Spiroptera carcinoma

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Johannes Fibiger (born April 23, 1867 in Silkeborg, Denmark; † January 30, 1928 in Copenhagen)

The Spiropterakarzinom ([ʃpirɔpterakarʦiˌnoːm], and [sp ...]) is in the stomach of infected Spiroptera experiment rats occurring pathological tissue augmentation , by its discoverer, the Danish pathologist Johannes Fibiger , mistakenly as cancer has been interpreted. This seemed to prove that cancer is an infectious disease . For this apparent evidence, Fibiger received the 1927 Nobel Prize in Physiology or Medicine for 1926.

The error did not emerge until 1935. Spiroptera carcinoma has since been regarded as the most highly awarded scientific error . The reasons for this error were essentially methodological errors and Fibiger's one-sided interpretation of the experimental data. Regardless of this, spiroptera carcinoma had a great influence on experimental cancer research, which received new impulses and subsequently generated some outstanding research results.

70 years after Fibiger's supposed discovery of spiroptera carcinoma, the bacterium Helicobacter pylori , which is responsible for most gastric cancer cases worldwide, was discovered in gastritis patients .

Oncological knowledge in Fibiger's time

Rudolf Virchow
Julius Friedrich Cohnheim
Theodor Boveri

At the beginning of the 20th century, infectious diseases such as influenza , pneumonia , syphilis or tuberculosis were the main causes of death in the population of the western world. Step by step it was discovered which causes ( etiologies ) play a role in the development of these diseases. First, the transmission mechanisms were clarified and the bacterial pathogens were identified with the development of usable light microscopes . This enabled the development of the first potent active ingredients, such as the Salvarsan against syphilis by Paul Ehrlich in 1909 . In contrast, the situation with cancer was completely different. The search for "the pathogen" was unsuccessful. In Fibiger's time there were three rival theories about the development of cancer that were lively debated in professional circles:

Virchow's stimulus theory

A number of pieces of evidence supported Virchow's stimulus theory. For example, as early as 1775 , Percivall Pott found with British chimney sweeps that testicular cancer , which was extremely common in this professional group at the time, was obviously triggered by soot that was deposited in the folds of the skin of the scrotum . In 1895, Ludwig Rehn noticed an increase in bladder cancer in chemical workers who came into contact with Fuchsin . The Kangri cancer , which only in Kashmir occurs, was first described in 1881. This squamous cell carcinoma results from chronic skin irritation ( erythema ab igne ) caused by a heating oven (the kangri ) worn under clothing .

With the stimulus theory some rare, rather exotic types of cancer could be explained; for the cause of the most common cancers, such as breast cancer , however, it did not provide any useful solutions. Even Virchow did not rule out a "cancer bacillus" that one might discover one day:

“The evidence of parasitic microorganisms in diseased parts, which has been increasing in number for a number of years, has given many […] the hope that a cancer bacillus will also be found. So far, the results of even the most ardent research have not been presented in a convincing demonstration. However, the possibility of such an occurrence cannot simply be dismissed; yes, one can admit that the discovery of a specific bacillus would be an important step forward in the diagnosis and prognosis of carcinoma. "

- Rudolf Virchow : 1888

"Cancer vaccination"

There was some pioneering work before Fibiger in the experimental generation of cancer in model organisms. The Russian veterinarian Mstislaw Alexandrowitsch Nowinski (1841-1914) transplanted malignant tumors in dogs to puppies between 1875 and 1876 , which grew there, partly metastasized and in turn could be transplanted to other puppies. In 1889, the German pathologist Arthur Nathan Hanau (1858–1900) succeeded in transplanting an epidermal carcinoma of the vulva from rats to other rats, ie a homologous tumor transfer ("cancer vaccination"). However, these test results only showed the transferability of an already existing disease to another individual. However, they did not help to clarify the causes of cancer.

