Fritz Köberle
Encyclopedia
Fritz Köberle was an Austrian-Brazilian physician
, pathologist and scientist
, discoverer of the neurogenic mechanism of the chronic phase of Chagas disease
, a human parasitic disease caused by Trypanosoma cruzi
, a protozoan.
, Austria
, and studied medicine
at the University of Vienna
, Austria, graduating magna cum laude in 1934. He began to work in the Institute of Pathology while a student and soon after graduation, in 1935, he was admitted as an assistant professor. With the annexation of Austria to Germany
(Anschluss
) by Adolf Hitler
, Köberle was drafted into the Army as a medical lieutenant and worked as a pathologist in the Central Army Hospital of Vienna. With the outbreak of the Second World War hostilities, Köberle was attached as field pathologist to the XII Army Group of the Wehrmacht
in 1940 and served in the fronts of France
, Belgium
, Poland
and Russia
. He was able to acquire during this period an enormous experience on the pathology of infectious diseases (bacterial dysentery
, typhus
, typhoid fever
, tularemia
and malaria
) as well as war-inflicted wounds, and performing more than four thousand autopsies
. After the war, Köberle returned to the University of Münster
as Privatdozent
, continuing his activities as professor and researcher of medical pathology until 1945. He returned shortly to the University of Vienna, and, in 1946, accepted a post as director of the Serological and Pathological Institute of the General Hospital of St. Pölten
, Lower Austria.
In 1952, he received an invitation which would radically change his personal and scientific life. A new medical school
was being established by the University of São Paulo
in the little-known city of Ribeirão Preto
, in the hinterland of the state of São Paulo
, Brazil
. The main objective of the state government was to increase the number of physicians in the rapidly developing hinterland, and its first dean, Dr. Zeferino Vaz
, a parasitologist
, medical research and professor of the University, wished to create a favorable environment for high quality medical research and teaching
in the new school. With this in mind, Vaz invited a number of foreign researchers to become chairmen of the basic and clinical departments, and Fritz Köberle had a good recommendation by Prof. Henrique da Rocha Lima
, a Brazilian medical researcher who had studied in Germany. Dr. Köberle accepted an invitation and moved with his family to the Medical School of Ribeirão Preto
in 1953. He soon organized the Department of Pathology, became its chairman, and began to assemble a small group of Brazilian researchers.
, or American trypanosomiasis, which had been discovered by another Brazilian physician named Carlos Chagas
, in 1910 (coincidentally, the year he was born). Even though 40 years had passed since its discovery, little was known about the peculiar manifestations of the chronic
phase of the disease, such as megaesophagus
, megacolon
, cardiomegaly
, heart ventricular aneurysm
, achalasia
, etc., and the mechanism of the causation of these several pathologies. By making good use of the extensive caseload of fatalities due to Chagas disease in the region of Ribeirão Preto and Southern Minas Gerais
, where it was endemic and widely prevalent at the time, Köberle studied initially the dilation pathologies of the digestive tract and proved, by extensively quantifying the number of neurons of the autonomic nervous system
in the Auerbach's plexus
, that: 1) they were strongly reduced all over the digestive tract; 2) that megacolon and megaesophagus appeared only when there was a reduction of over 80% and 55% of the number of neurons, respectively; 3) these pathologies appeared as a result of the disruption of the neurally integrated control of peristalsis
(muscular annular contraction) in those parts where a strong force is necessary to impel the luminal bolus
of food or feces
; and 4) European idiopathic
megaesophagus
and Chagas megaesophagus appeared to have the same etiology
, namely the degeneration
of the Auerbach's myoenteric plexus.
