March 2017

The Man Who Blamed Aging on His Intestines

The productive, bizarre career of Nobel laureate and early aging researcher Elie Metchnikoff.

By Luba Vikhanski

Illustration by Hannah K. Lee

One day in late December 1899, Elie Metchnikoff, one of the world’s most famous biologists, woke up to discover he had found the key to immortality. That, at least, was what the popular French daily Le Matin announced on its front page that morning. A jubilant headline blared in block letters LONG LIVE LIFE!—DOCTOR METCHNIKOFF AND THE STRUGGLE AGAINST DEATH. Sub‐headings throughout the article, which dwelt on Metchnikoff’s new research on aging at the Pasteur Institute in Paris, were no less dramatic: A VISIT TO THE ALCHEMISTS ON RUE DUTOT—THE ELIXIR OF ETERNAL YOUTH—AT THE INSTITUTE OF MIRACLES—OLD AGE DEFEATED. A few days later, in an editorial on the prospects for the upcoming century, the paper gushed, “None of us should despair to see the year 2000! We’ll reach the age of the patriarchs, and Monsieur Metchnikoff will be damned only by heirs to fortunes.”

Before long, press around the world picked up news of the miracles being wrought on rue Dutot. The horrified Metchnikoff started receiving letters from the elderly in France and elsewhere begging him to help them not to die. “Metchnikoff is really annoyed by the noise journalists make around his name,” Metchnikoff’s assistant Jules Bordet wrote to his wife in Belgium. “It’s a bit of his own fault, he should have chucked them out more vigorously.”


But chucking people out was out of character for Metchnikoff. Journalists, his comrades‐in‐arms in the sacred mission of popularizing science, had always appreciated the ease with which they could knock on his door at any time, be it to discuss his own work or that of scientists elsewhere. So when the sensational headlines began to appear, Metchnikoff countered the reports by granting ever more interviews. In February 1900, he pleaded with a Los Angeles Times reporter, “I’ve been a victim of the hasty journalists. I work and hope, but I promise nothing. I regret very much—please say that I regret very much—all the talk that has arisen about my researches.”

Metchnikoff had gained worldwide fame as the first modern scientist to claim that human beings have inner curative powers, later to be called the immune system. He had discovered the first immune mechanism known to science: mobile cells he called phagocytes, which swallow microbes and debris. Phagocytes at first sounded so outlandish that Metchnikoff’s theory of immunity was branded “an oriental fairy tale” by one prominent contemporary researcher. It was ultimately accepted—and even earned Metchnikoff the 1908 Nobel Prize in Physiology or Medicine—but it took 100 years for scientists to fully appreciate the roles phagocytes play in the body. These cells are now known to take part in a host of vital body processes and, in one way or another, are thought to be involved in almost all diseases.

In his research on aging Metchnikoff again directed his attention to phagocytes—and again came up with bold, imaginative ideas that were to have surprising but lasting effects on people’s lives. This work, along with accompanying philosophical writings, was to turn his name into a household word in Europe and America. One British magazine in 1911, relying on an international poll, was to pronounce him to be one of “ten greatest men now alive.”

“Aging is a disease that should be treated like any other.”

Metchnikoff knew that in addition to defending the organism, phagocytes performed maintenance, devouring damaged tissue. In studying autopsy samples of the elderly, he came to the conclusion that these cells had devoured a portion of their brain and body tissues.

Remarkably, after the phagocytes were done devouring, the results appeared the same in damaged organs and in aged ones. When Metchnikoff looked, for instance, at defective kidney tissue under the microscope, he was unable to tell whether the defects had been produced by microbes, alcoholism, chronic lead poisoning, or old age. In all these cases, some of the healthy kidney cells had been replaced with scar tissue. Similarly, in the bones of the elderly, healthy matrix had been eaten up by giant cells, leading to osteoporosis. Exactly the same happened when bone was invaded by microbes causing leprosy or tuberculosis.

