet" cured syphilisPaul Ehrlich imagined a "magic bullet" that would strike disease without harming the patient, and in 1909 his lab found Salvarsan, the first modern antimicrobial drug and first cure for syphilis.
- Paul Ehrlich treated malaria with a synthetic dyeNoticing that malaria parasites soak up methylene blue, Paul Ehrlich tried the dye as a treatment, and two patients' fevers subsided, an early step toward designed synthetic drugs.
- Paul Ehrlich foresaw antibodies and receptorsPaul Ehrlich's side-chain theory proposed that cells carry receptors that bind specific toxins, an idea about antibodies that helped earn him the 1908 Nobel Prize.
- Paul Ehrlich made diphtheria antitoxin reliableWorking with Emil von Behring in the 1890s, Paul Ehrlich devised ways to measure the strength of diphtheria antitoxin, so doctors could give children safe, reliable doses.
Sources
- Paul Ehrlich Wikipedia
- Paul Ehrlich, Biographical NobelPrize.org
- Arsphenamine Wikipedia
- Trypanrot Wikipedia (German)
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.