Heinrich Wilhelm Waldeyer

The artificial creation of a cancerous tumor in an experimental animal was first achieved in 1915 - two years after the publication of Fibiger's work - by the Japanese Katsusaburō Yamagiwa (1863–1930) and his assistant Koichi Ichikawa . They brushed the insides of the ears of guinea pigs with tar oil . After about 250 days, tumors developed on the skin areas treated in this way. From today's perspective, Yamagiwa's work was groundbreaking and established a completely new field of work in experimental oncology .

Parasite theory

The parasite theory had many followers in Fibiger's time. As early as 1911, the Königsberg district doctor Hans Abramowski claimed that the Opisthorchis febriens worm was a cancer pathogen that was transmitted to humans through the consumption of raw or undercooked fish. The worm, which prefers to colonize the bile ducts and pancreas, could cause cancer through chronic inflammation in these organs.

The Leiden professor Reinder Pieter van Calcar saw protozoa , which in turn colonized nematodes, as the cause of the development of cancer. He himself inoculated protozoa, which he isolated from intestinal parasites and cockroaches, on dogs. He then found infiltratively growing and metastasizing “malignant adenomas ” and carcinomas in the test animals . The results from the tar brushing, which are actually a clear indication of Virchow's stimulus theory, were ascribed to the action of protozoa. Van Calcar found in his experiments that the animals, which he had protected from contact with protozoa by means of special protective measures, developed carcinomas less often than the comparison group.

Genetic modification due to oncogenes

Heinrich Wilhelm Waldeyer laid the foundations for the current state of knowledge of cancer as early as 1867. He postulated that cancer arises from an induced transformation of normal cells into malignant cells. These degenerate cells first multiply locally, penetrate healthy tissue (infiltration) and then spread through the lymphatic or blood system (metastasis). However, Waldeyer's remarks were purely descriptive and consequently did not contain any statements about the mechanisms of cancer development. In 1914, one year after Fibiger's first publication on spiroptera carcinoma, Theodor Boveri provided groundbreaking approaches to this with his postulates that are still valid today. Boveri postulated that cancer develops from a single cell whose genetic information has previously been altered. He suspected the chromosomes to be the location of genetic information . He saw tumors as the result of an abnormal chromosome constitution. For tumor development, he suspected an evolution of tumor cells towards increasing malignancy. The cells would lose certain properties, in particular their ability to react to signals from other cells. This leads to the autonomy of the tumor cells. He also suspected that there were genes in normal cells that inhibit cell growth. Loss of these genes would lead to transformation into a cancer cell. Boveri died a year after its publication, and his postulates were long forgotten.

Francis Peyton Rous discovered the first oncogene in 1911. Using a cell-free, ultrafiltered extract of a muscle tumor ( sarcoma ) from a chicken , he was able to generate new tumors in other chickens by injecting it into other chickens. A bacterium or even a multicellular parasite could be excluded as a pathogen, as these were completely separated off by the filter. Rous suspected a virus in this extract. Very little was known about viruses that could not be made visible at the time. The virus was later detected and named Rous sarcoma virus in Rous' honor . Today, the oncogene of the Rous sarcoma virus is considered to be evidence that altered genes can be the cause of cancer.

Fibiger's discovery

The American cockroach is one of the intermediate hosts of the nematode Gongylonema neoplasticum .
A putative spiroptera carcinoma in the stomach of a spotted rat that was fed American cockroaches

Since 1900 Johannes Fibiger was Professor and Director at the Institute for Pathological Anatomy at the University of Copenhagen . In 1907, during histological work on the stomachs of wild brown rats ( Rattus norvegicus ) and house rats ( Rattus rattus ) , he noticed that many of the animal carcasses in the forestomach had epithelial hyperplasia with papilloma formation. However, these tumors did not metastasize or infiltrate the surrounding healthy tissue . These tumors did not colonize other areas of the digestive tract . To his surprise, however, he found roundworms (nematodes) and their eggs in some of these tumors . The roundworm was identified by Hjalmar Ditlevsen , an assistant at the Zoological Museum of the University of Copenhagen, as a new nematode species belonging to the “spiropterid group”. In the following, detailed zoological description, the nematode was given the species name Spiroptera neoplastica . The epithet neoplastica chose Fibiger and Ditlevsen because of the alleged effect of the nematode, neoplasia '(from ancient Greek νέος Neos ' new' and πλάσσειν plassein , shape 'form', modern Greek : δυσπλασία ), so neoplasm = tumor. 1915 introduced the American zoologist Brayton Howard Ransom found that Spiroptera neoplastica definitely the kind of Gongylonema belongs. He therefore suggested that this newly discovered species should be called Gongylonema neoplasticum in the future . Ditlevsen agreed to Ransom's suggestion, and since then this nematode species, for which there is currently no German-language name, has been called Gongylonema neoplasticum . At the time of Fibiger's discovery, there were already reports of "cancer bacilli" and various parasites that were linked to the development of cancer, but no researcher had experimentally succeeded in inducing cancerous tumors artificially and specifically in test animals . Being the first to do this was the driving force behind Fibiger's further work.

