Paul Ehrlich’s magic bullet

Once in a while, the entertainment industry tires of making movies about comic-book characters and looks to science history to provide gripping tales of adventure – usually with fewer gun battles and explosions.

In 1940, for example, filmmakers gave us Dr Ehrlich’s Magic Bullet, a biographical film starring renowned American actor Edward G Robinson in the title role as Dr Paul Ehrlich.

The “magic bullet”, in the Hollywood telling of the story, refers to the (spoiler alert) ultimately successful quest to find a treatment for syphilis in the first decade of the 20th century. But in a broader context, the work earned Ehrlich the 1908 Nobel Prize in physiology or medicine (which he shared with Russian researcher Ilya Mechnikov) and, according to the Nobel Prize organisation’s biography of Ehrlich, made him “famous as one of the main founders of chemotherapy”.

The Nobel biography says Ehrlich’s aim was “to find chemical substances which have special affinities for pathogenic organisms, to which they would go, as antitoxins go to the toxins to which they are specifically related, and would be, as Ehrlich expressed it, ‘magic bullets’ which would go straight to the organisms at which they were aimed”.

As for Hollywood’s version of the story, a review in the New York University Langone Health academic medical centre Litmed (Literature arts medicine database) says: “Despite the slow pace and the 1940s schmaltz, students find this film informative and inspiring”.

Ehrlich was born on 14 March 1854 in Strehlen, Lower Silesia, in what is now Poland. He attended the gymnasium at Breslau, Poland, and universities in Poland, France and Germany. He earned his doctorate of medicine in 1878 and was appointed assistant to a professor at the Berlin Medical Clinic.

Some of Ehrlich’s earliest work was in the study of dyes that could be used to examine specific organs, tissues and cells. He found that certain dyes had predictable reactions with various cells, and he also tested dyes for therapeutic properties.

A 2003 paper, ‘Paul Ehrlich’s doctoral thesis: a milestone in the study of mast cells’, published in the British Journal of Haematology, noted that it was while working on his doctoral thesis, ‘Contribution to the theory and practice of histological dyes’, at Leipzig University that Ehrlich first described a type of cell, which he called “mast cells” (Mastzelle).

The British Society for Immunology says mast cells “are long-lived tissue-resident cells with an important role in many inflammatory settings, including host defence to parasitic infection and in allergic reactions.

“(They are) located at the boundaries between tissues and the external environment, for example, at mucosal surfaces of the gut and lungs, in the skin and around blood vessels. Mast cells are key players in the inflammatory response as they can be activated to release a wide variety of inflammatory mediators, by many different antigens including allergens, pathogens and physiological mediators.”

The Nobel Prize organisation says that in 1882 Ehrlich “published his method of staining the tubercle bacillus”, which brought him to the attention of Robert Koch, described by the US Centres for Disease Control and Prevention as one of the “founders of the science of bacteriology…best known for his discovery of Mycobacterium tuberculosis, the organism that causes tuberculosis”, for which he was awarded the Nobel Prize in Physiology or Medicine in 1905.

In 1890 Koch appointed Ehrlich as one of his assistants at the newly established Institute for Infectious Diseases “and Ehrlich then began the immunological studies with which his name will always be associated”, according to the Nobel Prize organisation.

In 1896 Ehrlich became director of a newly established medical research institute at Steglitz in Berlin, where he continued his work on immunology.

He demonstrated that, as with chemical reactions, the toxin-antitoxin reaction is “accelerated by heat and retarded by cold”. He also established the necessity of establishing a “fixed and invariable standard for measuring the antitoxin content of a serum”, which “formed the basis of all future standardisation of sera”.

The work led Ehrlich to formulate his “side-chain theory of immunity”.

In a separate article, the Nobel Prize organisation wrote that Ehrlich’s side-chain theory explained immunity and how antibodies were formed.

“Although we now know that some of his ideas were incorrect, this theory allowed him to accomplish important work and provided the groundwork for later researchers in this field.”

Ehrlich believed all cells had a variety of special receptors that he called side-chains, which “worked like gatekeepers or locks for the cell”. Each had a unique structure, and only substances matching this structure were allowed to enter the cell.

Their primary function was to absorb nutrients for the cell, but they also allowed toxic substances to enter. Ehrlich thought the body defended itself against these toxins by producing excess side-chains matching the toxin, which flooded the body and neutralised free toxins by attaching to them.

“The toxin was wiped out and remaining healthy cells protected.

“Ehrlich had hit upon the key concept that the body produces substances, which we today call antibodies, to help in the destruction of invaders.”

As for his “magic bullet”, Ehrlich and his team’s treatment for syphilis was made available in 1910 under the name Salvarsan. It was also known as 606, because the successful compound, the main therapeutic ingredient of which was arsenic, was the 606th tested by the researchers.

Ehrlich, who reportedly eschewed physical exercise and smoked 20 cigars a day, suffered a heart attack and died on 20 August 1915.