I Contain Multitudes

To understand our microbiome, we must go back and look through the history of Earth. Yong asks the reader to look at the planet’s history as a one-year span. In this analogy, it is December 31st, and humans have only existed for a total of 30 seconds in that entire year. In comparison, microbes have existed since March, and until October, they had the entire planet to themselves (7).

In that period, microbes were changing the way the planet functioned. The bacteria drove the conversion of nitrogen, carbon, sulfur, and phosphorus into compounds that animals and plants would eventually use. They made their own food through photosynthesis and released oxygen in such great amounts that they changed the atmosphere of Earth. Microbes are everywhere and have always been an incredibly important part of our ecology (8). In fact, not only do they shape how we exist today, but we also evolved from bacteria.

Before eukaryotes, or multicellular organisms, were plentiful in the world, there were two different groups of life: bacteria and archaea. We know much less about archaea, but they are known to exist in very extreme environments. These two groups coexisted until, by evolutionary happenstance, a bacterium merged with an archaeon. This merge trapped the bacteria within the archaeon, and many scientists believe that eukaryotes descended from that merge. The bacteria eventually became the mitochondria of the body of the cell that the archaeon provided (9). We can even look at our genes today and see many that bear resemblance to archaea and bacteria, just as all our cells have mitochondria, a prominent result of this important merge. The pivotal addition of mitochondria allowed us to have bigger and more complex cells, because we had the additional energy to put into growth (10).

This growth allowed us to eventually grow big enough to have colonies of bacteria live on top of and within us. So many bacteria colonize us that they add up to a few pounds living within us (10). Most of us view our interaction with bacteria through the negative that they bring. Many of us think about illnesses or disease because for most of us bacteria are synonymous with “germs” that make us sick. A small fraction of bacteria are pathogenic, or capable of making us sick. The bacteria that reside within our microbiome are an important player in our ability to break down food and toxins, access nutrients, and protect us from dangerous pathogenic bacteria.

There is not a portion of our lives as biologic organisms that are untouched by our microbiome: “Our alliances with microbes have repeatedly changed the course of animal evolution and transformed the world around us” (13). There is an invisible world living with us and playing a key role in our lives. Yong closes the chapter by making a case for the subject of his book: “Microbes matter. We have ignored them. We have feared and hated them. Now, it is time to appreciate them, for our grasp of our own biology is greatly impoverished if we don’t” (14).

All science starts with a discovery. In the case of bacteria, we turn to a Dutch lens maker, who, as a hobby, looked at droplets of water under his world-class lenses. Prior to his discovery, bacteria were completely unknown to the world; no one had thought to look for organisms beyond what the human eye could see. Antony van Leeuwenhoek was born in 1632 (27). He spent his life as a city official and lens maker. The compound microscope and telescope had just been invented, and discoveries of what was on the other end of that lens were plentiful.

Leeuwenhoek was not a scientist by training, but he taught himself how to make lenses with a highly skilled technique, and he also had a curiosity for what he could see through them. Using these lenses, he began looking at droplets of water and found clouds of algae and tiny creatures swimming around. He was the first person to see these tiny organisms. He described in detail what he saw, providing some of the earliest observations of protozoa and bacteria. His description of protozoa follows:

The motion of most of these animalcules in the water was so swift, and so various upwards, downwards, and round about that ’twas wonderful to see […] and I judged that some of these little creatures were above a thousand times smaller than the smallest ones I have ever yet seen upon the rind of cheese (29).

In 1676, Leuwenhoek took his findings to the Royal Society. He described to them:

[They were] incredibly small; nay, so small, in my sight, that I judged that even if 100 of these very wee animals lay stretched out one against another, they could not reach the length of a grain of course sand; and if this be true, then ten hundred thousand of these living creatures could scarce equal the bulk of a coarse grain of sand (30).

Though it took some time, Leeuwenhoek’s letter containing his observations was published in 1677 (30). Rather than divulging his lens-crafting trade secrets, Leeuwenhoek showed these tiny organisms to people of high status to assure the Royal Society that his findings were real. At the same time, many struggled to duplicate his work. Robert Hooke, a British polymath who published his observations of minute things in a 1665 best-selling book titled Micrographia, even failed at first, before he turned to the single-lens microscope and was able to corroborate the data (30).

Leeuwenhoek was the first person not only to see microbes, but also to see the microbes that inhabited his own body. In 1683 he sampled some plaque from his teeth and observed “long, torpedo-shaped rods that shot through the water ‘like a pike’, and smaller ones that spun around like a top” (31). He died in 1723 as one of the Royal Society’s most famous members and never divulged his methods for building his spectacular microscopy images.

Leeuwenhoek’s work was driven by delight and curiosity of the microbes, but these tiny creatures started to be labeled as the bad guys. In 1762, Austrian physician Marcus Antonius von Plenciz claimed, “Every disease has its organism” (32). He was the first to claim microbes caused sickness by multiplying in the body. Louis Pasteur demonstrated that bacteria could cause fermentation and decay and postulated they might also cause disease.

