A Guide To The History Of Antibiotics

In the fight against harmful bacteria, antibiotics are one of our best weapons. You’ve probably had to take them before, to treat or prevent an infection, but how much do you know about them?

Here you’ll learn everything you need to know about antibiotics and how they have become so important to the field of medicine. Before we even knew what antibiotics were, or even what bacteria were, we used antimicrobial materials to treat infections.

Starting from there, we’ll take you through the history of antibiotics, explaining the discovery of penicillin and other landmark moments until we arrive at the present day. Then, we have also explored the state of antibiotics today and concerns about how antibiotics will be used in the future.

Since we’re dealing with a combination of history and science, we have provided links to support the information in this guide. You can also use them to read even deeper into these fascinating substances and how important they are to modern medicine.

Before we get into the details – what are antibiotics?

There’s no use in learning the history of antibiotics if you don’t know what they are, so let’s cover that first.

Antibiotics are antimicrobial substances, meaning they kill or stop the growth of microorganisms. When those microorganisms are the cause of an infection, it kills them and stops the infection from worsening or spreading.

Because of the nature of antibiotics, they only work on infections that are caused by bacteria. In fact, they are the most important tools in our fight against bacterial infections that can cause harm. Antibiotics that have wider use are known as broad-spectrum antibiotics while others are narrow-spectrum antibiotics, so they have more specific uses.

Antibiotics are commonly used when:

• The infection is very transmissible, so it will spread and infect others.
• The infection won’t go away without antibiotic intervention.
• The infection will take too long to go away without antibiotic intervention.
• The infection is causing more serious complications.

Since antibiotics are antibacterial, they don’t work on infections or illnesses that aren’t caused by bacteria, like viruses. In those cases, antiviral drugs are better suited to fighting the problem virus. This means antibiotics can’t be used to treat every problem, and there are concerns about doing so, as we’ll have covered by the end of this guide.

Antibiotics are commonly administered via ingestible tablets and liquids or topical sprays and lotions. In more serious cases, they can also be injected straight into the bloodstream or into muscle tissue. Antibiotics are typically prescribed in set amounts – a course that must be completed for full effectiveness.

The Brief History Of Antibiotics

So, now we know what antibiotics are and how we use them in the modern-day. With that context, you can better appreciate the history of antimicrobial treatments and antibiotics, which go back much further than you may expect.

Ancient Antibiotics

To fully understand antibiotics, let’s start at the very beginning. You’ve probably heard some stories, like Alexander Fleming and the discovery of penicillin, but there are even earlier examples where antimicrobial substances were used. At any rate, we have more on Fleming and his incredible discovery later in this guide.

Let’s start in ancient Egypt, approximately 2,000 years ago. Human bones from this period have been found to contain traces of tetracycline. For context, tetracycline is an antibiotic that was patented in 1953, so how were ancient Egyptians taking it?

We can only theorize, with two main theories being generally accepted. The first is simple: microbes somehow contaminated the bones afterward or during the process of unearthing and storing them. While possible, some hold this to be statistically unlikely.

The second, more interesting theory is that it came from the Nubian diet common in the area. This comes from anthropologist George J. Armelagos and medicinal chemist Mark Nelson, who hypothesized that an ancient beer is to blame. It was probably added during fermentation, from barley plants and the Streptomyces bacteria contained in them. Don’t worry, it’s one of the good bacteria.

Moldy bread was also applied topically to wounds in ancient Egypt, along with civilizations in China, Greece, and Serbia. It was thought that doing this prevented infection and now, in hindsight, it was likely because they were introducing penicillin to the area.

Before Modern Antibiotics

But first, let’s slow down. Before the discovery of penicillin and modern antibiotics, humans were almost defenseless against aggressive bacterial infections. That includes diseases like rheumatic fever, pneumonia, tuberculosis, and gonorrhea, and just the slightest cut could land you in hospital. Once there, treatment was largely based on superstition, guesswork, half-truths, and a little hope.

Simple infections like strep throat and ear infections often proved debilitating or fatal. Other infections, like bacterial meningitis, killed a majority of children that it contacted. Those that survived did so with the disabilities that come with meningitis infections, like deafness, partial paralysis, and learning difficulties.

