All About Antibiotics

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Podcast Transcript

One of the biggest changes to humanity over the last 100 years has been the increase in life expectancies. 

One of the biggest reasons for the increase in life spans has been the development and use of antibiotics. 

Yet, the development of antibiotics was often accidental, and now they have become so ubiquitous it is actually becoming a problem. 

Learn more about antibiotics, their discovery, and their future on this episode of Everything Everywhere Daily.

One of the reasons why it took antibiotics so long to be developed is that for most of human history, we had absolutely no idea what caused most diseases. 

Civilizations and cultures around the world had different explanations for what caused diseases. In the West, they call it evil humors or miasmas. In the East, diseases may have been blamed on an imbalance in chi, and in many other cultures, it was due to spirits and the gods. 

The point being, that no one really had a clue what actually caused diseases. 

The person who actually discovered the existence of microorganisms was Antonie van Leeuwenhoek. In the late 17th century, he used a self-designed microscope to observe the tiny lifeforms that existed in a drop of water, in addition to observing cells. 

However, van Leeuwenhoek never made the connection that some of these tiny organisms could be responsible for causing disease.

Throughout the 18th and 19th centuries, even though significant advancements were being made in physics and chemistry, there was little progress made on the cause of diseases. 

If you remember back to my episode on Ignaz Semmelweis, he discovered that doctors washing their hands would dramatically reduce fatalities in the maternity hospital where he worked. Despite such a simple remedy, there was enormous resistance to his suggestion because it didn’t it fit with the prevailing theory of diseases. 

Likewise, when John Snow discovered the cause of the cholera epidemic in London, he didn’t know what was causing cholera. He just knew that the source of the problem was a particular water pump.

It wasn’t until the latter half of the 19th century that evidence began to mount for what became known as the germ theory of disease. Louis Pasteur of France and Robert Koch of Germany were the leading figures behind the acceptance of the germ theory of disease. 

The germ theory of disease is so important and receives so little attention that I will dedicate an entire episode to it in the future. 

Prior to the discovery that germs were the cause of many diseases, there were many ancient cultures that had stumbled upon treatments for diseases that attacked microbes even though they didn’t know it. 

There is chemical evidence of the antibiotic tetracycline that has been found in bones in ancient Nubia dating back to approximately the years 300 to 500. The source of the tetracycline was believed to have come from beer.

There have been traces of the chemical artemisinin, which is used to treat malaria, found in plants that have been used for centuries in traditional Chinese medicine.

Through trial and error, many people found molds and plants that could treat infections or illnesses. These were effectively antibiotics insofar as chemicals in the mold or plants could kill bacteria. 

It wasn’t until the late 19th and early 20th centuries that the germ theory of disease finally led to the creation of antiseptics and antibiotics that would target harmful bacteria.

The very first antibiotic drug ever commercially released was Arsphenamine, or compound 606. It was created in the lab of the Nobel Prize winning research physician Paul Ehrlich in 1907.

After testing hundreds of arsenic-based compounds, a Japanese researcher named Sahachiro Hata, working in Ehrlich’s lab, discovered that this compound was able to attack the bacteria that caused syphilis without harming the patient.

This really is key when it comes to antibiotics. Finding a substance that can kill bacteria is relatively easy. The problem is that bacteria is a cell, and our bodies are also made up of cells. If you kill the bacteria but also kill your own cells, you’ve only made things worse. 

Arsphenamine was released to the public in 1911 under the name Salvarsan.

Despite the success of Arsphenamine, there weren’t many antibiotics released in the years after. The process of having to test hundreds of chemicals to find something that could both kill or inhibit the growth of bacteria while, at the time, not harming human cells was very difficult.

However, there was an accidental breakthrough which occurred in 1928. 

A Scottish researcher by the name of Alexander Flemming was working at St Mary’s Hospital in London, England. He was studying various strains of the Staphylococcus aureus bacteria. 

Before going on vacation with his family in August 1928, he prepared several cultures of the bacteria and put them aside on his laboratory table before he left. When he returned on September 3, he and an assistant examined the samples and found that one had sat with its cover off the entire time. 

That sample had a blue-green mold that developed. The bacterial colony didn’t grow near the mold but grew normally further away.

He figured that there must have been something in the mold that inhibited the growth of the bacteria. 

He took a sample of the mold, grew more of it, and found that it exhibited the same properties. 

He later created a broth out of the mold and was able to concentrate the substance that was inhibiting bacterial growth. 

He dubbed the new substance taken from the Penicillium fungi: Penicillin. 

