In the Age of Antibiotics

Lemuel Angelo M. Rayel

February 28, 2019

 OUTLINE

Thesis statement: Throughout its age, the antibiotic, if understood and used properly, can continue
to aid man’s health and attest to the wonderful world in which he lives.

I. The discovery of antibiotics

A. Life before antibiotics

1. The ancient and medieval periods

2. The renaissance and early modern periods

B. The pioneering work of Paul Ehrlich

C. The breakthrough of Sir Alexander Fleming

D. The debut of antibiotics

1. Development of sulfa drug

2. Production of penicillin

3. Extraction of streptomycin

II. The nature of antibiotics

A. The definition

B. The mechanism of action

1. Detection of target

2. Destruction from without

a. Cell wall
 b. Cell membrane

3. Destruction from within

a. Ribosomes

b. Nucleic acids

c. Proteins

C. Excretion from the body

III. The classification of antibiotics

A. According to source

1. Natural

2. Semisynthetic

3. Synthetic

B. According to bacterial influence

1. Bacteriostatic

2. Bacteriolytic

C. According to range of activity

1. Broad-spectrum

2. Narrow-spectrum

IV. The limitations of antibiotics

 A. Allergic reactions

B. Damages to tissues and organs

C. Superinfections

1. Bacterial resistance

2. Microbiome upheaval

D. Supergerms, or superbugs

1. The prologue to bacterial resistance

2. The process of bacterial resistance

3. The propagation of bacterial resistance

E. Limited targets

V. The solutions to antibiotic limitations

A. Increasing safety in the body

1. Following prescription

a. Right schedule

b. Right dosage

2. Talking to the doctor

3. Preventing diseases

B. Increasing potency in the body

 1. Decreasing antibiotic exposure

2. Eliminating resistant bacteria

3. Combining multiple drugs

4. Good physician-patient relationship

C. Increasing research concerning antibiotics

VI. The production of antibiotics

A. Production of early antibiotics

1. The demand of antibiotics

2. The popularization of antibiotics

a. Discovery of culturing techniques

b. Discovery of high-yielding molds

B. Production of commercial antibiotics

1. Culturing

2. Extracting

3. Processing

4. Testing and standardizing

5. Packaging and marketing

C. Production of newly discovered antibiotics

 1. Testing

2. Approval and patent granting

3. Manufacturing of generic versions

VII. The research for antibiotic advancement

A. Already discovered about antibiotics

1. Current kinds of antibiotics

2. Diseases being treated by current antibiotics

B. To be discovered about antibiotics

1. New kinds

2. New sources

3. New knowledge on antibiotic, bacterial and bodily influences

4. New technological and scientific advancements

C. The far future of antibiotics

1. Probable successors

a. Probiotics

b. Bacteriophages

2. Looming sunset of the antibiotic era

 Lemuel Angelo M. Rayel, 1

In the Age of Antibiotics

Humans inhabit a world of infinite wonders. Indubitably, they tread on a raw and priceless

gem that awaits its coarse conundrum surfaces to be unraveled and its brilliant beauty unveiled.

However, the tools of mankind were proven to have only merely scratched the surface of this

globular jewel, for, not more than a century ago, a “surface wonder” was discovered. It was the

wonder drug now known as antibiotic. Contained by humble, microscopic mold spores already

drifting in the air humans themselves breathe, the antibiotic has unquestionably testified to more

mysteries left unearthed in this awesome world and altered the shape of medicine into an

unparalleled, more lustrous fashion. Its wonder is affirmed, even before the age of antibiotics.

The antibiotic finds its precursors in the ancient ways of treating infections dating back to

1500 B.C. The Chinese and Egyptians during this time used moldy and fermented products to treat

wound infections. For so long they would have dressed with bread molds infected wounds, which

would sometimes heal, sometimes not.1 Because ancient people believed that diseases were caused

by bodily dysfunctions and demonic curses, early doctors and tribal societies interchanged magic

and medicine. Thus, treatment of infections also included herbal medicines, rituals, and sorcery.2

However, on the brink of the Middle Ages, Christian influence on medicine established a more

charitable and less mythical fashion of treating infections.3

The Renaissance saw advancements on mankind’s understanding of the functions of the

human body, as well as treatment of infections and diseases. During this time the nature of

pathogens began to unfold and apprehension of it drastically improved.4 In the late 17th century,

man gained a wide scale of understanding of bacterial infections when the great French chemist

Louis Pasteur first discovered what he called bacteria. He also devised theories and made effective,
 Lemuel Angelo M. Rayel, 2

helpful techniques and treatments out of this discovery.5 Since then, early modern science and

medicine have never been the same, and both turned the majority of their attention towards fighting

man’s centuries-old “micro-enemy.”

Scientists who succeeded Pasteur developed hundreds of drugs that successfully killed

harmful pathogens, yet they faced a rather disturbing and dangerous dilemma—substances of such

ability would have also proven fatal to the infected patient. Because of the need for drugs that

would be selectively toxic, the German bacteriologist Paul Ehrlich developed a theory about a

“magic bullet” and worked on it. In 1909 his works and experiments led him to develop

arsphenamine (which he called Salvarsan), the first cure specifically designed for a disease, which

is the deadly syphilis.6 Although Salvarsan, being arsenic-based, proved too toxic for widespread

use, the pioneering work of Paul Ehrlich aroused the interests of other scientists to search for that

magic bullet.7

In the fall of 1928, a Scottish bacteriologist named Alexander Fleming indeed accidentally

found a magic bullet—marking the dawn of the antibiotic age. For study purposes Fleming was

culturing colonies of the disease-causing bacteria Staphylococcus aureus on Petri dishes filled with

a medium (gelatinlike food for cultures) when one day a green mold grew in one of the dishes.

