Ehrlich, Paul (1854–1915)

Paul Ehrlich was immensely important in the fields of chemistry, immunology, and histology. Perhaps his greatest contribution to public health was his discovery of Salvarsan, also known as 606, the first organic antisyphilitic. Martha Marquardt, his secretary for 13 years, describes his life as ‘one long fight for the promotion of medical science in the service of mankind’ (Marquardt, 1951, p. vi).

Born on March 14, 1854, in Strehlen, Germany, to prosperous innkeepers Ismar and Rosa, Ehrlich's fascination with science was fostered from an early age by his grandfather, a natural scientist, and his cousin, Karl Weigert, a bacteriologist. Ehrlich excelled in [Page 307]Latin and the sciences throughout school, earning a Doctor of Medicine degree at Leipzig in 1878.

A fervent researcher, nearly all Ehrlich's waking hours were consumed with planning, executing, or contemplating his latest experiment. Though he spent time—at least early in his career—treating patients, it was always the histology and inquiry into the staining of tissues with aniline dyes (to differentiate cell types) that intrigued him most. His methods led to the development of the Gram stain many years later.

After Robert Koch's discovery of the tuberculosis bacillus in 1882, Ehrlich set out to stain the organism and succeeded quickly. Thus began a partnership between Ehrlich and Koch, as well as the capability for rapid diagnosis of tuberculosis, even in the absence of symptoms. Ehrlich contracted the disease during his research and spent 2 years recovering in Egypt. In 1889, Ehrlich returned to science and began working in Koch's newly established Institute for Infectious Disease in Berlin. It was there in 1892 that colleague Emil von Behring discovered the diphtheria antitoxin. It was Ehrlich, however, who optimized the practical use of the serum when he quantified dosage in terms of a standardized measurement obtained through animal studies. This procedure became standard protocol in vaccine development.

Ehrlich's work led him to the formulation of the side-chain theory, his explanation of antibody production. Ehrlich postulated the existence of cellular receptors that attract foreign chemicals and bind them specifically. Once bound, if the chemical did not kill the cell, Ehrlich believed the cell would produce many more receptors, some of which would separate and float through the bloodstream to become antibodies. Ehrlich also worked to find compounds he termed magic bullets, which could target pathogenic organisms and destroy them without harming the surrounding host tissues. Ehrlich recognized antibodies as a natural magic bullet and sought to synthesize similar agents to kill trypanosomes and spirochetes. He called this field ‘chemotherapy’ to distinguish it from the prevailing drug research of the day in which investigators sought to remedy symptoms rather than destroy the causative agent. In 1908, Ehrlich was awarded the Nobel Prize in Medicine for his work in immunity.

It was at the Institute for Experimental Therapy in Frankfurt, of which Ehrlich was director from 1899 to 1915, where he made his most famous discovery, Salvarsan. Ehrlich worked to create derivatives of Atoxyl (arsanilic acid), an effective but toxic drug. He produced and tested hundreds of compounds, including 606, which was initially deemed ineffective by an assistant. Two years later, a Japanese apprentice, Sahachiro Hata, used 606 to treat syphilis-infected rabbits and found it to be highly efficacious. After repeated tests in a variety of animal models, Ehrlich and Hata announced the finding to the world, and soon after, they were inundated with requests from physicians to begin clinical testing. The drug proved much safer and more successful than mercury or other common treatments available at that time and was given the name Salvarsan. Though supplanted by penicillin in the 1940s, Ehrlich's discovery greatly reduced the prevalence and negative sequelae of syphilis and yaws worldwide and paved the way for chemotherapeutic investigation as we know it today.

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