Paul Ehrlich

German biochemist and bacteriologist

• Born: March 14, 1854
• Birthplace: Strehlen, Prussia (now in Poland)
• Died: August 20, 1915
• Place of death: Bad Homburg, Germany

Ehrlich, who founded modern hematology and chemotherapy, also won a Nobel Prize for work that led to the development of a diphtheria antitoxin dosage. He also devised a method of measuring the effectiveness of serum, and he was praised for his theory of immunity and for his work in histology-produced tissue-staining techniques. He is best remembered, however, for his development of the arsenic compound number 606, which was used as a treatment of syphilis.

Early Life

Paul Ehrlich (AYR-lihk) was born at Strehlen, Prussia, the child of a prosperous Jewish family. From his father, who was an eccentric innkeeper, Paul derived his hasty manner of speech, his excitability, and his interest in natural science. His cousin Karl Weigert, who was nine years his elder, was a model to Ehrlich, and they remained friends for the rest of their lives.

Paul began his education at the age of six, when he entered the local primary school. He attended the St. Maria Magdalena Humanistic Gymnasium. For the next eight years, he boarded at the house of his form-master. Although he was proficient in Latin and mathematics, he did poorly in German composition.

After he was graduated in 1872, Ehrlich spent a disappointing semester at Breslau University before transferring to the University of Strasbourg. His tutor at the University of Strassburg was the first professor to introduce the chemical outlook into medicine. Under his supervision, Ehrlich discovered a new variety of mast cells through his staining experiments. Having passed his Physikum, Ehrlich returned to the University of Breslau, where he continued his studies in pathology and anatomy in 1874. His primary influences at this time were the pathologist Julius Cohnheim, the physiologist Rudolf Heidenhain, and the botanistFerdinand Julius Cohn. Despite the pessimistic predictions of such authorities as Robert Koch, Ehrlich passed his examinations. Ehrlich continued experimenting with dyes in Leipzig, where he continued his university studies. In 1877, Ehrlich published a paper on the properties of these dyes. This same year, he passed the state medical examinations. His doctoral dissertation was based on his first analytical studies of staining methods. Ehrlich was graduated in 1878 as a doctor of medicine.

After leaving the university, Ehrlich became assistant, and later the senior house physician, at the renowned medical clinic of the Charité Hospital in Berlin under the direction of Friedrich von Frerichs. During his term at the hospital, Ehrlich’s reputation as an expert stainer grew. Since he was also a lecturer at the university at this time, students and well-known university professors came to visit him. Eventually, Ehrlich’s discovery of tubercule bacilli through staining led to a collaboration with Robert Koch. Together with P. Grauman, he undertook the first treatment of patients with tuberculosis in the Moabit Hospital in Berlin.

In 1883, Ehrlich married Hedwig Pinkus, the daughter of a prosperous textile industrialist of Neustadt, Upper Silesia. One year later, Ehrlich was made titular professor at Berlin. His life took a turn for the worse, however, when Ehrlich’s kindly chief at the Charité Hospital, Frerichs, died. Frerichs’s successor, who did not understand the importance of Ehrlich’s research, forced him into the exhausting routine of clinical medicine. As a result, Ehrlich contracted tuberculosis and was forced to retire to Egypt for two years with his young wife until he had recovered from the disease. After receiving Koch’s newly discovered tuberculin treatment, Ehrlich never had a recurrence.

After his return from Egypt in 1889, Ehrlich established a private laboratory in Berlin, where he continued to work on his own ideas on a small scale and at his own expense. That same year, Koch offered Ehrlich a position at the newly founded Institute for Infectious Diseases, where he could conduct his research. This was the beginning of a new phase in Ehrlich’s career: the study of bacteriology. Despite his appointment as extraordinary professor at Berlin University in 1891, Ehrlich worked for Koch for three years without pay. In 1892, Ehrlich assisted Emil von Behring in developing a diphtheria serum. In 1896, Behring arranged for Ehrlich to be appointed director of the Serum Institute at Steglitz. Even though he realized that he would have to forfeit any profits made from the production of the diphtheria serum, Ehrlich was delighted by the appointment because it allowed him to spend more time on his research. The institute was housed in a disused bakery and a stable, which he used for laboratory animals. Hampered by a small budget, Ehrlich still accomplished much.

Life’s Work

Ehrlich’s supervisor was so impressed with Ehrlich’s work that he arranged for the construction of a much larger facility, the Institute for Experimental Therapy, at Frankfurt, and he appointed Ehrlich director, a position that Ehrlich held for the rest of his life. The institute had two primary functions: the control of immunotherapeutic agents, such as diphtheria antitoxin, and research and training in experimental therapy, which is the function to which Ehrlich devoted himself and his disciples. The first of Ehrlich’s activities at Frankfurt involved the development of the side-chain theory, which he expounded before the Royal Society. He described the diphtheria toxin’s two distinct attributes toxicity and antitoxin-binding powers and demonstrated how one of the two different chemical groups in the toxin molecule (the antaphore) aligns the toxin molecule to the side-chains, or receptors, thereby exposing the cell to damage. In 1901, Ehrlich digressed briefly from his chemotherapy research as the result of a grant the institute received from the Theodor Stern Foundation to finance cancer research. After successfully grafting tumors on mice, Ehrlich found that single injections of slightly virulent cell suspensions induced high degrees of immunity against transplanted tumors.