Instead of deeming it a ruined science experiment, he examined the phenomenon and noticed a

halo around the mold where no bacteria grew. He soon discovered that a chemical produced by

the mold had killed the bacteria and could also kill many other types of bacteria. He then injected

the substance in mice, and to his astonishment, they showed no signs of harm or hurt. Fleming

called this same chemical, which was derived from the molds of Penicillium genus, penicillin, the

world’s first effective magic bullet.8

 Lemuel Angelo M. Rayel, 3

This extraordinary breakthrough gradually led to the debut of the antibiotic as a medical

“superweapon”. In 1934 Gerhard Domagk, a German physician, synthesized the first sulfa drug,

or sulfonamide, that was used to treat streptococcal diseases.9 As for the premier antibiotic,

although Sir Alexander Fleming in 1928 proved that penicillin killed harmful bacteria without

harming the infected, it was not yet proven that it could actually treat diseases because of the

difficulty in extracting it in large amounts—until 1941.10 13 years after penicillin was discovered,

the team headed by Howard Florey and Ernst Chain mass-extracted it and also proved its efficacy

even when diluted a million parts to one.11 Then in 1943 Russian-born American microbiologist

Selman Waksman isolated another potent antibiotic called streptomycin from a fungus of

Streptomyces genus and developed a cure for tuberculosis.12 Waksman was also the one who

coined the name “antibiotic.”13

This term, “antibiotic,” comes from two Greek words that mean “against life.”14 This is

actually quite befitting as antibiotics are substances derived from microbes that hinder the spread

of or decimate bacteria, fungi, and other microbes that harm the body.15 Antibiotics differ from

antimicrobials in that the latter are laboratory-synthesized substances based on the by-products of

certain microorganisms. Both are now used interchangeably to mean any substance that fights

infectious microbes.16 In addition, medicines such as sulfa drugs, popularly called “antibiotics,”

are really “antibacterial agents,” which is the technical term for drugs that are completely

synthetic.17

The mechanism of action of antibiotics begins with the detection of their target. Antibiotics

are able to target both prokaryotic (without nucleus; e.g. bacteria) and eukaryotic (with nucleus;

e.g. fungi, yeasts) cells.18 Because prokaryotic cells also contain cell walls, and most of today’s

antibiotics focus their offenses on these cells, the bacterium will be used as an example. However,
 Lemuel Angelo M. Rayel, 4

the process is almost identical to the eukaryotic cells. Antibiotics selectively attack bacteria by

being drawn to a substance or process in that bacteria that is absent in human cells. Thus, they

greatly harm the invaders, but should deal very little damage to the host.19

After antibiotics lock their target, they stop them in two ways. They destroy the bacteria

from the outside or inside. From the outside antibiotics detect the unique chemicals and molecular

composition in the bacteria’s cell walls. Then they prevent the construction of those walls so that

they die from the harsh environment.20 They can also cause leaks in the bacterial cell membrane,

causing them to lose vital chemicals and die.21

Furthermore, antibiotics attack from inside by entering bacterial cells and disrupting their

chemical processes. They can bind to and attack the bacteria’s protein factories, ribosomes, which

are also chemically unique from human ribosomes. They can trap the bacteria’s nucleic acids, stop

the retrieval and duplication of their genetic information, and disable their ability to reproduce.

Also, some antibiotics, such as sulfa drugs, imitate the building blocks used by bacteria to generate

necessary substances, such as folic acid, for its basic processes. The bacterial cells make a mistake

into choosing the sulfa drug, folic acid cannot be made, and the bacteria soon die from the

abnormal chemical process.22 After they finish their job, antibiotics are filtered from the blood by

the kidneys and liver and then expelled from the body through urine and feces excretion.23

The attack method of each antibiotic may widely differ, but they can still be classified in

three ways—the first being apropos to the source of antibiotics. Those that are purely produced

from natural sources, such as penicillin, are called natural antibiotics.24 When these natural

antibiotics are chemically altered, semisynthetic antibiotics are produced. These partly nature-

made, partly man-made drugs can be easier to intake or have more lasting effects in the body.
 Lemuel Angelo M. Rayel, 5

They, too, such as ampicillin, (a more powerful derivative of penicillin), can fight wider ranges of

bacteria.25 Finally, as scientists learned that some antibiotics have very simple chemical structures

and can be produced more easily by using laboratory chemicals than by isolation from microbes,

they began to manufacture synthetic antibiotics, such as chloramphenicol.26

How antibiotics counter microbial infections is another way to classify them. Antibiotics

could be bacteriostatic, meaning they impede bacterial growth long enough for the body’s immune

system to build its offenses and fight off the infection.27 Examples of these are chloramphenicol,

erythromycin, tetracyclines, nitrofurantoin, and sulfonamides.28 On the other hand, bactericidal,

also called bacteriolytic antibiotics,29 actually kill the bacteria.30 They include neomycin,

novobiocin, penicillin, streptomycin, vancomycin, and many others.31

Antibiotics can finally be classified according to their range of activity, that is, their

effectiveness against two different types of bacteria: gram-negative and gram-positive bacteria.

