"What works for E. coli works for elephants" - François Jacob

There is a moment when the before and after are completely different.
A decisive moment from which there is no return.
After looking at the bacteria under the microscope,
A world without germs, a biology without germs, could no longer exist.

The discovery of invisible creatures changed many things.
Nature opened up a new world for me as I began to see creatures that were too small to see.
It tells us what causes disease and shows us how to prevent and treat it.
It also gave hints as to where life originated and why parents and children resemble each other.
This vast body of biological knowledge and applications has been the result of the diverse efforts of many scientists who studied bacteria.
In this book, this is divided into several keywords.
A collection of the crucial research that has shaped everything in microbiology, particularly bacteriology.
Jacques Monod's statement, "What works for E. coli also works for elephants," clearly shows that microbiological research is not limited to studying small bacteria, but is at the forefront of uncovering the secrets of all life on earth.

It has been less than 200 years since Pasteur discovered that life must come from life, but now humans are repeatedly trying to create artificial life using the power of computers.
The mysteries of evolution, previously impossible to experiment with due to time constraints, are now being revealed, albeit in a limited way, through the short life cycle of E. coli. Molecular biology, which discovered vast uncharted continents by discovering genetic material, including DNA, is now relentlessly opening up new realms of knowledge and industry, developing exciting tools like PCR, restriction enzymes, and gene scissors.
The principles of life discovered in bacteria are now preparing to advance into new areas.
For us, who stand on that very border, this book shows us the past, where we stand now, and where the unknown world ahead stretches.

The invention of the petri dish, the creation of solid media from agar, and the development of infection tools such as twigs were all done by Koch and his disciples.
So to speak, they pioneered a new field by designing and creating the basic tools of modern bacteriology.
Koch pondered for quite some time how to cultivate pure bacteria.
Then I figured out that nothing from outside could enter a liquid droplet that didn't come into contact with anything else.
Koch took inspiration from this and created a simple incubation device.
--- p.63

He had submitted an abstract to a conference (the Australian Society of Gastroenterology) to present on bacteria found in the stomach, but he kept the rejection letter from the conference organisers.
It was a polite but cold rejection letter stating that only 56 of the 67 submitted abstracts were accepted for publication.
Among the 11 abstracts rejected for publication, one was the one that would win the Nobel Prize 20 years later!
--- p.75~76

Marshall's discovery of Helicobacter pylori is considered to be more than just the discovery of a single pathogen causing a disease.
Why is that? In the 1980s, most of the pathogens causing major infectious diseases were already known.
In this context, Marshall's discovery was a symbolic event that showed that diseases that had not been considered infectious were caused by bacteria.
If bacteria cause peptic ulcers, what about multiple sclerosis or rheumatoid arthritis? Or even Alzheimer's? Couldn't that also be a type of infectious disease? Now, the perspective and scope of how we view bacteria and microorganisms have shifted.
--- p.85

It is certain that after the publication of his paper, Fleming also spent some time considering whether penicillin could be used as a treatment.
(……) Perhaps the biggest reason for the waning interest was that penicillin was a substance that was very difficult to isolate.
As Fleming wrote in his paper, penicillin was not easily separated because it did not dissolve in ether or chloroform, and it was not easy to concentrate. In addition, it was very unstable and easily disappeared even if left alone.
So, I thought it would be difficult to have any clinical expectations.
What may be strange, or even regrettable, is that Fleming attempted to solve the problem of separation and concentration solely by himself or his team of biologists.
This is even more evident when we consider that Howard Florey of Oxford University later solved this problem and developed a cure through experts from various fields including microbiology and chemistry, including Ernst Chain and Norman Heatley.
--- p.99

There is one scientific question about Fleming's discovery.
The point is that no one has been able to replicate the exact situation in which Fleming discovered penicillin.
It is said that even Fleming could not reproduce it.
That is, when the mold in the paper was grown in the same location as in the photo while staphylococci were growing in a culture dish, the same phenomenon as in the photo presented in Fleming's paper did not appear.
Of course, Fleming's photo was not manipulated.
So how did this happen?
--- p.102

(Bacterial) phages have great specificity for bacteria.
Phages do not attack all bacteria.
Because it targets only specific bacteria, it can treat infections without destroying the microbial community within the human body.
Additionally, since the phage ceases to function when the host bacteria dies, there are no side effects beyond the desired effect.
Its advantages include that it is non-toxic to animals, plants, and the environment, and that it rapidly multiplies even with a small amount of treatment. Furthermore, because the place where phages multiply is the place where infection occurred, the effect appears quickly.
Another advantage is that it is effective for patients who are allergic to antibiotics and works against bacteria that form biofilms, which are difficult to treat.
It is also worth noting that it is simple and inexpensive to produce.
--- p.124

Bacteriologists call bacteria that are purple "gram-positive bacteria" and bacteria that stain red "gram-negative bacteria."
As the arbitrary classification of bacteria into Gram-positive and Gram-negative bacteria based on staining results was found to have a structural basis, the two taxa were considered to be naturally classified, that is, evolutionarily differentiated taxa.
--- p.131~132

The Gram staining method was rediscovered in the mid-20th century.
In particular, in 1974, Pierce Gardner, then a professor at Harvard Medical School, argued that Gram staining should be included in the medical examination of patients with acute bacterial infections and that the results should be provided to primary care physicians.
It was emphasized that Gram staining is basic medical information for determining whether a patient has a bacterial infection and the type of bacteria.
In particular, whether the infecting bacteria are gram-positive or gram-negative is crucial in selecting first-line antibiotics to treat infectious diseases.
--- p.140

