Probiotic Philosophy

A Brief History

Renowned microbiologist and Nobel laureate Joshua Lederberg coined the term “microbiome” in 2001 to represent “the ecological community of commensal, symbiotic, and pathogenic microorganisms that literally share our body space.’’ He added that these companion microbes “have been all but ignored as determinants of health and disease.” Clearly, with the emergence of microbiomics as a large multidisciplinary field of scientific inquiry, this is no longer true, but Lederberg may have overstated the degree of past neglect. An historical review shows that the interdependence of human beings and microorganisms has long been an important, albeit slighted, focus of research in the life sciences and biomedicine, and modern health practices have frequently taken the form of microbial diplomacy.

On June 13, 2012, the National Institutes of Health (NIH) announced the completion of the Human Microbiome Project (HMP), a five-year census of microbial communities living on and inside human bodies. The next day, a series of papers reporting the project’s findings were published simultaneously in Nature and several Public Library of Science (PLOS) journals.

More than 200 investigators from more than eighty top-flight research institutions had participated. They had sequenced DNA from more than 5,000 samples of microbial populations swabbed from volunteers’ mouths, skin, and guts, and identified and mapped the locations of more than ten thousand bacterial species.

The results made headlines in scientific journals, newspapers, and popular magazines around the world. Nature hailed the achievement as a biomedical milestone, a huge step in understanding “our microbial selves.” The Economist redrew Leonardo da Vinci’s Vitruvian Man as a grotesque human-microbe chimera and proclaimed “microbes maketh man.”

Writing for The New Yorker, Michael Specter provided a vivid description of early childhood intended, obviously, to make readers question their perceptions of the natural world and their ordinary experiences within it: “We leave the womb without a single microbe. As we pass through our mother’s birth canal, we begin to attract entire colonies of bacteria. By the time a child can crawl, he has been blanketed by an enormous, unseen cloud of microorganisms — a hundred trillion or more.”

Journalists reporting on the HMP emphasized three messages: 1) Human beings are now obliged to understand themselves as ecosystems; 2) the invisible but teeming microbial hordes covering us from head to toe, inside and out, are mostly friendly and beneficial, important for the maintenance of good health; and 3) as hosts, human beings have behaved atrociously. At best, we have been thoughtless, ill mannered, and uncouth.

Some participating researchers portrayed the HMP as a science-based challenge to the “war on germs” that the medical profession has been waging with chemical weapons for over a century. Julie Segre, a senior investigator at the National Human Genome Research Institute (NHGRI), told the New York Times, “I would like to lose the language of warfare. It does a disservice to all the bacteria that have co-evolved with us and are maintaining the health of our bodies.”

The metaphor’s persistence is understandable. The principal business of doctors, from the middle of nineteenth century through the first half of the twentieth, was combating infectious diseases. By the 1940s, physicians (and their allies, public health officials, bioscientists, and pharmaceutical makers) had made significant progress. Pneumonia and tuberculosis were no longer leading causes of death in industrialized countries. Chronic diseases of age and lifestyle — cardiovascular diseases and cancers — had supplanted them.

The institutional power of the medical profession was tied to its victory in the war against infectious diseases, and only in the last twenty years have practitioners belatedly come to recognize the severity of the problem of bacterial resistance caused by the overuse of antibiotics. Yet, it is a mistake to call the warfare metaphor entirely inapt or anachronistic, for at least two reasons. One is that modern medicine continues to battle pathogenic bacteria. The objective is to neutralize or destroy — that’s warfare. Secondly, the warfare metaphor never represented the zeitgeist of twentieth century biomedicine in its totality.

The rise of metagenomics has not engendered a conceptual paradigm shift. The dominant philosophy of twentieth century bioscience, biomedicine, and bioindustry may have been antibiotic, but it always coexisted with strands of probiotic theory, research, and production. And now, while tremendous advances in the speed, convenience, and economy of DNA sequencing have permitted scientists to generate novel insights into the composition and functions of human microbiota, the findings of the HMP and related initiatives serve not as revelations of human-microbe symbiosis but rather as enriching reminders.

