Fig. 1. Watercolor by Paul Langerhans: The island of Usedom, where the Langerhans family spent the holidays, about 1863 [9].
His father remarried 2 years after Anna’s passing, and luckily the stepmother was loved by the children. Langerhans states, in his curriculum vitae, which was written for his final examination in 1865, that his stepmother virtually replaced his real mother and the family life was happy and cheerful. His father, Paul Langerhans senior, was the son of a wealthy architect and attended the Grey Monastery (Graues Kloster), one of the most prestigious gymnasiums (the equivalent of a grammar school) in Prussia. Otto von Bismarck, the first chancellor of united Germany, attended this school at the same time. He studied medicine and the title of his dissertation was De Amputationem Artuum. He graduated in both medicine and surgery as, in 1842, the two topics still required separate specific graduations. His private praxis in Berlin was running very well. Langerhans senior participated actively in the revolution of 1848 – he was fighting on the barricades in Berlin for democracy and against the troops of the Prussian king. Together with the famous Pathologist Rudolf Virchow, in 1861 he founded the liberal party (Deutsche Fortschrittspartei). Rudolf Virchow was his best personal friend. Over the years Langerhans senior became more and more involved in politics and abandoned his work as a medical doctor. He was an elected member of the city council of Berlin and of the parliament in Prussia, and he was elected to the Reichstag from 1891 to 1903. He became honorary citizen of Berlin in 1900 and died in 1909 at the age of 89 years. As a member of the liberal party he was like Rudolf Virchow, continuously fighting against the conservative political actions of Bismarck and his successors.
Paul Langerhans often spent his holidays in Heringsdorf on the island of Usedom, and his watercolor with a view of the beach proves his talent as a painter (Fig. 1). He went to the same renowned gymnasium as his father, and had already made his decision to study medicine when he was 14 years of age. Rudolf Virchow gave advice on how he should organize his medical studies. For the preclinical studies he proposed the University of Jena. This university was at the time the leading place for critical modern research. The “German Darwin” Ernst Haeckel, was teaching there – attacked unabashedly by conservatives and particularly the Catholic Church. With his direction already planned, 2 weeks after his excellent baccalaureate, Paul Langerhans registered at the University of Jena (Fig. 2). He was the first student to register for the recently established course on human histology, by Ernst Haeckel (Fig. 3).
Fig. 2. Paul Langerhans at the age of 19 years, 1869 [9].
Fig. 3. Langerhans was the first to register for Prof. Haeckel’s lecture at the University of Jena [9].
Langerhans stayed 3 semesters in Jena and witnessed Haeckel speaking on “Darwin’s theory about the development of species.” This lecture was later followed by a nationwide, very controversial, discussion. Another lecture Langerhans attended was on the “natural history of Coelenterata.” he would subsequently go on to study the latter topic in Madeira.
For his clinical studies Langerhans moved home to Berlin, one of his teachers was Rudolf Virchow. Finally, in the summer of 1867, Langerhans began with the work on his thesis about the histology of the pancreas – a proposal of Rudolf Virchow. However, after 3 months he stopped working on this project and set another priority. The reason for this was an award by the University for the best histological research on the nerves of the skin. He submitted his work entitled: “Fiant observations microscopicae de corpusculorum tactus alterationibus pathologicis, praesertim in morbis cutis et systematis nervosa.”
On May 14, 1867, the prize committee, consisting of three professors (one of them being Rudolf Virchow) awarded the prize to Paul Langerhans. The award, a golden coin, had a value of 25 Dukaten, which represented slightly more than 80 g of 999 gold – even today, this could still be considered as a convincing motivation for students to work on a project. We will brush aside what happened to this golden coin.
A year later, Langerhans published his corresponding work “On the Nerves of the Human Skin” in Virchow’s archive [2] (Fig. 4). He believed to have described in this paper a new type of epidermal nerve cells. Using the gold chloride technique, invented by Julius Cohnheim, he detailed dendritic non-pigmentary cells in the epidermis and regarded these cells as “intraepidermal receptors for extra cutaneous signals of the nervous system.”
These cells were an enigma for dermatology for over a century before researchers recognized their immunological function. Today we know that the Langerhans cells fulfil a receptor-like function, but in a very different way than Langerhans originally thought. It was Sigmund Merkel, in 1875, who was the first to name the dendritic cells in the skin after Langerhans. However, for decades there was not much interest in these cells until the work of Inga Silberberg in the group of R.L. Baer in New York, who discovered their importance in the mechanism of allergic reactions.
Fig. 4. From the publication “About the Nerves of the Skin,” 1868 [2, 9].
Since then, a slew of publications has tried to unveil the functions of these cells which migrate throughout the body. Generally, dendritic cells take care of the capture, uptake, and processing of antigens. They play an important role in the process of infection, for example, with HIV or HPV viruses. Langerhans cells also contain langerin – a protein of importance in immune mechanisms. Langerin, on mucosal Langerhans cells of the human genital epithelium, binds to HIV-1 and subsequently internalizes it into Birbeck granules to be degraded.
After this intermission, Paul returned to work on his thesis. He described nine types of cells in the pancreas. The ninth group of cells he labeled as being small, quite homogenous cells which are located together in small groups (Zellhäufchen). At the end of the short description of these cells he stated that he has no clue about their function (Fig. 5). Initially it had been his intention to continue his work with experiments on the function of the pancreas but he found that it was technically impossible for him to study the function of the pancreas without being able to keep rabbits he was using alive, even for a while. Only 20 years later, Minkowski and von Mering managed to perform a pancreatectomy in dogs while also being able to keep them alive. It is, by the way, astonishing that nobody before Langerhans had the idea to inject vermilion or any other color into the aorta before studying the histology of the pancreas.
After his doctorate, Langerhans had no further dealings with the pancreas and the cell clusters he described went unnoticed. That was, of course, until Prof. Édouard Laguesse, in Lille, became aware of the peculiar
