Johannes Fibiger

views updated May 18 2018

Johannes Fibiger

Johannes Fibiger (1867-1928) was a Danish bacteriologist and pathologist who made important research contributions to the study of diseases such as diphtheria, tuberculosis, and cancer, as well as important advances in clinical research methodology. He received the 1926 Nobel Prize in Physiology or Medicine for his research on parasites and cancer in rats.

At that time, Fibiger was believed to be the first person to induce cancer in a laboratory setting. It was later shown that he had not actually caused cancer in his sample of rats. Despite the fact that his award-winning finding was disproved, Fibiger made other important contributions to cancer research, particularly with respect to the role of individual predispositions in cancer development.

Early Life and Education

Johannes Andreas Grib Fibiger was born on April 23, 1867 in Silkeborg, Denmark. He was the second child born to Christian Fibiger, a local physician, and Elfride Muller, a writer. He was named after his father's brother, who was a clergyman and a poet. When Fibiger was only three years old, his father died of apoplexy and he moved to Copenhagen with his mother and sister. His mother supported her family by writing short stories, journals, and cookbooks. In 1882 she also established the Copenhagen Cooking School, the first of its kind.

Fibiger's mother was preoccupied with supporting her family and spent little time with her children's education. Fibiger was sent to an elementary school run by one of his uncles. He was a diligent student who was interested in insects and botany. He spent all of his holidays with another uncle, the Reverend Johannes Fibiger, who helped raise him and supported his education. At the age of 16 Fibiger passed his matriculation exam and began to study zoology and botany at the University of Copenhagen. He paid for his education by teaching and working at the zoology laboratory at the university.

While Fibiger was studying he lived at home with his mother. His mother's cooking school had flourished and expanded to include a restaurant. A distant cousin, Mathilde Fibiger, also the daughter of a physician, came to work at the school as a teacher and an accountant. When Fibiger was 21 years old, he became engaged to her. She continued to live with his family and friends until Fibiger finished school and they could be married. Fibiger completed his medical degree in 1890. For the next few years he worked as a physician at various hospitals, including the famous research laboratories of Robert Koch and Emil von Behring in Germany. On August 4, 1894 he finally married Mathilde Fibiger and the couple had two children together.

Diphtheria Research

Fibiger returned to the University of Copenhagen where he worked as an assistant in a bacteriological laboratory. He also pursued his doctorate with research on diphtheria, a childhood virus that caused its victims to suffocate. During Fibiger's time, diphtheria was a major public health concern throughout Europe. Fibiger made three important contributions to studying the disease. First, he discovered better ways to grow the bacteria in a laboratory setting. Second, he proved that there were two different forms of the bacillus, which was important to understanding how the disease was transmitted. Third, and most importantly, Fibiger produced a serum against the disease.

In 1895 he received his doctoral degree from the University of Copenhagen. Fibiger then went to work as a junior physician at Blegdamshospitalet in Copenhagen where he continued to work on diphtheria. At that time there had been no proof that a serum was effective against diphtheria. Fibiger believed that the lack of proof was a result of how the experiments were conducted and not a result of an ineffective serum. In 1896 Fibiger convinced his superior at the hospital, Professor Sorensen, to conduct a more controlled experiment on the diphtheria serum. Between May 13, 1896 and May 13, 1897 patients admitted to the hospital received the standard treatment or standard treatment plus the diphtheria serum. They were assigned to either the experimental or the control group depending on the day they arrived at the hospital. After the yearlong experiment, only eight out of 239 patients in the serum group had died, while 30 of the 245 patients in the control group had died. This was strong evidence in favor of the serum.

According to an October 1998 article in the British Medical Journal, this "was the first clinical trial in which random allocation was used and emphasized as a pivotal methodological principle. This pioneering improvement in methodology, combined with a large number of patients and rigorous planning, conduct, and reporting, makes the trial a milestone in the history of clinical trials." In this respect, Fibiger was ahead of his time in realizing the importance of random error and bias in clinical experiments. Fibiger established a reputation for himself as a careful scientist who paid attention to detail. However, the methodological improvement of a controlled clinical trial had little immediate impact on the research community. Random assignment in clinical experiments was not fully appreciated until after Fibiger's death. Nonetheless, the International Medical Congress published the results of his study in 1897. The study had an important practical consequence as the demand for the proven diphtheria treatment led to the creation of the Serum Institute.

