Alone in an agar dish, an E. coli bacterium lives just as it would in the bowels of a dog or the Pope. Swaying flagella propel the organism through solute like a ship through ice floes. A few carbon atoms separate sustenance from excrement. A handful of chemical interactions comprise its biography—its family history. Awareness extends no further than the pores of its membrane, so it thrives without concern for consequence. Poison or panacea, it cannot perceive the role it plays in any greater system.
The Western psyche places humanity in a similar isolation. In 1967, Lynn White Jr., a founder and president of the Society of History and Technology claimed that the Judeo-Christian worldview of Europeans and Americans places Westerners apart from nature, and was therefore responsible for the ecological crisis that arose in the 20th century. White points to the creation myth for making a strong distinction between man, formed in God’s image, and the rest of creation, which lacks a soul. According to White, this attitude still pervades modern worldviews that claim to be uninformed by Christianity. Starting with the Industrial Revolution, it has caused Western countries to unforgivingly exploit natural resources and ignore the biological or environmental costs of technological applications. To White, humans see themsleves as an entity separate from the rest of the natural world, not a functioning cog within it.
Western scientists tend to regard their practice as objective and distant from religion. However, they would be wrong to claim that the Judeo-Christian conception of human ascendancy has not influenced their discipline. According to modern neuroscience and philosophy of mind, humans have a unique neural complexity that inexplicably gives rise to consciousness and self-awareness. This complexity is exactly what E. coli lacks by virtue of being a single-celled organism, and what dogs (owners hope) possess to some degree. Consciousness is often the basis for determining the value of a life, featuring heavily in moral discussions on abortion, animal cruelty, and maintenance of those in persistent vegetative states. These debates presume that lives with higher degrees of consciousness have more value. By extension, human life should be treated with the utmost respect and care while low-minded organisms, such as bacteria, require little consideration.
This anthropocentrism is evident in the history of bacterial medicine, which has been more a struggle for dominance than an attempt to explore the possibility of symbiosis. In the second half of the twentieth century, doctors worldwide abhorrently misused and over-prescribed antibiotics to patients. As a result, our ingrained response to microorganisms tends toward cruelty—antibiotics disrupt their capsular membranes, unzipping their skin. Their exposed insides quickly perish in the environment they’ve learned to thrive in.
The Human Microbiome Project, launched in 2008, aimed to uncover the potentially positive relationship between us and our microbiome, the 100 trillion bacteria that live in our bodies. This was a pioneer study tasked with classifying one hundred trillion organisms and the relationships they have with each other and with their host. The best tool available to researchers was broad gene sequencing. This mission was comparable to identifying every inhabitant of New York City, how they know each other, and what their jobs are just by looking at a list of their genetic markers. The project was able to uncover a lot about what is alive in our bodies, but almost nothing about why it’s there. The variations in these bacterial populations between individuals also pose a challenge to understanding: the two most distant people on earth are still 99.9 percent genetically similar, but two relatives only share about about 20 to 30 percent of their gut bacteria. Our microbiome is a dynamic community. We are initially seeded at birth with the bacteria in the vaginal canal or amniotic sac. After that, our bacterial content is determined by our diet, and our interaction with our habitat, and the people surrounding us. Our limited understanding of the microbiome inhibits our ability to manipulate it in a meaningful way.
Our understanding of the microbiome would be more complete if a probiotic research agenda had been encouraged in the past. Theodor Escherich started microbiome research in the 1880s by studying the bacteria living in the intestines of children. Escherich discovered Escherichia coli and numerous other bacterial species living inside both healthy children and children suffering from intestinal disease. This finding was puzzling. At the time, bacteria were almost exclusively known to cause disease. White’s hypothesis suggests that to Westerners, their presence in healthy bodies challenged the notion that these bacteria were wrongfully encroaching on human endeavors. Investigating this peculiarity wasn’t perceived as favorable for Europeans and Americans at the time. In addition to complicating ideology, bacteria posed a tangible threat to humanity. Industrialization in the West had caused unprecedented crowding, promoting infectious disease, especially among working class populations. Roughly one fifth of children born in American households in 1850 did not live to 1860. Their mothers fared only slightly better. Nuanced work like Escherich’s wasn’t prioritized, and bacteriological research adopted an agenda focused on learning how to kill bacteria.
Projects that sought to remove bacteria were immensely successful, positively reinforcing the perceived need to separate them from humans. The first major public health victory for this antibacterial cause came in the 1850s. Louis Pasteur developed heating methods to kill the microbes that putrefied milk and wine. His success encouraged others to pursue antibacterial research. The scientific history of the remaining century is largely populated by characterizations of bacteria-borne illnesses, earning those involved the highest scientific honors in Europe. The success of this project continued into the 20th century, with the implementation of Penicillin in World War II, which healed battlefield infections and treated pneumonia, ultimately giving Allied troops a distinct advantage later in the war.
There was no reason to explore the symbiotic relationships suggested by Escherich’s work. This mentality bled into the medical community. Antibiotics weren’t widely available to the public until after the war, but doctors and patients alike welcomed them with open arms. Ever since, antibiotic overuse has been a major trend in American healthcare. As recently as 2016, the Centers for Disease Control and Prevention reported that one third of antibiotic prescriptions are unnecessary. Today, we know that our self-enforced biological isolation was not without consequence. Accelerated antibiotic resistance is currently one of the largest threats to global health and development. The industrialized world faces a new breed of allergies, autoimmune disorders, and inflammatory diseases unknown before the antibiotic era.
