Paul Langerhans 1847-1888Joseph H. Barach, M.D.

PITTSBURGH. PENNSYLVANIA

Time and history weave patterns with seemingly un-related facts, as the weaver of a Persian rug blends variedthreads through his loom to produce a design of agelessbeauty. So it is with the facts of medical knowledge.Gathered and contributed by many workers, they mayseem inconclusive or even insignificant at the time oftheir publication. But when they have been properlyassembled and wisely interpreted, they, too, make pat-terns — of knowledge, if not of beauty. Such are thematerials of scientific achievement in medical history.

Today, every medical student the world over knows ofthe islets of Langerhans. Their textbooks tell them thatthe islets of Langerhans are cellular structures withinthe pancreas, and that these structures have an impor-tant relationship to diabetes. But very few know any-thing about Paul Langerhans; who he was, when andwhere he lived, and how he made his discoveries. Thename of Langerhans has already endured in medicine for85 years, and it will undoubtedly be preserved in medicalannals for centuries to come.

The most complete source of biographical informationon Paul Langerhans is an essay by Morrison,1 whose in-terest in Langerhans was motivated by a search for out-standing contribution to medicine made by men still intheir undergraduate years. This was an interesting ap-proach to the biography of a man, and it should be ofparticular interest to members of the American DiabetesAssociation.

Paul Langerhans, working in Virchow's laboratory atthe Berlin Pathological Institute, began the study ofanatomy of the pancreas in 1867 and reported his find-ings in 1869. A similar instance of medical discovery byan undergraduate student of medicine occurred on thiscontinent within our own lifetime. At the University ofToronto, a graduate student in physiology while still anundergraduate student of medicine, working with Dr.Frederick Banting in 1921-1922 became the co-discov-erer of insulin. His name is Charles Best. Never under-estimate the powers of a medical student! That is some-thing for oldsters to keep in mind, as we tread the

corridors of our schools of medicine.Paul Langerhans was born in Berlin on July 25, 1847.

His father, Dr. Paul Langerhans, was a physician; hismother (nee Keibel) was a cousin of Franz Keibel, theeminent histologist. One brother, Robert Langerhans, anassistant to Virchow, was professor of pathology andanother brother, Richard Langerhans, was an honoredpractitioner of medicine in Berlin. As a student in Jena,Paul was the pupil of Ernst Haeckel, his "adored teacher."Later in Berlin, Paul was influenced particularly by JuliusCohnheim and Rudolf Virchow, with both of whom hehad developed close friendships. In all of this we see whatcan happen when good seed is planted in good soil, andwhen a good inheritance finds a good environment.

In the time of Langerhans, Claude Bernard had alreadydemonstrated that the pancreas played an important rolein the digestion and assimilation of carbohydrate, proteinand fat. At that time the pancreas was simply describedas a racemose gland, containing a mass of infiltrating fat.The adjective racemose was applied in a purely morpho-logic sense, intended to convey the picture of a racemeplant in which the flowers are attached to short stalkswhich spring from the main stem, like the flowers of thelily-of-the-valley. This description is quite applicable tothe appearance of the glands of external secretion of thepancreas, but unfortunately it revealed little more thanthat.

Of the existing knowledge pertaining to physiology ofthe pancreas at that time, Langerhans said, "There is in-deed hardly another organ in which there is such glaringcontrast between the brilliant results of physiologic re-search and the complete darkness in the realm of anato-mic knowledge. Practically all that receives any thoroughconsideration from the anatomic point of view is therelationship of this gland to the peritoneum or whetherthe opening of this or that excretory duct is at a higheror lower level."

Langerhans' early observations were made on the rab-bit; later he studied the salamander, guinea pig, dog, cat,pigeon, snake, frog, hen, as well as man. He studied the

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JOSEPH H. BARACH, M.D.

fresh and fixed state of pancreatic tissue, fragmenting thetissues into minute particles for microscopic study. Aftermaceration of pancreatic tissue he differentiated ninedifferent types of cells. Of these, one type in particularpuzzled him greatly. "This cell," he said, "is a small ir-regularly polygonal structure, with brilliant cytoplasm;free of any granules with distinct round nuclei of moder-ate size. These cells lie together in considerable numbers,diffusely scattered in the parenchyma of the gland."Langerhans said he did not know the nature of the cells,and he felt that the best that he could do at the timewas simply to call attention to them as deserving of se-rious study.

Later, observers found these cells present in the pan-creas of all vertebrates. Twenty-four years later, Laguesse,a French histologist, noted these clusters of cells in thehuman pancreas, identified them as the ones already de-scribed by Langerhans, and called them "the islets ofLangerhans." Laguesse expressed his opinion that thesecells were the seat of an internal secretion of the pan-creas.

Between the time of Langerhans' observations in 1869and those of Laguesse in 1893 Kiihne and Lea in 1882demonstrated an intimate relationship between these cellsand the capillaries and nerves of the pancreas. And thenDogiel in 1893 further showed that there was no con-nection between these cells and the duct system of thepancreas.

During the year 1870 Paul Langerhans travelledthrough Northern Africa and Asia Minor. He wroteletters home to Virchow, commenting on leprosy, on theskull measurements of bedouin and fellahin, and he com-mented in general on the backward state of medicine inthe near east, as he saw it in the city of Jerusalem andelsewhere. Toward the end of that year, Langerhans re-turned to Germany. The Franco-Prussian War was rag-ing, and he took clinical service in a Berlin hospital andambulance service at the front.

After the war he worked with the famous Carl Crede,director of the obstetric and gynecologic wards at theCharite Hospital in Leipsig. Crede's name became widelyknown in connection with silver ointment. There Langer-hans engaged in research and teaching for four years; hispublications on the histology of the heart, genital organsand other subjects appeared in Virchow's Archives.