Metchnikoff wondered: Was aging simply a chronic disease caused by microbes or poisons? His answer: “Aging is a disease that should be treated like any other.”

He hypothesized that phagocytes, provoked by infection or poisoning, were responsible for the deterioration of tissue in old age. In other words, as in his theory of immunity, his beloved phagocytes were yet again granted a star status—but surprisingly, they were no longer heroes but villains. Aging appeared to him as a Darwinian struggle of sorts between stronger and weaker cells.

We now know that aging is an extremely complex process, nudged along by hundreds of genes. Phagocytes are but one theme in this symphony. Their primary job is to maintain tissues in good order, even if their accumulated effects lead to damage later in life. Yet Metchnikoff, certain he had identified the villains, started developing strategies to protect body tissues against phagocytes. Perhaps a vaccine could eliminate the microbes that overly excited the phagocytes? He tried, unsuccessfully, to prepare a vaccine from such startling sources as digestive juices of moth larvae, flies, and dung beetles, whose innards are known to destroy microbes.

FEASTING PHAGOCYTEPictured above in green, a white blood cell (a type of phagocyte) devours a red blood cell, shown here as purple. Metchnikoff hypothesized that phagocytes, provoked by infection or poisoning, were responsible for the deterioration of tissue in old age.
National Institutes of Health / Stocktrek Images

In the midst of these studies, Metchnikoff had been careless enough to discuss his ideas with journalists, who trumpeted the reports on his research as if it were a miracle in the making. From then on, they were to hang on his every word, hailing him as “the successful Ponce de León,” referring to the 16th‐century Spanish explorer who had searched for an island with a fountain of youth, instead finding Florida. Marveling at the passion with which Metchnikoff delivered his public lectures, the journalists delighted in describing his “small, mischievous eyes” twinkling behind thin-rimmed spectacles, his shaggy beard and his “undisciplined hair, lying in heaps, tangled like wheat after a thunderstorm.” And Metchnikoff, who turned into what today would be called a media personality, never disappointed them or their readers, promising at least to reveal the mechanisms of aging if not eliminate it altogether.

“Scientists have been neglecting aging, which nonetheless presents a problem of great interest,” he announced in his first research paper on the biology of aging in the Annales de l’Institut Pasteur in 1901. In that paper, he turned to the most telltale sign of aging: the whitening of hair.

Finding pigment‐filled cells in graying hairs, Metchnikoff reached the conclusion that a subclass of phagocytes was causing the hair to lose color by gobbling up its pigment.  (According to modern science, the whitening of hair is a genetically controlled process that has to do with the hair follicles ceasing to produce pigment. But Metchnikoff was not entirely off the mark in his interpretation, as phagocytes do play a role in removing pigment during the normal hair growth cycle.)

The newspapers had a great deal of fun with these findings. Le Temps evoked the famous case of Queen Marie Antoinette, whose hair had supposedly turned white overnight before she was beheaded. Le Figaro quoted Metchnikoff as saying that women who curled their hair with a hot iron were possibly delaying its whitening, since heat could damage pigment‐eating cells. Le Petit Parisien cited a prominent Parisian physician as suggesting that the recently discovered X‐rays might be even more helpful than heat in protecting the hair from the “color‐eating cells.”

Metchnikoff, in the meantime, was trying to figure out why we die. He soon developed a theory of aging aimed at extending human life.

In April 1901, after crossing an unusually calm English Channel, Metchnikoff for the first time exposed his newly formulated theory of aging to the public in the notoriously rainy Manchester. He traveled there to receive the Wilde Medal of the Manchester Literary and Philosophical Society, the first foreigner to achieve this honor. In the society’s compact lecture hall, he delivered an hour‐long lecture in French, “The Flora of the Human Body,” in which he outlined his brand‐new explanation of why we age and die too soon.

