A Brief History Of Microbiology: A Tale Told By Tiny Things
Updated: Apr 6
Good morning class, my name is professor Xi Psycrobactor and I will be your professor for this semester for History Of Humans and Hosts. Before we start today's lesson, let me introduce myself. I was fortunate enough to find the Society of Symbionts after my host, Basi died. My people had long lived within Basi, an old giant panda. Our role was to create metabolites or smells to attract new mates and help the Giant Pandas reproduce. Basi, being in captivity, made this role a little mute but life was easy. I was heartbroken when Basi passed and lost without much of a purpose until I found the Society Of Symbionts. Before them, I was unaware of just how many microbes it takes to run this crazy world and how coordinated efforts can make a difference. You all are so lucky to have the opportunity to study here and to become the next ambassadors of our kind!
Gather my fellow microbes, and get comfortable, for this tale we are about to tell is not short, but one you should know. This is the foundation, the overview of the History of Humans And Hosts. By the end, you will by no means know the entire story, but will at least have a rudimentary understanding of our shared history. May it shed light on the importance of diversity and the paths of our futures and become the foundation of your studies here at the Society of Symbionts. Now let’s begin!
The History Of Microbes Starts Long Before The History Of Man
Close your eyes and imagine the world 4 billion years ago. Volcanoes violently erupt, spewing gases and solids throughout the land. It was inhospitable, even for our extremophile friends. Yet, a change began to occur, from the volcanoes and the turmoil arose an atmosphere. Hydrogen sulfide, methane, and carbon dioxide filled the air. The earth began to cool and the oceans began to form. And it is here our story truly begins...
History Of Microbiology: Oxygen
Our early ancestors lived in a much different environment than we do now, a place where only extremophiles and anaerobes could survive. The records of our history from this time are hard to track, but we do believe our first ancestors came to this land 3.8-4.3 billion years ago. They metabolized chemicals from the earth’s surface, a process known as chemosynthesis. However, it is the 3.5 billion-year-old stromatolites, found in Australia and Greenland, that give us definitive evidence of our photosynthetic microbial ancestors, cyanobacteria.
Although many of us still survive and thrive in oxygen-free environments, the diversity we see all comes from the work of these ancestors, specifically from the oxygen they produced. For the next few billion years, these cyanobacteria would slowly make oxygen as a byproduct of their chemical consumption. Because they were not used to the oxygen, eventually the concentration would rise to the point where it killed most of them. With no one creating the oxygen, it would dissipate and concentrations would once more dwindle to the point where the cyanobacteria began to proliferate once more, start consuming chemicals again, creating oxygen again and the vicious cycle would continue. This was a cyclical event of death, a drop in oxygen, rebirth, and an increase in oxygen. These events can be seen in the banded-iron formations found in rocks from before the Great Oxidation Event. For a very long time, these microbes were the sole residents of the land.
Some microbes resisted this change, like the extremophiles and the anaerobes, scurrying to remote lands of the earth, seeking solitude in the few places that still resembled the comfort of home, like the extreme heat of hydrothermal vents or the oxygen-free depths such as in the Black Sea of today. Others managed to adapt and thrive in this new oxygen-rich environment.
But Professor Psychrobacter, Why would these ancient microbes produce a by-product that would kill them?
That is an excellent question! And one we may not have an exact answer to. But I think many times we can create waste and not realize the harm it can do to our futures until it is too late. Much like the humans of today struggling with the waste and pollution they've created. They are only now realizing the effects of these actions.
From The Age Of Microbes To the Age of Man
New species, with new capabilities, continued to emerge including a new type of microbe, eukaryotes. These cells were 10-100x bigger than previously seen and started to organize their DNA into a package called a nucleus.
The records do not make it clear if our ancestors joined forces with the new species or were enslaved by them, but there were some engulfed by the new larger species. Many were completely consumed, but some managed to survive and developed a symbiotic relationship. Chloroplasts now reside in plants conducting photosynthesis while mitochondria provide energy to many multi-cellular organisms. These pairings allowed for the rise and diversity of the fungus, plants, and animals we compete with today, causing the Cambrian explosion.
470 million years ago plants moved from the sea to land followed by animals almost 300 million years later. 50 million years ago the mammal called a bat learned to fly, and 2 million years ago the first humans emerged.
