- Person
- Paul Ehrlich
- Lived
- 1854–1915
- Field
- Immunology & chemotherapy
- From
- German
The story
How does the body learn to fight a specific poison or germ? In the 1890s Paul Ehrlich, working first in his own laboratory and then at Robert Koch's Institute for Infectious Diseases in Berlin, studied the question experimentally. He made mice immune to the plant poisons ricin and abrin by feeding them small but increasing doses, and found that immunity to one poison gave no protection against the other. He also showed that newborn mice could receive protective antibodies from their mothers, including through milk.
From this work, and from his efforts to standardise diphtheria serum, came his side-chain theory. Borrowing Emil Fischer's 1894 image of an enzyme fitting its substrate like a key in a lock, Ehrlich proposed that cells carry chemical side chains on their surface, each able to bind a particular toxin. When a toxin locks onto them, the cell makes extra side chains, and the surplus is released into the blood as antibodies that neutralise the toxin before it can do harm. He published the first part of the theory in 1897 and its full form in 1900, in a lecture to the Royal Society in London.
Ehrlich later expanded the theory with terms such as amboceptor that are no longer used, and he proposed an extra immune molecule that he called complement. Some details proved wrong, but its central insight was right: immunity depends on specific chemical binding between molecules, and the receptor's specificity exists before it ever meets its target. He also argued, as early as 1906, that the body must have mechanisms to stop the immune system attacking its own tissues.
In 1908 Ehrlich shared the Nobel Prize in Physiology or Medicine with Élie Metchnikoff in recognition of their work on immunity. Ehrlich was honoured for giving immunology a theoretical basis and for his work on the strength of serums, while Metchnikoff, at the Pasteur Institute, had studied the cellular side of immunity.
The side chains that Ehrlich later renamed receptors became a founding idea of both immunology and pharmacology, and he is often called the father of immunology.
Why it matters
Ehrlich's picture of specific receptors and antibodies anticipated modern immunology and the antibody drugs now used to treat cancer and autoimmune disease.
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 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.
- Paul Ehrlich’s trypan red opened the attack on trypanosomesScreening over 100 dyes in Frankfurt, Paul Ehrlich’s team found trypan red, which killed trypanosomes in infected animals, an early chemotherapy victory that led to arsenic drugs.
Sources
- Paul Ehrlich Wikipedia
- Treasures from the Rare Book Room: Corpora non agunt nisi fixata University of Pittsburgh Health Sciences Library System
- Side-chain theory Wikipedia
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.