He later stated, “When I woke up just after dawn on September 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world’s first antibiotic, or bacteria killer. But I suppose that was exactly what I did.”

Penicillin was a massive breakthrough. It was a naturally occurring antibiotic that worked on a wide range of bacteria including staphylococcus, streptococcus, and diphtheria. While it didn’t work on everything, it worked on many of the most common types of harmful bacteria that humans encountered. 

Fleming was awarded the Nobel Prize in Physiology in 1945, was knighted, and was named one of the Top 100 most important people of the 20th century by Time Magazine. 

While the discovery of penicillin was undoubtedly important, it didn’t make an impact on the lives of average people right away. He published his results in 1929, but he himself didn’t see any immediate applications. 

It wasn’t until 1939 that a team of researchers led by Howard Florey were able to grow, harvest, and purify penicillin from mold cultures. The United States Department of Agriclutlure created a system for the mass production of penicillin. 

Testing done on animals found that penicillin had little to no negative impact. 

It became one of the strategic assets of the Allies in WWII. It was considered to be a wonder drug that saved thousands of lives.

While work was being done on penicillin, another antibiotic was released in 1935. Named Prontosil, it was the first of a family of antibiotics known as sulfonamides. 

After the war, the quest was on to find more antibiotics that functioned similarly to penicillin, but worked against a wider variety of bacteria. 

The 1950s and 1960s saw the discovery of dozens of new antibiotics.

For the most part, these antibiotics were extremely successful. They resulted in treatments for a wide variety of bacterial infections and diseases, many of which had plagued humanity for thousands of years. 

In no small part, antibiotics were responsible for the increase in life spans throughout the world. 

However, there was a problem. 

More and more antibiotics were perscribed, and there were more and more antimicrobial and antiseptic products put on the market. People began to associate the idea of germs and microbes generally with bad things. 

It turned out there were bad microbes, but there were also good microbes. Antibiotics and antibacterial agents usually couldn’t distinguish between the two. 

One important discovery, which is still not totally understood, was the importance of the microbiome, which lives in our digestive system. While we don’t exactly know how our gut’s microbiome functions with the rest of our body, there is a general consensus that it is really important.  

Taking heavy doses of antibiotics can wipe out much of your microbiome, which can cause problems. 

There was another problem as well, which might be an even bigger problem. 

Evolution and natural selection. 

Bacteria can reproduce and evolve rapidly.  If an antibiotic can kill 99.99% of bacteria, there is then the question of the remaining 0.01%.  The tiny number of bacteria it doesn’t kill may be resistant to the antibiotics. 

The resistant bacteria will then multiply, and soon, you are left with a bacteria that causes the same problem but is now resistant to the antibiotic that previously worked. 

Moreover, bacteria aren’t like larger multicellular organisms. It is possible for bacteria to engage in what is known as Horizontal Gene Transfer. This is when one bacteria species shares part of its genetic makeup with another bacterial species. 

You might think that the solution is just to throw more antibiotics at the problem. That might work, but over time, it will just result in bacteria resistant to multiple types of antibiotics. 

Antibiotics have, in some respects, become a victim of their own success. They were often casually prescribed without a second thought. They were cheap and had few negative consequences. The result was that over time, more and more antibiotics have become ineffective as more strains have become resistant. 

Moreover, as so many people take antibiotics, including their use in agriculture, many of them pass through us and end up in the water supply, where a larger number of bacteria can develop resistance to them. 

This overuse of antibiotics has been coupled with an increased use of antibacterial cleaning agents in homes.  The lack of early exposure to microbes by children might be responsible for compromised immune systems, which never develop the ability to fight microbes because they never encountered them.  

As bacteria are becoming more resistant, new antibiotics are not being developed as rapidly anymore. While there are many different antibiotics on the market, most of them fall into several major categories. 

Between 1935 and 1968, there were twelve new antibiotic categories discovered. Between 1969 and 2003, only two were discovered. 

An estimated 23,000 people a year, in just the United States, die annually now due to infections by strains of bacteria that have developed resistance to antibiotics. 

In addition to trying to discover more new antibiotics, one of the solutions is to simply use antibiotics more judiciously. Stop overprescribing antibiotics and use them only when necessary for both humans and animals. 

People also need to stop dumping old antibiotics down the drain. Throwing antibiotics in the trash is a better solution than letting them get into the water supply. 

The development and widespread use of antibiotics was one of the most important medical innovations of the 20th century. Millions of lives have been saved by their use.

However, we now may be suffering from too much of a good thing. In order to continue to allow antibiotics to be effective, we might have to use them less to ensure that when we do use them, they remain effective.