Paul Ehrlich

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Paul Ehrlich (March 14, 1854 – August 20, 1915) was a German scientist who won the 1908 Nobel Prize in Physiology or Medicine. He is noted for his work in hematology, immunology, and chemotherapy. Ehrlich predicted autoimmunity calling it "horror autotoxicus". He coined the term "chemotherapy" and popularized the concept of a "magic bullet". He is credited with the first empirical observation of the blood-brain barrier and the development of the first antibiotic drug in modern medicine.

Biography

Paul Ehrlich was born into a Jewish family in Strehlen, in the Prussian Province of Silesia (now in Poland). As a schoolboy and student of medicine he was interested in staining microscopic tissue substances. In his dissertation at the University of Leipzig, he picked up the topic again ("Beiträge zur Theorie und Praxis der histologischen Färbung"). He married Hedwig Pinkus (then aged 19) in 1883. The couple had two daughters named Stephanie and Marianne. After his clinical education and habilitation ("Das Sauerstoffbedürfnis des Organismus") at the Charité in Berlin in 1886 he received a call from Robert Koch to join the Institute for Infectious Diseases in Berlin (1891).

Ehrlich spent two years in Egypt, recovering from tuberculosis. Thereafter he worked with his friend Emil Adolf von Behring on the development of the diphtheria serum.

These works inspired Ehrlich's famous side-chain theory (Seitenkettentheorie) from 1897. This theory explained the effects of serum and enabled measurement of the amount of antigen. In 1896 Ehrlich became the director of the newly founded Institute of Serum Research and Examination (Institut für Serumforschung und Serumprüfung) in Steglitz (Berlin). In 1899 the institute was moved to Frankfurt (Main) and extended into the Royal Institute of Experimental Therapy (Institut für experimentelle Therapie). Here Ehrlich researched chemotherapy and infectious diseases. In 1904 Ehrlich became honorary professor of the University of Göttingen.

Ehrlich received the Nobel Prize for Medicine together with Ilya Ilyich Mechnikov in 1908. In 1906 he discovered the structural formula of atoxyl, a chemical compound which had been shown to be able to treat sleeping sickness. Following this discovery, he tried to create a less toxic version of the medicament. In 1909 he and his student Sahachiro Hata developed Salvarsan, a treatment effective against syphilis. This work was of epochal importance, stimulating research that led to the development of sulfa drugs, penicillin and other antibiotics.

Ehrlich died of a stroke in Bad Homburg in 1915, aged 61.

"Magic Bullet"

His life is depicted in the movie The Magic Bullet, which focused on Salvarsan® (arsphenamine, "compound 606"), his cure for syphilis. His work illuminated the existence of the blood-brain barrier.

The "magic bullet" concept comes from the experience of 19th century German chemists with selectively staining tissues for histological examination, and in particular, selectively staining bacteria (Ehrlich was an exceptionally gifted histological chemist, and invented the precursor technique to Gram staining bacteria). Ehrlich reasoned that if a compound could be made that selectively targeted a disease causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. Hence, a "magic bullet" would be created that killed only the organism targeted.

A problem with the use of the magic bullet concept as it emerged from its histological roots is that people confused the dye with the agent of tissue selectivity and antibiotic activity. Prontosil, a sulfa drug whose active component is sulfanilamide, is a classic example of the fact that color is not essential to antibiotic activity.

The concept of a "magic bullet" was fully realized with the invention of monoclonal antibodies.

References and further reading

• Nobel Museum: Biography of Paul Ehrlich
• Paul Ehrlich, pharmaceutical achiever
• Paul Ehrlich's publications (ordered chronologically, as full-text PDF)
• Film Annotations Dr. Ehrlich's Magic Bullet
• Bernhard Witkop (1999) Paul Ehrlich and His Magic Bullets—Revisited Proceedings of the American Philosophical Society 143:4 p.540-557.