Revisiting the 1981 Nobel Prize to Roger Sperry, David Hubel, and Torsten Wiesel on the occasion of the centennial of the Prize to Golgi and Cajal

In 1981 the Nobel Prize for Medicine or Physiology was awarded to Roger Sperry for his work on the functional specialization of the cerebral hemispheres, and to David Hubel and Torsten Wiesel for their work on information processing in the visual system. The present paper points to some important links between the work of Sperry and that of Hubel and Wiesel and to their influences on neuroscience in the best tradition going back to Cajal.     

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).     

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.     

Giuseppe Levi: mentor of three Nobel laureates

Giuseppe Levi (1872-1965), Professor of Anatomy at the University of Turin, had broad research interests and was a pioneer of in vitro studies on cultured cells. He provided a number of contributions on the nervous system, especially on the plasticity of sensory ganglion cells. An influential and magnetic teacher and mentor, he gathered around him a large group of brilliant students. He has the peculiar primate to count among his students three Nobel laureates in Physiology or Medicine: Salvador Luria, Renato Dulbecco, and Rita Levi-Montalcini. For all three of them, the internship in Levi's laboratory provided an exceptional initial stimulus. They remained in close contact with each other and with Levi even after the 1940s when they migrated to the United States for political and racial reasons, engaging in different fields of research. Rita Levi-Montalcini, who was awarded the Nobel Prize (1986) for the discovery of Nerve Growth Factor, was stimulated and assisted in her work by Giuseppe Levi during the difficult years of World War II. With Giuseppe Levi, she pursued early studies on the relationships between neural centers and their peripheral target of innervation, and she has witnessed in her writings the enthusiasm of her mentor.     

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.     

Willem Einthoven and the Development of the String Galvanometer. How an Instrument Escaped the Laboratory

In 1901 the Dutch physiologist Willem Einthoven invented the string galvanometer. It was an instrument capable of recording weak electrical pulses in the human body. He used it to investigate the human heartbeat and in 1924 was awarded the Nobel Prize for medicine or physiology for the discovery of the mechanism of the electrocardiogram. Soon after his first publication he contacted a number of Dutch and international instrument makers with a view to persuading them to produce his apparatus. The correspondence between Einthoven and these instrument makers gives us an insight into the process from prototype through to sellable instrument. It also reveals that these instrument makers had an important part to play in the earliest development of the string galvanometer on its way to becoming an electrocardiograph. The first impression that the string galvanometer made on instrument makers appears to have been an important guiding factor in the direction taken by the technological development of the apparatus. Secondary considerations such as financial and legal matters were decisive in whether or not the instrument was actually made.     

Nobel laureates at the Stazione Zoologica Anton Dohrn: phenomenology and paths to discovery in neuroscience

The practice of science usually involves more than a solitary genius in a solitary room, coping with the problem of her/his life. From the second half of the 19th century onwards, scientific research, especially in the field of the Natural Sciences, has grown into a more and more complex practice, which often entangles very special needs, in terms of research objects, techniques, sources, and perspectives. A few special places, such as the Stazione Zoologica di Napoli, have represented in this period the focal points of an ever growing international scientific network, promoting independent research, exchange and diffusion of novel practices and techniques and unrestricted confrontation. The so-called "Naples experience" has been cited by a large number of renowned scientists of the last two centuries as a key moment in their scientific life. Here we have tried to test it against the experience of three great scientists par excellence, i.e. three Nobel laureates (T. H. Morgan, Otto Warburg, J. D. Watson). The different experiences they have had at Naples represent, in our view, three different moments of the professional life of almost every scientist. Therefore, we have chosen to present them as a phenomenology. The final section is dedicated to a survey of the Zoological Station's contribution to neurosciences, especially to the Naples experience of the Nobel Prize winner Sir Bernard Katz and his assistant Ricardo Miledi, between 1965 and 1970. Their work on the squid at Naples allowed probing and quantitative refinement of results already obtained on different animals and contributed to reinforce the long lasting neurophysiological tradition of the institute.     