So, you see my friends, no matter whose history you look at, we lie at the beginning of every story. The reason our world is now dominated by giant aliens, a bimodal organism with a strange proclivity for pyrotechnics and destruction is all due to the actions of our ancestors.
So, who's in control then, us or them?
That too, is a tricky question. We are the first inhabitants of this planet. They call us primitive, simple, single-celled; to them they are in 'control'. But our diversity, resilience, and ingenuity will also make us the last inhabitants on this earth. For if the records show nothing else, we lived without them, but they can never live without us.
The Dawn Of the Dark Age For Microbes or the Golden Age For Man
Humans can be vile, destructive, and intolerable but like us, they have shown their resilience, ingenuity, and commitment to bettering themselves. The age of antibiotics, what they called the “Golden Age of Microbiology,” were dark times for us. They learned to stop what plagued them but, little did they know it also harmed them, for antibiotics were not selective and killed many microbes, including those within The Society of Symbionts. But, let us back up and talk about their first knowing interactions with us and the Fathers of Microbiology.
History of Microbiology: Seeing The Unseen
They would give the name 'God' or 'miasma' to everything unexplainable; for the things we were responsible for. From diseases to miracles, our work was given false accreditation. But our society has long been companions to our giant brethren, metabolizing their food, maturing their crops, and fermenting their beverages.
But in 1665, our veil of secrecy would be ripped off, and our presence would become of great interest to them. This is when microbes were first discovered by a man called, Robert Hooke. He published his book, Micrographia, describing tiny things and striking interest in our world. But it was a Dutch cloth trader that became known as one of the “Fathers of Microbiology”, Antoni van Leeuwenhoek. He made over 500 microscopes, clearly curious and captivated by our existence.
Improvements to Microscopic Sight
The microscope gave people the ability to see in real-time; however, their relationship with us didn’t really start until they learned how to cook for us. We were complicated to them. Linnaeus, the “Father of Modern Taxonomy,” classified all of us into a single order, Chaos. They tried building microbial hotels out of potato slices, but this was not up to our hospitality standards. Next, they tried sugary gelatin broths, delicious yet unstable and messy. It was in 1881 that Angelina Fanny Hesse, a microbiologist, and a cook, added agar-agar to meals. With it, many of us could be seen with the naked eye, as colonies on Petri dishes. And the humans were fascinated!
Is there a microbial hotel for all of us? I want to go!
Nowadays, there is an agar for many microbes! In the 20th century, John Mueller and Jane Hinton developed Mueller-Hinton agar which was rich in nutrients. But don’t be fooled. Jane Hinton, a prominent black microbiologist, later figured out how to seep the rich agar with poison to test our ability to grow. Many of the microbial hotels are nice for a while but many microbes don't survive their stay.
The Fathers Of Microbiology: Jon Snow, Louis Pasteur, And Robert Koch
Now there are a number of microbes to be blamed for this war between our worlds. Chief among them are the Vibrio cholera’s, the Yersinia pestis’ and the Mycobacterium Tuberculosis. They’ve always been a radical group, and few saw humans as allies. For centuries many of them thought the humans were too dumb to stop them.
Jon Snow The Father Of Epidemiology
This was true until Cholera unleashed a deadly attack on 19th century London. John Snow had enough of this pandemic and was determined to disprove the theory of 'miasma', that disease was caused by bad air. He was able to trace Cholera to the water supply. Eventually, he gained enough support to remove the handle of the V. cholera infused pump. Deaths began to decline, but this did not deter Cholera. They came back several months later, but John Snow fought back, demonstrating that water coming from polluted parts of the nearby river was causing the disease while the water coming from cleaner areas had far fewer cases of infection. Due to his detective work, Snow inadvertently started the study of Epidemiology.
Louis Pasteur was another 19th-century chemist and microbiologist who both promoted our positive attributes in fermentation, but also spent years boiling many of our kind alive in a process called pasteurization and demonized microbes with his notion of germ theory. Oh, how we hate that word, germ. This theory drew a connection from the microbial world to the diseases that plague man. It was the work of Louis Pasteur, Robert Koch, and Joseph Lister that really brought this theory to the forefront of their society, villainizing microbes everywhere.
