Abstract

One century ago, Christiaan Eijkman was appointed Professor of Bacteriology and Hygiene at the University of Utrecht, The Netherlands. Despite his appointment to teach bacteriology, Christiaan Eijkman made his main contribution to medical science not in bacteriology but in nutrition. He discovered that beri-beri was not an infection but a nutritional deficiency (later called vitamin deficiency) and received the Nobel Prize for Medicine in 1929 for these observations. These landmark studies were made in the former Dutch East Indies. As professor of bacteriology he established an important school of medical microbiology in The Netherlands.

Christiaan Eijkman was born on 11 August 1858, in the rural village of Nijkerk, The Netherlands, as the seventh of ten children. His father, a schoolmaster, was running a boarding school at the time. Early on, Eijkman proved to be an exceptionally bright youngster with a desire to study medicine. Since financial resources were limited, to obtain a medical training he signed up for the colonial army; the Department of War then paid the bill. In this way, Christiaan Eijkman joined the army in the Dutch East Indies after finishing his medical studies to obtain a Ph.D. degree in physiology. The title of his Ph.D. thesis was: ‘Polarisation in the Nervous System’.

In 1883, Eijkman sailed to the Dutch East Indies, where a colonial war had broken out in the province of Atjeh. Eijkman was soon struck by the number of soldiers incapacitated by beri-beri, known in colonial medical circles as polyneuritis endemica perniciosa. He discovered that beri-beri was endemic and that both native and European soldiers were afflicted by the disease. Very soon he came to the conclusion that the disease must be of infectious origin and he decided to make a thorough study of beri-beri in order to discover its bacterial source.

After a two-year stay in the East Indies, Eijkman obtained permission to return to The Netherlands because of his wife's ill health. Soon after his return to Holland Eijkman's wife died. Eijkman was obsessed by the problem of beri-beri and decided to visit Robert Koch in Berlin to learn some basic bacteriological techniques. There, the party of three Dutch scientists : Eijkman, Winkler and Pekelharing was formed, to study beri-beri.

In 1885, Eijkman returned to the Indies, first as an assistant of Pekelharing and Winkler, who after one year, however, both returned to Holland. Both were convinced that beri-beri was an infectious disease caused by exotoxin-producing bacteria that cause nerve cell degeneration. During their research, they had isolated micrococci from the blood of patients and claimed that these microorganisms played a crucial role in the pathogenesis of the disease. They appealed to the Governor-General of the East Indies to maintain the laboratory facilities they had been using and to transform the building into a Laboratory for Pathology and Bacteriology. Eijkman was relieved from his military service and became the first director until 1896. Interestingly, today this laboratory is a modernized edifice and houses the ‘Indonesian Institute for Molecular Biology’ under the directorship of Professor Sangkot Marzuki.

The cultures of micrococci left by Winkler and Pekelharing were used by Eijkman in animal models. The results, however, were not successful. Shortly afterwards, one of Eijkman's French assistants showed him chickens suffering from polyneuritis, which was very similar to the symptoms seen in patients with beri-beri. Eijkman's assistant alerted him to the change in feeding from 10 June through 22 November. During that period, the chickens were fed cooked rice, leftovers from the army hospital. Sick chickens were seen from 10 July until November. After November, the chickens were fed normal chicken fodder and no sick animals were seen from then on. The experiment with cooked rice and chicken fodder was repeated. Once more, it showed that chickens fed cooked rice almost all died, while no deaths were observed among normally fed poultry. Eijkman could hardly believe his own conclusion that an ordinary item like rice had been the cause of beri-beri in chickens. He arrived at the hypothesis that certain chemical components in rice were changed biochemically by the normal intestinal flora and that these biochemical derivatives were neurotoxic. He was not able, however, to find toxins in either the gastrointestinal tract or the nerve tissues.

After reading Eijkman's work on beri-beri and discussing the results, the Inspector-General of Public Health in the Dutch East Indies, Mr. Vorderman, interviewed all district health inspectors and found that in 34 of the 63 prisons where white (polished) rice was served, beri-beri was endemic; of 27 prisons where red (unpeeled) rice was the main diet only one prison occasionally had beri-beri cases. The Health Inspector immediately decreed that red rice should be served to all prison inmates. Almost overnight beri-beri was eliminated from prison populations. This Health Inspector, a superb organizer who translated Eijkman's work into a practical decree, saved thousands of lives.

When Eijkman returned to Holland, he left behind a polemic war between scientists who still believed in the infectious nature of beri-beri and those who were convinced of a dietary deficiency. Meanwhile, the High Commissioner of the Dutch East Indies appointed Grijns and Boorsma to determine the component in rice that seemed to prevent beri-beri. Ultimately, Grijns delivered the final blow to the infection/toxin theory. It was impossible to induce the sickness in chickens injected with sera.

Not long after his return to The Netherlands, Eijkman was appointed Professor of Bacteriology and Hygiene at the University of Utrecht. Eijkman, who developed a broad spectrum of interests, established the Department of Hygiene in Utrecht. He worked on the physiology of bacteria and remained interested in wholesome diets and social medicine. Together with Beijerinck, Eijkman founded The Netherlands Society for Microbiology in 1911 and became its second chairman. Later, he became a foreign associate of the National Academy of Sciences in Washington. From 1912 to 1913, he was nominated rector of Utrecht University. In 1923, he was awarded the John Scott Medal in Philadelphia; in 1924, he became an Honorary Fellow of the Royal Sanitary Institute in London; and in 1929, he was appointed corresponding member of the Wiener Gesellschaft fuü r Microbiologie (Vienna). In that same year, he also received the Nobel Prize for his work on beri-beri. The results of that work saved millions of lives. Unfortunately, his health was then deteriorating and prevented him from travelling to Stockholm for the occasion and his lecture was therefore read in his absence.

We honour Christiaan Eijkman by commemorating the 100th anniversary of his inauguration as Professor of Bacteriology and Hygiene and as the founder of the Department of Hygiene in Utrecht, The Netherlands, now called the Eijkman-Winkler Institute. Eijkman's name and work are also remembered in Indonesia, in particular by the Indonesian Institute for Molecular Biology which stands on the original site of Eijkman's former laboratory.

For a more detailed account and further references, see

[1]

Verhoef
J.
(
1998
)
Christiaan Eijkman: Early Nobel winner for beriberi research
.
ASM News
64
,
688
692
.

[2]

Verhoef
J.
Snippe
H.
Nottet
H.S.L.M.
(
1999
)
Christiaan Eijkman
.
Antonie van Leeuwenhoek
75
,
165
169
.