Are the Economies of Canada and the United States Integrated? Evidence from Cointegration Analysis

In recognition of his contributions to the development of the method of cointegration analysis for analyzing nonstationary time series, late Sir Clive William John Granger (September 4, 1934–May 27, 2009) was awarded the Nobel Memorial Prize in Economic Sciences in 2003. Since then, this method has become a dominant paradigm in empirical economic research. However, this method is not without critics. This article is one in a series to point out some inconsistent arguments used in the development of the method of cointegration analysis. To illustrate by example, we apply the method of time series cointegration analysis and present statistical evidence that supports the proposition that the economies of Canada and the United States are integrated. We conclude this article by laying out a foundation to formally criticize the method of cointegration analysis in subsequent research.     

The 1932 and 1944 Nobel Prizes in physiology or medicine: rewards for ground-breaking studies in neurophysiology

In 1932 Sherrington and Adrian were awarded the Nobel Prize in Physiology or Medicine "for their discoveries regarding the functions of neurons" and in 1944 Erlanger and Gasser were awarded the same prize "for their discoveries relating to the highly differentiated functions of single nerve fibres." Sherrington made important discoveries on the reflex functions of the spinal cord, formulated the concept of the "synapse," defined the principle of the "final common path," studied "reciprocal innervation" and showed that central inhibition was an active phenomenon. He distinguished three types of receptors: extero-, intero-, and proprioceptive, studied the proprioceptive reflexes in the decerebrate animal and mapped their pathways in the spinal cord. Adrian made fundamental discoveries on the function of single nerve fibers, developed new techniques for the amplification of the weak signals and discovered that increased stimulation resulted in increased frequency of the impulses, the amplitude being unaffected. Erlanger and Gasser introduced the cathode-ray oscillograph and demonstrated the existence of three main groups of nerve fibers, A, B, and C, the conduction velocities of which were in approximately linear relationship with the fiber diameter, the A-fibers being the fastest and thickest and the C-fibers the slowest and having the finest diameter. Together the contributions by the four Laureates paved the way to modern neurophysiology.     

The impossible interview with the man of the neuron doctrine. Interview by Edward G Jones

This paper follows the form of that by Mazzarello that precedes it (Mazzarello, 2006) and presents an imaginary interview with Santiago Ramón y Cajal in December 1906. A few days earlier Cajal had been awarded the Nobel Prize for Physiology or Medicine, an award that he shared equally with Professor Camillo Golgi. Golgi had been recognized for his work as a pioneer into investigations of the nervous system, primarily on account of his discovery of the "black reaction" of silver chromate impregnation of whole nerve cells and their processes. Cajal had been recognized for his implementation of that method and for laying with it the foundations of what was to become modern neuroanatomical science. Paradoxically, the two awardees had been led by their researches to diametrically opposed views of the organization of the nervous system. Golgi believed in a continuous network of axons that formed the basis of all the integrative properties of the nervous system, while Cajal had provided the information that led to the formulation of the neuron doctrine that saw the nervous system as being made up of chains of discontinuous cells joined by polarized functional contacts that we now call synapses. The paper takes the form of an interview with Professor Cajal in the Grand Hotel Stockholm. His responses to questions posed by the imaginary interviewer are all taken from Cajal's own writings.     

Nikolai V. Konovalov (1900-1966): his role in the development of neurology and the creation of the Institute of Neurology of the Russian Academy of Medical Sciences

Nikolai V. Konovalov (1900-1966) has left a significant imprint in the history of Russian neuroscience. He was among the coryphaei of international and national neurology. Along with the large number of fundamental scientific papers that have determined several aspects of the development of neuroscience, his contribution has been equally important to the establishment and development of one of the distinguished Russian scientific centers - the Institute of Neurology of the Russian Academy of Medical Sciences, which he headed from 1948 until 1966.     

Pearl S. Buck and phenylketonuria (PKU)

In 1921, Pearl S. Buck gave birth to a daughter, Carol, who became severely retarded and was eventually institutionalized at the Vineland Training School in New Jersey. To help pay for her daughter's care, Buck wrote The Good Earth in 1931, and then other novels and biographies about her life in China, for which she was awarded the Nobel and Pulitzer Prizes, and honored around the world. Years later, she published The Child Who Never Grew, a short piece about her daughter's retardation that also revealed her desperate search for answers and good clinical care. Asbj?rn F?lling distinguished phenylketonuria (PKU) from other forms of childhood retardation in the mid-1930s, and new assays and biochemical findings eventually led to ways to circumvent the devastating effects of PKU. But for Carol Buck, these advances came too late. It was not until the 1960s that physicians confirmed that her severe retardation was caused by PKU.     