Probiotic philosophy

Nothing exemplifies the recent probiotic renaissance in science and medicine more than the acceptance of fecal transplantation as a viable alternative to the use of antibiotics in the treatment of gastrointestinal infections (and perhaps other conditions as well — practitioners have reported salutary effects on disorders ranging from rheumatoid arthritis to insomnia and depression). Preparations of stool from healthy donors are implanted in the intestines of patients. The idea is to displace populations of pathogenic microbes by introducing friendly bacteria capable of restoring ecological balance to the gut.

Fecal transplantation has a long history, dating back at least to the Dong-jin dynasty in fourth century China. Ge Hong, a traditional healer, wrote about using orally administered fecal preparations to treat food poisoning and severe diarrhea. He claimed to cure patients at death’s door. In the sixteenth century, during the Ming dynasty, the Ben Cao Gang Mu, the encyclopedia of traditional Chinese materia medica, described the successful use of various fecal solutions, suspensions, and powders in cases of acute gastrointestinal illness.

The first transplant in the United States was reported in 1958 in the journal Surgery. Four physicians at the University Colorado School of Medicine documented the successful treatment of four patients with acute pseudomembranous colitis (PMC, now known to be caused by Clostridium difficile). Three were desperately ill with severe bloody diarrhea, extreme dehydration, and high fever. After receiving fecal enemas, the patients’ symptoms ceased abruptly. All made swift recoveries.

Over the next several decades, dozens of transplants were performed annually in a handful of hospital and research institutions as experimental therapies. Despite consistently positive results in trials, the procedure was never broadly adopted, perhaps partly due to the “ick factor” and partly due to the fact that the first large outbreaks of infections caused by new, highly virulent, antibiotic resistant strains of C. difficile did not emerge until 2004. But now it appears that because of the dire medical need, physicians and patients alike are overcoming their aversion to the procedure. It is being widely touted as a “miracle cure,” but it’s not a new discovery.

The “probiotic philosophy” may have been overshadowed by medical crusades to vanquish pathogens, but it has inspired a lot of productive activity nonetheless. It serves as the basis for a thriving industry. Revenues from global sales of probiotic products, including foods containing live microorganisms — yogurt, kefir, various cheeses, sauerkraut, tempeh, miso soup, sourdough bread, and sour pickles, for example — are projected to surpass US$28 billion in 2015. There is also a growing market for “prebiotic functional foods” containing fibers, soluble and insoluble, that “good” bacteria indigenous to the human digestive tract can metabolize.

In the post-war era, US consumption of probiotic and prebiotic products lagged behind Europe and Japan in relative terms, but the market began slowly to blossom after Congress passed the Dietary Supplement Health and Education Act in 1994. The act permitted unrestricted marketing and sales of natural products in the absence of scientific evidence showing that they pose health risks.

The peer-reviewed scientific evidence on the efficacy of probiotics in restoration or maintenance of health is mixed. The Yale Workshop for Probiotics, an international group of physicians and scientists from leading academic institutions, has met three times since 2004 to review the available evidence and make recommendations to clinicians. For certain strains of bacteria and certain indications the evidence is strong. In most cases, however, the results of meta-analyses are inconclusive.

But the lack of scientific support was never the industry’s biggest problem. Efforts to increase sales in the United States were hindered to a greater extent by the fact that the large segments of the potential market were unaccustomed to (the idea of) consuming bacteria as health foods. Consumers were urged by marketers to buy products that kill bacteria, but not advised by medical professionals or public health officials to eat or drink bacteria. The passage of the Dietary Supplement Health and Education Act permitted priobiotics manufacturers to advertise safety and wholesomeness, if not to promote specific health claims.

The tide was turning in the life sciences and biomedicine as well. By 2001, the year Joshua Lederberg coined the term microbiome, researchers had begun, in increasing numbers, to entertain hypotheses inspired by the probiotic philosophy (for a variety reasons, chief among them were technical advances that made it possible to take broad surveys of microbial populations and the problem of drug resistant pathogens that made it imperative to find alternatives to conventional antibiotic therapies).

Investigators picked up guiding ideas formulated decades earlier by respected researchers such as Elie Metchnikoff, René Dubos, and Theodor Rosebury, pioneers who understood microbes as Lederberg urged: as neighbors in shared ecosystems, for good or ill. Like contemporary microbiome scientists, they made bacterial communities objects of study, targets of therapy, and subjects of popular discussion.