Eleven years later, Robert Koch was studying the anthrax epidemic in Germany. The bacteria Bacillus anthracis was found in the tissue of victims. He put that bacteria into a mouse, which died. He then took the microbes from the mouse and injected them into a new mouse, continuing this process for 20 generations; each time, the mouse died. He had shown that anthrax was caused by a bacterium and that germ theory was correct (32).

After a small hiatus, microbes were rediscovered as tiny, disease-causing monsters. Through the lens of Charles Darwin’s book On the Origin of Species, microbes became a part of the game of friend or foe. Yong quotes microbiologist René Dubos, who explained how Darwinism shaped views on microbes:

Through this historical accident, the germ theory of disease developed during the gory phase of Darwinism, where the interplay between living things was regarded as a struggle for survival, when one had to be friend or foe, with no quarter given […] This attitude moulded, from the beginning, all later attempts to control microbial diseases. It led to a kind of aggressive warfare against microbes, aimed at their elimination from the sick individual and the community (33).

This caused a surge in discoveries of the microbes behind major diseases and new tools to study them. Once able to identify disease-causing bacteria, scientist looked to eliminate them. Joseph Lister used antiseptic techniques to avoid contaminations. Other people searched for ways to keep bacteria at bay to further cures for disease, sanitation, and food preservation (33). This kill-on-site view of bacteria persists today. Microbes are synonymous with death and disease.

Martinus Beijerinck was studying another way that microbes impacted our world, involving the breakdown of chemicals. In 1888, he found bacteria that could turn nitrogen from the air into ammonia that plants could use. He also found bacteria that could move sulfur in the ground and atmosphere (34). These discoveries led to a new era in which people talked about “good germs” that had use in our lives. On top of the bacteria that fermented our food and replenished our soil, microbiologists discovered microscopic algae, fungi on tree roots, and carpenter ants that harbored bacteria within them. Microbiologists had stumbled upon the world of symbiosis, a form of coexistence between organisms (35).

Symbiosis directly challenged the views of Darwinism and survival of the fittest, and it didn’t entirely fit with the idea that microbes were the bad guys in our world. Not only were scientists discovering harmless bacteria in the guts of carpenter ants, but they were finding that we humans had an abundance of microbes within our digestive tract. Isaac Kendall, in 1909, “described the gut as a ‘singularly perfect incubator’ for bacteria whose activities were ‘not in active opposition to those of the host’” (36). Thus began the search to discover what the bacteria in our bodies were all about. Some still saw our microbial guests as illness causing, while others thought they might be a key to a long life. Public health advisors encouraged people to rid their bodies of germs and use antibacterial products to cleanse their homes. This push led to the discovery of antibiotics and halted the study of the microbes within us.

It wasn’t until 1962 that Theodor Rosebury published his nearly 40-year quest to characterize the microbiome of humans (38). His book was ground-breaking and described the bacteria that lived on or in each part of our bodies. He spoke about microbial colonization of babies after birth, bacteria that produced vitamins and antibiotics, and ones that prevented infections by pathogens (38). The research into our symbiont friends thus began again.

René Dubos began to study the importance of bacteria in animal systems; he raised germ-free mice and noted abnormalities in their digestive and immune systems as well as shorter life spans (39). It seemed that these bacteria were important for the longevity and function of the mice, and potentially, that they might be important to humans as well. However, while many bacteria had been discovered, there were still many that did not grow in laboratory settings. A new technique was needed.

In the late 1960s, Carl Woese began to analyze bacteria using 16S rRNA, which was a molecule found in all bacteria (40). He also looked at DNA, RNA, and proteins to analyze these bacteria. By 1976, he had studied 16S rRNA from 30 different microbes. This technique allowed Woese to discover that a particular bacterium—or what he first thought was a bacterium—found in hot sewage didn’t have 16S rRNA that matched other bacteria. These weren’t bacteria; these were different organisms entirely. Woese dubbed this organism, Methanobacterium thermoautotrophicum, as an archaebacteria, or archaea (41). He published his findings in 1977 to much skepticism.

The use of 16S RNA to study bacteria brough the use of sequencing of DNA or RNA from an environment to discover a whole plethora of bacteria. Scientists could thus identify new bacteria without the need to culture them in the lab. The first time an organism was discovered from genes alone was in 1984, and the field was completely changed: “In the 1980s, all known bacteria had fitted nicely into a dozen major groups, or phyla. By 1998, that number had blossomed to around 40” (42). Today, we are up to 100 groups, the majority which have never been cultured (42). The technique was given the name metagenomics (the genomics of communities) by Jo Handelsman.

It wasn’t until 2005 that the first samples were gathered from human volunteers and sequenced. David Relman collected samples from different locations in the volunteers’ intestines and identified almost 400 species of bacteria and one archaeon, the majority of which were novel (44). In the early 2000s, the microbiome was brought to the forefront and even dubbed as an “essential organ.” The trip was long and took deviations, but this is the story of the discovery of bacteria and how they changed and shaped science over the years. Now we could study them in earnest.