Bacteria itself was only observed by English scientist Robert Hooke in 1665, then later by Belgian clothier Antoni van Leeuwenhoek when he studied his own saliva and plaque in 1675. He started practicing antibacterial hygiene to get rid of them, later becoming credited with the discovery of bacteria alongside Hooke.

Bacteria were then further explored by revered microbiologist Louis Pasteur in 1860, along with concepts like vaccination and pasteurization, the latter being named after the French chemist. Pasteur’s work in identifying and removing bacteria has saved an uncountable number of lives in the centuries since.

The Beginning Of The Antibiotic Era

That brings us to the start of the antibiotic era, which is best attributed to two names – Ehrlich and Fleming.

Paul Ehrlich was a German scientist who won the 1908 Nobel Prize for Physiology/Medicine. His cousin was also the first person to stain bacteria and the pair often worked with methylene blue to do it. By identifying bacteria, Ehrlich theorized that there could be a “magic bullet” that targeted and destroyed the bacteria without harming the surrounding body tissue.

In 1909, Ehrlich worked with Alfred Bertheim and Sahachiro Hata to develop a cure for syphilis – arsphenamine. Without going into too much detail, syphilis is often caused by a bacterium called Treponema pallidum, which arsphenamine stopped. In 1912, they refined it into neoarsphenamine that had less dangerous side effects, since arsphenamine had too many arsenical compounds in them. By many accounts, arsphenamine was the first modern antibiotic, if not the first antimicrobial that was used to target bacteria specifically.

It should be noted that at this point, the term “antibiotic” hadn’t even been coined. Ehrlich used the term chemotherapy – literally meaning the use of chemicals to treat diseases.

Then, in 1928, the famous and accidental discovery of penicillin happened. This was when Alexander Fleming returned from a holiday on the 3^rd of September and checked on Petri dishes full of Staphylococcus, a bacteria that causes boils and other unpleasant symptoms. The bacteria had been stopped by an accidental growth of mold, which secreted Penicillium notatum that stopped bacterial growth.

Isolating the Penicillium notatum with help from assistants Stuart Craddock and Frederick Ridley, Fleming wrote a paper in 1929 but didn’t fully explore the therapeutic properties of penicillin.

That came later when Howard Florey and Ernst Chain led a team at Oxford University that created purified penicillin in 1939. Its properties were documented in 1940 and then it was being used on humans in 1941. Penicillin was then nicknamed “the wonder drug” and used to treat soldiers throughout the second World War, after which Florey and Chain won a Nobel Prize for Medicine in 1945, along with Sir Alexander Fleming.

The Word Antibiotic

Even with Fleming’s discovery, the word antibiotic was still not mainstream.

Dermatologist Francois Henri Hallopeau had used the word to describe substances that stopped the development of life in 1871, though this was vague and lacked medical context. It was also spelled ‘antibiotique’ because he was French. “Antibiotic” literally means against life.

Having discovered streptomycin and many other antibiotics, and having received news of Fleming’s discovery, it was an American biochemist and microbiologist Selman Waksman who coined “antibiotic” as we know it today. Waksman chose the term “antibiotic” to describe substances or compounds that were made from living organisms but also combated other living microorganisms.

He basically clarified that antibiotic means against life, but more helpfully, it means against bacterial microbes and not anything else.

Antibiotic Proliferation

Penicillin is now thought of as the first mainstream antibacterial medication. The story of its discovery is widely taught as a happy accident that has since saved many lives.

As the first commercially successful antibiotic, it also started an arms race as companies discovered, produced, and marketed other antibacterial medications. Starting with penicillin, companies like Pfizer and Merck scaled up the production of the antibiotic and overcame challenges associated with reliably isolating and harvesting the beneficial antimicrobial substance.

Every year, millions of Americans get prescribed antibiotics as outpatients. As a result, there are hundreds of antibiotics available to medical practitioners nowadays. Like we said earlier in this guide, some have broad-spectrum uses while others are used for a much narrow scope of infections. We can’t go through them all but they do typically fall into one of several groups:

With antibiotics becoming a common and important weapon in the war against bacteria, they were prescribed for decades with little restrictions placed on them. The period between 1940 and 1962 is sometimes referred to as the golden era of antibiotics due to all of the novel antibiotics being discovered and offered on the market to treat any ailment.

