11.2: The Microbes that Couldn’t Be Found

At about the same time that scientists first puzzled over their food extracts, some physicians were at work on similarly vexing problems, which at first seemed unrelated to nutrition. One line of research had started in the 1880s, sparked by an epidemic of beriberi that had broken out when the Dutch were taking over Indonesia. Though beriberi was long familiar to medical science (it had been identified by Chinese physicians thousands of years before), its cause remained a mystery.

Beriberi was characterized by weakness, which worsened as the disease progressed. In fact, the very name means “I cannot.” This weakness would be accompanied by various kinds of physical degeneration, commonly resulting, for example, in the inability to walk. The course of the disease was like a slow, painful, and helpless surrender to death.

The Dutch administrators pleaded for help with the mounting plague. Besides humane considerations, it was politically embarrassing. They had set up hospitals and medical care for people in the areas of Indonesia under their control, and even built fine, modern rice mills for their inhabitants. Yet, it was in these regions that the beriberi struck hard. In contrast, there was little beriberi in the lands held by rebels who fought against Dutch sovereignty.

The Dutch Crown responded by sending physicians, chief among them, Dr. Christiaan Eijkman. It happened that at that time, Europe was enthralled by the exciting new knowledge of how microbes caused disease. Predictably, Eijkman was instructed to find the microbe that caused beriberi, halt the epidemic, and heal the infected.

Pretty Rice, Beriberi, and the Puzzling Chicken Cure

At his hospital in Java, Eijkman kept an experimental colony of chickens. In an attempt to infect them, suspecting that perhaps food was the carrier of the “beriberi microbe,” he ordered that they be fed on the rice from the new government mills. The chickens began to weaken. Soon they were clearly victims of polyneuritis (a multiple inflammation of the nerves), the bird version of beriberi. The rice must carry the infection, Eijkman thought.

Certainly there could be nothing wrong with the rice itself. It was the best available, finely polished white by the modern mills to remove all traces of the brown hull. Yet Eijkman could find no bacteria from the rice under his microscope.

Then inexplicably, the chickens began to get well. Confused, Eijkman checked to see if there had been any change in their care. He learned that the caretaker, appalled that chickens were being fed the beautifully polished white rice, had switched them to the cheap, brown rice from the native mills.

Suspecting something of the truth, Eijkman fed the brown, native rice to his beriberi patients. They, too, began to recover. After many experiments, Eijkman had to conclude that infection wasn’t the problem. Instead, there was something in the hulls, something that was missing from the lovely white rice. He had no idea what it was, but he was sure that it was the difference between beriberi and good health.

Upon returning home to his university post, Eijkman entitled his first lecture, “The Truth Need Not Necessarily Be Simple.”

Pigeons, Beriberi, and the Curative Extract

In 1910, a 26-year-old Polish biologist named Casimir Funk arrived at London’s Lister Institute and set up a colony of pigeons. Preoccupied with the reports of both Eijkman and the scientists who were making food extracts, he was convinced, as were many others, that the two lines of research were connected.

With a diet of refined grain, Funk soon induced beriberi in his pigeons. Then he made an extract from the sweepings of a grain mill—the hulls left on the mill floor—using hundreds upon hundreds of pounds of sweepings to make ounces of extract. He gave the extract to the dying pigeons. Within hours, they were on their feet, pecking for food.

The world thrilled to Funk’s announcement of his findings. He had found a new key to curing disease, the missing essence of nutrition captured in a bottle. What cures might not be on the way?

Goldberger, Pellagra, and the Deepening Mystery

Only a year after Funk’s announcement, the U.S. Public Health Service sent Dr. Joseph Goldberger into the American South. His mission: to find the microbe which was disabling, and eventually killing some 200,000 southerners, with a disease called pellagra.

The name pellagra came from Italy. It means rough skin, referring to the fact that the first signs were rashes on sun-exposed areas of the body, rashes which developed into sores and then fissures. Then diarrhea began, and with it pains in the back, and then throughout the body. With the pain, came exhaustion, sleeplessness, and extreme irritability of the whole nervous system. In the end was madness, then death.

Healing Pellagra with Food

The more Goldberger studied pellagra, the more he was convinced that there was no infection link among victims. The main arguments for the belief that pellagra was infectious were that most patients were poor and lived under substandard sanitary conditions; the disease seemed to cluster in poverty-stricken areas and institutions.

Like Eijkman, Goldberger could find no microbes. But he did find certain living patterns common to the areas and institutions where pellagra was rife. Especially, he found certain dietary patterns.

He found that those with pellagra typically had enough to eat. Checking diets against the known nutrients, Goldberger saw that they got carbohydrates from corn, rice, sweet potatoes, greens, and sweet syrups. They got enough fat, particularly from fried foods and the gravy served with the corn and rice. But Goldberger was unsure about protein. Corn was the protein staple. Hadn’t corn been the protein staple in pellagra outbreaks in Italy, too? And elsewhere?

He set up an experiment in a pellagra-ridden orphanage. Curiously, all the children in the orphanage were not afflicted with pellagra. The infants were well, but they got milk. And the children over 12 were also free of pellagra, but they had heavy work to do, so they were given beans and meat. The children in between had pellagra.

So Goldberger, using federal funds, supplemented their diets with meat four times a week, peas and beans all winter, and an egg a day. The pellagra disappeared. The plan also worked in controlled tests in prisons and elsewhere.

Microbe or Malnutrition? Goldberger’s Test

The Public Health Service and many local physicians still were not convinced that pellagra was not an infectious disease. So on May 7, 1915, at the U.S. Pellagra Hospital in Spartanburg, South Carolina, Goldberger took a final step. He had shown that he could prevent or cure pellagra with food, and that he could induce it with a restricted diet. Now he had to prove that it wasn’t infectious.

To develop this proof, Goldberger, his wife, and a few other hardy volunteers made themselves the guinea pigs. They took some of the stool from a pellagra patient and stirred it into some flour. To this they added skin scales from the sores of other pellagra patients. Then each of the human guinea pigs swallowed some of this noxious mixture. Finally, they injected one another with blood from a pellagra patient.

Surely, if pellagra were an infectious disease, they would soon get pellagra. But they remained healthy. Goldberger had been right. Pellagra was not caused by a microbe. Rather, it was caused by a nutritional deficiency.