With research into the microbiome now picking up where Escherich left off after 120 years, it appears that this new threat has engendered a paradigm shift in bacteriological research objectives. While previous campaigns to remove bacteria may have been informed by a notion of human singularity and autonomy, the modern probiotic agenda acknowledges our symbiotic evolutionary history with bacteria. Bacteria are several billion years older than multicellular life, and the microbiome has likely coevolved alongside its hosts for hundreds of millions of years, a miracle of biological fine-tuning. The Endosymbiont Theory claims that mitochondria and chloroplasts, the parts of the cell responsible for respiration and photosynthesis, are primitive bacteria. They infected our ancestors, but were a disease vital to our proliferation. There was never a moment in plant or animal life that wasn’t touched by our predecessors. As far as biology is concerned, bacteria are the closest thing we have to a benevolent shepherd.
Although microbiologists today barely understand the profound impact the microbiome has on health, it is not too late to explore medical applications that integrate bacteria rather than separate them. Certain microbe manipulations have demonstrated enhancements in metabolism, immunity, endocrine signaling, neurologic signaling, and even cancer resistance. Though these mechanisms remain nebulous, a number of conditions previously deemed genetic are now known to be related to changes in microbial populations. A recent study at Yale University found that mice who were genetically predisposed to Inflammatory Bowel Disease (IBD) developed a different gut microbe population than control mice, causing colon inflammation. When these flora were transferred to the intestines of healthy mice, they developed IBD symptoms. Since these symptoms are tied to measurable changes in gut bacteria, artificially altering the microbiome may curb symptoms.
However, our limited understanding of the roles of these various bacteria hinders our ability to artificially manipulate the microbiome. We cannot yet inject specific bacteria to achieve a desired effect like we can with genes. Instead, we have to replace the entire microbiome with another one that doesn’t cause symptoms. This rough-hewn method is called Fecal Microbiota Transplantation (FMT). FMT requires transplanting the fecal matter from a healthy individual’s colon, which contains a large sample of their body’s native bacteria, into that of an unhealthy individual. Prior to transplantation, the recipient needs to take a round of antibiotics to eliminate all previously residing bacteria. The fecal matter in question needs to be screened for disease before it is mixed with water and placed orally or rectally.
FMT is a crude method, but it is the first major revelation resulting from the new probiotic agenda, and the first significant application of the work started by Escherich. Due to its lack of specificity, it is currently only approved by the Federal Drug Administration (FDA) to treat one condition—recurrent Clostridium difficile Infection (rCDI). In the case of rCDI, FMT is an antidote to the pitfalls of antibiotic misuse. When hospitals prescribe general antibiotics to patients unnecessarily or incorrectly, which the CDC reports may occur in 30–50 percent of cases, the bacteria that protect the gut against infection from Clostridium difficile are suppressed, allowing C. diff to take hold of the patient’s intestines. Once infected, antibiotics usually cannot uproot C. diff while it wreaks havoc on the digestive system. Roughly half a million Americans are infected with C. diff every year, and about 30,000 die. Luckily, FMT is a fast and effective way to replenish the flora that keep the pathogenic bacteria at bay. Ninety percent of FMT recipients experience remission of rCDI symptoms after their first treatment. Across half a million cases, implementing FMT instead of prescribing vancomycin could be saving the healthcare system over a billion dollars per year.
Although FMT is highly effective against C. diff and has been approved as a treatment option, it is not as widely available to patients as it should be. Physicians still hesitate to use such an invasive and unusual method when there are always more antibiotics to prescribe. Many people suffering from C. diff have to take their lives into their own hands and perform FMT on themselves, using a friend or relative’s poop and methods they gleaned from a Youtube video. The Fecal Transplant Foundation is an organization that hopes to eliminate the need for this risky procedure. They help point people seeking FMT towards appropriate resources. They also educate physicians on the procedure, hoping to make them more comfortable with it, and therefore, willing to provide it to patients. OpenBiome is another such organization that focuses on the safety of the fecal sample. By making safe fecal samples more widely available, they decrease the cost of sample acquisition and increase the number of providers who can perform FMT.
Given overwhelming supporting evidence, FMT may become the go-to treatment for C. diff within twenty years. However, with millions of Americans suffering from inflammatory bowel diseases and obesity, this one small victory is unsatisfying. In 2016, a woman named Hanna spoke on Only Human, a podcast produced by WNYC, about her experience living with ulcerative colitis. Hanna lives in constant discomfort and fear of intestinal bleeding or not making it to a toilet. She can’t speak to her friends about her condition because they’ve reacted to it with disgust. She had to move home to Oregon, away from her husband in Brazil, in order to manage her health. Her condition isolates her, and exerts control over her life in addition to her body. Hanna decided to try FMT on herself after exhausting all other options, after which she experienced complete remission. Feeling as though she was once again in command, she decided to move back with her husband. About a week later, she relapsed, and though she attempted the same procedure over and over again, she has yet to experience remission. Hanna still suffers, but now with a taste of relief lingering on her tongue.
The drive to unnecessarily eliminate pathogenic bacteria in the past was motivated by the immediate health concerns and ideologies prevalent after industrialization. This practice held back the development of probiotic perspectives, which recognize the evolutionary import of bacteria and the dangers of their elimination. Bacteriology has finally begun to utilize a two-pronged approach. FMT, a new antithesis to antibiotic treatment, has salvaged the grace of our biological chaperones that was lost in an era of overenthusiastic antagonism. But FMT has not realized its potential, and neither has microbiome research. Clinical trials of FMT on various inflammatory bowel diseases show promise, but their efficacy and implementation are limited. Funding dictates the amount of detail that research can uncover, and regulatory agencies such as the FDA decide whether people will find care in hospitals or in their own bathrooms. But progress in both research and clinical applications hinges on how readily this new conception of our relationship to bacteria is adopted. A select few have found solace, but many more wait hopefully, praying for relief.
SAM FREDERICKS B’19 doesn't mind a bit of dirt under his nails.