Studying the typical features of the Chagasic myocardium pathology, characterized by damage to its electrical conduction pathways, heart arrythmia, aneurysm
of the ventricular apex, cardiomegalia and sudden death by ventricular fibrillation
, Köberle and his group of collaborators were able to prove that they were caused also by an extensive denervation of the parasympathetic (55% and sympathetic
(35%) intrinsic cardiac nervous networks, leading to a control imbalance of contraction, cardiac failure, cardiomegalia and hypoxia
. He named this constellation of effects as cardiopathia parasympathicopriva. Other less typical phenomena observed in Chagas disease, such as bronchiectasis
and myelopathy
were also studied by Köberle under the new prism of his neurogenic theory.
Thus, with his classical and detailed scientific studies, Köberle proposed for the first time a unified and radically different (and polemical) view of the etiopathogeny of Chagas disease, characterizing it as a disease of the autonomic nervous system, which establishes itself during the acute phase and provokes long term and slowly installing denervation. Since the trypanosoma does not seem to damage neurons directly, Köberle and other researchers have hypothesized the action of a neurotoxin
, cytotoxic factors or autoimmune mechanisms.
Dr. Köberle retired from the University of São Paulo in 1976, but soon moved as visiting professor to the Medical School, of the State University of Campinas, in Campinas
, São Paulo, where one of his sons, Gottfried Köberle, is a professor of Orthopedics
. He worked there until his death, in 1983, in Americana
. Another son, Roland Köberle, is a professor in Physics
at the University of São Paulo at São Carlos
.
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
, pathologist and scientist
Scientist
A scientist in a broad sense is one engaging in a systematic activity to acquire knowledge. In a more restricted sense, a scientist is an individual who uses the scientific method. The person may be an expert in one or more areas of science. This article focuses on the more restricted use of the word...
, discoverer of the neurogenic mechanism of the chronic phase of Chagas disease
Chagas disease
Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking insects of the subfamily Triatominae most commonly species belonging to the Triatoma, Rhodnius,...
, a human parasitic disease caused by Trypanosoma cruzi
Trypanosoma cruzi
Trypanosoma cruzi is a species of parasitic euglenoid trypanosomes. This species causes the trypanosomiasis diseases in humans and animals in America...
, a protozoan.
Life
Fritz Köberle was born in EichgrabenEichgraben
Eichgraben is a town in the district of Sankt Pölten-Land in the Austrian state of Lower Austria....
, Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
, and studied medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
at the University of Vienna
University of Vienna
The University of Vienna is a public university located in Vienna, Austria. It was founded by Duke Rudolph IV in 1365 and is the oldest university in the German-speaking world...
, Austria, graduating magna cum laude in 1934. He began to work in the Institute of Pathology while a student and soon after graduation, in 1935, he was admitted as an assistant professor. With the annexation of Austria to Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
(Anschluss
Anschluss
The Anschluss , also known as the ', was the occupation and annexation of Austria into Nazi Germany in 1938....
) by Adolf Hitler
Adolf Hitler
Adolf Hitler was an Austrian-born German politician and the leader of the National Socialist German Workers Party , commonly referred to as the Nazi Party). He was Chancellor of Germany from 1933 to 1945, and head of state from 1934 to 1945...
, Köberle was drafted into the Army as a medical lieutenant and worked as a pathologist in the Central Army Hospital of Vienna. With the outbreak of the Second World War hostilities, Köberle was attached as field pathologist to the XII Army Group of the Wehrmacht
Wehrmacht
The Wehrmacht – from , to defend and , the might/power) were the unified armed forces of Nazi Germany from 1935 to 1945. It consisted of the Heer , the Kriegsmarine and the Luftwaffe .-Origin and use of the term:...
in 1940 and served in the fronts of France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, Belgium
Belgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
, Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
and Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
. He was able to acquire during this period an enormous experience on the pathology of infectious diseases (bacterial dysentery
Dysentery
Dysentery is an inflammatory disorder of the intestine, especially of the colon, that results in severe diarrhea containing mucus and/or blood in the faeces with fever and abdominal pain. If left untreated, dysentery can be fatal.There are differences between dysentery and normal bloody diarrhoea...
, typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
, typhoid fever
Typhoid fever
Typhoid fever, also known as Typhoid, is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica, serovar Typhi...
