Johannes Andreas Grib Fibiger (23 April 1867 – 30 January 1928) was a Danish physician and professor of
anatomical pathology
Anatomical pathology (''Commonwealth'') or Anatomic pathology (''U.S.'') is a medical specialty that is concerned with the diagnosis of disease based on the macroscopic, microscopic, biochemical, immunologic and molecular examination ...
at the
University of Copenhagen
The University of Copenhagen ( da, Københavns Universitet, KU) is a prestigious public university, public research university in Copenhagen, Copenhagen, Denmark. Founded in 1479, the University of Copenhagen is the second-oldest university in ...
. He was the recipient of the 1926
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
"for his discovery of the ''Spiroptera carcinoma''". He demonstrated that the
roundworm
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...
which he called ''Spiroptera carcinoma'' (but correctly named ''
Gongylonema neoplasticum'') could cause stomach cancer (
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
) in rats and mice. His experimental results were later proven to be a case of mistaken conclusion. Erling Norrby, who had served as the Permanent Secretary of the
Royal Swedish Academy of Sciences
The Royal Swedish Academy of Sciences ( sv, Kungliga Vetenskapsakademien) is one of the Swedish Royal Academies, royal academies of Sweden. Founded on 2 June 1739, it is an independent, non-governmental scientific organization that takes special ...
and Professor and Chairman of
Virology
Virology is the Scientific method, scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host (biology), ...
at the
Karolinska Institute
The Karolinska Institute (KI; sv, Karolinska Institutet; sometimes known as the (Royal) Caroline Institute in English) is a research-led medical university in Solna within the Stockholm urban area of Sweden. The Karolinska Institute is consist ...
, declared Fibiger's Nobel Prize as "one of the biggest blunders made by the Karolinska Institute."
While working at the Institute of Pathological Anatomy of University of Copenhagen, Fibiger discovered new roundworms in 1907 from wild rats. He suspected that the roundworms were responsible for stomach cancer in those rats. In 1913, he reported that he could experimentally induce cancer in healthy rats using the roundworms. His discovery was considered "the greatest contribution to experimental medicine" at the time. In 1926, he was nominated for the Nobel Prize in Physiology or Medicine along with
Katsusaburo Yamagiwa, who had experimentally induced carcinoma by painting crude coal tar on the inner surface of rabbits' ears in 1915. However, they were considered undeserving, and the 1926 prize was not given. In the next year Fibiger alone was retrospectively chosen for the 1926 Nobel Prize.
After his death, independent researches proved that ''G. neoplasticum'' cannot cause cancer. Tumours and cancer produced by Fibiger were due to
vitamin A deficiency
Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia (ni ...
. Historical reassessment of Fibiger's data revealed that he had mistaken non-cancerous tumours for cancerous tumours.
His research method on diphtheria is regarded as the origin of an important research methodology in medicine known as controlled
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
.
Biography
Fibiger was born in Silkeborg, Midtjylland, Denmark. He was the second son of Christian Ludvig Wilhelm Fibiger and
Elfride Fibiger (''née'' Müller). His father was a local physician and his mother, an author. He was named after his uncle, who was a clergyman and a poet.
His father died of internal bleeding when he was three years of age, after which the family moved to Copenhagen where his mother earned their living by writing. His mother established there the first cooking school, the Copenhagen Cooking School.
His namesake uncle supported Fibiger for his education. In 1883, at age 16, he passed his matriculation and was enrolled at the University of Copenhagen to study zoology and botany. He self-supported by teaching and working at the laboratories. He graduated in 1883. He continued for a medicine course and earned his medical degree in 1890. For a few months he worked as a physician at different hospitals, and also continued to study under
Robert Koch
Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the Vibrio ...
and
Emil Adolf von Behring
Emil von Behring (; Emil Adolf von Behring), born Emil Adolf Behring (15 March 1854 – 31 March 1917), was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery ...
in Berlin. Between 1891 and 1894, he was assistant to C. J. Salomonsen at the Department of Bacteriology of Copenhagen University. From 1894 he joined the
Royal Danish Army Medical Corps, where he served till 1897. It was during his army service that he completed his doctoral thesis ''Research into the bacteriology of diphtheria''. The University of Copenhagen awarded him a doctorate degree in 1895. He continued the diphtheria research at Blegdamshospitalet in Copenhagen, working as a Junior Physician.
[ In 1897, he was appointed ]prosector
A prosector is a person with the special task of preparing a dissection for demonstration, usually in medical schools or hospitals. Many important anatomists began their careers as prosectors working for lecturers and demonstrators in anatomy and p ...
at the Institute of Pathological Anatomy of University of Copenhagen. He was promoted to full Professor and eventually its Director in 1900. He also served as Principal of the Laboratory of Clinical Bacteriology of the Army from 1890 to 1905), and Director of the Central Laboratory of the Army and Consultant Physician to the Army Medical Service in 1905.
