Hans Christian Joachim Gram

Born 1853
Died 1938

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Danish pharmacologist and pathologist, born September 13, 1853, Copenhagen; died November 14, 1938.

Biography of Hans Christian Joachim Gram

Hans Christian Joachim Gram was the son of Frederik Terkel Julius Gram, a professor of jurisprudence, and Louise Christiane Roulund. Taking up studies in the natural sciences early, Gram received a B.A. from the Copenhagen Metropolitan School in 1871 and was an assistant in botany to the zoologist Japetus Steenstrup (1873-1874). All through his life he took a deep interest in plants, an interest leading him to the foundations of the pharmacology of his time and the use of the microscope.

Gram soon developed an interest in medicine, and in 1878 he obtained his M.D. from the University of Copenhagen. In the following years he served as intern/assistant from 1878 to 1883, becoming resident physician at he Municipal Hospital of Copenhagen (Kommunehospitalet). In 1882 he received the gold medal for a university essay concerning the number and size of human erythrocytes in chlorotics. The following year he defended at Copenhagen his doctoral thesis on the size of the human erythrocytes (habilitation thesis).

From 1883 to 1885 Gram travelled in Europe, studying pharmacology and bacteriology at Strassburg, Marburg, and Berlin. He was habilitated for pharmacology at the University of Copenhagen, being Privatdozent 1886-1889. In 1891 he became lecturer of pharmacology, and later that year was appointed professor, a position he maintained with inspiring diligence until 1900. That year he retired from his chair in pharmacology in order to concentrate his efforts in medicine, being appointed ordinary professor of pathology and therapy. Already in 1892 he had become chief physician in internal medicine, department A at the Kongelige Frederiks Hospital and Rigshospitalet. He held this position until 1923, the year he retired from his chair.

Bugs of colour – or no colour
Gram’s early works concerned the study of red corpuscles in man with a particular reference to their size and health. He was one of the first to see that macrocytes are characteristic in pernicious anaemia and that there was often an increase in red cells in jaundice. The work that earned him international recognition, however, was his method for staining bacteria. In 1884, while he was working with Karl Friedländer (1847-1887) in Berlin, Gram’s method was published in Friedländer’s journal Fortschritte der Medizin.

While examining lung tissue from patients who had died of pneumonia, Gram had discovered that certain stains were preferentially taken up and retained by bacterial cells. In the first step, he dried a fluid smear on a glass slide over a burner flame and poured Gentian (crystal) violet solution over it. After a water wash, he added Lugol’s solution - potassium triiodide solution - which acted as a mordant to fix the dye if possible. Then he poured ethanol over the slide to wash away the dye. Certain bacteria (pneumococci, for example) retained the colour (gram-positive), while other species bleached (gram-negative).

A few years later, German pathologist Carl Weigert (1845-1904), director of the Senckenberg Foundation in Frankfurt, added a final step of staining with safranine. Gram himself never used counterstaining for gram-negative microbes.

The man
Gram was a very modest man and in his initial publication he stated, «I have therefore published the method, although I am aware that as yet it is very defective and imperfect; but it is hoped that also in the hands of other investigations it will turn out to be useful. After his appointment as professor of internal medicine, he published four volumes of clinical lectures which became standard reading in Denmark. He was a fine clinician whose thorough and meticulous examinations were sometimes found to be too extensive for his students’ and assistants’ liking, but the thorough clinical grounding he gave them was appreciated in their practice. Following his retirement in 1923 he lived inconspicuously until his death.

From 1902 to 1909 he published his four-volume Klinisk-therapeutiske Forelæsninger, which shows his interest in rational pharmacotherapy in clinical science.

In addition to his university post, Gram had a large private practice in internal medicine; and as chairman of the Pharmacopoeia Commission, 1901 to 1921, he cleared the field of many obsolete therapeutics. After his retirement in 1923 he resumed his former interest in the history of medicine.

Gram married Louise I. C. Lohse in 1889; she died eleven years later.

Gram was a member of Det kongelige Sundhedscollegium (Royal Health Commission) in 1893. He was made honorary member of Svenska Läkaresällskapet in 1905, Verein für Innere Medizin in 1907, and Dansk Selskab for Intern Medisin in 1932. Kristiania University, now University of Oslo, awarded him the M.D. honoris causa in 1912; and the king awarded him the Dannebrog Commander’s Cross, first-class in 1912, and the Golden Medal of Merit in 1924.

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