Ge Hong, fourth century Chinese herbalist and a 1908 caricature of Elie Metchnikoff entitled “The Manufacture of Centenarians.”

Good bacteria

Biologist Elie Metchnikoff was born in Russia in 1845, the youngest son of a member of the Tsar’s Imperial Guard. He studied natural science at the University of Kharkov in the Ukraine, and spent the first half of his scientific career as an itinerant university professor in Russia, Germany, France, and Italy.

In 1883, while conducting experiments with starfish larvae in Messina, Sicily, Metchnikoff discovered phagocytosis, the process in which specialized immune cells swallow and destroy infection-causing germs. Others later named the cells phagocytes. The discovery was widely acclaimed. Metchnikoff subsequently spent several years in Odessa before moving to the Institut Pasteur in Paris, where he became director after Pasteur’s death in 1895.

Today, Metchnikoff is best known for his many fundamental contributions to immunology, but at the end of his career, he achieved great fame for proposing that intestinal microbes have health-giving properties. His idea presented a solution to a common medical problem of the time.

In the late nineteenth-century, the leading explanation for all manner of ailments was the presence of “putrefying” bacteria in the gut that poisoned the body. In extreme cases, doctors advised removing the colon to rid the body of “intestinal toxemia.” Metchnikoff subscribed to this general model of disease, and theorized biological mechanisms at the cellular level.

He formulated a general model of senescence: putrefying bacteria secrete toxins, which poison cells; compromised cells then become targets for the body’s army of phagocytes, which destroy them; the body is weakened, becomes progressively infirm, and finally dies. But he also proposed that fortifying healthful bacterial populations in the intestines could block this process, sustain health, and extend life.

When in his fifties, he began to test his theories by treating himself. Famously neurotic, he grew increasingly anxious and depressed about aging. In an effort to increase his vitality and prolong his life, he sought to rid his intestines of harmful bacteria that hastened cellular breakdown by countering them with friendly microbes.

The friendliest he found were in Bulgarian yogurt, a staple food that he suspected was responsible for the astonishing longevity of peasants in certain Bulgarian villages. Metchnikoff theorized that the yogurt’s lactic-acid producing properties established “useful” flora in the gut that promoted health.

He tried to find experimental evidence for his theory, but the complexities of cultivating intestinal bacteria proved too great for turn-of-the-century laboratories. Then, insisting that “rational deductions from observation” were adequate proofs, he began to experiment on himself, and systematically added cultures of various lactic-acid producing bacteria in sour milk to his diet.

He swore by the effects on his health, preached the benefits of bugs, and laid out his ideas in two popular books, The Nature of Man: Studies in Optimistic Philosophy, published in 1903, and The Prolongation of Life: Optimistic Studies, which appeared in 1907 (a year before Metchnikoff was awarded a Nobel Prize for his contributions to immunology).

The books presented arguments for the curative and restorative properties of probiotics, foods that promote the health of both gastrointestinal microflora and their human hosts. They also proposed a new science of aging. Metchnikoff’s term for it is still used today: gerontology.

Metchnikoff’s status as an eminent scientist helped spawn a booming industry for commercial preparations of Bacillus bulgaricus in Europe and the United States. By 1910, the “good” microbe had, according to the Washington Post, “achieved a notoriety hardly excelled by the most famous and dreaded of the pathogenic bacteria whose names have become household words.”

Advertising Acidophilus

Acidophilus milk was a peculiar product. An advertisement in the June 1928 issue of the trade magazine Printer’s Ink read: “It is not a drug, though it is sold in drug stores. It is scarcely a medicine, though prescribed by physicians. It is simply a scientific means for re-implanting in the intestinal tract healthful bacilli which nature intended to be there.”

Acidophilus products had two markets — it was sold first to doctors, but dairy farms and distributors almost instantaneously saw the potential to sell to the general public. Pitches to medical professionals focused on the value of the product for treating specific ailments. But when acidophilus milk took its place beside a host of other popular health products available to the consuming masses, the claims became much broader. Acidophilus was touted as a tonic and revitalizer for mind and body, an antidote to the “rush of modern life,” and a remedy for “our faulty diet” and “lack of proper exercise.”

