The 19th-Century Crank Who Tried to Tell Us About the Microbiome
Science, we are told, advances one funeral at a time1, but sometimes it progresses through resurrections.
The French chemist Antoine Béchamp (1816–1908) was a life-long rival to the great microbiologist Louis Pasteur. Pasteur invented pasteurization and vaccines for rabies and anthrax and discovered that many diseases are caused by invisible germs. Béchamp was a bitter crank who argued that microbes became dangerous when the health of the host—its “terrain” or environment—deteriorated. Béchamp was comprehensively wrong: Pasteur’s germ theory of disease, which describes how sicknesses are caused by bacterial infections (as well as by viruses that invade our cells), or else by genetics, aging, and accidents, is supported by evolutionary theory and all the observations of modern medicine. Today, Béchamp is invoked only by anti-vaxxers and disciples of alternative medicine who believe that food is medicine.
Jason Pontin (@jason_pontin) is an Ideas contributor for WIRED. He was formerly the editor in chief and publisher of MIT Technology Review; before that he was the editor of Red Herring. Now he is a senior partner at Flagship Pioneering, a firm in Boston that funds companies that solve problems in health, food, and sustainability. Pontin does not write about Flagship’s portfolio companies nor about their competitors.
Béchamp was comprehensively wrong, but not absolutely so. His idea that microorganisms are necessary to good health, and that beneficial microbiota are pathogenic under the wrong conditions or in the wrong place, is now the standard view of researchers who study the microbiology of animals and plants. A new science of the microbiome—meaning, simply, the microorganisms in an environment—emphasizes that all plants and animals on Earth evolved in combination with microorganisms and asks how microbiota interact with their hosts. Over the last 17 years, we have learnt that countless functions in living things, from digesting food to regulating the immune system to germinating seeds, rely on microorganisms. More recently still, microbiome science has attracted huge sums of venture capital to fund companies that treat hitherto intractable diseases or swell agricultural yields. (Disclosure: Flagship Pioneering, where I am a partner, has created several microbiome companies in therapeutics and agriculture.)
What changed? According to Justin Sonnenburg, a professor of microbiology at Stanford University and the author of The Good Gut, our new emphasis on the functional importance of the microbiome is the product of three events. First, beginning in 2001, scientists observed that mice with different microbiota had different biologies, suggesting that resident bacteria could modulate the host’s gene expression. Second, in 2006, researchers demonstrated that gut microbes could cause changes in a host’s phenotype, such as obesity. Finally, gene sequencing technologies developed for the human genome project were turned upon microbes in international projects like the Human Microbiome Project, freeing scientists from the limitations of culturing bacteria and revealing how microbial genes expressed themselves in their hosts. “People realized that [the microbiome] wasn’t some quirky, beautiful thing in biology, but was functionally crucial,” says Sonnenburg.
Microbiome science is a revolution in how humans understand and control biology. Pasteur’s theory of disease bequeathed to medicine a metaphor that germs were constantly besieging animals (battles in wars that were ultimately lost when bacteria overtook a corpse and it decayed). The metaphor was not the microbiologist’s fault; Pasteur knew we wouldn’t be healthy without microorganisms. But as Ed Young explains in his wonderful 2016 book, I Contain Multitudes: The Microbes within Us and a Grander View of Life, “Microbes… were cast as avatars of death. They were germs, pathogens, bringers of pestilence…. [Scientists] discovered the bacteria behind leprosy, gonorrhea, typhoid, tuberculosis, cholera, diphtheria, and plague… Bacteriology became an applied science, which studied microbes in order to repel or destroy them.”
But sterility is impossible in nature. Microbes cover everything and intrude everywhere. Microorganisms flourish at the bottom of the cold sea and in the vents of boiling hot springs; bacteria can even survive in radioactive waste. Between one to ten percent of the mass and half the cells in animals are microbiota. Sterility is also undesirable. Symbionts provide metabolic capabilities lacking in animals, such as vitamin B synthesis in termites and the digestion of grass in cows, and they modulate cellular signaling networks that regulate functions necessary for animal health, receiving in return nutrients and protection. Many plants are equally dependent on microbes: peas, clover, soy, and beans have nodules on their roots that host bacteria, fixing nitrogen from the air in the plant. In payment, the plants feed their commensal friends with sugars.
You, too: Your cells have around 20,000 to 25,000 genes, but your microbiome boasts 500 times more. More than 98 percent of your bacteria can be found in your colon; but other parts of your body have their own colonies where microbes have evolved to survive upon the oily plains of your face, in the humid swamps of your armpits, or on the slick rocks of your mouth. Your microbiota are mostly harmless, but many are functionally important to you also, crowding out more harmful microbes, teaching your immune system to recognize enemies, and influencing behavior like your appetite. One third of human milk is composed of sugars called oligosaccharides, but babies cannot digest them; the sugars are food for microbes, which furnish infants with essential nutrients that grow their brains and proteins that seal their guts.
Microbiologists often urge us to think of the microbiome as an organ, and it is. But the truth is weirder: animal and plants are multi-organismal creatures, composed of both animal or plant cells and microbial cells. We can only understand animals and plants by comprehending how they interact with the communities of microorganisms that live within and on their surfaces. But this insight was originally Béchamp’s; he understood that what we now call “dysbiosis” was just an imbalance or maladaption of the microbiome. He was the first to propose that some cancers were caused by bacteria. He would have been unsurprised to learn that a bacterial overgrowth in the small intestine leads to poor absorption of nutrients, which in turn cause unpleasant or serious symptoms, or that disturbances of the vagina’s microbiome can increase the risk of infection by HIV. In microbiology, the idea of terrain is today quietly resurgent. Janelle Ayres, a professor of immunobiology at the Salk Institute, is seeking to replace antimicrobials, such as vaccines, antivirals, and antibiotics, used to fight infections with the beneficial microbes in our guts for “damage-control therapeutics.”
These kinds of scientific resurrections occur from time to time in a complication of Thomas Kuhn’s episodic model of scientific progress (which holds that science advances as “paradigms” are overthrown when they no longer explain the world). The 18th century French naturalist Jean-Baptiste Lamarck believed that characteristics acquired in life could be inherited by succeeding generations, imagining that the giraffe’s long neck was the result of generations of prodigious stretching. The discovery of the structure of DNA buried Lamarkism, except in the Soviet Union, where it was Stalinist dogma. But over the last fifteen years, a new field called epigenetics has demonstrated that methylation, a chemical modification of DNA induced by the environment, can alter our genes: a remarkable echo of Lamark’s original thesis.
Sonnenburg cautions, “Many would say we still don't really understand [microbiome] functions now, but we do grasp their importance.” In common with many scientists, he wants to know a few things. First, what is a healthy microbiome anyway? “Humans evolved with an ancestral microbiome, which was lost during industrialization. Could the Western microbiome be a dysbiotic community that predisposes Westerners to chronic diseases?” Second, how quickly can researchers develop the microbiome for precision healthcare? “It’s individual, it's connected to most of our biology, and it's malleable: it seems perfect.” Finally, Sonnenburg wonders whether we want to rebuild our ancestral microbiome at all. Instead, he speculates, we might optimize our microbiomes for different goals at different points in life. ”A marathon runner might want something different from a pregnant woman, and a patient who needed immunotherapy might want something else.”
In other words, can humans cultivate a better terrain for their symbionts? Put so, it doesn’t seem implausible. “Nothing is the prey of death, all is the prey of life,” said Béchamp.
1 The actual maxim by German physicist, Max Planck is less pithy: “A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and new generation grows up that is familiar with it.”
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