From 1906 onward, Ehrlich’s work was mainly dedicated to the study of chemotherapy, which he believed should take into account the action of appropriate artificial chemical compounds on the body cells as well as on the disease-producing parasites. His work was facilitated by the George Speyer Haus for Chemotherapy, which was built for the sole purpose of furthering Ehrlich’s chemotherapeutical research. In 1907, Ehrlich and his assistant Alfred Bertheim synthesized several hundred derivative compounds from atoxyl, an arsenic compound that had been used by H. W. Thomas and A. Reinl in 1905 to cure trypanosome-infected rodents. Lecturing before the German Chemical Society in 1908, six weeks before he was awarded the Nobel Prize in Physiology or Medicine, Ehrlich described a derivative compound of atoxyl called arsenophenylglycine. Although this compound had proved very effective in the treatment of certain treponemal diseases in test animals, it was less satisfactory in treating fowl spirillosis and human syphilis.

With the arrival of Sukehachiro Hata from Tokyo in the spring of 1909, Ehrlich’s search for a stable agent that would eradicate syphilis in human beings accelerated . After performing hundreds of experiments on infected test animals, Hata confirmed Ehrlich’s suspicion that compound number 606 (dihydroxy-diamino-arsenobenzene-dihydrochloride) worked best, even though a previous assistant of Ehrlich had determined otherwise. Ehrlich’s announcement of the invention of number 606 on April 19, 1910, at the Congress for Internal Medicine was greeted with tremendous enthusiasm. The product was patented in Germany under the name Salvarsan, and in the United States it became known as arsphenamine.

While the invention of Salvarsan brought Ehrlich worldwide acclaim, it also presented him with a multitude of problems. Soon after the announcement of his discovery at the Congress for Internal Medicine, Ehrlich was inundated with requests from doctors, clinics, and individuals for the serum. Initially, he requested that doctors pick only a small number of the most important cases on which to use the drug in the event that unforeseen consequences arose. By the end of the year, sixty-five thousand doses had been sent free of charge. He was asked to examine and give his opinion on mixtures, cures, salves, and healing ointments and to undertake such preposterous experiments as the effectiveness of petroleum in cases of cancer. There were also problems with the drug itself. If number 606 was injected improperly, the result was often necrosis at the site of the puncture. In addition, syphilis tended to recur in untreated cases. In 1912, he devised another derivative from arsenic, number 914, which was introduced for clinical use under the name of Neosalvarsan.

Nevertheless, the honors bestowed on him more than compensated for the grief he suffered. Ehrlich was renominated for the Nobel Prize in 1912 and 1913 for his contributions to chemotherapy. He also received the Liebig Medal (1911) and the Cameron Prize (1914), as well as twelve orders and five honorary doctorates. In 1914, he also became professor at the new Frankfurt University.

Ehrlich’s health declined rapidly in 1914, largely because of all the slanderous charges that were made against him. The Reichstag, forced to debate the merits of Salvarsan, had no sooner endorsed the drug than Ehrlich was called as a defense witness for the Frankfurt Hospital, when a newspaper claimed that prostitutes had been forcibly subjected to the drug. After suffering a slight stroke in 1914, Ehrlich entered a sanatorium for treatment and rest in August, 1915. He died of a second stroke on August 20 in Bad Homburg, Germany.

Significance

Ehrlich’s research established the principle that biological activities are determined by specific chemical relationships and are quantitatively measurable. His adherence to this principle resulted in the founding of two branches of medicine. First, Ehrlich founded modern hematology by developing techniques for staining the various types of blood corpuscles. He also founded modern chemotherapy through his efforts to find human-made cures for diseases, such as the diphtheria antitoxin and the compound Salvarsan, a remedy for syphilis. In addition, he produced strains of cancerous tumors that are used in experiments with cancer-fighting substances.

Bibliography

Bauer, H. “Paul Ehrlich’s Influence on Chemistry and Biochemistry.” Annals of the New York Academy of Sciences 59 (1954): 150-167. This detailed biography concentrates on the ways in which the field of medicine has advanced as a result of Ehrlich’s contributions.

Bell, Elaine, and Lucy Bird. “Autoimmunity.” Nature 435, no. 7042 (June 2, 2005): 583. Describes how Ehrlich first predicted the concept of autoimmunity and conducted experiments regarding the concept.

Browning, C. H. “Emil Behring and Paul Ehrlich: Their Contributions to Science.” Nature 175 (April, 1955): 570-575, 616-619. Concentrates on the research that Ehrlich conducted with the assistance of Behring. Explains how Behring’s approach to science complemented Ehrlich’s scientific method.

Marquardt, Martha. Paul Ehrlich. New York: Henry Schuman, 1951. Personal recollections of Ehrlich by his secretary. Biographical details are balanced by interesting anecdotes that provide insights into the personality of this eccentric scientist.

Rhodes, C. P. “Paul Ehrlich in Contemporary Science.” Bulletin of the New York Academy of Medicine 30(1954): 190-197. Short but fairly comprehensive biography. Emphasizes Ehrlich’s scientific achievements.