After his first dissections, Fibiger examined over 1,000 mouse and rat stomachs, but did not find any "spiroptera carcinoma" in any of the specimens. Fibiger wanted to stop working in this area when he found the tumors and nematodes he was looking for in rats from a Copenhagen sugar factory . He noticed a large number of cockroaches at the factory , which led him to suspect that the cockroaches are intermediate hosts for Gongylonema neoplasticum . In laboratory tests, Fibiger actually identified the American cockroach ( Periplaneta americana ) and the common cockroach ( Blatta orientalis ) as intermediate hosts for Gongylonema neoplasticum . He succeeded in transferring Gongylonema neoplasticum to the German cockroach ( Blattella germanica ) as an intermediate host.

A mouse with a subcutaneously transplanted spiroptera carcinoma (1st generation, 84 days after implantation)

The nematode originally came from South America and the West Indies and was brought in by ship with its intermediate host and the sugar. In his first attempts to artificially induce cancerous tumors with Gongylonema neoplasticum , Fibiger fed seven laboratory rats with American cockroaches. After the natural death of the experimental animals, he examined them extensively. In all of them he found the nematodes in the forestomach. In one rat he also saw epithelial hyperplasia and in the two longest-lived rats also strong proliferation , deep growth and heterotopia of the epithelium, combined with inflammation and pronounced papilloma formation. He interpreted this as the incipient and less common carcinoma formation . He was also able to transfer the nematode to laboratory mice, guinea pigs , wood mice , rabbits, squirrels ( Sciurus vulgaris ) and brown-breasted hedgehogs, but none of these species found carcinoma formation. In a larger series of experiments, he fed 91 "colored and white" rats with cockroaches. He had previously fed the cockroaches with rat excrement containing spiroptera eggs and sugar water so that they ingested Spiroptera neoplastica as an intermediate host . The rats were examined after natural death. Fibiger found papillomatous changes in the forestomach in 22 animals and carcinomatous changes in 12 of these animals. He determined the incubation period to be three to four months. In two animals he found small lung metastases that contained neither nematodes nor their eggs. Fibiger believed that the tumors were caused by a toxin from the nematodes.

In 1913 he published his results for the first time. In the introduction to this article, he referred to the results of Stephanos Kartulis , who had frequently diagnosed bladder cancer caused by the flukes, Schistosoma haematobium , in patients with schistosomiasis (schistosomiasis) . Fibiger's publication caused a sensation in the professional world because he seemed to be the first to succeed in experimentally triggering a malignant tumor. Completely new possibilities seemed to open up for research into the pathogenesis of cancer and future treatments. Shortly after its publication, Fibiger received a variety of different honors. For example, he became a member of the prestigious Swedish Medical Society ( Svenska Läkaresällskapet ). The Danish Medical Society elected him their President of the Cancer Commission. Numerous honorary doctorates from various well-known universities followed. Fibiger later reported successful subcutaneous transplants of spiroptera carcinoma, for example over four generations, to mice.