These two divisions concern the chemical composition of bacterial cell walls. Broad-spectrum

antibiotics, such as ampicillin and tetracycline, affect both types of bacteria.32 Contrary to this,

narrow-spectrum antibiotics are those that affect only gram-negative bacteria, like gentamicin, or

gram-positive bacteria, like penicillin.33

The efflorescence of these “wonder drugs” seemed inevitable. Their budding stage finally

over, antibiotics of all kinds were soon ensconced in every medical cabinet. The gift of nature

enhanced by man’s scientific and technological intervention has certainly saved millions of lives

since then. However, although antibiotics were created not to affect humans in any negative way,

they do have limitations and adverse effects induced by nature and by man as well.
 Lemuel Angelo M. Rayel, 6

One natural aftereffect of antibiotics in some people is allergic reactions. These occur when

the body overreacts at a certain allergen that has entered the body—in this case, an antibiotic or a

substance formed by the chemical reaction of a blood protein and the antibiotic. The overreaction

is translated in the body as production of too much histamine into the bloodstream. In normal

amounts, histamine is produced by the body to counter or regulate an allergen. However, the

“histamine-overload” produces the discomforts a person allergic to antibiotic suffers.34

Reactions include skin rash, asthmatic symptoms, shock, other typical allergic reactions,

or worse, death. One to ten people out of a hundred who take penicillin suffer allergies. In addition,

according to the National Institute of Health in the United States, 90% of drug allergic reactions

are caused by only three drugs, two of which are antibiotics.35 Thankfully, although all antibiotics

can cause allergic reactions, only a few people are susceptible to these.36

Antibiotics can also cause damage to human tissues and organs. Although they are selective

in attacking only bacterial cells, their chemicals could still react with those of the body’s, causing

unwanted side effects. Antibiotics, especially in pill form, may induce upset stomach or diarrhea

a few days after they have been taken. They can also damage the kidneys and liver where they are

filtered. Damages to these organs may be slight, and tissues can easily be repaired. These are,

however, not always the case.37

Of course, neither antibiotics, nor natural bodily defenses are the only ones to blame for

health mishaps on antibiotic intake. The abusive human consumers also perform a huge role in a

tragic pogrom play called superinfection. Superinfections occur when antibiotics, especially the

broad-spectrum ones, kill too many bacteria, including commensals, which are bacteria that are

beneficial to the body. After this “holocaust,” thousands of unaffected, dormant bacterial spores
 Lemuel Angelo M. Rayel, 7

would hatch or a few malignant survivors would multiply in enormous numbers, yet only a few

commensals would be able to limit this cataclysmal growth.38 Apparently, these virulent

superinfections are harder to control and cure, seeing they involve stronger bacteria that are more

drug-resistant.39

In addition, because superinfections upset the natural microbiome (microbe community) in

the gut where humans’ “fellow roommates” mainly thrive, the sudden demise of commensals will

cause abnormal effects in the body. Two related effects are weight gain and obesity. This antibiotic

aftereffect is taken advantage of by farmers who raise livestock and by pediatricians whose infant

patients are underweight. In fact, an experiment conducted in 1954 by Naval Medical Research

Unit on marine recruits showed that those who took placebos (pharmacologically inert drugs)

gained 2.7 kilograms, but all those who took antibiotics gained up to 4.8 kilograms!40

The theoretical reasons behind these results are astonishing as the results themselves. One

assumption is the extermination of the bacteria Helicobacter pylori in the gut. Now H.pylori causes

serious gastric and duodenal ulcers in abnormally large populations in the body, but when

regulated, they hamper the production of ghrelin, a hunger-inducing hormone. However, since the

advent of antibiotics, the bacteria have never been detected in more than 90% of children in most

developed nations where antibiotics are given rather liberally.41

Another theory is the overgrowth of other bacteria, after their competitors were

exterminated by antibiotics. George Weinstock, Ph.D., a microbiologist, asserted that “certain

bacteria overgrowing in the gut may increase an inflammatory response in adipose tissue, ramping

up fat storage and weight gain.”42 These reasons contribute to the increasing health cases of people

with metabolic syndrome, which is a combination of diabetes, hypertension, and other

 Lemuel Angelo M. Rayel, 8

cardiovascular diseases.43 Superinfections are truly threatening phenomena inside the human body,

causing not only imminent obesity, but also horrifying drug-resistance.

Sad to say, infections do not need to enter the “super” stage for bacteria to become resistant.

They can be resistant, not only through overuse, but also through the simple continuous exposure

to antibiotics.44 Resistant bacteria return to war armed with newly developed defenses and

equipped with substances that can by-pass attack systems and subdue those that men call

“champions.” The results would render the antibiotic outnumbered, impotent, and down on its

knees, waving a white flag.45

Resistant bacteria began to drastically increase in 1940’s when antibiotic popularity and

human ignorance led to the use of antibiotics on diseases that those drugs could not cure. One such

example of sheer folly is using antibiotics for the common cold and sore throat, which are viral

infections! Then, in the 60’s and 70’s, it was accidentally discovered that little quantities of

antibiotics added to animal feeds improved animal health, growth, and mass. Today, animals raised

for human consumption consume almost half of all the produced antibiotics in the United States

alone! Resistant bacteria that result from the said practice could be transferred to other animals

and eventually to humans.46

Bacteria become resistant by undergoing micro-evolution. This means that they adapt to

antibiotic offenses—practically similar to what happens when people are vaccinated. Resistant

bacteria can then impart and spread their newly acquired ability by exchanging plasmids (a type

of DNA) with others, by collecting DNA pieces from dead bacteria, and by simply bequeathing

their traits to their progeny.47 Because of these and the smaller world in which everyone is
 Lemuel Angelo M. Rayel, 9

somehow interconnected, it is not far-off that bacteria that are resistant to multiple antibiotics,

fittingly called superbugs, would rapidly increase in number and intensity.48

In reality, in 2015, one of the most shocking news from China pervaded the medical world

that day: resistance has already developed against Colistin. Colistin is a powerful antibiotic—

powerful as there was virtually no resistance against it. This was because it was very seldom used,

being potentially harmful to the liver. Notwithstanding, it was a perfect last-resort drug and bane

for resistant bacteria—but not anymore, and the feeding of Colistin to Chinese livestock for many

years is largely culpable.49 On top of this unprecedented immunity to a super-antibiotic,

antimicrobial resistance has already killed 23,000 people in 2017 in the United States alone.50

