__1909: __After searching through hundreds of potential chemicals, a German immunologist discovers a compound that can selectively kill the parasitic spirochete that causes syphilis. The following year, he sends 65,000 free samples of the drug, now known as the first modern chemotherapy agent, to doctors all over the world.

Since his research career began in the 1870s, German physician Paul Ehrlich had been searching for chemicals that could kill infectious microbes without harming their human hosts. He coined the term chemotherapy to describe the type of drug he was looking for, saying, "We must search for magic bullets. We must strike the parasites, and the parasites only, if possible, and to do this, we must learn to aim with chemical substances!"

In the early 1900s, Ehrlich began building a vast library of chemicals that he hoped might have specific bug-fighting powers. He started by studying the arsenic-like compound Atoxyl, known to kill syphilis but too toxic for use in humans. Ehrlich and his vast army of assistants from the Royal Institute of Experimental Therapy in Frankfurt began brewing hundreds of slight variations of the Atoxyl chemical.

Ehrlich and Japanese student Sahachiro Hata produced their 606th preparation of an arsenobenzene compound in 1907. Ehrlich watched on Aug. 31 two years later, as Hata injected chemical No. 606 into a rabbit with syphilitic ulcers. The next day, no live spirochetes could be found on the animal's ulcers, and within three weeks, the ulcers were completely gone.

After testing the drug on mice, guinea pigs and many more rabbits, Ehrlich and Hata sent their miracle cure to the chemical firm Hoechst, which marketed it under the name Salvarsan. The drug became an almost instant success around the world, although many criticized Ehrlich for creating a chemical that might encourage promiscuity.

Like today's chemotherapy drugs for cancer, Salvarsan didn't come without risks. Made from 32 percent arsenic, the drug could cause severe tissue damage and even death if not injected directly into a vein. Although Ehrlich warned the medical community about the chemical's toxicity, critics accused him of marketing a dangerous drug and getting rich off the proceeds.

Ehrlich won the 1908 Nobel Prize in Physiology or Medicine for his work on immunity, but only two years later was charged with criminal negligence for promoting Salvarsan. Eventually, the charges were dismissed, and Ehrlich's most vocal critic was sent to prison for libel.

In the midst of supervising the preparation of huge quantities of Salvarsan for the German army in World War I, Ehrlich died of a stroke in 1915. Physicians continued to use Salvarsan and its less toxic sister, Neosalvarsan, to treat syphilis until the late 1940s, when penicillin replaced Neosalvarsan (substance No. 914) as the syphilis treatment of choice.

Today, Ehrlich is considered the father of chemotherapy, and he's also credited for inspiring Alexander Fleming's discovery of penicillin in 1929. The 1940 Hollywood biopic Dr. Ehrlich's Magic Bullet chronicles the events of his inspiring but controversial life.

Source: Various

*Image 1: Paul Ehrlich and assistant Sahachiro Hata in the laboratory.

Artist: Robert Thom/"Great Moments in Medicine" series, collection of the University of Michigan Health System, gift of Pfizer.

Image 2: Clipping from The New York Times, Feb. 9, 1912. *

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