  • Representations from Fibiger's Nobel Prize lecture on December 12, 1927

  • A pronounced papilloma in the stomach of a rat

  • In comparison, the stomach of a healthy rat

  • A nematode embedded in the epithelium of the gastric fundus

  • Micrograph of ripe Gongylonema neoplasticum eggs

  • Larva of Gongylonema neoplasticum coiled in a spiral in the muscle of a cockroach

  • One male (above) and one female (below) specimen of Gongylonema neoplasticum

Fibiger's Nobel Prize nominations

Between 1922 and 1927 Johannes Fibiger was nominated a total of sixteen times by various scientists for the Nobel Prize in Physiology or Medicine . His work was therefore subjected to special scrutiny several times by the Nobel Committee for Physiology or Medicine . In 1922 and 1923, committee member Gunnar Hedrén ruled that Fibiger had not brought "the greatest benefit to mankind" with his discovery , as Alfred Nobel wanted for the Physiology or Medicine Prize. He recommended to wait until a final judgment about the worthiness of Fibiger's discovery could be made before the award.

In 1926, Fibiger received three nominations. His work was again reviewed, along with the work of Katsusaburo Yamagiwa, who was also nominated. Also Félix Hubert d'Hérelle and Otto Warburg were nominated for the Nobel Prize 1926th The Nobel Committee requested two separate reports on Fibiger's and Yamagiwa's work. The two Swedish pathologists Folke Henschen and Hilding Bergstrand , both professors at the Karolinska Institute , prepared a report on each candidate. Henschen praised Fibiger's work and its significant impact on cancer research as a whole. He quoted the renowned cancer researcher Archibald Leitch with the words:

“But a new era dawned on cancer research when Johannes Fibiger of Copenhagen presented his brilliant experiments on the production of gastric cancer in rats. Then, for the first time could it be said that cancer had been produced experimentally beyond all doubt, and exploration into the etiology of cancer became practical problems. "

“A new era in cancer research dawned when Johannes Fibiger from Copenhagen presented his brilliant experiments on the production of gastric cancer in rats. As a result, cancer could be produced experimentally for the first time without any doubt and research into the etiology became a practice-oriented task. "

- Archibald Leitch

Henschen, who was a personal friend of Fibiger, was also very positive about Yamagiwa's discovery. Yamagiwa was inspired by Fibiger's work, published two years before him. In contrast to Fibiger, Yamagiwa's tar brushing had meanwhile established itself as the method for experimental cancer production in oncology. It was much easier to carry out and provided reproducible results. The tar brushing has been used in cancer research laboratories around the world and has already made some new discoveries and developments possible. Henschen came to the conclusion that the experimental carcinomas were worthy of the Nobel Prize and proposed a price split between Fibiger (for the discovery of the experimental spiropteran carcinoma) and Yamagiwa (for the discovery of the experimental tar carcinoma).

Bergstrand, on the other hand, came to a much more cautious result. Although he paid tribute to the work of Fibiger and Yamagiwa, he saw in them only an experimental confirmation of clinical facts that had long been known. He cited work-related cancer among chimney sweeps and radiologists as examples. In addition, neither of the discoveries made any contribution to elucidating the genesis of malignant tumors. Literally he argued:

"An experimental confirmation of a previously known fact is, of course, always welcome, although its importance can, in this case, not be considered of the significance that it is worthy of the Nobel Prize."

"The experimental confirmation of a previously known fact is of course always good, but in this case the meaning cannot be regarded as sufficient enough to be worthy of the Nobel Prize."

- Hilding mountain beach

Bergstrand also questioned the future significance of both discoveries for cancer research. He was of the opinion that the results of other researchers, namely those of Otto Warburg, would become more important in the future. In his summary, he doubted that the results of the two nominees would be of great importance in solving the cancer puzzle. Both discoveries are not worthy of the Nobel Prize.

As a result, there was a dispute between Henschen and Bergstrand. This came about when Bergstrand urgently recommended that Félix Hubert d'Hérelle receive the award. Henschen rejected d'Hérelle as the laureate because he did not work alone in the field and he alone could not have the honor of discovering bacteriophages. The committee requested a third opinion from John Sjöqvist . The confirmed Henschen's assessment of d'Hérelle's work. Bergstrand's rejection ultimately led Henschen to abandon his proposal for the shared Nobel Prize and was now in favor of a prize-giving to Fibiger alone. The Nobel Committee finally decided not to award the 1926 Nobel Prize in Physiology or Medicine .

