ANIMALCULESA Dane to Remember
Although partially mistaken in identifying a nematode as the cause of a rat tumor, Johannes Fibiger deserves recognition for proposing the first link between a microorganism and cancer—and for founding experimental oncology
This year sees the 90th anniversary of a historic publication by Johannes Fibiger who, according to traditional ridicule, received a Nobel Prize for the clearly erroneous notion that nematodes cause malignant tumors. Although he worked with rats, the Danish physician believed that parasitology held secrets to the aetiology of some human cancers too.
These ideas have seemed rather silly to several writers who have been able to reflect with hindsight upon the false trails and frustrating mirages which have always accompanied cancer research. William S. Beck, in his otherwise excellent book Modern Science and the Nature of Life (Macmillan), records the Dane's contribution in these words as part of a passage outlining wrong-headed speculations: “Many stories of this kind could be told. In 1926, the Nobel Prize was awarded to a man named Fibiger for ‘proving’ that cancer was caused by certain small worms.” Beck then leaves his readers to chuckle at the man's naivety.
Now it is true that by honoring Johannes Andreas Grib Fibiger “for his discovery of the Spiroptera carcinoma,” the individuals at the Caroline Institute (who select the winners in physiology or medicine) implied that he had identified the specific agent of a form of cancer. Perhaps as a consequence of their wording, the authorities became unduly cautious, not only about cancer aetiology, but more widely about the risk of prematurity in bestowing their uniquely prestigious accolades. This was probably why Peyton Rous, who in 1911 had reported his discovery of a virus causing cancer in chickens, had to wait 55 years, until he was 87, to receive the 1966 prize for physiology or medicine.
Yet Fibiger did not generalize his conclusions to suggest that he had located the cause of cancer. Only later commentators have done that. More important, the meticulous Dane has rarely been credited for the considerable impact which his efforts had on the course of experimental oncology.
To appreciate Fibiger's influence, we should remember that in 1907, when he began his cancer studies, the field was in a somewhat confused condition. The English surgeon Sir Percival Pott had deduced that chimney sweeps often succumbed to scrotal cancer because they were exposed continually to coal tars in soot. But repeated attempts in both Europe and the United States to create tumors by rubbing tar into animals' skin had failed. Even after months of application, the skin of rabbits, rats, mice, and other recipients remained normal.
So, despite Pott's persuasive work, the experimental study of cancer languished. Rival explanations for the origin of malignancy proliferated with corresponding vigor. The theory that prolonged irritation was a contributory factor emerged strongly from observations on occupational cancers. But far from there being any proof, researchers were totally unable to reproduce malignant tumors, by this or any other means, in the laboratory.
Enter Johannes Fibiger, who had followed in his father's footsteps by qualifying in medicine, and subsequently worked with both Robert Koch and Emil von Behring and later held the chair of pathological anatomy at Copenhagen University. He was a founder and editor of Acta Pathologica et Microbiologica Scandinavica.
It was an accidental observation that triggered his researches into the causation of maligancy. He noticed, in the stomach of some rats, tumors which in turn contained a parasitic nematode, later called Spiroptera neoplastica. Neither the cancer nor the worm were known previously. Clarifying the relationship between the two demanded a long, painstaking investigation in which Fibiger's scrupulous approach belies the sarcasm of his later detractors.
First, he tried but failed to elicit tumors by feeding rats with either the nematodes or their eggs. Then he looked into Spiroptera's life cycle and realized that it passed part of its time in the cockroach. The eggs produce larvae in the intestines of this intermediary host, and these then enter its striated muscles, where they become encysted. Rats are not infected by consuming the parasite directly, only by eating infected cockroaches.
Sexually mature worms develop in the rat stomach, in the forepart of which tumors may then appear. These are malignant, sometimes yielding metastases. They are also capable of being transplanted into healthy rats. By revealing this sequence of events in 1913, Johannes Fibiger showed why the tumors he had discovered were so rare: they appeared only when rats ingested the parasite as larvae—and even then not with predictable certainty. Fibiger's work had two consequences for cancer research. First, it established the experimental study of malignant disease, by showing for the first time that cancer could be induced in laboratory animals. Ninety years later, with cancer research reliant on a range of disciplines, from epidemiology to molecular genetics, the significance of this shift may appear less than striking. In fact, it marked a historic thrust in the advance of medical science.
Johannes Fibiger's other contribution was to convince scientists that chronic irritation could indeed trigger the emergence of cancer. It was probably both mechanical and chemical irritation from the Spiroptera parasites, rather than any specific oncogenicity, that precipitated the development of the rat tumors. Although the explanation of his work is uncertain to this day, its role as a stimulus to others is not at issue.
One direct result was that in 1915-16 the Japanese oncologist Katsusaburo Yamagiwa succeeded, where others had failed, in producing skin cancer by rubbing coal tar repeatedly into rabbits' ears. We can trace this advance, together with consequent work by Sir Ernest Kennaway at the Royal Cancer Hospital in London, and the trail of research leading to modern concepts of promoters and inducers of malignancy, to the Dane's dogged efforts.
So the 1926 Nobel Prize for Physiology and Medicine went to Copenhagen. It did so not because anyone was convinced that Fibiger had pinpointed the agent of cancer, but because his work had laid the foundations for a major forward movement. According to the official record of their deliberations, the mandarins of the Caroline Institute adjudged that Yamagiwa's studies, though apparently more spectacular, did not have “the same degree of originality” as those of the Dane. For once, the Nobel authorities displayed rare discernment in selecting the scientist to receive their unique award.
Now that we are aware of the roles of papillomaviruses in cervical cancers, Helicobacter pylori in stomach cancers and hepatitis B virus in hepatocellular carcinoma, Fibiger's studies on Spiroptera neoplastica no longer seem outré. Nevertheless, we should applaud the rigor of his work—and recall his Nobel Prize as the first official recognition that microorganisms play a role in the etiology of cancer.
It would be reassuring to record that the years of controversy surrounding both the great Dane and the 1926 award have ended. But the signs are not hopeful. In some places, indeed, ridicule seems to have been replaced by embarrassed silence. Several prestigious bibliographical reference works have no entry on Fibiger at all. One example is the recently published Cambridge Dictionary of Scientists (edited by David, John, Ian, and Margaret Millar, Cambridge University Press, Cambridge, 2002). Fibiger's sole appearance in this book, which contains biographies of over 1300 individuals, is as just a name in a list of Nobel laureates in “psychology or medicine” (sic). This is not impressive.