What’s more horrifying is that according to scientific studies, superbugs could kill more people in

the world than cancer would in the year 2050!51

Superbugs and other resistant bacteria can change the composition of their cell walls so

that antibiotics who should invade them could not get in. They can pump out and “vomit” the

drugs. They can confuse the antibiotics and switch the molecules that allow then to be located as

targets. They can even retaliate by producing substances that will destroy the drug before it

destroys them.52

The very first antibiotic, which erstwhile held the names “magic bullet” and “wonder

drug,” can already be neutralized by several bacteria that produce penicillinase,53 a type of beta-

lactamase enzyme.54 β-lactamase disables certain antibiotics that carry the integral molecule, β-

lactam, by dismantling that same compound through hydrolysis.55 In fact, the first bacteria to fall

under antibiotic might, Staphylococcus aureus, can already resist the penicillinase-insensitive

methicillin, giving rise to the term “methicillin-resistant Staphylococcus aureus” (MRSA). Now
 Lemuel Angelo M. Rayel, 10

MRSA refers to S. aureus bacteria that are immune to all kinds of penicillin—the same bacteria

that cause tens of thousands of people across the world each year to ruefully bite the dust.56

The limitations of antibiotics do not end there, for another serious quagmire arises. The

targets of antibiotics are very mostly limited only to bacteria. This is because the cellular structures

of other microbes, such as fungi and parasites, are very similar to those of humans. Also, on the

case of viruses, they attack the body by invading and taking over human cells, so killing them may

also involve damaging human cells.57 There is some glint of light here, in that some antibiotics,

such as erythromycin and tetracycline, can fight large viruses or cure virus-caused inflammations.

Furthermore, a few antibiotics, such as metronidazole, can treat parasitic and protozoal

infections.58

Scientists and health officials have laboriously addressed to these progressing problems by

devising solutions that all people need only follow, for the safety and potency of antibiotics are at

stake. Following prescription is crucial in assuring the treatment AND safety of the patient. If the

medication is too financially hurting, one can find generic equivalents of the drug.59 Sticking also

to the treatment duration and dosage is important. Helen Signy, a writer for the magazine Reader’s

Digest Asia, explained, “Feeling better does not mean that all the bacteria have been killed or that

an infection has been totally eradicated.”60 Partially treated infections such as streptococcal ones

could lead to heart or kidney problems and other fatal diseases.61

Talking to the doctor is a must. The patient should tell him about other medicines he is

taking, whether they are simple food supplements, prescription drugs, or over-the-counter drugs.

A doctor must be informed of any allergic reactions, health history and status, and troubles in

medicinal intake (e.g., trouble in swallowing or remembering to take medicine).62 This is important
 Lemuel Angelo M. Rayel, 11

because antibiotic chemicals can interact with other chemicals in drugs, food, and blood, causing

side effects or allergic reactions.63 Doctors will then change or stop the prescription, if this is so,

to prevent further adverse repercussions. Of course, if one really wishes a virtually drug-free life

and escape these dreadful impediments, he must practice healthy lifestyle and abstain from

disease-causing habits and activities.64

Antibiotic potency could be further escalated by preventing antibiotic resistance of bacteria

and, consequently, by decreasing or regulating human and animal exposure to antibiotics.65 To

prevent unnecessary drug intake, milk and food supplies should constantly be monitored for

antibiotic content.66 Doctors should avoid overprescription of antibiotics, especially on mild cases

of infections. In addition, the American Medical Association suggests that using normal cleansers,

such as alcohol, and soap may be better than using antibacterial handsoaps and wipes, especially

those which have no credible names. Because the latter two may not be potent enough or are not

left on the skin long enough, they tend to leave a residue that would only kill the weaker bacteria,

but leave the stronger ones to grow and even resist therapeutic antibiotics.67

The resistant microbial strains should be eliminated at once to stop its spread. The instant

that a resistant microbe is detected, health officials should alert health providers and doctors so

that they can control its spread and, if possible, terminate its existence. 68 Another method in

controlling bacterial resistance is to combine two or more different antibiotics. Doing this would

make it harder for the resistant bacteria to avoid the dual offenses of the drugs, lessen the chance

of side effects because of the decreased dosage of each individual drug, and reduce the likelihood

that more resistant bacteria would evolve.69

 Lemuel Angelo M. Rayel, 12

Cooperation and coordination with the doctor must be observed ritually. If one complied

with the schedule and dosage of treatment, bacteria would be “properly” eliminated and not

provided the help they need to drastically spread and adapt.70 On the other hand, in cases of

diagnoses of viral infections such as bronchitis, stomach flu, or common cold, one should early

ask his physician of the possibility of a non-antibiotic prescription.71 Thus, superinfection and drug

resistance would be fully controlled.