In 1927 the Karolinska Institute received seven nominations for Fibiger. Another special review was ordered. Otto Warburg, Julius Wagner-Jauregg and Charles Scott Sherrington were also nominated. The committee again instructed Henschen and Bergstrand to prepare a report; this time about Fibiger and Warburg, one report per reviewer. This year, too, the opinions of the two experts in the case of Fibiger differed widely. Bergstrand recognized the impetus and inspiration of Fibiger's work for cancer research, but ultimately it was only evidence of an ancient theory. He also admitted that Yamagiwa was inspired by Fibiger's work, but that his work was a completely independent achievement. Once again he questioned the clinical relevance of Fibiger's discovery, which had not yet made any contribution to the elucidation of the etiology of spontaneous tumors in humans. In his report, Henschen came to a completely different conclusion. The past year has further strengthened his opinion on Fibiger's discovery. The number of nomination letters that the committee had received this year from high-ranking scientists also confirms its opinion. He highlighted the impetus for all cancer research - also referred to by Bergstrand - that Fibiger had triggered with his work, especially at a time when there was no progress in oncology. With Fibiger, a new era in cancer research has begun. In the case of Otto Warburg, however, Bergstrand and Henschen came to the same conclusion. Warburg was nominated for his hypothesis that cancer cells have a special anaerobic metabolism. The two experts criticized the fact that the facts on which the Warburg hypothesis was based were insufficient. Warburg's work was assessed by a third reviewer, Einar Hammarsten , Professor of Chemistry and Pharmacy at the Karolinska Institute. Hammarsten was - in contrast to Bergstrand and Henschen - convinced of the importance of Warburg's discovery. With these three reports, the committee came to the conclusion that both Warburg and Fibiger were worthy of the Nobel Prize. It unanimously proposed that half of the Nobel Prize for Physiology or Medicine, which had not been awarded in the previous year, be awarded to Warburg and Fibiger and that of 1927 to Julius Wagner-Jauregg “for discovering the therapeutic importance of the malaria vaccination in the treatment of progressive paralysis ".

However, the Nobel Assembly of the Karolinska Institute rejected the committee's proposal and ordered that Fibiger should receive the prize for 1926 alone. The reasons for this decision are still unknown. Otto Warburg received the Nobel Prize in Physiology or Medicine in 1931.

Awarded the Nobel Prize to Fibiger in 1927

Johannes Fibiger

Johannes Fibiger received the Nobel Prize for being the first to succeed in reproducibly producing cancer in a laboratory animal in a controlled experiment. The laudation on December 10, 1927 was given by Wilhelm Wernstedt (1872–1969), Dean of the Karolinska Institute. Wernstedt said that it had long been assumed that there was a causal link between cancer and prolonged mechanical, thermal, chemical or actinic irritation of the tissue. In some cases these are occupational diseases. For example, the cancer in radiologists, chimney sweeps and chemical workers are examples of cancer infections that some believed to be caused by radioactivity or chemical irritation. However, all attempts to trigger these cancers in laboratory animals have failed. The search for the "cancer bacillus" as the cause of the cancer was also unsuccessful. Worms would also have been considered as possible causes of cancer, but the proponents of this theory would often have been viewed as dreamers . At this point in time, when there was no clear idea about the cause of cancer, Fibiger was the first to succeed in producing cancer experimentally in 1913. For the first time, the experimental transformation of normal cells into cancer cells would have been successful. It has been shown convincingly that cancer is not always caused by a worm, but that the cancer can be caused by an external stimulus. For this reason alone, Fibiger's discovery is of inestimable importance. In his further remarks, Wernstedt emphasized the impetus from Fibiger's work that these would have given cancer research as a whole. For this immortal research work, Johannes Fibiger would be awarded the Nobel Prize for Medicine in 1926 on that day (“ It is for this immortal research work that Fibiger is today awarded the Nobel Prize for Medicine for 1926. ”).

