Published by the Students of Johns Hopkins since 1896
April 24, 2024

How the germ theory of disease developed

By ALLISON CHEN | October 18, 2018

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In the 19th century, polished white rice was increasingly sought after in Japan. Advances in technology allowed grains to be mechanically milled rather than processed by hand, with the outer and inner husks removed and the remainder polished to a glossy white. This rice was easy to store, lasted longer than its predecessors and, to some, probably tasted better. 

At around the same time, a disease known in Japan as kakke had become a serious public health concern across the nation. Symptoms included weakness and loss of sensation in the legs and feet, swelling, fatigue, and, in severe cases, heart failure. It resembled conditions described in Chinese and Japanese texts from antiquity, indicating that kakke was not a new disease. However, some physicians observed that it had become more serious since. Kakke afflicted all social classes, though it was more prevalent in large cities and especially rampant among the Japanese armed forces. 

In the 1880s, a medical officer in the Japanese Navy, Kanehiro Takaki, began to investigate the high incidence of kakke among those on military ships. Trained in Great Britain, Takaki used the epidemiological techniques he had learned abroad to narrow the list of potential causes, eventually zeroing in on diet. 

At the time, white rice was a navy staple, and in some cases it was provided for free while sailors had to purchase other types of food. Takaki noted that while an approximate 1-15 ratio of protein to carbohydrates in a diet was considered healthy, Japanese sailors, who subsisted primarily on white rice, had between a 1-17 and a 1-32 ratio in their diet. This and other observations, including that officers able to afford a varied diet were in better health than their men who relied on the free rice, led Takaki to suspect that kakke was a result of dietary protein deficiency.

Takaki persuaded reluctant authorities to change the navy diet and eliminate the old monetary system. Old regimens were supplemented with more meats and vegetables, as well as bread, milk, beans and other varied foods. 

Within a decade after the rations were changed, kakke went from affecting approximately 30 percent of Japanese navy personnel annually to affecting fewer than one percent. Despite the success of Takaki’s methods, however, his protein deficiency hypothesis was not air-tight: 

Kakke had been observed in individuals consuming large amounts of protein, and its absence had also been reported in populations consuming less protein. Aside from these inconsistencies, there remained another tantalizing explanation for the cause of kakke. The germ theory of disease had been gaining traction and prominence since its proposal by European scientists in the mid-19th century, and it remained plausible that kakke might be the result of a pathogen.

Christiaan Eijkman was, initially, supposed to find this microorganism. Kakke was not a disease unique to Japan; it had also become a serious problem in East and Southeast Asia, where it was known as beriberi. Eijkman was part of a team dispatched by the Dutch government to present-day Indonesia to investigate the disease. 

While the alleged beriberi bacteria remained elusive, Eijkman soon noticed that certain chickens in his laboratory appeared to be affected by a beriberi-like disease that could not be transmitted between animals. Upon further investigation, he found that the chickens had, for several weeks, been receiving surplus polished rice in place of their usual feed. Eijkman guessed that some substance or organism in the white rice itself was responsible for beriberi, and that it could be counteracted by something in the rice polishings discarded during processing. 

This something turned out not to be an antidote or anti-bacterial but a critical substance in its own right. In the early 1910s, Polish researcher Casimir Funk isolated a compound from rice polishings which was shown to cure beriberi-afflicted birds. Funk named it “vitamine,” the first part of the term due to its importance, the second because he thought the compound was an amine. Eventually, as more such factors were discovered, not all of which were amines, the term was changed to “vitamin.” 

We now know that beriberi is a result of low levels of thiamine, or vitamin B1. Thiamine is found, among other places, in the outer layers of rice removed during polishing. 

Other conditions, including scurvy, rickets and pellagra, would soon be explained by a similar lack of some essential vitamin. Only a half-century after the germ theory of disease was introduced to the world, hypotheses of those factors which cause illness had changed again. Diseases were no longer necessarily attributed to the presence of some pathogen but could also be the result of a vitamin deficiency. The idea of conditions being diet-related, previously discussed in general or practical terms, now had a specific mechanism within the discovery of vitamins. Takaki had been on the right track in more ways than one. 


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