Bacterial boom-to-bust

Metchnikoff was not a model spokesperson for the efficacy of the bacillus. He died in 1916 at the unremarkable age of 71, decades short of the Bulgarian centenarians he sought to emulate. In 1924, the American Medical Association’s Council on Pharmacy and Chemistry moved to discredit claims made for B. bulgaricus therapies. Researchers had found that the bacterium did not survive in the human gut. They concluded that it was unlikely to be the magic aging tonic that Metchnikoff had proposed.

But the idea of using intestinal microbiota to preserve or recover health was not abandoned. In 1921, Harry Cheplin and Leo Rettger of Yale University proved that Bacillus acidophilus, a close relative of Metchnikoff’s Bacillus bulgaricus, could be implanted successfully in the intestines. They published their results as a monograph entitled A Treatise on the Transformation of the Intestinal Flora. Like Metchnikoff, they saw potential commercial value in probiotics, but went further and sought to capitalize on their finding. They applied for a patent on the production of acidophilus milk.

In 1923, Cheplin went into business to make and sell the preparation. He founded Cheplin Biological Laboratories and put advertisements in the American Journal of Medical Sciences and Journal of the American Medical Association to extoll the healthful benefits of acidophilus milk — the regulation of bowel movements, relief from intestinal gas and abdominal pain, and the restoration of energy. The ads encouraged doctors to prescribe the product to their patients.

Sensing an opportunity, dairy and pharmaceutical companies followed suit. A host of acidophilus products soon flooded the market. An advertisement for Lederle’s preparation encouraged consumers to “Exchange the Germs of Decay for the Germs of Health.” Consumers responded enthusiastically, and swallowed acidophilus in copious amounts. And B. bulgaricus did not disappear entirely. Diary products containing it were still sold through the 1930s.

Consumer and medical demand for acidophilus declined during World War II, as the federal government and the pharmaceutical industry organized a massive effort to develop penicillin. The drug promised to save millions of lives, including American soldiers wounded while fighting overseas. In 1943, Bristol Meyers purchased Cheplin Laboratories and converted its factory into a penicillin plant, one of many private operations working in this way to support the war effort.

Pharmaceutical grade penicillin made headlines when it became available in 1944. It proceeded to transform the practice of medicine, and society at large, as well. Antibiotics replaced probiotics in the public imagination.

The great success of antibiotics opened up a new postwar market for germicides — antibacterial agents promoted as improved disinfectants, superior to those developed during the Progressive Era as a part of the public health movement. New chemicals such as hexachlorophene wiped out microbes and could be added to cleaning products without introducing a strong antiseptic smell.

Consumer demand for antibacterial soaps, detergents, and air fresheners grew five-fold in the latter half of the 1950s, from $200 million to $1 billion annually. Squeaky-clean became an American ideal. By the mid-1960s, antibacterial products took over the personal soap market, and accounted for over 50 percent of sales by the end of the decade. Dial’s hexachlorophene-laced soap, the first to market in 1948, led the charge. Americans became known as the greatest germophobes in the history of human civilization, and the market for probiotics shrank to a vanishing point.

“Body Ecology” and the FDA

In 1972, the US Food and Drug Administration (FDA) began a safety and efficacy review of over-the-counter drugs. Products containing antibacterial additives, including popular soaps, were caught in the net as well. The agency’s panel of expert dermatologists and skin bacteriologists released its draft guidelines in 1974. The group was worried that antibacterial soaps could harm normal protective skin flora and encourage the growth of pathogens. The guidelines recommended a ban on additives in soaps intended for everyday use. And if the FDA would not act, the panel declared, then Congress should.

The rule change would have been a major blow to the soap industry. David Duensing, CEO of Armour-Dial, the first company to introduce an antibacterial product, sent a telegram to FDA Commissioner Charles C. Edwards. He protested the speculative nature of the panel’s claims and the lack of controlled studies to support them. The agency backed down. Forty years later, in December 2013, the FDA shifted the burden of proof and required manufacturers to provide data showing that their products prevented the spread of germs and did not pose long-term safety risks.