Two days later, Fibiger gave his Nobel Prize lecture at the Karolinska Institute in English. First, he reflected on the work of Arthur Nathan Hanau and Henri Moreau on the transplantation of tumors, as well as the three important theories of the development of cancer at the time: Virchow's stimulus theory, Cohnheim's theory of embryonic germ dispersal and the theory that cancer ascribed to parasites. Until recently, all attempts to induce cancer in healthy test animals by chemical or physical stimuli or by transplanting embryonic tissue and a wide variety of microorganisms would have failed. He briefly mentioned the results of a French working group that had succeeded in 1910 in generating cancerous tumors using X-rays, as well as the experiments of Peyton Rous with the "invisible viruses". But he mentioned the doubts that still existed as to whether the new tissue formation was really a “real cancer”. With the nematode Gongylonema neoplasticum , the first successful method for the systematic experimental production of cancer in laboratory animals was developed. In the following, Fibiger reported in detail on his research on spiroptera carcinoma. He then went into human cancers caused by worms such as pair leeches. Gongylonema neoplasticum has never been found in a human, but the related worm Gongylonema pulchrum . However, no case of cancer caused by G. pulchrum is known. At all, there is so far no evidence that worms play an important etiological role in the pathology of cancer in humans. Nor can it be deduced from his research results that cancer is usually triggered by parasites. He interpreted the results of his work on spiroptera carcinoma as evidence of Virchow's stimulus theory. He suspected that the carcinogenic effects of certain worms were caused by the excretion of carcinogenic toxins by the nematodes. In the further course of his lecture, Fibiger dealt with the predisposition in cancer. Age is a major factor in the predisposition to cancer. This is a long-accepted doctrine for all types of cancer. The results of his experiments on spiroptera carcinoma, but also other attempts to produce cancer in test animals, for example by brushing with tar, would contradict this doctrine. Under the same test conditions, young test animals would develop tumors just as often and just as quickly as old test animals. At the end of his lecture, he repeated the statement that there is still no convincing evidence for the microbial origin of cancer in humans, even if more recent research shows that micro-parasites and viruses can cause cancer.

Just a few weeks after receiving the Nobel Prize, Johannes Fibiger died on January 30, 1928 in Copenhagen. He died of right heart failure after multiple phlebothromboses led to massive pulmonary embolism . He also suffered from colorectal cancer and therefore had a coecostomy .

Refutation of Fibiger's results

In 1918, five years after the first publication on the artificial generation of spiroptera carcinoma, Fibiger's histological findings were questioned by Frederick D. Bullock and George L. Rohdenburg of Columbia University . They came to the conclusion that the cellular changes are not carcinomas, but hypertrophy of the epithelium of the gastric mucosa . However, Fibiger's reputation quickly ended the criticism. In addition, other prominent histopathologists also came to the conclusion that they were carcinomas. It should be noted that at this time the histological techniques were still in their infancy and were by no means standardized . In the years that followed, no other cancer researcher succeeded in reproducing Fibiger's results. Tumors were rarely found in the test animals. The reasons for this have not yet been finally clarified, but there are a number of indications. What is certain is that the "cancerous tumors" described by Fibiger were not malignant changes and that the nematodes found in the tumors were not responsible for the benign cell growths observed.

It would take over 20 years for Fibiger's findings to be disproved. One of the reasons for this is that Fibiger's method was rarely used by cancer researchers because of its complexity. The tar brushing from Yamagiwa, which is much easier to carry out, provided significantly more reproducible results and was much more popular among experts. In 1935 a working group around the oncologist Richard Douglas Passey (1888–1971) at the University of Leeds published their study results on spiroptera carcinoma. Passey and his colleagues found that the infected test animals did not develop cancerous tumors if they were given a full diet. The lung metastases in Fibigers experiments were - so Passeys hypothesis - by a lack of vitamin A triggered. It is also known in humans that hypovitaminosis of vitamin A promotes the formation of cancerous tumors, especially from the epithelium of the mucous membranes. Passey suspected that the hypovitaminosis in Fibiger's animal experiments had increased the infection caused by the nematodes and that the irritation of the gastric mucous membranes possibly led to the alleged carcinomas observed. The histological recordings of the benign changes published by the working group are very similar to Fibiger's photos.