Cancer Research

In 1900 Fibiger was hired by the University of Copenhagen to direct the Institute of Pathological Anatomy where he was dedicated to building a successful research program. Fibiger and his colleague, C.O. Jenson, conducted ground-breaking research on tuberculosis in cattle. Contrary to popular opinion, they demonstrated that humans could contract tuberculosis from the milk of infected cattle. Their findings contributed to the passage of stricter government regulation of milk, which, in turn, led to fewer adolescent deaths due to tuberculosis.

Fibiger then went on to study tuberculosis in rats, which led to a discovery that would eventually win him a Nobel Prize. In 1907 Fibiger found stomach tumors in three wild rats that he had dissected. Within the tumors he found a new type of roundworm which he and a colleague called Spiroptera neoplastica. Fibiger believed that the worms caused cancer and he sought to reproduce this phenomena in a laboratory setting. Initially he was unsuccessful. However, Fibiger later tested new specimens from a sugar factory infested with mice and cockroaches. From his new sample he found that 75 percent of the mice had the roundworm Spiroptera neoplastica and 20 percent of those that had the roundworm also had stomach tumors. Fibiger concluded that the cockroaches were infected with the cancer causing roundworms and they, in turn, infected the mice. Fibiger proceeded to test his idea in the laboratory by feeding infected cockroaches to wild mice and rats that he caught specifically for his research.

Fibiger was able to reproduce what he believed were cancerous stomach tumors in his sample of mice and rats. He was thus believed to be the first person to produce cancer experimentally in a laboratory, which was considered a major breakthrough in cancer research. He officially announced his discovery to the Royal Danish Academy of Science in 1913 and later published his results in the Journal of Cancer Research, which brought him international acclaim. In 1926 he was awarded the Nobel Prize in Physiology and Medicine for his discovery and in 1927 he received the Nordhoff Jung Cancer Prize.

Research Refuted

Within a few years after publishing his results, Fibiger's study was challenged by other researchers who claimed that the tumors were not caused by worms and that they were not even cancerous. Additionally, Fibiger's methods were criticized because he did not have a control group that was not fed cockroaches. Opponents to Fibiger also could not replicate his results because, at that time, there was not a standard strain of laboratory rats and Fibiger caught his sample of mice and rats in the wild.

Fibiger refuted his opponents' claims until his death. After World War I he left his work in parasitology to pursue the research of two Japanese scientists who painted the ears of rabbits with coal tar to induce cancer. Fibiger conducted similar studies and reported that cancer did not occur with the same frequency either between or within species. He was one of the first cancer researchers to emphasize the importance of individual predisposition in cancer development. Fibiger's final project before his death involved developing a vaccine for cancer using matter from malignant tumors. Fibiger became ill while in Stockholm for the Nobel festivities. He was taken to a hospital and diagnosed with colon cancer. He died of a massive heart attack on January 30, 1928 in Copenhagen.

After his death Fibiger's award-winning research was resoundly refuted. New research on vitamins that had only just begun after Fibiger's own study would eventually show that the lesions found in Fibiger's rats were most likely the result of a vitamin A deficiency. This discovery did not completely disprove Fibiger's claims. However, in conjunction with the other criticisms of the study, this new research made it unlikely that Fibiger actually did first induce cancer in laboratory animals. Later research suggested that the worms could have been a coincidence rather than a cause because the worms could have been carrying a cancer-causing virus. American pathologist Peyton Rous made this discovery just three years after Fibiger's study, but he had to wait until 1966 before he received the Nobel Prize for discovering cancer-causing viruses.

Scientific Impact

While some have gone so far as to claim that Fibiger's Nobel Prize was a mistake, others still credit him for important cancer research. The conclusions from his 1907 study were wrong, but the research was nonetheless a contribution to the field. In fact, more recent work on cancer has shown that parasites still might play a role in the cancer process. For example, a parasite similar to that found by Fibiger has been shown to cause cancer in dogs and a different kind of parasite has been linked to stomach cancer. In a December 9, 1994 article in the Sunday Telegraph Robert Matthews summed it up best when he wrote, "Almost 70 years after his death, Fibiger may have been right after all—but for the wrong reasons."

Fibiger may be best known for this one error, but he made significant contributions to the study of diphtheria, tuberculosis, and cancer in his lifetime. He published 79 scientific papers and founded and edited the journal Acta Pathologica et Microbiologica Scandinavica. In addition to teaching and research, he served the professional medical community in many roles, including president of the Danish Medical Society, president of the Cancer Committee of the General Association of Danish Physicians, and president of the Northern Association of Pathologists. He served on many academic boards and was the member of many professional organizations, including the Royal Danish Scientific Society. He also received honorary degrees from Louvain and Sorbonne in Paris.