Most of the time, however, these devised solutions are not completely promulgated and

followed, due both to ignorance and obstinacy. Because of these the number of cases of resistant

bacteria has never been so high. Right now, even more digits are constantly being added to the

present figure. This fearsome, yet true fact does propel scientists to continue and intensify both

antibiotic search and research.72

After the ushering of the antibiotic age through Sir Fleming’s work, the limitations of

antibiotics subsequently became apparent, instigating worldwide expeditions for new antibiotics

and widespread endeavors to produce more refined kinds of these drugs. As was noted before,

penicillin was not readily usable for more than a decade after its discovery in 1928. Since England

was at war with Germany, factories were not available for mass extraction and production of

penicillin. So, Florey and Chain, along with other English scientists, asked the United States to

lend a hand. Soon, it was discovered that the penicillium mold can grow on and inside the

medium.73

Combining efforts, resources, and intellect, the two powers catalyzed the inception of

antibiotics in medical cabinets. American pharmaceutical companies and factories began to

produce large amounts of pure penicillin—up to more than 6,000 kilograms at that time. It certainly
 Lemuel Angelo M. Rayel, 13

was an opportune moment in 1945, when antibiotic treatment was a tremendous need and lifesaver

for the soldiers and other affected people during the Second World War.74 Later penicillin

production boomed further and its availability to consumers skyrocketed to great heights when

scientists isolated the drug from a high-yielding penicillin mold.75 As a result of these series of

events, antibiotics have been constantly produced in no meager quantities.

Currently, antibiotics are commercially produced in enormous amounts by employing a

technique in culturing microbes. Breeding is done in large culturing vats, called fermenters, which

stir the medium so that the mold can multiply in it.76 After a strain has been cultured, the substance

produced by billions of microbes is extracted.77 Of course, synthetic drugs do not follow this

fermenting procedure; they are, on the contrary, synthesized in laboratories.78 After the isolation

stage, the extracted substance can be processed to improve and develop its chemical composition.79

The production of semisynthetic antibiotics involves this third stage.

The succeeding stage involves the testing and production standardization processes. All

drug manufacturing practices—safety procedures, production processes, equipment functions,

quality maintenance, etc.—should undergo thorough technician examinations. These should also

pass through government standardizations, though the methods may vary in each country.80 This

being done, the pharmaceutical company will package the produced antibiotics, which may be in

branded or generic form, and then sent to medical marketplaces.81

In a rather special event of a discovery of a new antibiotic, scientists and/or health officials

will first test it on experimental organisms such as rodents to ensure its safety and efficacy.82 After

animal tests they will test the new drug on humans. In the United States, this testing consists of

three phases. In the first phase, the drug is tested on 20-80 people. Results from this phase
 Lemuel Angelo M. Rayel, 14

determine the toxicity of the drug in humans, the reaction of the body to the drug, and the dosage

that is safe for each age.83

The second phase involves 100-200 people, each with the same particular disease. This

phase measures and deems the effectivity of the antibiotic in favor of the patients’ conditions and

against the disease. In the third phase, the new antibiotic is tested on thousands of patients. This

final stage seeks to further establish the safety, effectiveness, and dosage of the antibiotic when

used on a wide scale. After the results of these three phases is tabulated and considered, drug

authorities, based on their findings, would decide whether to permit the production of the new

drug, or not.84 In summary the development and tests combined would take about 10 years for the

new antibiotic to come into fruition as a purchasable drug.85

Other testing methods commonly used on already known antibiotics can also be added to

the tests done on newly discovered drugs. One called the sensitivity test determines the diseases

an antibiotic can cure or the antibiotics that are effective against a disease. For the former purpose,

the new antibiotic is placed on different dishes containing different types of cultured pathogenic

microbes. Obviously, the prize is marked when a certain type of bacteria does not grow around the

antibiotic.86 A modified technique, employed for the purpose of measuring an antibiotic’s degree

of strength against certain types of bacteria, is called the well method.87

Given that the new antibiotic was approved by drug administration, the maker or head of

the pharmaceutical firm is granted a permit and patent. Only then can he claim special

manufacturer’s rights and proceed to commercially and exclusively produce, market, and sell the

drug.88 A drug patent usually lasts for 17 years, giving the maker about 7 years to be the only

producer of the drug (minus the 10-year worth of drug developing and testing). After his patent
 Lemuel Angelo M. Rayel, 15

expires, generic forms of the drug can be made.89 These generic antibiotic versions contain

technically the same ingredients as the branded ones, but are cheaper due to improved

manufacturing process and the higher number of suppliers of the drug.90

An antibiotic patent has kept money flowing in the manufacturer’s pocket for 7 years; its

infection-fighting properties has kept bodies functioning well for about 70 years; yet just its

research has already kept scientists’ mind boggled and busy for over 100 years since the concept

of a magic bullet entered Paul Ehrlich’s mind around the year 1900. Advancements from over a

century’s research are very evident right now.

Presently, medical markets offer a relatively wide array of antibiotics to consumers.

Commonly prescribed antibiotics can be grouped into six divisions according to their chemical

compositions. These groups are the penicillin group (e.g. amoxicillin, ampicillin), cephalosporins

(e.g. cefadroxil, cephalexin), fluroquinolones (e.g. norfloxacin, ofloxacin), macrolides (e.g.

clarithromycin, erythromycin), tetracyclines (e.g. doxycycline, minocycline), and other

miscellaneous antibiotics (e.g. metronidazole, trimethoprim). Most, if not all, of these antibiotics

are not proprietary drugs and can only be obtained from a pharmacist through a physician’s

prescription.91

Through antibiotics mankind has long since been able to vanquish numerous fearsome

diseases known. Now antibiotics can cure pneumonia, tetanus, tonsillitis, tuberculosis, diphtheria,

otitis, plague, cholera, meningitis, and many more. These truly puissant drugs can fight infections

such as streptococcal, staphylococcal, pneumococcal, fungal, and chest, intestinal and urinary tract

infections. They can subdue venereal diseases, rheumatic fever, typhoid fever, and some viruses.92

Some can also even slow down cancer growth!93 Thanks to antibiotics, scientific studies, and, of
 Lemuel Angelo M. Rayel, 16

course, the Great Physician, the diseases that pose dangerous threats to each living individual can

now be controlled.