In 1952 the two Americans Claude R. Hitchcock and Elexious T. Bell repeated the experiments of Fibiger at the University of Minnesota . However, they modified it so that some of the test animals were nourished with sufficient vitamin A, while the other part was undersupplied with this vitamin. Fibiger had fed his test animals with white bread and water. From conversations with several bakers , Hitchcock and Bell researched that there was a very high probability that Fibiger's white bread contained neither eggs nor milk , i.e. it was largely free of vitamin A. In their test animals with vitamin A deficiency, they found, in addition to the nematode infection, the far-reaching "cancerous" papillomas described by Fibiger. They identified these changes as benign. When they studied Fibiger's microphotographs, they came to the conclusion that these were also benign changes.

Fibiger's mistake

Controlled studies were rarely done in cancer research at the time Fibiger was conducting his experiments. With a comparison group of animals that were kept under identical conditions and fed with non-infected cockroaches instead of infected cockroaches (“ placebo group”), there would have been a high probability that the test results would not have been misinterpreted. Paradoxically, Fibiger himself was one of the first scientists to conduct randomized controlled trials, for example in his diphtheria trials - but not in his trials on spiroptera carcinoma. His test animals were essentially wild rats, which, depending on their age, previous way of life and ancestry, brought considerable uncontrolled fluctuations into each test series. Today, specially bred animals are used for scientific animal experiments that have the smallest possible differences and are of the same age. In Fibiger's time, the need for a balanced diet for laboratory animals was unknown, just as a lack of vitamin A promoted the development of spontaneous tumors.

Reception and aftermath

The poor reproducibility of the experimental cancer induction and the errors in the awarding of the Nobel Prize to Fibiger caused considerable uncertainty among the responsible Nobel Committee in the following years. It would be 40 years before an oncologist was awarded the prize again. The very old Francis Peyton Rous received it in 1966 for "his discoveries in the field of tumorigenic viruses", which he made in 1910.

In the 1950s, the esophageal worm ( Spirocerca lupi ) was identified as a parasite similar to Gongylonema neoplasticum , which has been shown to cause esophageal cancer in dogs .

Exactly 70 years after Fibiger's supposed discovery of spiroptera carcinoma, the two Australian physicians Barry Marshall and John Robin Warren discovered the bacterium Helicobacter pylori in gastric biopsies from gastritis patients in 1983 . They found that this bacterium is responsible for a number of gastric diseases, particularly gastric cancer. Stomach cancer is the second leading cause of cancer-related death after lung cancer, with over 700,000 deaths worldwide each year. Marshall and Warren received the 2005 Nobel Prize in Physiology or Medicine for their work on H. pylori .

The model of cancer development, which is scientifically accepted today, is based on the work of Theodor Boveri and Karl Heinrich Bauer . According to these results, cancer is a genetic disease. The transition from body cells to tumor cells takes place through a genetic change. External factors such as certain stimuli, for example from ionizing radiation, certain chemicals, viruses, bacteria or chronic inflammatory processes can enable or at least accelerate the transition. Bauer's mutation theory could be confirmed experimentally with the help of DNA analysis towards the end of the 20th century. The parasite theory is therefore obsolete today , even if certain parasites can trigger malignant tumors through chronic irritation. The recognized causal chain in this case is: parasite → chronic stimulus = chronic inflammation → gene modification → tumor and not parasite → tumor . Regardless of these findings, other theses on the development of cancer are still advocated in certain alternative medicine circles. For example, the Russian chemist Tamara Lebedewa has been spreading the claim since the mid-1990s that all cancers are caused by the single cell Trichomonas vaginalis . The so-called Clark therapy is also based on the theory that cancer is invariably caused by parasites, especially leeches such as the giant intestinal leeches .

