PAUL EHRLICH: BIOGRAPHY, SIDE CHAIN THEORY, OTHER CONTRIBUTIONS - BIOGRAPHIES - 2024

Paul Ehrlich (1854-1915) was a renowned physician and researcher, whose works were forceful for the development of disciplines such as immunology. Ehrlich's innovative proposals highlighted the importance of infection prevention, which continues to represent a great challenge for humanity.

The theories raised by Ehrlich have been perfected and consolidated with the passage of time, achieving that branches of medicine such as chemotherapy develop widely; their works were decisive for obtaining antibiotics, antitumor drugs and cytotoxic substances.

Source: Paul Ehrlich (1915). Via Wikimedia Commons

Ehrlich was endowed with great research skills and possessed an enthusiastic and persevering personality, which allowed him to apply the scientific method to perfection and to draw the conclusions of his observations.

Biography

Personal life

Ehrlich was born in Strehlen (Poland) in the year 1854. His parents were Rosa Weigert and Ismar Ehrlich, who worked as an administrator in a lottery sales office. In 1883 he married Hedwig Pinkus and from this relationship he had two daughters: Stephanie and Marianne.

He was a teacher at the University of Berlin (1887) and worked as a doctor at the Charité hospital in the same city.

Ehrlich was a passionate and relentless worker, much loved and admired by his friends, associates, and students. However, he was not taking care of his health; In 1889 he became infected with tuberculosis, which is why he decided to travel to Egypt for a time in order to improve his situation.

However, the start of the First World War brought him down greatly, for which he suffered a mild heart attack. Plus, he was a heavy smoker, not counting the grueling drug deliveries he made to the German army during the war. All these factors affected his health and he died in 1915 as a result of a second heart attack.

Applied studies

Ehrlich studied medicine at the universities of Freiburg, Strasbourg, and Leipzig. In these institutions he developed his interest in the selectivity of tissues and cells to capture the different dyes. This led him to carry out important work and research in the area of ​​histology with these substances.

One of Ehrlich's most influential teachers was the anatomist Waldeyer (1836-1921). The teachings of this professor were forceful in the development of his doctoral thesis. In this way he obtained his doctorate in Leipzig, being the subject of the thesis experiences on staining in animal tissues.

Main research: side chain theory and other contributions

Contributions in the area of ​​hematology

Ehrlich, during his work as a doctor, managed to determine the affinity of blood cells through the dyes. He detailed the technique to fix the smears of the blood samples on glass and also specified how to color these samples once adhered to the glass.

He was a forerunner in the technique of staining tissues and certain bacteria. This he achieved through the use of methylene blue, with which he managed to color Mycobacterium tuberculosis or Koch's bacillus. This staining was later modified by German doctors Ziehl and Neelsen.

Ehrlich published his findings in 1882 and they were soon used by other researchers, becoming the basis for Gram's (1884) staining method. Additionally, his observations and staining techniques allowed Ehrlich to determine that blood was made up of cells that differed in morphology.

In this way, he classified some of the main cells of the immune system (lymphocytes and leukocytes), as well as detected the so-called accessory cells (neutrophils, mast cells, eosinophils and basophils). Likewise, he made a treatise on anemia, which was published.

Contributions in immunology

In 1890, Robert Koch (1843-1910) offered Ehrlich a position as an assistant researcher. This allowed him to begin his work on immunity.

Thanks to this, he demonstrated in his research that the human body responds to the action of substances produced by bacteria (toxins) through the production of certain elements (antitoxins).

Likewise, it showed that antitoxins are found in human serum and that the reaction between toxin and antitoxin is specific. In addition, he observed that the antitoxin concentration in the serum of the individuals was not the same and that it was influenced by variables such as temperature.

He also observed that antitoxin levels in serum are not constant, so he devised a method to normalize the exact concentration of these substances. This contribution was essential and served as a platform for all serum quantification procedures and their use in analysis and diagnostic tests.

Side chain theory

The findings mentioned above led Ehrlich to develop his theory on side chains. Today it is known that this theory corresponds to the interaction between the immunoglobulins produced by B lymphocytes and the receptors found on T cells.

This revolutionary idea raised the presence of chemical and non-biological interactions between the toxin molecule and the antitoxin. In this way, he introduced what would later become the concepts of antigen and antibody.

In addition, he raised the existence of two units in the toxin: the toxophore and the haptophore. His theory indicated that the part called toxophore (toxic part) was coupled to units that he called toxophiles (side chains) found in cells.

Ehrlich inferred that blood cells were endowed with side chains that functioned as receptors for toxins or antitoxins.