The culprit, he announced, was the body’s flora—microscopic organisms inhabiting our internal organs, primarily the large intestine, or colon, the body’s largest microbe container. The idea that waste products in the intestines poison the human body went back at least to ancient Egyptians. In the late 19th century, with the establishment of the link between germs and disease, this belief had gained new validity, turning into a short‐lived obsession among physicians. The contents of the gut were thought to putrefy and release toxins through the action of bacteria.  Physicians were attributing anything from headaches and fatigue to heart disease and epilepsy to these toxins, having their patients swallow disinfecting mixtures containing charcoal, iodine, mercury, or naphthalene to “sterilize” the intestines.

People would develop an “instinct” for death, just as they have a need for sleep.

Metchnikoff conceded that intestinal flora could be beneficial too, but most of these microbes, he argued, exert a harmful effect on the body, “and this leads to premature aging of our tissues and organs.”

Lashing out with a bitter invective against the colon, Metchnikoff, as a zoologist and a Darwinist, pointed to the animal origins of human beings. In our evolutionary past, the colon had helped mammals to survive. It contained not only microbes that facilitated the digestion of plant food but also remnants of digested food, enabling the animals to chase prey and escape predators without stopping to empty their bowels. Humans, on the other hand, he said, “derive no benefit from this organ,” particularly since they cook their food, making it easier to absorb. Though the colon was already known to play a role in the absorption of water and minerals, Metchnikoff believed it was less essential in this respect than the stomach or the small intestine. He was certain the colon should have long been eliminated by natural selection, if only the latter were more effective.

What crystallized from these ideas was Metchnikoff’s very own law of longevity. He took on the riddle that some of the greatest minds had tried to solve since antiquity: is there some hidden natural clock that dictates the length of life? Aristotle had noted that larger animals tended to live longer than smaller ones, an observation that works as a broad principle but has too many deviations to qualify as a general rule. In the 19th century, scientists had proposed a rule by which maximum longevity of living beings was said to be proportional to their period of growth. One French biologist pronounced this ratio to be 5 to 1 in mammals, which allotted humans a life span of about 100 years. But the ratio was too arbitrary to furnish an explanation; a particularly upbeat version was 7 to 1, instantly extending maximum longevity to 140 years.

GERMOPHOBES UNITEGameshow host Howie Mandel shaves his hair and prefers to fist bump instead of shaking hands, for purposes of hygiene. Metchnikoff boiled his food before eating it to avoid ingesting harmful bacteria.
Michael Tran / Getty

Metchnikoff proposed his own explanation. “I’m almost inclined to derive a general rule: The longer the large intestine, the shorter the life,” he declared. Of the small animals that can be kept as pets, he said, birds such as canaries live up to 20 years, as do goldfish, and turtles live even longer. In contrast, mice live three or four years at most, and they are the only small pets to have a proper colon. The numerous exceptions to this rule did not disturb him in the least. He argued, for instance, that elephants lived long despite having a very large colon thanks to peculiarities of their intestinal flora.

Just as he had promised his enraptured Manchester audience, upon returning to Paris Metchnikoff threw himself into the conquest of aging. What intrigued him most were the bodies of aging humans. He organized supplies of tissue samples of the old deceased from the morgue, scoured the newspapers for reports on unusual longevity, and sought out the elderly wherever he went to learn how they coped with life’s approaching end.

In contemplating matters of life and death, Metchnikoff discovered a tragic paradox that certainly applied to himself if not to everyone else: The closer one gets to life’s end, the more one wants to live. As a result, he noted, people end up dying just when their “life instinct” is the greatest. “Our strong will to live runs counter to the infirmities of old age and the shortness of life. That’s the greatest disharmony of human nature,” he proclaimed in his first philosophical book, The Nature of Man: Studies in Optimistic Philosophy, published in Paris in the spring of 1903.

If people attained a “natural” span of life, uninterrupted by disease, malnutrition, or accidents—he estimated such a life span to be “significantly above a hundred years”—no one would fear death, he claimed. Not only that, people would die willingly. They would develop an “instinct” for death, just as they have a need for sleep.

Metchnikoff said grapes were covered with so much dust that eating them was “suicidal.”