literature

  • Anita Kildebaek Nielsen, Eivind B. Thorling: Johannes Fibiger (physiology or medicine 1926) - Backing the wrong horse? In: Henry Nielsen, Keld Nielsen (eds.): Neighboring Nobel: The history of thirteen Danish Nobel prizes. Chapter 14, Aarhus University Press, 2001, pp. 461f. ISBN 87-7288-899-7 .
  • IM Modlin, M. Kidd, T. Hinoue: Of Fibiger and fables: a cautionary tale of cockroaches and Helicobacter pylori. In: Journal of clinical gastroenterology. Volume 33, Number 3, September 2001, pp. 177-179, ISSN  0192-0790 . PMID 11500602 .
  • J. Clemmesen: Johannes Fibiger. Gongylonema and vitamin A in carcinogenesis. In: Acta pathologica et microbiologica Scandinavica. Supplement. Number 270, 1978, pp. 1-13, PMID 362817 .
  • Göran Liljestrand: The prize in physiology or medicine. In: The Nobel foundation (Ed.): Nobel, the man and his prizes. 3rd edition, Elsevier, 2007, ISBN 1-4067-4114-0 , pp. 139-277.
  • JC Petithory, J. Théodoridès, L. Brumpt: A challenged Nobel Prize: Johannes Fibiger, 1926. In: Histoire des sciences médicales. Volume 31, Number 1, 1997, pp. 87-95, ISSN  0440-8888 . PMID 11625107 . (French)

Footnotes

  1. ↑ Described by Fibiger Mus decumanus , as was customary at the time.
  2. ↑ Described by Fibiger Mus rattus , as was customary at the time.
  3. ↑ From Fibiger as Periplaneta orientalis referred
  4. ↑ From Fibiger as Phyllodromia germanica referred

Individual evidence

  1. ↑ C. Kirchhoff: Genius and Error. (PDF; 161 kB) In: MaxPlanckForschung , Heft 3, 2008, pp. 58–59.
  2. ↑ Y. Gorina et al. a .: Trends in Causes of Death among Older Persons in the United States. (PDF; 359 kB) In: Aging Trends . No. 6, National Center for Health Statistics, 2006, based on data from Deaths: Leading Causes of 2002. NVSR, Vol. 53, No. 17.
  3. ↑ R. Virchow: The pathological tumors. 30 lectures held during the winter semester 1862–1863 at the University of Berlin. Volume 1, August Hirschwald 1863, p. 74.
  4. ^ J. Cohnheim: Lectures on general pathology. A handbook for doctors and students. 2nd edition, Volume 1.2, Berlin, 1882.
  5. ^ S. Sell: Stem cell origin of cancer and differentiation therapy. In: Critical Reviews in Oncology Hematology . Volume 51, Number 1, July 2004, pp. 1-28, ISSN  1040-8428 . doi: 10.1016 / j.critrevonc.2004.04.007 . PMID 15207251 . (Review).
  6. ↑ R. Behla: About increased and endemic occurrence of cancer. In: Zentralblatt für Bakteriologie . Volume 24, pp. 875-879. limited preview in Google Book search
  7. ↑ a b H. Abramowski: On the parasitic cancer theory. In: Journal of Cancer Research . Volume 9, Number 2, 1910, pp. 385-391. ISSN  1432-1335
  8. ↑ Max Mosse, Gustav Tugendreich: Illness and social situation. JF Lehmanns, 1913, p. 609.
  9. ↑ Wolfgang Hiddemann , Claus R. Bartram : Die Onkologie. 2nd edition, Springer, 2009, ISBN 3-540-79725-4 , p. 199. Restricted preview in the Google book search
  10. ^ EF Neve: Kangri-burn cancer. In: British medical journal. Volume 2, Number 3287, December 1923, pp. 1255-1256, ISSN  0007-1447 . PMID 20771404 . PMC 2317796 (free full text).
  11. ↑ SV Gothoskar, KJ Ranadive: Experimental studies on the aetiology of "Kangri cancer". In: British Journal of Cancer . Volume 20, Number 4, December 1966, pp. 751-755, ISSN  0007-0920 . PMID 5964606 . PMC 2008146 (free full text).
  12. ↑ Hans-Werner Altmann, Franz Büchner: Handbook of general pathology. Volume 6, Springer, 1956, p. 376.
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