Here’s a rundown of how each subsequent antibiotic group was discovered:

• After penicillin, aminoglycosides were discovered by Selman Waksman, specifically streptomycin. It was part of the antibiotic discoveries that led to Waksman coining the term. With Albert Schatz and Elizabeth Bugie, they found the antibiotic in Streptomyces griseus and observed its efficacy against tuberculosis.
• Cephalosporins were discovered in 1945 by Sardinian scientist Giuseppe Brotzu, who got them from the runoff of a sewage system. Oxford University, with help from Guy Newton and Edward Abraham, conducted further research and worked with the states to guarantee larger-scale production in the 1950s.
• Chloramphenicol was next, being found in 1947. It was secreted by the naturally occurring Streptomyces venezuelae in soil. It was quickly used to curtail typhus outbreaks in Asia and South America in 1948 and was FDA approved in 1949.
• In 1948, the first tetracyclines were discovered as a natural product of actinomycete. Like with cephalosporins and chloramphenicol, they entered production in the ‘50s.
• Macrolides were then discovered in the 1950s after Filipino scientist Abelardo B. Aguilar isolated erythromycin from Streptomyces erythreus (which is now known as Saccharopolyspora erythraea). Aguilar’s discovery was on behalf of Eli Lilly and Company and unfortunately, Aguilar received no credit or compensation for the discovery.
• Later, in the ‘60s, George Lesher accidentally distills nalidixic acid and it becomes the predecessor for quinolone antibiotics (despite the acid being a naphthyridine). All quinolone antibiotics offered for mass consumption are fluoroquinolones, which have since been tagged with many side effect concerns by the FDA and other regulatory authorities.

Since these discoveries, very few new antibiotics have been discovered.

While many people benefited from this golden age, the overuse of antibiotics can create antibiotic-resistant bacteria. When that happens, the bacterial infections can’t be stopped by the usual treatments, sometimes becoming even more aggressive and dangerous as a result. It is essentially evolution – the bacteria evolve to overcome the antibiotic and become harder to beat as a result.

Naturally, antibiotic-resistant bacteria have become a matter of concern in recent years. We cover this in more detail in the next section of this guide.

Before we cover resistant bacteria and the other problems that can come with antibiotics, let’s discuss the future of antibiotics as it seems right now.

The Future Of Antibiotics

As it stands, antibiotics are becoming more and more restricted to prevent bacteria from developing any resistance. This is done by modifying the existing antimicrobial substances that we have so that they can become more effective, exhibit fewer side effects, and not trigger bacterial mutations that can develop into antibiotic immunity.

It should be noted that antibiotic immunity seems to be an inevitability when using it to fight bacteria. We can, however, slow down this process and get more use out of the antibiotics we have for longer.

There are also cases like syphilis and the arsenicals that are used to treat it, which worked for decades with virtually no known cases of arsenic-resistant syphilitic bacteria developing. Then penicillin came along and, similarly, penicillin has proved very effective against syphilis for decades. Other STDs, like gonorrhea, have developed aggressive resistance to penicillin, making harsher antibiotics like azithromycin or ceftriaxone necessary for treatment.

Put simply, it seems that bacteria react differently to antibiotics, evolving at different paces to overcome the antimicrobials we throw at them. This is good news, allowing us to focus on problematic bacteria while the others stay vulnerable to our antibiotic treatments.

More encouraging news came out last year in 2020, before the onset of the pandemic, where research into the human gut gave a brighter view of the future. As you may have heard, the human gut is full of good bacteria (and bad bacteria when infected). The same can be said for our mouths and, when compared, researchers found a difference in the amount and severity of resistant bacteria.

So, why is that important? It gives us valuable insight into how resistances develop and propagate in different microbiomes – those being the mouth and the gut. The differences were so much that, if you compared mouth bacteria with somebody across the planet, they’d be more similar than the bacteria that can be found in your own gut.

With gut research advancing, we are discovering more about the microorganisms there and how they impact our lives. Some of them are shocking, like the idea that your gut is a second brain, and as microbiome research continues we may learn more about resistant bacteria and how to curtail them.