Paul Ehrlich and Sahachiro Hata. Source:

Hata Memorial Museum. Via Wikimedia Commons

The Basics of Immunochemistry

With the studies and findings on the quantification of the toxin and diphtheria antitoxin, Ehrlich was able to lay the groundwork for immunochemistry.

Later, his contributions on the phenomena of lysis, agglutination and precipitation of erythrocytes and bacteria expanded the field of action for the use of serum in the identification and differentiation of pathogenic bacteria.

Later, this knowledge was developed more widely and was not limited to bacteria. Today they are used in immunological tests that detect the existence of an antibody or an antigen in human serum.

The start of chemotherapy

In 1889, Ehrlich was hired in Frankfurt to do public health work and was given the position of director of the Institute for Experimental Therapeutics. Thanks to this position, he was able to study the chemical composition of drugs.

On the other hand, he investigated the correlation between the chemical constitution of drugs and their form of action on the cells to which they are directed. His idea was to search for substances that have specific affinity for microorganisms that cause diseases.

This was the beginning of chemotherapy, a technique that aims to attack infections through synthetic chemicals.

Furthermore, Ehrlich differentiated chemotherapy from pharmacology and divided it into three classes: organotherapy (use of hormones), bacteriotherapy (management of immunological elements), and experimental chemotherapy, which is based on the notion of selective affinity.

The experimental chemotherapy was revolutionary since it demanded to find molecules directed to the origin of the disease without harming the organism.

Treatment of syphilis

Ehrlich conducted significant research in his search for an effective therapy for the organism that causes syphilis, Treponema pallidum. He tried arsenic oxides, but these caused unexpected effects such as optical damage in patients. For this reason, he was highly criticized by his opponents and even by the Orthodox Church.

These failures led him to carry out a series of tests to test the activity of a wide variety of substances that could be used in the treatment of syphilis, but without affecting the individual.

In this way, it effected the binding of a variety of molecules from a molecule that had relevant antimicrobial activity. In this way, it was able to improve its potency, but at the same time it reduced toxicity in patients.

By modifying the way these substances were synthesized, Ehrlich obtained some solutions that implied greater safety and efficacy in the treatment of syphilis. Then he tested his hypotheses and established the conditions for the administration of the drug.

The rise of antibiotics

Ehrlich succeeded, through the incorporation of a substance in the blood of a patient, to eliminate the causative agent of the disease without harming the organism. These findings symbolized the beginning of a new stage for the therapeutic discipline.

Thanks to these experiences, medicines such as antibiotics, antitumor drugs and cytotoxic substances that are labeled with antibodies were developed.

Other contributions and concepts

The contributions of Paul Ehrlich's research are innumerable. In addition to his main findings, this scientist also managed to demonstrate the activation experienced by some substances when entering the human body, these being inactive outside the body.

Similarly, he evidenced the existence of compounds capable of controlling microbial infections without having to eliminate the pathogen, which allowed him to define the concept of biostatic molecules.

Finally, Ehrlich was able to visualize at that time the resistance of bacteria to antibiotics. Today this phenomenon is considered a serious public health problem throughout the world.

Awards and distinctions

Paul Ehrlich during his life received many recognitions and distinctions from various countries. He was part of innumerable scientific societies and was awarded in 1908 with the Nobel Prize in Physiology and Medicine for his important work in immunology.

In addition, he was awarded the Cameron Prize in Edinburgh and, in a very special way, he received the honorary recognition of Chemistry in Germany and the Congress of Medicine in Lisbon.

References

1. Villanueva-Meyer M. Paul Ehrlich (1854-1915): Visionary pioneer of hematology, chemotherapy and immunology. Retrieved on January 6, 2020 from: galenusrevista.com
2. Chuaire, L., Cediel J. (2008). Paul Ehrlich: From Magic Bullets to Chemotherapy. Retrieved on January 6, 2020 from: redalyc.org
3. Argüelles Juan-Carlos (2008). Microbes and the 1908 Nobel Prize in Medicine (Ehrlich and Mechnikov). Retrieved on January 7, 2020 from: es / analesdebiologia
4. Paul Ehrlich Biographical. Retrieved on January 7, 2020 from: nobelprize.org
5. Kay AB. (2016). Paul Ehrlich and the early history of granulocytes. Retrieved on January 7, 2020 from: nlm.nih.gov
6. PBS (1998). A Science odyssey. People and discoveries: Ehrlich finds cure for syphilis. Retrieved on January 6, 2020 from: pbs.org
7. Ruiza, M., Fernández, T., Tamaro, E. (2004). Biography of Paul Ehrlich. Retrieved on January 6, 2020 from: biografiasyvidas.com