Antibiotics and the indigenous flora

At this moment in history, René Dubos was moving in exactly the opposite direction. Dubos is a towering figure in the history of microbiology, the history of medicine, and the history of ecology. Today, he is known as “the father of antibiotics,” but as postwar America became increasingly germophobic, he promoted a distinctly counter-cultural understanding of human-microbe relationships.

René Dubos

Born in France and trained originally as an agricultural soil scientist, Dubos moved to the United States in the 1920s and earned a PhD in microbiology at Rutgers University under Selman Waksman. Waksman was a soil microbiologist who advocated studying bacteria in situ, in native environments, and chided colleagues in medical bacteriology for experimenting exclusively with pure, isolated cultures. Waksman’s bias had a profound influence on Dubos’s approach to bacterial research.

In 1927, biochemist Oswald Avery invited Dubos to join his laboratory at the Rockefeller Institute for Medical Research (now Rockefeller University) in New York City. Avery was searching for a way to attack Streptococcus pneumoniae, the bacterium that causes pneumonia and host of other serious illnesses, including meningitis, pericarditis, and osteomyelitis. He wanted to dissolve the polysaccharide capsule that encloses the entire bacterial cell and contributes to its virulence by protecting it from host immune responses.

Dubos started mining soil samples for antibiotic compounds. He understood soils as self-purifying environments naturally equipped to maintain an ecological balance. He introduced pieces of the capsule into soil samples and looked for “defensive” or “restorative” chemical responses from native microbes. After three long years, he found, in a sample from an acidic New Jersey cranberry bog, an enzyme capable of breaking down the capsule.

The enzyme could not easily be purified and detoxified, and it didn’t work well in serum, but Dubos continued to refine his methods. In 1937, he discovered a bacterium, Bacillus brevis, that manufactures two compounds with antibiotic properties: gramicidin and tyrocidine. Gramicidin became the first clinically administered antibiotic.

Selman Waksman called Dubos’s work “the stimulus which flooded with bright light the whole previously unillumined field of antibiotics.” He employed Dubos’s soil enrichment techniques himself, to discover streptomycin, for which he was awarded the Nobel Prize in Medicine in 1952.

As Dubos observed the adoption of antibiotics by physicians, and the rush of the biomedical establishment into antibiotic discovery programs, he criticized both groups for being too narrowly concerned with discrete pathogenesis. He cautioned against reckless efforts to hunt down and eradicate microbes responsible for illnesses with no regard for the impact of antibiotic agents on normal bacterial flora, and he warned that bacterial resistance to antibiotics should be expected.

In 1944, Dubos abandoned antibiotics and turned to the study of tuberculosis, which afflicted his wife, Marie-Louise. The condition was especially useful for investigating host-microbe interactions because tubercular infections can be latent or active. If exposure to a pathogen is not a sufficient condition for disease, he reasoned, there must be other causal factors. In 1952, he co-authored a book, entitled The White Plague: Tuberculosis, Man and Society, which addressed the complexities of tuberculosis, including the social complexities of its transmission and it association with urbanized industrial society.

Dubos argued that health and disease were adaptive responses of organisms to environmental conditions, and that normal and pathological states ought to be viewed as outcomes of complex, interactive processes involving multitudes of living things. He knew from his training in soil science that the microbial world was immensely rich and diverse, far more, he believed, than could be imagined by captives to monocausal etiology. He began devising methods for the study of bacterial ecologies.

In 1961, he changed the name of his research unit from Bacteriology and Pathology to Environmental Medicine, and began conducting comparative experimental studies with specific pathogen-free and wild type strains of mice, observing how the animals, intestinal flora, and environmental inputs interact to shape life processes.

In this groundbreaking work, Dubos and collaborators cultured samples taken from mice at every stage of development in order to map out ecological succession in microbial populations. They generated a great mass of empirical evidence to show that naturally forming microbiota play important roles in shaping and reshaping physiology, metabolism, and morphology, and are implicated not only in disease but in states of health as well.