, tularemia
Tularemia
Tularemia is a serious infectious disease caused by the bacterium Francisella tularensis. A Gram-negative, nonmotile coccobacillus, the bacterium has several subspecies with varying degrees of virulence. The most important of those is F...
and malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
) as well as war-inflicted wounds, and performing more than four thousand autopsies
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
. After the war, Köberle returned to the University of Münster
University of Münster
The University of Münster is a public university located in the city of Münster, North Rhine-Westphalia in Germany. The WWU is part of the Deutsche Forschungsgemeinschaft, a society of Germany's leading research universities...
as Privatdozent
Privatdozent
Privatdozent or Private lecturer is a title conferred in some European university systems, especially in German-speaking countries, for someone who pursues an academic career and holds all formal qualifications to become a tenured university professor...
, continuing his activities as professor and researcher of medical pathology until 1945. He returned shortly to the University of Vienna, and, in 1946, accepted a post as director of the Serological and Pathological Institute of the General Hospital of St. Pölten
Sankt Pölten
Sankt Pölten is the capital city of the State of Lower Austria in northeast Austria. With inhabitants , it is Lower Austria's largest city...
, Lower Austria.
In 1952, he received an invitation which would radically change his personal and scientific life. A new medical school
Medical school
A medical school is a tertiary educational institution—or part of such an institution—that teaches medicine. Degree programs offered at medical schools often include Doctor of Osteopathic Medicine, Bachelor/Doctor of Medicine, Doctor of Philosophy, master's degree, or other post-secondary...
was being established by the University of São Paulo
University of São Paulo
Universidade de São Paulo is a public university in the Brazilian state of São Paulo. It is the largest Brazilian university and one of the country's most prestigious...
in the little-known city of Ribeirão Preto
Ribeirão Preto
Ribeirão Preto is a municipality and city in the Northeastern region of the state of São Paulo in Brazil. It is nicknamed Brazilian California, because of a combination of an economy based on agrobusiness plus high technology, wealth and sunny weather all year long. With 605,114 inhabitants,...
, in the hinterland of the state of São Paulo
São Paulo (state)
São Paulo is a state in Brazil. It is the major industrial and economic powerhouse of the Brazilian economy. Named after Saint Paul, São Paulo has the largest population, industrial complex, and economic production in the country. It is the richest state in Brazil...
, Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
. The main objective of the state government was to increase the number of physicians in the rapidly developing hinterland, and its first dean, Dr. Zeferino Vaz
Zeferino Vaz
Zeferino Vaz led the construction, establishment and development of the Unicamp university, in the interior of the State of São Paulo, Brazil in the 1960s and 1970s...
, a parasitologist
Parasitology
Parasitology is the study of parasites, their hosts, and the relationship between them. As a biological discipline, the scope of parasitology is not determined by the organism or environment in question, but by their way of life...
, medical research and professor of the University, wished to create a favorable environment for high quality medical research and teaching
Medical education
Medical education is education related to the practice of being a medical practitioner, either the initial training to become a doctor or additional training thereafter ....
in the new school. With this in mind, Vaz invited a number of foreign researchers to become chairmen of the basic and clinical departments, and Fritz Köberle had a good recommendation by Prof. Henrique da Rocha Lima
Henrique da Rocha Lima
Henrique da Rocha Lima was a Brazilian physician, pathologist and infectologist. He discovered Rickettsia prowazekii, the pathogen of epidemic typhus. Rickettsia prowazekii was named after German zoologist Stanislaus von Prowazek.Henrique da Rocha Lima received his M.D. degree from the Medical...
, a Brazilian medical researcher who had studied in Germany. Dr. Köberle accepted an invitation and moved with his family to the Medical School of Ribeirão Preto
Faculdade de Medicina de Ribeirão Preto
Faculdade de Medicina de Ribeirão Preto is a medical school of the University of São Paulo located in the city of Ribeirão Preto, state of São Paulo, Brazil, founded 1952...
in 1953. He soon organized the Department of Pathology, became its chairman, and began to assemble a small group of Brazilian researchers.
