A Silesian childhood
Paul Ehrlich was born on March 14, 1854, in Strehlen, a small town in Prussian Silesia that is now Strzelin in Poland. His father, Ismar Ehrlich, was an innkeeper, distiller and royal lottery collector, and a leader of the town’s Jewish community; his mother was Rosa Weigert. Science ran in the family: Rosa’s nephew, Karl Weigert, would become a distinguished pathologist and one of the first scientists to stain bacteria with dyes, and his influence on his younger cousin was profound.
Ehrlich went to the Maria-Magdalenen-Gymnasium in Breslau (now Wrocław), then studied medicine at the universities of Breslau, Strasbourg, Freiburg and Leipzig. He was not a conventional student. He was captivated by the brilliant new synthetic aniline dyes being produced by the German chemical industry and spent hours experimenting with how they coloured different tissues. In 1878 he took his medical doctorate at Leipzig with a dissertation on the theory and practice of staining animal tissues, the seed of everything that followed.
Colouring the invisible
That year he became an assistant to Professor Theodor Frerichs at the Charité hospital in Berlin, who gave him freedom to pursue his dyes. Ehrlich showed that stains could be classified as acidic, basic or neutral, and that different cells and structures took them up selectively. Using this insight he distinguished the various types of white blood cells by their granules, described the mast cell, and laid the foundations of modern haematology. The idea that a chemical could seek out one particular kind of cell and leave others untouched would guide his whole career.
On March 24, 1882, he attended Robert Koch’s historic lecture announcing the discovery of the tuberculosis bacillus. The very next day he improved Koch’s method for staining the organism, and his technique became the basis of the Ziehl–Neelsen stain still used to diagnose tuberculosis, and an influence on the Gram stain used throughout bacteriology. In 1887 he qualified as a university lecturer in Berlin and won the Tiedemann Prize of Frankfurt’s Senckenberg Society. His laboratory work also carried a personal cost: he contracted tuberculosis himself, and in 1888–89 travelled to Egypt and elsewhere to recover.
Immunity and the side-chain theory
In 1890 Koch invited him to join his new Institute for Infectious Diseases in Berlin, and Ehrlich turned to immunology. Working alongside Emil von Behring on the antitoxin against diphtheria, then a leading killer of children, he devised ways to standardise the strength of the serum so that doctors could give reliable doses. His methods became the basis for the standardisation of sera worldwide. The collaboration ended in a bitter dispute over credit and profits when the Hoechst company marketed the remedy in 1894.
In 1896 the Prussian government made Ehrlich director of a new Institute for Serum Research and Testing in Steglitz, Berlin. There he formulated his famous side-chain theory of immunity: that cells carry receptor “side chains” that bind specific toxins, and that the body responds by producing surplus receptors which are released into the blood as antibodies. Parts of the theory proved wrong, but its central idea, that immunity rests on specific chemical binding between molecules, anticipated modern immunology. In 1908 he shared the Nobel Prize in Physiology or Medicine with Élie Metchnikoff “in recognition of their work on immunity”.
The magic bullet
In 1899 Ehrlich moved to Frankfurt as director of the new Royal Prussian Institute for Experimental Therapy, and from 1906 also of the neighbouring Georg-Speyer-Haus, funded by the philanthropist Franziska Speyer. There he turned his oldest idea into a research programme. If dyes could stain specific cells, and antibodies could bind specific toxins, then it should be possible to make chemicals that would bind to disease-causing organisms and kill them while sparing the patient. He called such a compound a Zauberkugel, a “magic bullet”, and he named the new science chemotherapy.
His method was as important as his vision. Rather than relying on chance, Ehrlich and his chemists systematically synthesised hundreds of related compounds, changing them step by step, and tested each one against infections in laboratory animals. Early work produced trypan red, which his Japanese assistant Kiyoshi Shiga showed was effective against the trypanosomes that cause sleeping sickness, and established the correct structure of atoxyl, an arsenic compound, opening the way to many new arsenical drugs.
Compound 606
In 1905 Fritz Schaudinn and Erich Hoffmann identified the spirochaete that causes syphilis, then a widespread, disfiguring and incurable disease treated with toxic mercury. Ehrlich set out to find a magic bullet against it. Among the arsenic compounds his team had already made was the 606th of the series, set aside in 1907 as ineffective against trypanosomes. In 1909 the Japanese bacteriologist Sahachiro Hata, who had come to Ehrlich’s institute and could reliably infect rabbits with syphilis, tested the discarded compound, and found it remarkably effective.
