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 islands in the pancreas again. It is, in itself, curious that Laguesse even had knowledge of Langerhans’ doctoral thesis. Only 150 copies were ever printed and the vast majority of them were to be found in German Universities. Today, only very few copies have survived; Björn Hausen found only 8 original copies worldwide.
At a meeting of the biological society in Paris in 1893, Laguesse reported on the peculiar structures in the pancreas and called them ilôts de Langerhans [1, 3]. Laguesse had already previously expressed the hypothesis that there were two forms of diabetes and that one of these had something to do with the pancreas.
It is very surprising that the doctoral thesis does not contain a single drawing – in contrast to the publication on the Langerhans cells of the skin. Paul was by no means lacking a talent for drawing. He was a very capable draughtsman and painter, a talent he shared with another renowned discoverer in diabetology, Frederik Banting.
However, Paul’s “godfather” Rudolf Virchow must not have been entirely satisfied with the thesis. The grade given for this doctoral thesis was moderate, although the work is dedicated to him “in reverence and gratitude.” Also, in his rigorosum Paul receives the worst grade of the three evaluating professors from Prof. Virchow – sufficient.
On March 18 Paul Langerhans received his certificate of passing the medical examination. Initially he continued to work in Prof. Virchow’s laboratory together with his lifelong best friend Friedrich Albin Hoffmann. Hoffmann wrote in his autobiography about Langerhans: “His winning nature and his great diligence made him very pleasant to me. We had lunch together at Töpfer’s hotel (just in front of the Charité hospital in Karlsr. 7), discussed what we were working on and what interesting sections Virchow had. Soon he took me with him to his parents’ house, where his father, his stepmother and his sister were most kind to me. I soon felt very comfortable in this entourage.” We also know from Hoffmann that Paul did not belong to any student fraternity, which was extremely unusual in German academic circles in the 19th century where it was practically obligatory.
Fig. 5. The thesis of Paul Langerhans with the description of the islets, 1869 [10].
Research trips to far-flung places were very popular with academicians at the time. Flora, fauna, and all manner of ethnological pieces were brought to Europe, researched, and exhibited. Langerhans also partook in such travels, probably to follow in the footsteps of Haeckel and Virchow. Fortunately for him he had a wealthy sponsor, namely his beloved grandmother, and, on February 18, 1870, he too set off on a voyage of research, to the Near East. Beforehand, in preparation for his upcoming journey, Langerhans wrote to Prof. Ernst Haeckel in Jena:
Highly respected gentleman!
On February 18 I intend to accompany the geographer Professor Kiepert on a five-month journey to Lower Egypt, Palestine, Syria and Istanbul. I would be very pleased if this itinerary and my, despite your efforts in this subject, only rudimentary knowledge combined with good will quantum satis were sufficient to carry out any zoological or similar order from you and I therefore ask you to write to me, if you have such an order.
With warm greetings from my father,
Your grateful pupil,
Paul Langerhans.
Prof. Kiepert and Langerhans