Problems With Antibiotics

As we’ve established, antibiotics changed the face of modern medicine and have saved millions of people over the last century. That doesn’t mean they’re perfect, however, as is the case with most drugs.

There are always benefits and drawbacks that need to be considered when a patient takes any medication, which becomes especially important if they’re taking more powerful antibiotics.

Let’s take a look at some of the problems with antibiotics, from their common side effects to their allergic reaction triggers, and then their biggest problem – the threat of multidrug-resistant bacteria.

Side Effects

First, let’s talk about side effects. Some of the most innocuous treatments in the world come with side effects and antibiotics are no exception. The kinds of side effects of antibiotics vary widely depending on your illness and the type of antibiotic you’re taking.

Side effects are more common with antibiotics than many drugs but, fortunately, they tend to be minor. Affecting approximately 1 in 10 people, the most common side effects cause trouble in the digestive system. While it can cause discomfort, they are typically mild and should pass once the treatment course is complete.

Here are some examples of these common side effects:

• Abdominal Pains
• Appetite Loss
• Bloating
• Diarrhea
• Indigestion
• Nausea
• Vomiting

Antibiotics in the tetracyclines and fluoroquinolones groups also carry unique, more severe side effects that should be known.

With tetracycline antibiotics, your skin can become sensitive to light, including artificial light sources. As such, anyone on these antibiotics should avoid prolonged light exposure to avoid skin damage and the medical issues that will come from that.

As for fluoroquinolones, they can have serious side effects that attack the muscles, joints, and nervous system of the person taking them. Again, this is very rare when the totality of fluoroquinolone use is considered, and the benefits that come from these powerful antibiotics.

Those taking fluoroquinolones should contact their doctor if they experience any of the following:

• Pain in the muscles, tendons, or joints in the elbows, knees, or shoulders.
• Numbness, tingling, or ‘pins and needles’ in any of those areas.
• Swollen lower body at the legs, feet, and ankles.
• Noticeable heart palpitations.
• Sudden shortness of breath.

Allergic Reactions

Along with side effects, there are also allergic reactions that need to be considered. While tetracyclines and fluoroquinolones carry the most severe side effects, it’s penicillins and cephalosporins that most often trigger allergic reactions.

As always, the reactions tend to be mild to moderate and don’t need to have any significant intervention. In most cases, keeping antihistamines around and then taking them to combat reaction symptoms should suffice.

Such mild allergic reactions will show the following symptoms:

• Coughing
• Wheezing
• Itching
• Throat Tightness
• Skin Rash/Hives

Of course, allergic reactions can also develop into anaphylactic reactions – anaphylaxis. These are severe allergic reactions that can and do threaten lives. Most people probably know anaphylaxis through peanut allergies, where it can trigger a fatal reaction through slight contact with nuts. Similarly, consuming shellfish or getting stung by a bee triggers this reaction in others. You’d be surprised at the things that can trigger anaphylaxis.

So, what does anaphylaxis look like? It can be tricky, as anaphylaxis starts off mild and gets worse over time, becoming debilitating. Here’s a list of symptoms, ranked by severity, that anybody taking antibiotics should look out for:

• Clammy, sweating skin.
• Stomach pains.
• Skin rashes/hives.
• Coughing or wheezing.
• Faster breathing pace, progressing into difficulty breathing.
• Faster heartbeats.
• Anxiety and confusion over where you are and what is happening.
• Losing consciousness and collapsing.

As we said, anaphylaxis can be life-threatening, so emergency medical assistance needs to be called if you or somebody around you is having anaphylaxis.

Antibiotic Resistance

While there has been more focus on antibiotic-resistant bacteria recently, there have always been certain bacteria that were harder to treat. For example, when penicillin was discovered it was ineffective at treating some strains of Staphylococcus aureus, which mainly caused skin infections in infected populations.

At the time, it was simply a limitation placed on the world’s latest wonder drug, but the problem has since gotten worse. That’s why antibiotic resistance is an important issue because antibiotics that once worked are becoming ineffective as bacteria are exposed and adapt to them.

As we said above, it’s like an evolutionary process. The bacterium either changes to protect itself and survive the antibiotic treatment or it attacks and renders the antibiotic inert. In both cases, the bacteria win and continue to wreak havoc on the body.

