Paul Ehrlich (1854-1915): Scientist and Visionary by Peter Beyfus
We have learnt a great deal about the COVID-19 virus since it impacted our lives in 2020; and the development of vaccines with breathtaking speed has impressed both the scientific fraternity and all of us who have little knowledge of the esoteric field of immunology. It seems appropriate now we are seeing a return to normal life, having suffered the privations of social restrictions for so long, to pay tribute to Paul Ehrlich, one of the pioneers of immunology and a major contributor to other medical advancements, specifically haematology, cancer research and chemotherapy; it was Erhlich who coined the phrase “magic bullet”. By necessity this biographical thumbnail sketch cannot do full justice to his many discoveries and the enormous debt later generations owe to Ehrlich and his collaborators who followed the trail blazed by other great epidemiologists: John Snow, Louis Pasteur, Joseph Lister and Ehrlich’s contemporary and friend Robert Koch.
Paul Ehrlich was born on 14 March 1854 into a prosperous Jewish family. Home was the country town of Strehlen in Prussian Silesia, near what is now Wrocław in Poland, but was formerly Breslau. He was the only son of Ismar Ehrlich, an innkeeper and distiller and prominent member of the Jewish community, but regarded as eccentric. Paul’s mother, Rosa Weigert was noted for her intelligence and industry. In 1860 he attended the local elementary school and from there went to the Gymnasium in Breslau. Ehrlich was an able student, conscientious, but far from being a child prodigy. He matriculated in 1872 and studied medicine at various universities, including Breslau, Strasbourg, Freiburg and Leipzig, receiving his medical degree from the latter university in 1878. He became a very good friend of his mother’s cousin, Carl Weigert, who became a renowned pathologist. It may have been Carl’s influence that stimulated Paul’s interest in histology and the use of chemicals to examine human cells. Although he had little formal training in Chemistry, he devoted much time to studying the subject and applied it techniques in his research. In 1883 Ehrlich married Hedwig Pinkus, with whom he had two daughters. While he was working at the Charité medical school and teaching hospital in Berlin, he caught Tuberculosis, apparently contracted in his laboratory. He and Hedwig went to Egypt in 1889 to help treat the condition. He returned to Berlin after a year, received Koch’s tuberculin treatment and never had a recurrence of the disease. In December 1914 he had a mild stroke and was advised to give up smoking cigars and to modified his diet. His health did not improve, however, and having spent a short time in a sanitarium died of a second stroke on 20 August 1915, aged 61. He is buried in the Jewish cemetery in Frankfurt.
So what were the clinical achievements of Paul Ehrlich, Nobel Laureate?
His scientific life can be divided into three phases, all of which were influenced by his deep understanding of the principles of chemistry and molecular interactions in various biological systems. In the primary stage of Paul Ehrlich’s research, dating from 1878-1890, he established the fundamentals of modern haematology and immunology. This involved identifying distinct classes of leucocytes, white blood cells, that our our main defence against infectious diseases. Along with developments in haematology, he classified a wide range of bacilli. In his early career he worked closely with his cousin, Carl Weigert, a pathologist who was experimenting with aniline dyes, a product of coal tar. Ehrlich began using these to stain biological tissue and researched selecting specific dyes to react with various organs, tissues and cells. Having found dyes reacted with components of blood cells, he speculated that perhaps there could be a therapeutic spinoff, namely applying dyes to kill harmful bacilli. His results in using methylene blue, to kill the malaria parasite were encouraging. Methylene blue is used to treat methemoglobinemia, a condition in which the blood loses its ability to carry oxygen through the body.
The secondary phase of Ehrlich’s work, 1891-1897, using the dye-staining technique, he formulated his side-chain theory (1897). Essentially, Ehrlich explained the interaction of antibodies in the blood and, importantly for modern immunology, how antibodies are produced. He proposed the concept of receptor-ligand bonding. This biochemical interaction at the molecular level explains how cells communicate. An example is when glucagon, a hormone secreted by the pancreas, binds to the receptor adipocyte, a fat storing cell, to produce fatty acids.
In the tertiary period of Ehrlich’s studies he was working on chemical compounds of arsenic that killed the parasites that caused sleeping sickness. It was one of those serendipity moments in science, when in 1909 Ehrlich and Sahachiro Hata, his Japanese bacteriologist assistant, found compound 606 (arsphenamine) that proved to be effective in treating the scourge of many centuries: Syphilis. And unlike other treatments it had little or no side effects. This became, of course, the trade name drug Salvarsan, and was used extensively until the discovery of penicillin in 1940.
Apart from being awarded jointly with Èlie Metchinikoff the Nobel Prize in Physiology or Medicine in 1908, Ehrlich received many other awards and tributes, a selection of which follows: he was made a full honorary professor of the University of Göttingen; in 1914 he was awarded the Cameron Prize of the University of Edinburgh; and as a lasting memorial the Institute for Serum Research and Serum Testing, originally in Berlin, was renamed Paul Ehrlich Institute in 1947. The Institute, these days located in Frankfurt, is a WHO collaborating Centre for quality assurance of blood products.
Paul Ehrlich’s research heralded what has been described as a “new era of medicine”, where standardisation of diagnoses and therapies became, to a large extent, based on the pioneering biochemical work of Ehrlich and his colleagues. Perhaps one of Ehrlich’s greatest legacies is his postulation of the future development of molecular biology and the way genetic research would help to produce pharmaceutical remedies for cancer. In recent times we have witnessed advances in oncology, where “personalised and tailored drugs” have been used with encouraging results to treat various cancers. He didn’t live to see the realisation of his hopes for the future of chemotherapy but his predicted “magic bullets” are fast becoming gold coated ones.