Works
While in Ribeirão Preto, Prof. Köberle noted that a promising field of research in pathology for the new department and himself could be Chagas diseaseChagas disease
Chagas disease is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking insects of the subfamily Triatominae most commonly species belonging to the Triatoma, Rhodnius,...
, or American trypanosomiasis, which had been discovered by another Brazilian physician named Carlos Chagas
Carlos Chagas
Carlos Justiniano Ribeiro Chagas, or Carlos Chagas , was a Brazilian sanitary physician, scientist and bacteriologist who worked as a clinician and researcher. He discovered Chagas disease, also called American trypanosomiasis in 1909, while working at the Oswaldo Cruz Institute in Rio de Janeiro...
, in 1910 (coincidentally, the year he was born). Even though 40 years had passed since its discovery, little was known about the peculiar manifestations of the chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
phase of the disease, such as megaesophagus
Megaesophagus
Megaesophagus is a condition in humans, cats and dogs where peristalsis fails to occur properly and the esophagus is enlarged. Normally, when the dog's esophagus is functioning properly, it acts as a muscle and pushes the food down the esophagus into the stomach. However, when a dog has...
, megacolon
Megacolon
Megacolon is an abnormal dilation of the colon . The dilatation is often accompanied by a paralysis of the peristaltic movements of the bowel...
, cardiomegaly
Cardiomegaly
Cardiomegaly is a medical condition wherein the heart is enlarged. It is generally categorized in the following manner:* Cardiomegaly due to dilation* Cardiomegaly due to ventricular hypertrophy** Left ventricular hypertrophy...
, heart ventricular aneurysm
Ventricular aneurysm
Ventricular aneurysms are one of the many complications that may occur after a heart attack . They usually arise from a patch of weakened tissue in a ventricular wall, which swells into a bubble filled with blood. This, in turn, may block the passageways leading out of the heart, leading to...
, achalasia
Achalasia
Achalasia , also known as esophageal achalasia, achalasia cardiae, cardiospasm, and esophageal aperistalsis, is an esophageal motility disorder involving the smooth muscle layer of the esophagus and the lower esophageal sphincter...
, etc., and the mechanism of the causation of these several pathologies. By making good use of the extensive caseload of fatalities due to Chagas disease in the region of Ribeirão Preto and Southern Minas Gerais
Minas Gerais
Minas Gerais is one of the 26 states of Brazil, of which it is the second most populous, the third richest, and the fourth largest in area. Minas Gerais is the Brazilian state with the largest number of Presidents of Brazil, the current one, Dilma Rousseff, being one of them. The capital is the...
, where it was endemic and widely prevalent at the time, Köberle studied initially the dilation pathologies of the digestive tract and proved, by extensively quantifying the number of neurons of the autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
in the Auerbach's plexus
Auerbach's plexus
A part of the enteric nervous system, Auerbach's plexus , exists between the longitudinal and circular layers of muscularis externa in the gastrointestinal tract and provides motor innervation to both layers of the mucosa, having both parasympathetic and sympathetic input, whereas Meissner's plexus...
, that: 1) they were strongly reduced all over the digestive tract; 2) that megacolon and megaesophagus appeared only when there was a reduction of over 80% and 55% of the number of neurons, respectively; 3) these pathologies appeared as a result of the disruption of the neurally integrated control of peristalsis
Peristalsis
Peristalsis is a radially symmetrical contraction and relaxation of muscles which propagates in a wave down the muscular tube, in an anterograde fashion. In humans, peristalsis is found in the contraction of smooth muscles to propel contents through the digestive tract. Earthworms use a similar...
