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. At a time when the spread of the Ebola virus is causing international
concern, it seems appropriate 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 spin off, 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 the 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 realization of his hopes for the future of
chemotherapy but his predicted “magic bullets” are fast becoming gold coated ones.