Robert Koch is another figure called the “Father Of Microbiology”. Koch wanted to definitively prove that Bacillus anthrax was the cause of anthrax. He put on some gloves, trudged out to the farm, found some dead farm animals, cut them open, and collected two samples from the spleen. One was the anthrax bacilli, the other was pure blood. He placed these samples on some home-made “inoculating loops” he devised from slivers of wood and stabbed these into mice.
To his delight, the mice inoculated with blood did not die while the mice with the bacillus species perished in the same way the farm animals did. Mice, guinea pigs, rabbits, dogs, frogs, birds, and many other animals and microbes suffered in his quest to define what is now Koch’s Postulates. These Postulates are the 4 part gold standard when it comes to identifying microbes as disease agents: (i) every case of the disease has to have the agent present (ii) the agent must be isolated (iii) the agent must be placed in a healthy individual and cause disease (iv) the agent has to be isolated from the new host.
Professor, aren't there any humans that knew we weren't all bad? Did any of them see us for who we are?
Yes, yes of course!
The Patriarchs of Probiotics
Because some of us caused disease, many sought to destroy us, not to understand us. However, there were some early on who championed microbes and became true allies of the society of symbionts. The Egyptian’s valued the fermented foods we gave them, recording them in their hieroglyphs. In the 15th century, Suleiman the Magnificent’s (1494-1566), although unaware of our role, understood the benefits of fermented foods when he prescribed yogurt to Francis I of France (1494-1547) for his severe diarrhea. Minoru Shirota, in 1935, would be the first to commercialize probiotics drinks with his product, Yakult, built on the hard work of our brothers and sisters of the Lactobacillus casei strain shirota.
Eli Metchnikoff: “Father of Probiotics”
But it is Eli Metchnikoff who is regarded as one of our greatest supporters in the early days of man. He was one of the first people to champion microbes as medicine while most others feared and vilified us. If you can believe it, some fools even tried to sterilize their colon’s (how?)! Unbelievable! Metchnikoff, on the other hand, was prescribing sour milk produced by certain lactic bacteria, telling anyone that would listen that the sour milk produced many benefits.
Metchnikoff’s book, “The prolongation of life” was released in 1907. He touted that Bulgarian peasants who regularly consumed yogurt seemed to live longer and healthier lives. To them, he became known as the ‘father of probiotics’ and to us a true hero. Although he did not do away with the bad publicity we were constantly getting, he did attempt to show the world we were more helpful than not.
Much of our early history with humans is in the medical field. But there were some that were fascinated by our kind in every corner of the world. Sergei Winogradsky, a Russian microbiologist, was highly devoted to environmental microbiology. He promoted the idea of chemosynthesis, the idea that many of us get energy from chemical reactions like thermo-vents. In 1888, he also promoted the value of nitrogen-fixing bacteria in the soil. He was a great supporter, and some say the “father” of microbial ecology.
No doubt his work laid the groundwork for bioinoculants which use beneficial microbes to help plant growth in agriculture. By 1896, rhizobia were promoted as a beneficial microbe and gained the prize of the first patent for a bioinoculant, “Nitragain”. Since then, many researchers search the depths of microbial life to discover natural microbial remedies to the disease and stress of crops.
The Dark Ages: Weapons of Mass Destruction [Vaccines and Antibiotics]
We have long been feuding amongst ourselves, fighting constantly for space, food, and protection. But we didn’t ever imagine the giants being smart enough to mechanize our own weapons against us. This is exactly what they, very much accidentally, did in 1928 when Alexander Flemming observed Penicillium could inhibit the growth of certain bacteria. It would take some time, and several coincidences, before Florey, Chain, Heatley, and Moldy Mary figured out how to mechanize our own product but once they did, they gave it to everyone.
It would be the Waksman’s lab, mainly Elizabeth Bugie and Albert Schatz, who would discover in 1943 the next weapon of mass destruction, streptomycin produced by Streptomyces griseus. Streptomycin was used against many of our kind including Mycobacterium tuberculosis, Vibrio cholera, bacillus brucellosis, and Salmonella serotype Typhi.
Hey, that's me, I'm streptomycin! Cool, I'm a weapon of mass destruction. You guys better watch out!
