The Museum for the History of the University of Pavia and the Birth of Histology

A brief overview is provided on the development of histology as an independent discipline at the University of Pavia, through documents and preparations preserved in the Museum for the History of the University. Studies on the organization of tissues and cells started blooming in the mid-1850s, when morphological observations were supported by significant technical advancements in microscopy and tissue preparation. The role of Albert Koelliker, the great father of European Histology in the second half of 19 th century, is also discussed. Koelliker had several contacts with Camillo Golgi and promoted the diffusion of Golgi's discoveries. The authors also underline the innovative role of Camillo Golgi in the histological approach to research and in the foundation of modern histology.     

The discovery of the Golgi apparatus

The existence of the cell organelle which is now known as Golgi apparatus or Golgi complex, or simply as 'the Golgi", was first reported by Camillo Golgi in 1898, when he described in nerve cells an 'internal reticular apparatus' impregnated by a variant of his chromoargentic staining. It soon became clear that the newly-identified cytoplasmic structure occurred in a variety of cell types. However, the reality of the organelle was questioned for decades, until it was finally ascertained with electron microscopy. The Golgi apparatus was destined to become a protagonist of the research in cytology and cell biology pursued in the second half of the twentieth century.     

Microscopy in Camillo Golgi's times

The research by Camillo Golgi in histology and pathology dates from 1865, the year in which he obtained his MD degree, to 1923, when his last scientific article was published. Beginning in the mid 1855s, microscope manufacturers in Europe started producing objectives based on the principle of immersion introduced in 1847 by Giovan Battista Amici. The immersion objectives greatly improved the resolution of microscopic observations at high magnifications. From 1860 to 1872, technological improvements in microscope optics and the practicality of their use provided a larger community of investigators effective tools needed to study the structure of the nervous system. This progress in microscopy was associated with the application of new histological techniques, mastered by the chromoargentic reaction introduced by Golgi in 1873. In 1872, further progress in microscopy stemmed from the application of notions of applied physics to the production of microscope optics. These developments in microscopy will be briefly reviewed here.     

Microscopy in Camillo Golgi's Times

The research performed by Camillo Golgi in histology and pathology dates from 1865, the year in which he obtained his MD degree, to 1923, when his last scientific article was published. Beginning in the mid-1855s, microscope manufacturers in Europe started producing objectives based on the principle of immersion introduced in 1847 by Giovan Battista Amici. The immersion objectives greatly improved the resolution of microscopic observations at high magnifications. From 1860 to 1872, technological improvements in microscope optics and the practicality of their use provided a larger community of investigators effective tools needed to study the structure of the nervous system. This progress in microscopy was associated with the application of new histological techniques, mastered by the chromoargentic reaction introduced by Golgi in 1873. In 1872, further progress in microscopy stemmed from the application of notions of applied physics to the production of microscope optics. These developments in microscopy will be briefly reviewed here.     

Golgi,Cajal and the Neuron Doctrine

Camillo Golgi and Santiago Ramón y Cajal shared the Nobel Prize in 1906 for their work on the histology of the nerve cell, but both held diametrically opposed views about the Neuron Doctrine which emphasizes the structural, functional and developmental singularity of the nerve cell. Golgi's reticularist views remained entrenched and his work on the nervous system did not venture greatly into new territories after its original flowering, which had greater impact than is now commonly credited. Cajal, by contrast, by the time he was awarded the Nobel Prize, was already breaking new ground with a new staining technique in the field of peripheral nerve regeneration, seeing the reconstruction of a severed nerve by sprouting from the proximal stump as another manifestation of the Neuron Doctrine. Paradoxically, identical studies were going on simultaneously in Golgi's laboratory in the hands of Aldo Perroncito, but the findings did not seem to influence Golgi's thinking on the Neuron Doctrine.     