“The purpose of human existence lies in going through a normal cycle of life, leading to a loss of the life instinct and a painless old age, bringing about a reconciliation with death,” he wrote in his book. In future writings, he was to clarify that “merely living longer” was not enough. The goal was to go through “a progressive evolution of the life instinct until the emergence of the death instinct.” The longer we live, the greater the chance of developing such an instinct, he argued, adding that in future generations, people could live 150 years.

Promptly translated into several languages, The Nature of Man enjoyed tremendous popularity around the world, going through five editions in Metchnikoff’s lifetime and remaining in print 100 years later. The book’s philosophical ideas were to earn Metchnikoff the moniker “Apostle of Optimism” in a 1909 New York Times profile.

In the meantime, Metchnikoff—ever a pragmatic utopist—focused on elaborating practical guidelines for achieving a normal life cycle. It’s not enough to define the purpose of life as a full cycle, he wrote in a preface to one of the book’s later editions: “One must also show how to achieve this normal cycle, overcoming all the obstacles in its way.”

Visitors who stopped by Metchnikoff’s lab at the Pasteur Institute around lunchtime could find him in his study, at a massive oak desk by a tall window, hovering like a sorcerer—some said like Dr. Faust—over a Bunsen burner to toast his bread or sterilize his knife, fork, and spoon. He abided by strict hygiene to prevent the entry of harmful germs into his gut, eating nothing raw and drinking water that had been filtered, then boiled. He plunged strawberries, dates, and other fruit—even peeled bananas, which he thought were insufficiently protected from microbes by their thick skins—into boiling water for several minutes before eating them.

Wherever he went, Metchnikoff preached what he himself practiced. When riding a train or an omnibus, he would explain to housewives how to keep their food free of germs. Entering a grocery store, he pleaded with the owner to protect the cheeses from flies by using a metal mesh and to serve the groceries, especially those to be eaten uncooked, by tongs rather than by hand.

Resentment and ridicule were often his reward. Bakers were angered by his claims that the Saint‐Honoré cake, a classic French dessert of puff pastry and cream, was dangerous because it was filled with uncooked beaten egg whites. His dire verdict on grapes—he said they were covered with so much dust that eating them was “suicidal,” not to mention that their seeds could cause appendicitis—brought upon him the wrath of the French Society of Viticulturists, echoed by the daily La Justice: “If one can’t eat fruit, drink unboiled water, or kiss those you love, it’s not certain that life would be worth living.”

Back in the lab, Metchnikoff tried to learn as much as possible about the germs that, despite all preventive measures, did manage to penetrate the body. Louis Pasteur had believed that in the human gut, microbes were of great service or perhaps even indispensable for digestion. Metchnikoff launched pioneering studies into gut microbes that became a central theme in his lab: determining what effect these microbes really exerted on the body. He believed that under certain circumstances, particularly during disease, some of them could cause a detrimental process akin to rotting that he called “intestinal putrefaction.”

The issue was controversial; some scientists believed no such process took place in the gut and if it did, that it wasn’t necessarily harmful. Yet others argued that even consumption of rotten food caused no harm, citing the peculiar preference for rotten fish and meat known to exist among people in Greenland, Polynesia, and a few other parts of the world.

EARLY PROBIOTIC PILLSTablets of milk-souring microbes manufactured in Paris according to Metchnikoff’s instructions around 1905 to 1910. The package insert states that they are composed of “pure cultures of lactic bacilli.”
Luba Vikhanski

A young doctor, Henry Tissier, had just then joined Metchnikoff’s lab after completing a thesis at the University of Paris on the intestinal flora of sick and healthy newborns. Metchnikoff assigned him to study the rotting of meat, which, he thought, could shed light on the supposed intestinal putrefaction. As Tissier and another researcher report in the Annales, in one of the experiments they swallowed pieces of rotten horsemeat to study its impact on their gut chemistry. (The reader may be relieved to know they did not get sick.) These were the kind of heroic acts Metchnikoff inspired in his assistants.