From his investigations on microscopic organisms, Dubos developed big picture views. He argued that all organisms (and superorganisms), all populations, and all communities — all forms of life, from single microbes to vast ecosystems — are shaped perpetually by interactions with their surroundings, and that their natural histories can be understood only by studying the webs of relationships in which they are enmeshed and which define their conditions of life.

Toward the end of his career, he began to reflect increasingly on the ways in which human beings, human groups, and societies interact with and transform environments. In 1965, he published a series of lectures he had delivered at Yale University, in a collection entitled Man Adapting. That book was followed by another, which was less technical, more philosophical, and unexpectedly popular: So Human an Animal: How We Are Shaped by Surroundings and Events. It was awarded a Pulitzer Prize in 1969.

Dubos’s late writings on humanity resonated with the burgeoning environmental movement of the late 1960s and early 1970s. The popular success of So Human an Animal made him an environmentalist icon at seventy years of age. His influence on contemporary social and ecological thought has endured, along with the maxim he coined in 1972 (as an advisor to a United Nation conference on the human environment): “Think Globally, Act Locally.”

Germfree Animals

Dubos used pathogen-free albino mice. They were derived from germfree animals bred by bacteriologist James Reyniers. Germfree animals have become standard experimental organisms for research on probiotics. They enable scientists to observe actions and interactions of specific sets of microbes in well-defined biological systems, and to distinguish between the effects of genes and microbiota.

Reyniers created the first germfree laboratory at the University of Notre Dame in 1935. He aimed to create “pure biological units” and thereby bring the “microbial variable” in biological systems under experimental control. Achieving this, he believed, would make biology a more exact science. He called his approach “gnotobiology,” the study of known (gnos) life (bios). For Reyniers, knowing a biological phenomenon required studying it in isolation as a “biological tabula rasa.”

Both before and after experimental exposures to microbes, germfree animals help scientists answer questions about the ways in which various kinds of bacteria are involved in normal development and metabolism.

Cleanliness is a sham

In 2006, microbiologist Stanley Falkow, one of the first prominent scientists to call for a “second genome project,” one that would sequence the human microbiome, published an article in the journal Cell on a probiotic theme: “Is Persistent Bacterial Infection Good for Your Health?”

Falkow began the article with words about the author of Life on Man, a book about human microbiota that enjoyed surprising success when published in 1969: “Theodor Rosebury reminded us 35 years ago that all life, including microbes, is a single community and that it would be a good idea to stop thinking indiscriminately of our unicellular companions as repulsive, contemptible, or even ferocious.”

Theodor Rosebury was a distinguished dental bacteriologist. He was trained as a dentist at the University of Pennsylvania. After earning his degree in 1928, he joined the Department of Bacteriology in the College of Physicians and Surgeons at Columbia University, to study how acids produced by Lactobacillus damage tooth enamel and contribute to dental caries. That work began an illustrious career in oral microbiology.

Theodor Rosebury

In 1950, Rosebury moved to Washington University in St. Louis, and in 1962, published Microorganism Indigenous to Man, an influential medical textbook, the first to provide a comprehensive survey of existing research on human-microbe interactions. It synthesized the findings of researchers in dental, epidermal, intestinal, nasal, ocular, otologic, and vaginal bacteriology. It was the crowning achievement of Rosebury’s academic career — it him took thirty years to pull it together.

Like Metchnikoff, Rosebury believed that well-tempered microbiota are indispensable for human health and the normal functioning of many bodily systems. And like Dubos, he emphasized the interdependence and connectedness of microbes and human beings with each other and many other creatures in larger, irreducibly complex webs of life. He coined the term “amphibiosis,” to refer to the protean character of relationships between bacteria species and human beings, which can be commensal, symbiotic, or parasitic, depending a broad range of contextual factors.

Rosebury turned to composing Life on Man after his retirement from research and teaching in the mid-1960s. The book became an instant commercial success. The publisher, Viking, sent out more review copies of Life on Man than any other offering in its catalog that year, and as accolades poured in, the press doubled the title’s advertising budget.

The book won a special commendation at the 1971 National Book Awards, and Rosebury was interviewed on popular television and radio programs, including The Today Show, The David Frost Show, and The Tonight Show with Johnny Carson. The book became a hit even though or perhaps precisely because it was overtly critical of modern conventions.