Science cites the assessment of University of Washington biochemistry professor Alan Weiner: “Almost every biologist and physician should give Woods an honorary Nobel Prize.”
--- p.156

Until the early 1940s, scientists believed that because bacteria reproduced through binary fission, all bacteria from a single bacterium were genetically identical.
So I thought it would be difficult to do genetic research with bacteria.
Shouldn't there be some detectable change to study genetics? However, in the 1940s and 1950s, it was discovered that not only does bacteria transmit genetic information through division (called vertical gene transfer), but also horizontal gene transfer, a method by which genetic information is transmitted between organisms, exists.
The discovery of horizontal gene transfer simultaneously expanded the concepts and methodology of genetics and brought about a dramatic paradigm shift in evolutionary biology.
--- p.199~200

There are three mechanisms that cause horizontal gene transfer in bacteria.
(……) However, the two mechanisms other than transformation, namely conjugation and transduction, were both discovered primarily by one scientist.
This changed our fundamental understanding of bacteria, gave genetics and molecular biology powerful tools, and broadened our perspective on evolution.
That scientist is Joshua Lederberg.
He was a typical genius scientist who discovered these things in his 20s.
--- p.200~201

His discovery was the first to reveal how genes can be exchanged between bacteria, meaning that genes can be passed on and received between different organisms, resulting in offspring with new combinations of genes.
That is, it is known that bacteria, like animals and plants, have sex.
--- p.202

The acquisition and spread of antibiotic resistance through horizontal gene transfer is a clear example of evolution.
Since antibiotics themselves act as evolutionary pressure, bacteria with antibiotic resistance are selected, and the bacteria's effective response to that pressure is horizontal gene transfer.
The impact of horizontal gene transfer on evolution can be seen not only in antibiotic resistance but also in phylogenetics.
--- p.214

We learn about Lenski's long-term evolution experiment, which leading evolutionary biologists Richard Dawkins and Jerry Coyne praised for providing experimental evidence for evolution.
In this study, the moment the research began is important, but the perseverance to continue the research is also impressive.
--- p.219

Samples were taken from Yellowstone's hot springs starting in 1965.
Then I noticed that there was a place where pink bubbles were forming, and I confirmed that the pink substance coming out of the hot spring water that was over 82 degrees Celsius was mixed with protein.
What are you talking about? It means that there is life.
It is a living organism that can produce healthy proteins and maintain life even at very high temperatures.
Brock immediately got to work.
A study on bacteria living in Yellowstone's hot springs!
--- p.212

In fact, in the invention and development of PCR itself, bacteria may not have been the main characters, although the DNA polymerase first used by Mullis was purified from E. coli.
However, the discovery of a thermophilic bacterium called Thermus aquaticus and the purification of a heat-resistant DNA polymerase from it are brilliant moments in bacteriology, and are significant achievements in that they led to the great technology called PCR.
--- p.257

It deals with restriction enzymes and the CRISPR-Cas system.
These are commonly referred to as 'genetic scissors', and they are substances or technologies that immediately became essential tools in modern biology after their discovery.
(……) It is not well known that these originate from the bacterial immune system.
(……) Shouldn't bacteria also be prepared for things that come to harm and kill them? Among the defenses bacteria have prepared against viral invasion are restriction enzymes and something called the CRISPR-Cas system.
We are doing all sorts of strange(!) things by taking advantage of this defense system that bacteria have.
--- p.261~262

They figured out how the CRISPR-Cas system works, but they went one step further.
In fact, that one step was a huge step forward.
After looking through all the components of the CRISPR-Cas system, I thought there might be something more I could do with it.
That is, the idea was that the desired DNA could be cut depending on the base sequence of crRNA inserted.
It was the discovery of gene editing tools.
And in order to make it easier to use, Doudna's lab designed and created a "single-guide RNA"—an RNA molecule that carries the guide information of crRNA on one side and acts as a handle to bind to DNA, which is the characteristic of tracrRNA on the other.
So to speak, Doudna and Charpentier 'invented' a genetic reprogramming tool based on a natural, bacterial tool called the CRISPR-Cas system.
--- p.277

Quorum sensing does not only occur between bacteria of the same species.
It occurs between bacteria of different species, and even between organisms belonging to different kingdoms or even different domains.
(……) Living things exchange signals like this to maintain a group and increase their chances of survival.
So scientists began to think of quorum sensing as indicating the 'sociality' of bacteria, and began to refer to the field that studies the collective behavior of microorganisms, or social behavior, as 'sociomicrobiology.'
--- p.230

This result strongly indicates that the composition of intestinal bacteria is the 'cause' of obesity in mice.
It also meant that obesity traits could be transmitted between individuals through fecal microbiota transplantation.
It was a very meaningful result.
Does this mean that transplanting the microbiome of a lean person into a human could help obese people lose weight without having to endure the arduous process of dieting? This finding goes beyond mere observation, offering hope that it could address one of modern man's greatest concerns.
Here we see why Gordon's research is a landmark not only in scientific terms but also in its public impact.
--- p.305

Even if they eat the same food or food, if there are more Firmicutes bacteria, they can transfer more calories to the host, such as mice or humans.
Firmicutes, which would have been a very useful bacterium in an era when food was scarce, such as the Neolithic Age, has become a useless and highly efficient bacterium in modern, developed countries where food is abundant.
(……) All things being equal, after one year, these extra calories will translate into a weight gain of approximately 5 kilograms.
Just because of the differences in the bacteria in my body.

--- p.306~307