Next, Metchnikoff instructed Tissier to study another type of chemical transformation of food: fermentation that causes milk to turn sour. Half a century earlier, it had been Pasteur who discovered that fermentation was the work of living organisms. Tissier wanted to find out why the microbes, instead of causing the milk to rot, rendered it sour but free from unpleasant types of decomposition. Was milk more stable than meat because of the sugar or certain proteins it contained?

Metchnikoff’s team supplied evidence for a different explanation: sour milk owes its stability to the lactic acid that microbes produce from milk sugar in the course of the fermentation. The acid acts as a preservative, keeping the milk palatable while preventing undesirable decomposition. It kills the microbes that could cause decomposition. Rot‐causing germs failed to grow when placed in the same broth with milk‐souring organisms, but when the scientists added soda, which neutralizes acids, the rot‐causing germs began to multiply immediately. “The milk microbes consistently produce large amounts of acid, which hinders the activity of the putrefaction bacteria,” Metchnikoff wrote in The Nature of Man.

If sour milk generally blocks rotting, he reasoned, perhaps it could block toxins in the gut. “Clearly, the slow intoxication, which weakens the resistance of our noble elements, can be arrested by sour milk, preferably of the type that doesn’t contain alcohol,” he wrote.

Just then one Professor Léon Massol of the University of Geneva provided Metchnikoff with a sampling of Bulgarian sour milk known in Bulgaria as yahourth or kisselo mleko. Stamen Grigoroff, a Bulgarian student in Massol’s lab, had found it to contain rod-like organisms, later called Lactobacillus bulgaricus, that generated particularly large amounts of lactic acid—25 grams per liter of milk. No less significant was Grigoroff’s observation that a surprisingly large number of centenarians lived in the region of Bulgaria in which the yahourth constituted the main dietary staple.

Rumors about large numbers of centenarians often circulated about mountainous villages or other regions with no reliable birth registers. But Metchnikoff’s desire to find a cure for aging was so strong, he did not seem to care whether the stories about Bulgarian centenarians were reliable or not. Suddenly, it all came together for him. On the one hand, the large intestine was infested with “bad” germs. On the other hand, milk‐souring microbes blocked the growth of such germs. And the sprightly, elderly Bulgarians consumed extraordinary amounts of sour milk. Metchnikoff’s hypothesis: Milk‐souring germs could help counter the harmful gut microbes responsible for aging.

It’s rare to be able to trace a global dietary trend to a single event, but the modern yogurt industry was arguably born in the lecture hall of the Society of French Agriculturalists in Paris on June 8, 1904—the day Metchnikoff delivered there a public lecture titled “Old Age.”

Metchnikoff urged his listeners to avoid eating raw food as much as possible. “It’s a source of all sorts of wild microbes,” he said. “Even if raw fruit and vegetables, such as strawberries, cherries, lettuce, and radish are washed, they retain some of the dust, earth, and sometimes excrement.” But avoiding harmful germs was not enough; beneficial ones had to be cultivated in the intestine, such as the one isolated from the Bulgarian sour milk. “Interestingly, this microbe is found in the sour milk consumed in large amounts by the Bulgarians in a region well‐known for the longevity of its inhabitants. There is therefore reason to suppose that introducing Bulgarian sour milk into the diet can reduce the harmful effect of the intestinal flora,” Metchnikoff said.

Within months of Metchnikoff’s lecture, milk‐souring germs had blossomed into an international business. Pharmacies throughout Europe and the United States were offering Bulgarian cultures in the form of tablets, powders, and bouillons. Metchnikoff had infused modern meaning into a health concept formulated by Hippocrates: achieving health through diet. There was no proof, only an idea. Neither Metchnikoff nor anyone else could have imagined the revolutionary impact it was to have on the diets of future generations worldwide.

Excerpted from Immunity: How Elie Metchnikoff Changed the Course of Modern Medicine, by Luba Vikhanski, with permission from Chicago Review Press. Copyright © 2016, all rights reserved.

This article was originally published on Nautilus in our “Aging” issue in May 2016.