Again, this assuring fact does not halt further research, nor does it tempt and compel

scientists to spare efforts in searching for “new news” that concern antibiotics. Scientists are able

to create new antibiotics and see its effectiveness on microbes using computers and virtual reality

devices.94 They are now diligently perusing and thumbing through the taxonomic pages for

organisms other than microbes that are potentially capable of producing antibiotics. Sharks and

frogs, which produce protein molecules called defensins, are being examined and tested and are

prospects for new sources of antibiotics.95

Furthermore, new molecules that stop infections by preventing them from breeding and

attaching to cells are being analyzed and experimented upon.96 Scientists continue to further their

understanding of the properties of antibiotics, bacteria, and human bodies, and their interactions

and influences on each other.97 They dig tirelessly for clues and answers to the anomalies and

mysteries that these three parties currently exhibit. In addition to this, scientists, along with

national governments and the general populace around the globe, have their eyes open and are

eagerly looking forward to new advancements in science and technology that will create an

enormous impact on medical research, especially on antibiotic study.98

“These drugs [antibiotics]…have such dramatic effects that they have often been called

wonder drugs.”99

“The chemical [antibiotic]…became one of the world’s most famous medicines.”100

“It [antibiotic] became the magic treatment for many diseases.”101

 Lemuel Angelo M. Rayel, 17

No more could history books emphasize the enormous impact antibiotics have entrenched

in the society in each passing decade. No greater praise for these drugs could be given anymore by

hundreds of encyclopedias that are yet to be published. To say that these antibiotic superweapons

have pros equally heavy with its cons is an objectionable understatement; that they have done more

harm on humanity than good an utter fallacy. Really, antibiotics are a powerful and wonderful gift

from Mother Earth.

Yet still, antibiotics are inexorably not without harm. Their most menacing drawback now

is that they are somewhat like “red carpets” for the glorious entrée of superbugs in the world. This

sure fact has caused scientists not only to develop better antibiotics, but also to find other

substances that would meet or beat the disease-fighting attributes of antibiotics while, at the same

time, eliminate the danger of superbug emergence and the superbugs themselves.

One probable candidate is probiotics.102 Although probiotics, or good bacteria, are

currently treated as just supplements, studies show that they are vital in maintaining the

microbiome. Admittedly, microbiome study is just in its infancy. But it is better born than not, for

scientists have just lately found out and understood how these gut “micro-amigos” do a capital job

of preventing foreign invasions.

They can signal the immune system whenever, for instance, gut commensals feel

threatened by flu virus, initiating volleys of immune and inflammatory responses to fight the

infection.103 They can also protect us from certain harmful invaders by releasing their very own

antibiotics called bacteriocins. The offenses of the bacteria species Lactobacillus salivarius in the

saliva and Staphylococcus epidermis on the skin are two illustrations of this fact.104 Moreover, as

was mentioned before, they deliver protection through colonization resistance. Their sheer
 Lemuel Angelo M. Rayel, 18

numbers in the gut leave practically no more space for foreign bacteria to colonize, suppressing

the growth of even resistant bacteria, which still have to compete with the good bacteria colony in

gut population size.105

Probiotics have already been proven to treat infections, especially those in gut. In

November 2010, the not-so-understood bacteria Clostridium difficile plagued a man. He was given

many doses of the powerful antibiotic vancomycin and had had almost all the bacteria inside him

decimated. Despite the efforts the plague kept recurring during his breaks from antibiotics. His

doctor suspected the cause and, so, he needed probiotics that would not come only billions in pills

but rather trillions—from another’s gut.106 This procedure is called fecal transplant, inoffensively

known as human probiotic infusion.107 Surprisingly, after just two transplants, the patient had

completely recovered from C. diff.108

Currently, probiotic research is still energetically ongoing. They are actually being tested

to fight STD’s, or sexually transmitted diseases. Some medical schools are now offering fecal

banking programs for those whose microbiome need refreshing after invasive therapies such as

chemotherapy and radiotherapy. Scientists also search for new, less difficult methods of fecal

transplants, like, for instance, taking them in lozenges. The once dreary future for probiotics as

main substitute for antibiotics has never been clearer.109

Aside from probiotics, another contender—equally prospective than the former—is the

bacteriophage. The bacteriophage is a virus which hunts and preys only on bacteria. The reason

for “phages’” impending succession of antibiotics is that they may be very effective in killing only

hazardous bacteria and not the good ones.110 This promising attribute of phages would theoretically
 Lemuel Angelo M. Rayel, 19

eliminate the dangers of allergic reaction, organ damage, superinfection, microbiome upheaval,

and superbug emergence and existence.

In a nutshell, each species of phages attacks only one kind of bacteria, although sometimes,

they may also attack bacteria related to the original one. This means that no good bacteria can be

harmed, no body cells would be destroyed, and, theoretically, no side effects would be induced.

To add to their list of advantages, phages are very numerous and common—their numbers in the

whole world would exceed the number of other organisms on earth combined!111 Phages, if one

day used for medical purposes, may be far cheaper than antibiotics.