Born of fire: The pursuit of the ‘white gold’

For more than 300 years, scores of historians and researchers have vigorously argued about the question who might have been the genuine inventor of European porcelain of Meissen fame: Johann Friedrich Böttger or Ehrenfried Walther von Tschirnhaus. Although the story of the invention of porcelain has been told countless times, the exact circumstances of its discovery are still shrouded in mystery. For a very long time the palm has been awarded to Böttger, but today, the scale is increasingly tilting toward Tschirnhaus. In this contribution, ancient letters and laboratory notes, and modern phase diagrams and microstructural investigation are being used to paint a picture of royal desire, efficient research organization, arduous labor, ingenious reasoning, but also treason, camouflage, bald lies, and perfidy.     

Rebelles with a Cause: Women in the Haitian War of Independence, 1802–04

This article studies the role of white, black and mulatto women during the last two years of the Haitian War of Independence, also known as the Haitian Revolution (1802–04). It might be expected that women's contribution was limited in wartime, but this article concludes otherwise. Desirable women were sought as prizes symbolic of a man's status in colonial society, or actively used their appeal to obtain political favours. Women of colour contributed to the rebellion in the fields of logistics, espionage and even combat. They also experienced martyrdom when convicted of aiding the rebel army. White women, in turn, were considered such an integral part of the colonial order that the rebels, led by Toussaint Louverture and Jean‐Jacques Dessalines, targeted them, as well as other civilians, during the fighting, then proceeded to exterminate all surviving whites after the rebel victory.     

The Neurophysiological Aspects of Pavlov’s Theory of Higher Nervous Activity: In Honor of the 150th Anniversary of Pavlov’s Birth

Whereas Ivan P. Pavlov (1849-1936) is well-known for his work on classical conditioning, his contribution to neuroscience, particularly his interest in the function of neural centers in the central nervous system, is not as widely known. During the last three decades of his life, Pavlov explored cortical processes by salivary reflex conditioning, a method he used to develop his theory of higher nervous activity. This theory outlined the function of the brain in higher organisms in their interaction with the changing environmental contingencies. As early as 1908, Pavlov outlined a neurophysiological theory as the physiological basis of his theory of higher nervous activity. He maintained that the neural processes of excitation and inhibition irradiate and concentrate among the cortical neural centers. Most of all, he emphasized the plasticity of the cortex in higher organisms’ in the Darwinian struggle for existence.     

Cajal's views on the Nobel Prize for physiology and medicine (October 1904)

In this report we present and discuss an unpublished letter written by Santiago Ramon y Cajal in October 1904 in relation to his possible nomination for the Nobel Prize for Physiology and Medicine. This letter shows that Cajal was aware of his previous nominations for the Prize. He was convinced that these nominations had not been successful because neither anatomy nor histology were among the sciences included in the Nobel Statutes' definition of Physiology or Medicine. He gives a list of the merits he thought might be used for a new nomination, which included only works concluded during the previous five years.     

The neurophysiological aspects of Pavlov's theory of higher nervous activity: in honor of the 150th anniversary of Pavlov's birth

Whereas Ivan P. Pavlov (1849-1936) is well-known for his work on classical conditioning, his contribution to neuroscience, particularly his interest in the function of neural centers in the central nervous system, is not as widely known. During the last three decades of his life, Pavlov explored cortical processes by salivary reflex conditioning, a method he used to develop his theory of higher nervous activity. This theory outlined the function of the brain in higher organisms in their interaction with the changing environmental contingencies. As early as 1908, Pavlov outlined a neurophysiological theory as the physiological basis of his theory of higher nervous activity. He maintained that the neural processes of excitation and inhibition irradiate and concentrate among the cortical neural centers. Most of all, he emphasized the plasticity of the cortex in higher organisms' in the Darwinian struggle for existence.     

Cajal's Views on the Nobel Prize for Physiology and Medicine (October 1904)

In this report we present and discuss an unpublished letter written by Santiago Ramón y Cajal in October 1904 in relation to his possible nomination for the Nobel Prize for Physiology and Medicine. This letter shows that Cajal was aware of his previous nominations for the Prize. He was convinced that these nominations had not been successful because neither anatomy nor histology were among the sciences included in the Nobel Statutes' definition of Physiology or Medicine. He gives a list of the merits he thought might be used for a new nomination, which included only works concluded during the previous five years.