Following that period he was elected to full professor-ship. Unfortunately he had to give up this position be-cause of active tuberculosis. To regain his health hemoved to the island of Madeira, hoping for a cure. Therehe continued his research in zoology. He recovered suf-ficiently while on Madeira to resume the practice ofmedicine.

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In 1885 he married Margarethe Ebart with whom,as he said, he enjoyed three years of complete happiness.In 1888, following a systemic infection, he developed aserious kidney complication and on July 20th of thatyear, at the age of 41, he died—and was buried inMadeira. Thus ended the career of a young man whohad made a brilliant and valuable contribution to med-icine and to human welfare.

As we know, medical discovery in any field does notbegin or end with one man. In the year after Paul Lan-gerhans' death, von Mering and Minkowski reported theappearance of diabetes after experimental pancreatec-tomy. In 1901 the paper by Opie in which he describedchanges in the islets of Langerhans furnished evidence ofthe association of these structures with carbohydrate me-tabolism.2 In a personal letter to me written February22,1952, Opie made the following interesting comment:"When I was a second-year medical student in pathology,I found a body queer to me in a cross section of thepancreas and asked Dr. Welch what it was. Welch toldme that these structures had been described by Langer-hans in an inaugural dissertation,3 and added; 'Find outall you can about them."Here was another medical studentat work! Today we have a full appreciation of the valueof Opie's contribution to the subject. His book on the

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PAUL LANGERHANS

pancreas was a byword in the medical world for manydecades.

One of the anatomists to make classical contributionsconcerning the structure of the pancreas was our con-temporary, Professor Richard R. Bensley. Bensley clari-fied to a large extent the relation of the islets of Langer-hans to the ducts of the pancreas, the independence ofthe islets from acinar tissue, and the cell types in theislets. It has been said that Banting expressed great ap-preciation of the work described in Bensley's HarveyLecture on the pancreas. In personal letters recently re-ceived from Russell M. Wilder and from Charles H.Best, both paid further tribute to Bensley. As I write,Professor Bensley has reached his eighty-fourth year, solet us honor the octogenarians in medicine as well as

the medical students.There are many more links in the chain of medical

history that binds the period of Langerhans and theperiod of Best. Only a few of them could be mentionedin this brief sketch of the life of Paul Langerhans, butthese few that I have noted are basic. They will stand forall time, linking the past with the present, and the futurethat is to come.

REFERENCES1Morrison, H.: Paul Langerhans; Contributions to the Micro-scopic Anatomy of the Pancreas (Berlin 1869). Bull. Hist. Med.5: Mar. 1937.2Houssay, B.A.: The Discovery of Pancreatic Diabetes. Diabetes1:112-16, March-April 1952.3Langerhans, Paul: Inaugural Dissertation, Univ. of Berlin1869.

BOOK REVIEWDIABETES AND PREGNANCY. Blood Sugar of Newborn

Infants during Fasting and Glucose Administration. ByJorgen Pedersen, M.D. No Price indicated. Paper. Pp.230. Illustrated. Danish Science Press Ltd. Copenhagen,1952.

This monograph presents a detailed summary of exten-sive and well-planned studies done in a lying-in hospital,Copenhagen, Denmark. It deals with carbohydrate met-abolism during pregnancy in diabetic and nondiabeticwomen and with carbohydrate metabolism in their in-fants. The first chapter reviews current knowledge ofcarbohydrate metabolism in mammalian fetuses andnewborn young. Subsequent chapters present an exten-sive review of previous investigations regarding carbo-hydrate metabolism in infants of nondiabetic and dia-betic mothers, maternal blood sugar and blood sugarof infants of diabetic and nondiabetic mothers at birth,in the first 24 hours of life and during later neonatalperiods, and to theories previously advanced regardinghomeostatic mechanisms of control.

The writer's own investigations are summarized inchapters dealing with blood sugar levels in the mothers,with regard to duration and treatment of their diabetes(including complications), blood sugar levels in theinfants of diabetic and nondiabetic mothers in the first24 hours and later neonatal periods, in relation to sex,birth, weight, gestation time, maternal anesthesia, cyano-sis at birth and after, maternal insulin dosage, responsesto oral glucose tolerance tests.

Some salient findings emphasized in the author's sum-

mary are as follows: 1. During the first 24 hours of life,the course of the blood sugar curve was, in general, thesame in infants of diabetic and nondiabetic motherswhen the infants were kept under standard conditions;2. Infants of diabetic as well as nondiabetic motherswithstood fasting 24 hours without exhibiting anyconstant decrease in blood sugar; 3. During the first24 hours, there was a negative correlation betweenthe mean blood sugar of the infant and the maternalmean blood sugar during the latter months of preg-nancy; 4. The infants blood sugar varied also withthe birth weight; this correlation being negativeamong the infants of diabetic and positive amongthose of nondiabetic mothers; 5. The mean blood sugarwas subject to wide variations, in infants of both diabeticand nondiabetic mothers; 6. No correlation was foundbetween symptons, such as cyanosis during the neonatalperiod and the infants' blood sugar; 7. Oral glucosetolerance tests during the first eight days of life werevariable in both infants of diabetic and of nondiabeticmothers.

In a final chapter the writer discusses hypotheses re-garding blood sugar regulations in newborn infants,including the homeostatic liver mechanism, withoutstating very definite conclusions but supporting as plau-sible the old hypothesis that maternal hyperglycemia inthe pregnant diabetic may lead to fetal islet cell hyper-trophy. An excellent bibliography includes 188 refer-ences.

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