Their most striking asset versus antibiotics is that, unlike the latter, phages are not

chemicals. They are, behaviorally speaking, living things. In an invasion of phages, a slight chance

can occur that some bacteria will survive their attack. So, if ever phages invade again and their

DNA was detected, these bacteria may evolve and become resistant to phages by immediately

cutting the phages’ DNA.112

If phage resistance does occur, phages would in turn evolve ways to by-pass this resistance

and be able to vanquish bacteria once more, as what they have been doing for millennia.113 At this

point good tidings will greet antibiotics, for they still may be able to catch up and play a role in

the “bacteriophage era” (if it ever arrives). By becoming resistant to phages, bacteria need to lose

their antibiotic resistance, so bacterial resistance to antibiotics OR phages won’t really be a grave

problem.114 To note phage treatment is just in experimental phase and needs further study and

extensive research and trial to be deemed fully operable.

Like the trial of human probiotic infusion, phage-cum-antibiotic treatments have been

successfully performed and are being researched upon. For example, a man was infected with the
 Lemuel Angelo M. Rayel, 20

advanced, multi-antibiotic resistant bacteria Pseudomonas aeruginosa in his chest cavity. These

seemingly invincible bacteria are very hard to kill and can even survive long periods of exposure

to outside environment and even alcoholic hand gels. Desperate, with their patient on the brink of

death, his physicians decided to inject tens of hundreds of phages, along with antibiotics the

formidable pathogens were resistant to, inside their patient’s chest. Amazingly, the man recovered

completely only a few weeks after the said therapy.115 Presently, phage treatment, especially in P.

aeruginosa infections, is slowly gaining recognition, phage research is intensifying, and just in

2016, the largest bacteriophage clinical trial was launched.116

Indeed, it can never be said that the wonderful era of antibiotics is still far from its sunset

stage.

Since the dawn of civilization, humans have already been waging their first wars, not on

their own kind, but on something probably far deadlier than them—pathogens. These microscopic

assassins had from time to time snuffed away the lives of millions of people and erased a

substantial portion of the world population. Then, just a century ago came into existence the

antibiotics, a wondrous substance that had put these deadly diseases in their rightful place, the

history books. Now another battle has emerged; it is now humans against antibiotics, particularly

on their baleful shortcomings. A new age of medical weapon already might be dawning and the

age of antibiotics might be drawing to a close. May the human race, as it delves deeper into the

earth’s infinite wonders, bid the latter age farewell with bodies hale and without ail.
 Lemuel Angelo M. Rayel, 21

ENDNOTES

Cynthia V. Sommer, “Antibiotics,” The New Book of Knowledge, Volume 1-A,

1

(Danbury, Scholastic Literary Publishing Inc., 2006), p. 310

Tonse N.K. Raju, M.D., “Medicine,” The New Book of Knowledge, Volume 12-M,
2

(Danbury, Scholastic Literary Publishing Inc., 2006), p. 206

3
Raju, p. 208

4
Raju, p. 208a-208b

5
Sommer, p. 310

6
Gail Kay Haines, “Ehrlich, Paul,” The New Book of Knowledge, Volume 5-E, (Danbury,
Scholastic Literary Publishing Inc., 2006), p. 118
7
Sommer, p. 310

8
John Hudson Tiner, When Science Fails, (Lewisville, Texas, Accelerated Christian
Education, Inc., 1995), p. 44
9
Raju, p. 209

10
Raju, p. 209

11
Tiner, p. 45
Hope Steele (volume editor), "What Medicines Come from Plants?” Illustrated
12

Encyclopedia of Science and Nature, Plant Life, (Hongkong, Time Life Asia, 2003), p. 132
13
Raju, p. 206

14
Steele, p. 132

15
Sommer, p. 306

16
Sommer, p. 306
 Lemuel Angelo M. Rayel, 22

M. Frances Dyra, (project editor), “Antibiotics,” Young People’s Science Encyclopedia,

17

Volume 2: An-Az, (Danbury, Children’s Press, Inc., 1963) p. 116

18
Sommer, p. 309

19
Sommer, p. 308

20
Sommer, p. 308

21
Sommer, p. 308

22
Sommer, p. 308-309

23
Sommer, p. 311

24
Sommer, p. 307

25
Sommer, p. 307

26
Sommer, p. 307

27
Sommer, pp. 307-308

28
Dyra, p. 116

29
Dyra, p. 116

30
Dyra, p. 116

31
Sommer, p. 308

32
Dyra, p. 116

33
Sommer, p. 308
 Lemuel Angelo M. Rayel, 23

34
Richard J. Wagman, M.D. (editor), “Allergies and Hypersensitivities,” The New
International Standard Medical and Health Encyclopedia, (Naples, Florida, Trident Reference
Publishing, 2006), p. 418
35
Wagman, p. 419

36
Sommer, p. 310

37
Sommer, p. 310-311

38
Sommer, p. 311

39
Sommer, p. 311

40
Jim Thornton, “The Dirty Little Secret of Perfect Health,” Men’s Health, (August

2012), p. 77

41
Thornton, p. 78

42
Sommer, p. 311

43
Sommer, p. 311

44
Sommer, p. 311

45
Kurtzgesagt-In a Nutshell, “The Antibiotic Apocalypse Explained,” (March 17, 2016),
http://youtu.be/xZbcwi7SfZE, retrieved July 21, 2018
46
Kurtzgesagt-In a Nutshell, http://youtu.be/xZbcwi7SfZE

47
Kurtzgesagt-In a Nutshell, http://youtu.be/xZbcwi7SfZE

48
Kurtzgesagt-In a Nutshell, http://youtu.be/xZbcwi7SfZE

Kurtzgesagt-In a Nutshell, “The Deadliest Being on Planet Earth—the Bacteriophage,”

49

(May 13, 2018), http://youtu.be/Yl3tsmFsrOg, retrieved July 21, 2018

 Lemuel Angelo M. Rayel, 24

50
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

51
Sommer, p. 312

52
Dyra, p. 116

53
Wikipedia, “Beta-lactamase,” [February 11, 2019 (last revision)],
https://en.wikipedia.org/wiki/Beta-lactamase, retrieved February 14, 2019
54
Wikipedia, https://en.wikipedia.org/wiki/Beta-lactamase