Colgi, Cajal and the Neuron Doctrine

Camillo Golgi and Santiago Ramon y Cajal shared the Nobel Prize in 1906 for their work on the histology of the nerve cell, but both held diametrically opposed views about the Neuron Doctrine which emphasizes the structural, functional and developmental singularity of the nerve cell. Golgi's reticularist views remained entrenched and his work on the nervous system did not venture greatly into new territories after its original flowering, which had greater impact than is now commonly credited. Cajal, by contrast, by the time he was awarded the Nobel Prize, was already breaking new ground with a new staining technique in the field of peripheral nerve regeneration, seeing the reconstruction of a severed nerve by sprouting from the proximal stump as another manifestation of the Neuron Doctrine. Paradoxically, identical studies were going on simultaneously in Golgi's laboratory in the hands of Aldo Perroncito, but the findings did not seem to influence Golgi's thinking on the Neuron Doctrine.     

The impossible interview with the man of the hidden biological structures. Interview by Paolo Mazzarello

This paper presents an "impossible interview" to Professor Camillo Golgi, placed in time in December 1906. The Italian Professor Golgi from Pavia has been awarded the Nobel Prize for Physiology or Medicine ex aequo with the Spanish anatomist Santiago Ramón y Cajal. Both scientists have obtained the award for their work on the anatomy of the nervous system. However, they have opposite views on the mechanisms underlying nervous functions. Golgi believes that the axons stained by his "black reaction" form a continuous anatomical or functional network along which nervous impulses propagate. Ramón y Cajal is the paladin of the neuron theory, a hypothesis questioned by Golgi in his Nobel lecture of Tuesday, December 11. After the ceremony, an independent journalist has interviewed Professor Golgi in the Grand Hotel in Stockholm. Excerpts about his education, his main scientific discoveries, and his personal life are here given (reconstructing the "impossible interview" on the basis of Golgi's original writings).     

Book Review

Gustaf Retzius (1842–1919), the Swedish anatomist and anthropologist, and Camillo Golgi were contemporaries. They met on several occasions and came in closer contact when Golgi, together with Ramón y Cajal, was awarded the Nobel Prize in Physiology or Medicine in Stockholm in 1906. Retzius came from an illustrious family. His father was professor of anatomy at Karolinska Institutet and Gustaf himself made a fast career. At 35, he was appointed to a professorship in histology, especially created for him at Karolinska Institutet, and later he became professor of anatomy in the same institution. Retzius was exceedingly productive, and published more than 300 scientific papers, most of which dealt with the nervous system and sensory organs. The majority of these were included in his magnificent volumes Biologische Untersuchungen, Neue Folge (Biological Investigations, New Series), which appeared from 1890 to 1921, and in Das Gehörorgan der Wirbelthiere (“The Acoustic Organ of Vertebrates”, 1881 and 1884), which may be his internationally better known contribution. Much of his work, especially on invertebrates, was based on Ehrlich's methylene blue method, but he also used the Golgi method early on. Particularly his studies of the innervation of the sensory organs became of great importance for the support of the neuron doctrine. His standing internationally was reflected in his membership in many of the most prominent academies abroad, as well as in invitations to him to give a “Croonian Lecture” in 1908 and “The Huxley Lecture” in 1909.     

Gustaf Retzius and Camillo Golgi

Gustaf Retzius (1842-1919), the Swedish anatomist and anthropologist, and Camillo Golgi were contemporaries. They met on several occasions and came in closer contact when Golgi, together with Ramon y Cajal, was awarded the Nobel Prize in Physiology or Medicine in Stockholm in 1906. Retzius came from an illustrious family. His father was professor of anatomy at Karolinska Institutet and Gustaf himself made a fast career. At 35, he was appointed to a professorship in histology, especially created for him at Karolinska Institutet, and later he became professor of anatomy in the same institution. Retzius was exceedingly productive, and published more than 300 scientific papers, most of which dealt with the nervous system and sensory organs. The majority of these were included in his magnificent volumes Biologische Untersuchungen, Neue Folge (Biological Investigation, New Series), which appeared from 1890 to 1921, and in Das Gehororgan der Wirbelthiere ("The Acoustic Organ of Vertebrates", 1881 and 1884), which may be his internationally better know contribution. Much of his work, especially on invertebrates, was based on Ehrlich's methylene blue method, but he also used the Golgi method early on. Particularly his studies of the innervation of the sensory organs became of great importance for the support of the neuron doctrine. His standing internationally was reflected in his membership in many of the most prominent academies abroad, as well as in invitations to him to give a "Croonian Lecture" in 1908 and "The Huxley Lecture" in 1909.     