Such bacteria are often called multidrug-resistant bacteria because they’re not just immune to one kind, like S. aureus resisting penicillin, but they’re collecting immunities to all the antibiotics that are thrown at them. It’s not uncommon for doctors to reach for a second or even third antibiotic when treating infections, because the first course didn’t make a dent.

This presents a public health concern, as these resistant bacteria kill more people than their non-resistant counterparts. Antibiotics are also widely used to keep cattle and other livestock free of diseases, so rampant bacterial infections would have a detrimental impact on the quality of consumables and related supply chains.

Without antibiotics to use against bacterial infections, there are concerns that the global life expectancy could be cut down by 20 years and 40% of deaths in the future will have been preventable in the 1980s, where antibiotic-resistant bacteria were virtually unheard of.

It’s important to remember that medical predictions can often lean towards pessimism, to prepare for worst-case scenarios. That said, after the context of the COVID-19 pandemic (a viral infection), everybody can understand the damage bacterial infections like tuberculosis, cholera, and anthrax can cause if they become more transmissible, untreatable, and deadly. Also consider that third-world deaths will be astronomical compared to Western countries, which have more infrastructure to handle infected populations.

So, what causes antibiotic resistance to develop in a bacterium?

• Overuse Of Antibiotics – This is where patients get antibiotics for mild illnesses. Even worse, some take antibiotics for viruses. Antibiotics won’t cure a viral infection or stop its spread, and they can even cause bad side effects. Antibiotics only help fight bacterial infections, not viral ones, so learn the difference.
• Not Completing A Full Course Of Antibiotics – When antibiotics get prescribed, patients are typically given a set of them to take over a set period. Often, the symptoms of infection subside and patients don’t finish the course.

The purpose of these courses is to kill the bacteria and purge them from your body. If any bacteria survives, it will live to fight another day and has a higher chance of learning how to beat the antibiotic that you were taking. Then, when that bacteria spreads somewhere else, it just might be harder to destroy.

Not overusing antibiotics and using them for the full duration of their prescribed course, are the surest ways to prevent antibiotic resistance. This doesn’t just get more use out of the antibiotics that we have, it also buys researchers valuable time to figure out how resistance occurs and stop bacteria from making those changes at a microbial level.

As we covered earlier, most modern antibiotics were isolated from soils and other natural sources decades ago, in the golden age of antibiotics. Some researchers do hold out hope that we can discover new antibiotics that bacteria won’t be resistant to.

In the hunt for novel antimicrobial diversity, we are pursuing methods like:

• Exploring marine soil and the seabed to find similar antibiotic-producing bacteria.
• Synthesizing antimicrobial substances by copying bacterial and fungal lipopeptides.
• Borrow antimicrobial peptides from animals and plants with those natural qualities.

While the situation with antibiotics and their overuse is grave, there is work being done to curtail its impact on the world and find new solutions to fighting bacteria. It’s up to everybody to use the antibiotics we still have responsibly, to buy valuable time and not allow bacteria to evolve.

Summary

That brings us to the end of our guide to the history of antibiotics. It’s an important topic that covers more than just history, especially since the biggest problems facing antibiotics have come from ignorance or a misunderstanding of how they work. That’s why we covered all of that and more in this guide.

After reading, you should now know what antibiotics are and how they came to be, along with the problems that face antibiotics throughout their continued use. They occupy a variety of antimicrobial substances that come with their own advantages and disadvantages, there’s no one antibiotic that can treat every bacterial infection.

While this means we have a tool for nearly every job, they are becoming dulled by the process of antibiotic resistance. As we use and misuse antibiotics, they are becoming ineffective at treating the same infections that they once cured, and this may pose a grave threat in the future.

Only time will tell if we discover effective ways of combating antibiotic/multidrug-resistant bacteria. The best the average reader can do is take antibiotics responsibly, by only getting them when absolutely needed and following the prescription advice of your doctor or medical professional. We may later find a solution that renders antibiotics obsolete and completely sidesteps the problem, who knows?

Whether you’re here because you’re interested in the field or you need help from antibiotics to fight an infection, educating yourself about these world-changing medicines is a great way to understand common illnesses and how we treat them.