Fibiger died of cardiac arrest
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
in Copenhagen on 30 January 1928.[
]
Contributions
Diphtheria research
Fibiger's doctoral research was on diphtheria. He developed more efficient method of growing bacteria in a laboratory setting. He discovered that there were two different forms (strains) of the diphtheria bacillus (''Corynebacterium diphtheriae
''Corynebacterium diphtheriae'' is the pathogenic bacterium that causes diphtheria. It is also known as the Klebs–Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834–1912) and Friedrich Löffl ...
'') that produce two different symptoms, now called nasopharyngeal and cutaneous diphtheria. He also produced a blood serum against the disease.[ He was known for his methodological system of research. One of his experiments from 1898 in which he tested the blood serum for diphtheria is regarded by some as the first controlled ]clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
.[ While working as a Junior Physician in Blegdamshospitalet, he tested his diphtheria serum among hundreds (484) patients. As would be in modern clinical trial, he separated serum-treated and untreated patients, and found that more of untreated patients died than the treated ones. According to an article in '']The British Medical Journal
''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origina ...
'' in 1998:
Cancer and parasitology research
While studying tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
in lab rats, Fibiger found tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s in some wild rats collected from Dorpat (officially Tartu
Tartu is the second largest city in Estonia after the Northern European country's political and financial capital, Tallinn. Tartu has a population of 91,407 (as of 2021). It is southeast of Tallinn and 245 kilometres (152 miles) northeast of ...
, now in Estonia) in 1907. Rats having stomach tumour (papilloma
A papilloma (plural papillomas or papillomata) ('' papillo-'' + '' -oma'') is a benign epithelial tumor growing exophytically (outwardly projecting) in nipple-like and often finger-like fronds. In this context, papilla refers to the projection cre ...
) also had nematodes and their eggs. He found that some tumours were metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
(cancerous). He hypothesised that the nematodes caused the stomach cancer. After years of investigation, he experimentally demonstrated in 1913 that the nematode could induce stomach cancer. He published his discovery in a series of three papers, and also presented them at the Académie Royale des Sciences et des Lettres de Danemark (Royal Danish Academy of Sciences and Letters
{{Infobox organization
, name = The Royal Danish Academy of Sciences and Letters
, full_name =
, native_name = Det Kongelige Danske Videnskabernes Selskab
, native_name_lang =
, logo = Royal ...
), and Troisième Conférence Internationale pour l’Étude du Cancer (Third International Conference for Researches in Cancer) at Brussels the same year. He knew that the nematode was a new species, and provisionally named it ''Spiroptera carcinom '' in 1914. With Hjalmar Ditlevsen, of the Zoological Museum of the University of Copenhagen, he described it as ''Spiroptera'' (''Gongylonema'') ''neoplastica'' in 1914. Ditlevsen revised the description in 1918, and gave the final valid name ''Gongylonema neoplasticum''. But Fibiger never used the formal scientific name, and persistently used ''Spiroptera carcinoma''.
Fibiger's experiment was the first to show that helminth parasites can cause cancer, and that cancer (tumour) can be experimentally induced. His discovery was supported by the experiment of two Japanese scientists Katsusaburo Yamagiwa and Koichi Ichikawa in 1918. Yamagiwa and Ichikawa demonstrated the induction of cancer (carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
) in rabbits. They showed that it was relatively easy to produce cancer was by painting coal-tar on the inner surface of the ear. A number independent experiments subsequently confirmed the cancer-inducing effect of coal-tar in mice. With such supporting evidence, Fibiger's work was regarded a milestone in cancer study.
Personal life
Fibiger was married to Mathilde Fibiger (1863–1954). Mathilde was his cousin who came to help her mother's business while he was studying medicine. They got married on 4 August 1894. Fibiger had been suffering from colon cancer, and a month after he received his Nobel Prize, he died of heart attack on 30 January 1928 due to his worsening cancer. He was survived by his wife and two children.[
]
Nobel Prize controversy
Nomination and selection
Fibiger was nominated for the Nobel Prize in Physiology or Medicine 18 times from 1920. In 1926, he received two nominations along with Katsusaburo Yamagiwa. Folke Henschen and Hilding Bergstrand were appointed by the Nobel Committee as assessors. They disagreed on each other's conclusion. Henschen was in favour of the nomination and concluded that "the experimental carcinoma is worthy of the Nobel Prize. It should therefore be just if the prize would be divided between Johannes Fibiger, the discoverer of the experimental spiroptera carcinoma, and Katsusaburo Yamagiwa, the discoverer of the experimental tar carcinoma." But Bergstrand opposed to it, concluding that "an experimental confirmation of a previously known fact... eferring to the prevalence of cancer among chimney sweeps and factory workers, an already established medical fact at the timecan, in this case, not be considered... that one cannot, at this point, find much support for the possibility that the work of Fibiger and Yamagiwa will have great importance in the solving of the riddle of cancer. Under such circumstances I do not consider these discoveries worthy of the Nobel Prize." The Nobel Committee could not make the final decision and decided not to give the prize for 1926. In the next year, Fibiger received seven nominations, and Yamagiwa was then excluded. Instead there were two other nominees, Otto Heinrich Warburg
Otto Heinrich Warburg (, ; 8 October 1883 – 1 August 1970), son of physicist Emil Warburg, was a German physiologist, medical doctor, and Nobel laureate. He served as an officer in the elite Uhlan (cavalry regiment) during the First World War ...
and Julius Wagner-Jauregg
Julius Wagner-Jauregg (; 7 March 1857 – 27 September 1940) was an Austrian physician, who won the Nobel Prize in Physiology or Medicine in 1927, and is the first psychiatrist to have done so. His Nobel award was "for his discovery of the therapeu ...