After extensive further testing, Hoechst marketed compound 606, arsphenamine, under the name Salvarsan at the end of 1910. It was the first genuinely effective modern antimicrobial drug, and demand was overwhelming. It had serious drawbacks, it was difficult to prepare and administer and could cause severe side effects, so Ehrlich’s team developed Neosalvarsan, compound 914, which was easier to use. Salvarsan and its successors remained the standard treatment for syphilis until penicillin replaced them in the 1940s.
Controversy and antisemitism
Success brought fierce attacks. In what became known as the “Salvarsan war”, critics accused Ehrlich of endangering patients and of enriching himself, and some argued that curing syphilis would encourage immorality. Paul Uhlenhuth disputed his priority. Much of the campaign carried antisemitic undertones, aimed at a Jewish scientist who had become one of the most famous men in Germany. In 1914 one of his accusers was convicted of criminal libel, but the ordeal left Ehrlich exhausted and depressed.
Ehrlich never abandoned his Jewish identity. He married Hedwig Pinkus, then nineteen, in 1883 in the synagogue at Neustadt (now Prudnik), and they had two daughters, Stephanie and Marianne, who married the mathematician Edmund Landau. He reached the highest honours the Prussian state could give, including the title of Real Privy Councillor with the style of “Excellency” in 1911, honorary doctorates from Chicago, Göttingen, Oxford, Athens and Breslau, the Liebig Medal of the German Chemical Society in 1911, the Cameron Prize of Edinburgh in 1914, and membership of eighty-one academies and learned societies around the world, yet he remained an outsider to many in the German establishment.
The man in the laboratory
Those who worked with Ehrlich remembered a modest, kind and tireless man, adored by his assistants, who insisted that every result be confirmed by repeated experiments before it was published. He ate little and smoked constantly, by the account of his secretary Martha Marquardt, whose biography gives a vivid picture of his Frankfurt years, as many as twenty-five strong cigars a day, a box of which he often carried under his arm.
The outbreak of the First World War in 1914 distressed him greatly, and at Christmas that year he suffered a slight stroke. His health declined, and on August 20, 1915, while on holiday at Bad Homburg, he died. Kaiser Wilhelm II sent a telegram saying that he and the entire civilised world mourned the meritorious researcher. Ehrlich was buried in the Jewish cemetery in Frankfurt.
Erased, then restored
Under the Nazis, Ehrlich’s Jewishness was used to erase him. His achievements were ignored, the Frankfurt street named after him was renamed, and Emil von Behring was held up instead as the model “Aryan” scientist. On Kristallnacht in 1938 a portrait of Ehrlich was slashed, and his grave was later desecrated. Outside Germany his reputation only grew: in 1940 Hollywood released Dr. Ehrlich’s Magic Bullet, starring Edward G. Robinson, which was nominated for an Academy Award for its screenplay and was suppressed in Nazi Germany.
After the war Germany restored his name. In 1947 the federal institute for vaccines and biomedicines, whose first director had been Ehrlich himself, was named the Paul Ehrlich Institute, and he was later honoured on a West German postage stamp in 1954 and on the 200-Deutsche-Mark banknote. The Paul Ehrlich and Ludwig Darmstaedter Prize, named partly in his memory, is today the most distinguished German award for biomedical research, and the Paul-Ehrlich-Gesellschaft für Chemotherapie in Frankfurt carries on the discipline he founded.
Legacy
Paul Ehrlich’s ideas run through modern medicine. His staining techniques made it possible to tell blood cells apart and diagnose diseases from tuberculosis to leukaemia. His work on antitoxins established how biological medicines are measured and standardised. His side-chain theory introduced the idea of receptors, now central to pharmacology. And his insistence that a drug must bind to its target to act, corpora non agunt nisi fixata, is still the first lesson of drug design.
Above all, he invented a way of discovering medicines: imagine a target, then systematically make and screen large numbers of chemicals until one hits it. That method, and the dream of the magic bullet, lie behind the antibiotics, cancer chemotherapies and targeted antibody drugs that have saved countless lives. More than a century after Salvarsan, pharmaceutical research still works in the way Ehrlich first showed it could.
Sources & further reading
Paul Ehrlich, Wikipedia · Paul Ehrlich, Biographical, NobelPrize.org · Treasures from the Rare Book Room: Corpora non agunt nisi fixata, University of Pittsburgh Health Sciences Library System · Researched from the sources above and checked against them. Spotted an error? Tell us.
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