Camillo Golgi's scientific biography

Born in Corteno, a tiny village in the province of Brescia, Camillo Golgi studied at the University of Pavia where he graduated in medicine in 1865 under the guidance of the psychiatrist Cesare Lombroso who sparked his vocation to study the brain. Golgi then began to learn histological techniques under the direction of the pathologist Giulio Bizzozero. In 1872 he moved to Abbiategrasso as chief of a hospital for chronic diseases. In a rudimentary laboratory he developed the silver-bichromate staining technique, the 'black reaction', which was a breakthrough for nervous tissue structure research. While in Abbiategrasso Golgi demonstrated the branching of the axons, and observed striatal and cortical lesions in a case of chorea. He returned to Pavia as Professor of Histology and General Pathology, and made a series of important discoveries that still bear his name: the Golgi tendon organ, the Golgi-Mazzoni corpuscles, another Golgi method to stain nerve cells based on the use of potassium dichromate and mercuric chloride, the canaliculi of the parietal cells of the gastric glands (Muller-Golgi tubules), the Golgi-Rezzonico myelin's annular apparatus (or Golgi-Rezzonico horny funnels), the cycle of malarian parasites (Golgi cycle), the relationship between recurrent malarian fever bouts and the multiplication of the Plasmodium in the blood (Golgi law), the relationship between the vascular pole of the Malpighian glomerulus and the distal tubule, the Golgi's pericellular nets and finally, and most importantly, the cytoplasmic 'internal reticular apparatus' (Golgi apparatus). In 1906 Golgi was awarded the Nobel prize for Medicine or Physiology. He died in Pavia on 21 January 1921.     

Camillo Golgi's Scientific Biography

Born in Corteno, a tiny village in the province of Brescia, Camillo Golgi studied at the University of Pavia where he graduated in medicine in 1865 under the guidance of the psychiatrist Cesare Lombroso who sparked his vocation to study the brain. Golgi then began to learn histological techniques under the direction of the pathologist Giulio Bizzozero. In 1872 he moved to Abbiategrasso as chief of a hospital for chronic diseases. In a rudimentary laboratory he developed the silver-bichromate staining technique, the ‘black reaction’, which was a breakthrough for nervous tissue structure research. While in Abbiategrasso Golgi demonstrated the branching of the axons, and observed striatal and cortical lesions in a case of chorea. He returned to Pavia as Professor of Histology and General Pathology, and made a series of important discoveries that still bear his name: the Golgi tendon organ, the Golgi-Mazzoni corpuscles, another Golgi method to stain nerve cells based on the use of potassium dichromate and mercuric chloride, the canaliculi of the parietal cells of the gastric glands (Müller-Golgi tubules), the Golgi-Rezzonico myelin's annular apparatus (or Golgi-Rezzonico horny funnels), the cycle of malarian parasites (Golgi cycle), the relationship between recurrent malarian fever bouts and the multiplication of the Plasmodium in the blood (Golgi law), the relationship between the vascular pole of the Malpighian glomerulus and the distal tubule, the Golgi's pericellular nets and finally, and most importantly, the cytoplasmic ‘internal reticular apparatus’ (Golgi apparatus). In 1906 Golgi was awarded the Nobel prize for Medicine or Physiology. He died in Pavia on 21 January 1921.     

Professor Camillo Negro’s Neuropathological Films

Camillo Negro, Professor in Neurology at the University of Torino, was a pioneer of scientific film. From 1906 to 1908, with the help of his assistant Giuseppe Roasenda and in collaboration with Roberto Omegna, one of the most experienced cinematographers in Italy, he filmed some of his patients for scientific and educational purposes. During the war years, he continued his scientific film project at the Military Hospital in Torino, filming shell-shocked soldiers. In autumn 2011, the Museo Nazionale del Cinema, in partnership with the Faculty of Neurosciences of the University of Torino, presented a new critical edition of the neuropathological films directed by Negro. The Museum’s collection also includes 16 mm footage probably filmed in 1930 by Doctor Fedele Negro, Camillo’s son. One of these films is devoted to celebrating the effects of the so-called “Bulgarian cure” on Parkinson’s disease.     