(muscular annular contraction) in those parts where a strong force is necessary to impel the luminal bolus
Bolus (digestion)
In digestion, a bolus is a mass of food that has been chewed at the point of swallowing. Once a bolus reaches the stomach, digestion begins....
of food or feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
; and 4) European idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
megaesophagus
Megaesophagus
Megaesophagus is a condition in humans, cats and dogs where peristalsis fails to occur properly and the esophagus is enlarged. Normally, when the dog's esophagus is functioning properly, it acts as a muscle and pushes the food down the esophagus into the stomach. However, when a dog has...
and Chagas megaesophagus appeared to have the same etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
, namely the degeneration
Degeneration
The idea of degeneration had significant influence on science, art and politics from the 1850s to the 1950s. The social theory developed consequently from Charles Darwin's Theory of Evolution...
of the Auerbach's myoenteric plexus.
Studying the typical features of the Chagasic myocardium pathology, characterized by damage to its electrical conduction pathways, heart arrythmia, aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
of the ventricular apex, cardiomegalia and sudden death by ventricular fibrillation
Ventricular fibrillation
Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest...
, Köberle and his group of collaborators were able to prove that they were caused also by an extensive denervation of the parasympathetic (55% and sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
(35%) intrinsic cardiac nervous networks, leading to a control imbalance of contraction, cardiac failure, cardiomegalia and hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. He named this constellation of effects as cardiopathia parasympathicopriva. Other less typical phenomena observed in Chagas disease, such as bronchiectasis
Bronchiectasis
Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
and myelopathy
Myelopathy
Myelopathy refers to pathology of the spinal cord. When due to trauma, it is known as spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy....
were also studied by Köberle under the new prism of his neurogenic theory.
Thus, with his classical and detailed scientific studies, Köberle proposed for the first time a unified and radically different (and polemical) view of the etiopathogeny of Chagas disease, characterizing it as a disease of the autonomic nervous system, which establishes itself during the acute phase and provokes long term and slowly installing denervation. Since the trypanosoma does not seem to damage neurons directly, Köberle and other researchers have hypothesized the action of a neurotoxin
Neurotoxin
A neurotoxin is a toxin that acts specifically on nerve cells , usually by interacting with membrane proteins such as ion channels. Some sources are more general, and define the effect of neurotoxins as occurring at nerve tissue...
, cytotoxic factors or autoimmune mechanisms.
Dr. Köberle retired from the University of São Paulo in 1976, but soon moved as visiting professor to the Medical School, of the State University of Campinas, in Campinas
Campinas
Campinas is a city and municipality located in the coastal interior of the state of São Paulo, Brazil. is the administrative center of the meso-region of the same name, with 3,783,597 inhabitants as of the 2010 Census, consisting of 49 cities....
, São Paulo, where one of his sons, Gottfried Köberle, is a professor of Orthopedics
Orthopedics
Orthopedics is the study of the musculoskeletal system. The Greek word 'ortho' means straight or correct and 'pedics' comes from the Greek 'pais' meaning children. For many centuries, orthopedists have been involved in the treatment of crippled children...
. He worked there until his death, in 1983, in Americana
Americana
Americana refers to artifacts, or a collection of artifacts, related to the history, geography, folklore and cultural heritage of the United States. Many kinds of material fall within the definition of Americana: paintings, prints and drawings; license plates or entire vehicles, household objects,...
. Another son, Roland Köberle, is a professor in Physics
Physics
Physics is a natural science that involves the study of matter and its motion through spacetime, along with related concepts such as energy and force. More broadly, it is the general analysis of nature, conducted in order to understand how the universe behaves.Physics is one of the oldest academic...
at the University of São Paulo at São Carlos
São Carlos
São Carlos is a city of 221,950 inhabitants in the state of São Paulo, Brazil. It is located at , at about 231 km from the city of São Paulo.-History:...
.
Miscellaneous
The square in front of the main entrance to the USP campus at Ribeirão Preto is named in his honor.External links
- Rezende, J.M.: Fritz Köberle and his studies on Chagas Disease (in Portuguese)