Rosebury explained that billions of microscopic creatures live on the skin, that their presence is essential for the maintenance of good health, and that the common practice of washing daily with antibacterial soap destroys them. He went on to assert that the American obsession with hygiene was based on a confused notion of cleanliness: “We need to live with life on man and ought to leave well enough alone.”

The tone was scolding, but as with Dubos’s writings on the environment, the message was in step with the times — or in counter-step, depending on one’s point of view. Rosebury expressed some sympathy for contemporary youth culture and “the hippies,” who were frequently described by “establishment” figures as filthy. “The hippies,” he wrote, “… see cleanliness as part of the sham of a hypocritical world.” The New York Times wrote that Life on Man had been written “not to entertain, but to protest.”

Appearing six years after Rachel Carson’s Silent Spring and just months ahead of the formal establishment of the Environmental Protection Agency, Rosebury’s thesis on the harm of antibacterial agents to human health mirrored growing concerns about environmental pollution and the exposure of wildlife to industrial toxins and pesticides. Readers made the connection. A letter from one to the author read: “You write as someone concerned about ecology, for surely we are doing to our environment what we do to ourselves.”

Rosebury’s ideas sound familiar to twenty-first century ears. So do those of Metchnikoff and Dubos. Microbiome scientists now insist, as did these early predecessors, that humanity should respect its bacterial companions and acknowledge what it shares with them: histories, spaces, and chances in life. The pendulum has swung back to the probiotic philosophy. Late technological innovations have enabled contemporary researchers to learn far more about “our microbial selves” than Metchnikoff, Dubos, or Rosebury could have imagined, but the fundamental premises are the same. Sometimes what is hailed as spectacularly new has deep historical roots.

A high altitude aerial photograph of West Texas grassland and a close-up of a human palm

The Ecology of the Human Skin (1965)

by Mary Marples

In 1965, Mary Marples, a microbiologist at the University of Otago in New Zealand, wrote a 972-page tome on epidermal microbiota called The Ecology of the Human Skin. The groundbreaking book likened ecosystems on the skin to those in soils. The skin is a vast territory, Marples explained. It has many niches and supports many distinct forms of life and bacterial communities. The moist armpit is like a fecund rainforest; the dry forearm is more like a desert, with sparser and hardier inhabitants. Marples’ book spurred researchers to investigate how to manipulate and balance microbial populations in order to treat various skin conditions, rather than simply targeting bad germs with chemical agents.

After reading an article on skin microbiota by Marples in the January 1969 issue of Scientific American, W.H. Auden wrote a poem: “A New Year Greeting,” (For Vassily Yanowsky).

A New Year Greeting

W.H. Auden, 1969

On this day tradition allots to taking stock of our lives, my greetings to all of you, Yeasts, Bacteria, Viruses, Aerobics and Anaerobics: A Very Happy New Year to all for whom my ectoderm is as Middle-Earth to me.

For creatures your size I offer a free choice of habitat, so settle yourselves in the zone that suits you best, in the pools of my pores or the tropical forests of arm-pit and crotch, in the deserts of my fore-arms, or the cool woods of my scalp.

Build colonies: I will supply adequate warmth and moisture, the sebum and lipids you need, on condition you never do me annoy with your presence, but behave as good guests should, not rioting into acne or athlete’s-foot or a boil.

Does my inner weather affect the surfaces where you live? Do unpredictable changes record my rocketing plunge from fairs when the mind is in tift and relevant thoughts occur to fouls when nothing will happen and no one calls and it rains.

I should like to think that I make a not impossible world, but an Eden it cannot be: my games, my purposive acts, may turn to catastrophes there. If you were religious folk, how would your dramas justify unmerited suffering?

By what myths would your priests account for the hurricanes that come twice every twenty-four hours, each time I dress or undress, when, clinging to keratin rafts, whole cities are swept away to perish in space, or the Flood that scalds to death when I bathe?

Then, sooner or later, will dawn a Day of Apocalypse, when my mantle suddenly turns too cold, too rancid, for you, appetising to predators of a fiercer sort, and I am stripped of excuse and nimbus, a Past, subject to Judgement.


— article by Funke Sangodeyi and Mark Jones

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