Ramón y Cajal erroneously identified as Camillo Golgi on a souvenir postage stamp

Focusing on a philatelic oddity that erringly identifies a picture of Santiago Ramón y Cajal as that of Camillo Golgi, this brief article examines official and unofficial stamp issues honoring the two great neuroanatomists, one from Spain and the other from Italy, who were early Nobel Prize winners in Physiology or Medicine.     

The Perineuronal Net: A Weapon for a Challenge

Theories and data do not always fit and sometimes are sources of conflicts among scientists. This is the case of a morphological structure, the perineuronal net, which was denied on the basis of an ideological conflict between two giants of neurosciences: Camillo Golgi and Santiago Ramón y Cajal. The perineuronal net is a reticular structure enveloping many neurons. Originally reported by Golgi in 1893 and 1898 and confirmed by several authors before the turn of the century, the perineuronal net was used by Golgi to support the reticular theory of the organization of the nervous system. Ramón y Cajal, the paladin of the neuronal theory who had also observed this anatomical structure, denied its existence suggesting that it was a fixation artifact. After Cajal's statements, only a few Italian scientists continued to work in this field, and after the 1930s the perineuronal net was forgotten. Only the recent advances in histochemical and immunocytochemical technology confirmed the existence of this structure opening new fields in functional neuroanatomy and neuropathology.     

The Golgi Stain: invention, diffusion and impact on neurosciences

The black reaction, invented in 1873 by Camillo Golgi (1843-1926, was the first technique to reveal neurons in their entirety, i.e. with all their processes. This important development passed unnoticed at first and only received wide international attention after a long delay. The Golgi stain was widely employed for almost thirty years and was directly responsible for major advances in our knowledge of the microscopic anatomy of the nervous system, as well as in other fields of study. In the hands of other researchers, the black reaction provided vital evidence that helped to establish the neuron theory. The Golgi stain was almost forgotten in the period between the two World Wars, but the introduction of the electron microscope to neurocytological resarch revived its use around the middle of the twentieth century. Today, the black reaction is still used extensively not only in combination with electron microscopy, but also as an autonomous technique in studies on the evolution, ontogeny, and organization of the nervous system.     

The perineuronal net: a weapon for a challenge

Theories and data do not always fit and sometimes are sources of conflicts among scientists. This is the case of a morphological structure, the perineuronal net, which was denied on the basis of an ideological conflict between two giants of neurosciences: Camillo Golgi and Santiago Ramon y Cajal. The perineuronal net is a reticular structure enveloping many neurons. Orginally reported by Golgi in 1893 and 1898 and confirmed by several authors before the turn of the century, the perineuronal net was used by Golgi to support the reticular theory of the organization of the nervous system. Ramon y Cajal, the paladin of the neuronal theory who had also observed this anatomical structure, denied its existence suggesting that it was a fixation artifact. After Cajal's statements, only a few Italian scientists continued to work in this field, and after the 1930s the perineuronal net was forgotten. Only the recent advances in histochemical and immunocytochemical technology confirmed the existence of this structure opening new fields in functional neuroanatomy and neuropathology.     

The Golgi Stain: Invention,Diffusion and Impact on Neurosciences

The black reaction, invented in 1873 by Camillo Golgi (1843-1926), was the first technique to reveal neurons in their entirety, i.e. with all their processes. This important development passed unnoticed at first and only received wide international attention after a long delay. The Golgi stain was widely employed for almost thirty years and was directly responsible for major advances in our knowledge of the microscopic anatomy of the nervous system, as well as in other fields of study. In the hands of other researchers, the black reaction provided vital evidence that helped to establish the neuron theory. The Golgi stain was almost forgotten in the period between the two World Wars, but the introduction of the electron microscope to neurocytological research revived its use around the middle of the twentieth century. Today, the black reaction is still used extensively not only in combination with electron microscopy, but also as an autonomous technique in studies on the evolution, ontogeny, and organization of the nervous system.