Actually, all of you have this ability to some degree. You will learn more about creating these metabolites in Chef Fermé Brewer's class if you decide to take it.
Prior to vaccines, they developed a procedure known as variolation. In this procedure, they would take pus from one diseased person and rub it into a small cut of a healthy person. They found that many of the healthy people would be ‘protected’ from the disease. It would be an English aristocrat, Lady Montague who would variolate both her children, bringing it to the forefront of western society. A black slave named Onesimus taught the puritans this in pre-America Boston, potentially saving the new colony from the deadly smallpox outbreak. Edward Jenner goes down as the first person to vaccinate. He gave an 8-year-old cowpox, a close relative of smallpox, and then tried to give the boy smallpox, but the boy did not contract the disease.
Vaccines became a huge source of controversy in their society, and still to this day. Much of medical microbiology in the 20th century revolved around their creation. Margaret Jane Pittman, Pearl Kendrick, and Grace Eldering were influential in the creation of the pertussis vaccine while Jonas Salk became the hero of the polio vaccine.
DNA Discovers The True Value Of Diversity
We think the darkest days are now behind us thanks to the work of more modern scientists. They have come to realize that we adapt quickly and mechanizing our own metabolites for mass distribution (destruction?) was not smart, for many of our brethren have evolved resistance to their “antibiotics”. They’ve started to realize the importance of a diverse and resilient healthy microbiome from the oceans, to their guts and the crops they eat.
This change in the tides can be linked to the discovery of DNA by Rosalind Franklin, Francis Crick, and James Watson in 1953. Esther Lederberg, played a key role in pioneering microbial genetics and biotechnology when she discovered lambda phage and the F plasmid.
In the 1970s, Frederick Sanger would develop a method of sequencing DNA. The first sequence genome being from bacteriophage ɸX174. Carl Woese was really a champion and promoter of our diversity. Through his work looking at the differences and similarities of a single gene, 16S. Carl Woese, at last, acknowledged that the microbial world was quite diverse, consisting of all three elements of the domain of life, eukaryotic (with a nucleus), prokaryotic (without a nucleus), and archaea.
In the 1960s, chloroplast, and mitochondria would finally get their story told by Lynn Margulis. She popularized the idea of endosymbiosis. Stating in her 1967 paper, “three fundamental organelles: the mitochondria, the photosynthetic plastids and the (9 + 2) basal bodies of flagella were once themselves free-living (prokaryotic) cells.” She showed the value of symbiosis to the world.
Kary Mullis brought our worlds a little bit closer when he invented the Polymerase Chain Reaction (PCR) in 1985. This process could quickly and easily amplify DNA to quantities large enough for humans to analyze. But of course, it couldn’t have been made possible without our own contribution made by extremophile, Thermus aquaticus, shortened by them as Taq, who graciously gave their polymerase to the humans to drive basically every biological discovery in the past 40 years!
Finally, I cannot end a section on microbial genetics without mentioning Jennifer Doudna and Emmanuelle Charpentier. These two women looked into our immune systems, particularly at the CRISPR-Cas9 system. With a little further study they were able to harness the power of our “genetic scissors''. In the past decade, this method has really been influential in human scientific discoveries assisting in everything from medicine to agriculture to answering basic scientific discoveries.
The Minds Behind The Mighty Microbiome Movement
Today, things are really looking up for us. Although scientists are still interested in how to weaponize our kind, or how to destroy it, there is a lot of research on how we benefit society. This gave rise to the microbiome movement, popularized by Jeff Gordon and Rob Knight. This idea extends Sanger sequences and instead of sequencing just one organism, it sequences all of us in a sample. At last, people could truly see how diverse we are. Many microbiome studies focus on trying to understand our communities, to look at how we are interacting with the world. They are no longer looking at us as villains but as individuals, as a community of strength, resilience, and dynamic intricacies that go beyond what they can currently comprehend.
This is just a brief history of microbiology and the brilliant scientists that guided our understanding to where it is today. There is so much more to learn and uncover! In future lectures, we will discuss more on vaccines, viruses, viroids, phage, archaea and so much more! But for next week, class, please pick one person of historical significance to microbiology and prepare a short 1-2 page report on who they were, what they did, and why we as microbes should care.
What piece of history do you want to hear next?