55
Thornton, p. 76

56
Thornton, p. 76

57
Sommer, p. 312

58
Dyra, p. 116

59
Helen Signy, “Take as Directed,” Reader’s Digest, (June 2010), p. 57

60
Signy, p.55

61
Signy, p.55

62
Signy, p.55

63
Richard P. Hoffmann, “Drugs,” The New Book of Knowledge, Volume 4-D, (Danbury,
Scholastic Literary Publishing Inc., 2006), p. 335
64
Signy, p.56

65
Raju, p. 203

66
Sommer, p. 311
 Lemuel Angelo M. Rayel, 25

67
Sommer, p. 312

Peter Dockrill (editor-in-chief), “Medical Update—Soap Dish,” Reader’s Digest,

68

(March 2003), p. 13
69
Sommer, p. 312

70
Sommer, p. 312

71
Sommer, p. 312

72
Thornton, p. 79

73
Steele, p.132

74
Tiner, p.46

75
Tiner, p.46

76
Sommer, p. 310

77
Sommer, p. 312

78
Raju, p. 209

79
Sommer, p. 307

80
Sommer, p. 307

81
Hoffmann, p. 336

82
Hoffmann, p. 336

83
Hoffmann, p. 335
 Lemuel Angelo M. Rayel, 26

84
Hoffmann, p. 336

85
Hoffmann, p. 335

86
Dyra, p. 116

87
Sommer, p. 309

88
Hoffmann, p. 336

89
Hoffmann, p. 336

90
Hoffmann, p. 336

91
Richard J. Wagman, M.D. (editor), “Commonly Prescribed Drugs,” The New
International Standard Medical and Health Encyclopedia, (Naples, Florida, Trident Reference
Publishing, 2006), p. 590-591
92
Dyra, p. 116

93
Steele, p.133

94
Sommer, p. 312

95
Sommer, p. 312

96
Sommer, p. 312

97
Sommer, p. 312

98
Raju, p. 208

99
Sommer, p. 306

Barbara Land, “Fleming, Sir Alexander,” The New Book of Knowledge, Volume 6-F,
100

(Danbury, Scholastic Literary Publishing Inc., 2006), p. 249

 Lemuel Angelo M. Rayel, 27

101
Sommer, p. 310

102
Peter Dockrill (editor-in-chief), “RD Health—Healing Power of Germs,” Reader’s
Digest, (September 2003), p. 133
103
Thornton, p. 75

104
Thornton, p. 75

105
Thornton, p. 75

106
Thornton, p. 74

107
Thornton, pp. 78-79

108
Thornton, p. 79

109
Thornton, p. 79

110
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

111
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

112
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

113
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

114
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

115
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg

116
Kurtzgesagt-In a Nutshell, http://youtu.be/Yl3tsmFsrOg
 BIBLIOGARPHY

Dockrill, Peter (editor-in-chief), “RD Health—Healing Power of Germs,” Reader’s Digest, September
2003

Dockrill, Peter (editor-in-chief), “Medical Update—Soap Dish,” Reader’s Digest, March 2003

Dyra, M. Frances (project director), “Antibiotics,” Young People’s Science Encyclopedia, Volume 2: An-
Az, Danbury, Children’s Press, Inc., 1963

Haines, Gail Kay, “Ehrlich, Paul,” The New Book of Knowledge, Volume 5-E, Danbury, Scholastic Literary
Publishing Inc., 2006

Hoffmann, Richard P., “Drugs,” The New Book of Knowledge, Volume 4-D, Danbury, Scholastic Literary
Publishing Inc., 2006

Kurtzgesagt-In a Nutshell, “The Antibiotic Apocalypse Explained,” March 17, 2016,

http://youtu.be/xZbcwi7SfZE, retrieved July 21, 2018

Kurtzgesagt-In a Nutshell, “The Deadliest Being on Planet Earth—the Bacteriophage,” May 13, 2018,
http://youtu.be/Yl3tsmFsrOg, retrieved July 21, 2018

Land, Barbara, “Fleming, Sir Alexander,” The New Book of Knowledge, Volume 6-F, Danbury, Scholastic
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Raju, Tonse N.K., M.D., “Medicine,” The New Book of Knowledge, Volume 12-M, Danbury, Scholastic
Literary Publishing Inc., 2006

Signy, Helen, “Take as Directed,” Reader’s Digest, June 2010

Sommer, Cynthia V., “Antibiotics,” The New Book of Knowledge, Volume 1-A, Danbury, Scholastic
Literary Publishing Inc., 2006

Steele, Hope (volume editor), "What Medicines Come from Plants?” Illustrated Encyclopedia of Science
and Nature, Plant Life, Hongkong, Time Life Asia, 2003

Thornton, Jim, “The Dirty Little Secret of Perfect Health,” Men’s Health, August 2012

Tiner, John Hudson, When Science Fails, Lewisville, Texas, Accelerated Christian Education, Inc., 1995

Wagman, Richard J., M.D. (editor), “Allergies and Hypersensitivities,” The New International Standard
Medical and Health Encyclopedia, Naples, Florida, Trident Reference Publishing, 2006

Wagman, Richard J., M.D. (editor), “Commonly Prescribed Drugs,” The New International Standard
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Wikipedia, “Beta-lactamase,” [February 11, 2019 (last revision)], https://en.wikipedia.org/wiki/Beta-

lactamase, retrieved February 14, 2019