. In addition to Henschen and Bergstrand, Einar Hammersten was appointed as the third assessor. On Fibiger, Bergstrand was of the same opinion, Hammersten was in favour. Hence the three nominees were recommended for the award. The Nobel Committee decided to give the 1926 prize jointly to Fibiger and Warburg, and the 1927 prize to Wagner-Jauregg. However, the authority at the Karolinska Institute disagreed with the recommendation for Warburg for undisclosed reasons, and Fibiger became the sole winner. (Warburg was eventually awarded the prize in 1931.)
Posthumous criticism and disproof
Fibiger's discovery was unchallenged during his lifetime. The only serious criticism was by F. D. Bullock and G. L. Rohdenburg. In 1918, they argued that the cancerous tumours produced in Fibiger's experiments were similar to non-cancerous tumours. Such tumours easily developed in epithelial cells. Fibiger defended "That these tumors are true carcinomata cannot, thus, be doubted, and the fact that they may occur in younger animals does not diminish our right to range them among the true malignant neoplasms."
It was only after Fibiger's death that the importance of vitamin A in cancer development was fully appreciated. Fibiger had used rats which were fed vitamin A-less diet. It was found that Vitamin A deficiency alone can cause tumours and cancers. The parasites had merely caused the tissue irritation (chronic inflammation) that drove the damaged cells into cancer; any tissue irritation could have induced the tumours. The major challenge came from Richard Douglas Passey, with his colleagues A. Léese, and J.C. Knox. They reported a new finding in 1935 that ''S. carcinoma'' do not cause cancer in rats. They concluded that Fibiger probably had mistaken metaplasia (a non-cancerous tumour) with malignant neoplasia (true cancer). In 1937, W. Cramer experimentally showed that Fibiger's tumour were not cancerous. The final disproof was shown by Claude R. Hitchcock and E. T. Bell. In 1952, they repeated Fibiger's experiments using advanced microscopy and histology, and conclusively demonstrated that the tumours due to ''G. Neoplasticum'' in rats were non-cancerous tumours. And the tumours were primarily due to vitamin A deficiency.
It is also claimed that exclusion of Yamagiwa was another mistake. Yamagiwa's work has become the primary basis for induction of tumours in cancer research. Because of this, some consider Fibiger's Nobel Prize to be undeserved particularly because Yamagiwa did not receive the prize. ''Encyclopædia Britannica
The (Latin for "British Encyclopædia") is a general knowledge English-language encyclopaedia. It is published by Encyclopædia Britannica, Inc.; the company has existed since the 18th century, although it has changed ownership various time ...
'' guide to Nobel Prizes in cancer research mentions Yamagiwa's work as a milestone without mentioning Fibiger.
Although ''G. Neoplasticum'' is non-carcinogenic, other helminth parasites such as ''Schistosoma haematobium
''Schistosoma haematobium'' (urinary blood fluke) is a species of digenetic trematode, belonging to a group (genus) of blood flukes (''Schistosoma''). It is found in Africa and the Middle East. It is the major agent of schistosomiasis, the most ...
'', ''Opisthorchis viverrini
''Opisthorchis viverrini'', common name Southeast Asian liver fluke, is a food-borne trematode parasite from the family Opisthorchiidae that infects the bile duct. People are infected after eating raw or undercooked fish. Infection with the par ...
'' and ''Clonorchis sinensis
''Clonorchis sinensis'', the Chinese liver fluke, is a liver fluke belonging to the class Trematoda, phylum Platyhelminthes. It infects fish-eating mammals, including humans. In humans, it infects the common bile duct and gall bladder, feeding on ...
'' are now established to cause cancer in humans.
See also
*Carcinogenic parasite
Carcinogenic parasites are parasitic organisms that depend on other organisms (called hosts) for their survival, and cause cancer in such hosts. Three species of flukes (trematodes) are medically-proven carcinogenic parasites, namely the urinary ...
References
Further reading
*''Nobel Lectures, Physiology or Medicine 1922–1941'', Elsevier Publishing Company, Amsterdam, 1965.
*
*
*
External links
* including the Nobel Lecture on 12 December 1927 ''Investigations on Spiroptera Carcinoma and the Experimental Induction of Cancer''
Biography from ''WhoNamedIt''
Biography from ''YourDictionary''
{{DEFAULTSORT:Fibiger, Johannes
1867 births
1928 deaths
Nobel laureates in Physiology or Medicine
Danish Nobel laureates
Danish bacteriologists
Danish pathologists
University of Copenhagen alumni
Academic staff of the University of Copenhagen
Rectors of the University of Copenhagen
People from Silkeborg
Burials at the Garrison Cemetery, Copenhagen