Phage Therapy: The answer to our prayers?

By Darnell Conteh

Intro
It was the year 1941 and lying on his deathbed, was a Reserve Constable Albert
Alexander waiting for his suffering to end. You see, Albert Alexander was in a
critical condition. Not able to move and in so much pain he cannot even remain
conscious. Unfortunately, Albert Alexander was suffering from one of the biggest
killers in the world. The disease that caused most of the deaths of the soldiers
from the Great War; bacteria. The microscopic, microorganisms staphylococcus
and streptococcus had entered Albert Alexanders body when he compromised
his primary defence system after, what seemed like, a harmless cut on his cheek
whilst he walked in his garden. At the same time, a Dr.Howard Foley and his team
were working on trying to find a way to use this new innovative drug which was
created thanks to a discovery from the Scottish scientist; Alexander Fleming. The
drug is penicillin. Penicillin is the secondary product from the yeast strain
Penicillium. Under environmental stress, Penicillium produces penicillin in order
to destroy bacterial cells and any other cells that are consuming its resources so
it can survive. The penicillin inactivates an enzyme in the bacterial cell wall,
which is necessary for cross-linking. This stops the production of the cell wall,
which kills the bacterial cell and thus renders it harmless. After a few trials, Dr.
Foley had managed to extract enough penicillin to treat Albert Alexander.
Immediately his temperature reduced and soon, he regained his appetite.
However, due to the lack of resources, Dr. Foley and his team could not make
any more penicillin to treat the infection. They resorted to extracting it from Mr.
Alexanders urine but weeks later they completely ran out and on the 15 th March
1941, he passed away.
However, after many successful trials and the discovery of batch culture,
penicillin has now been available to the mass market. Many people have since
been saved due to the discovery of this wonder drug and in 1945, Dr. Foley and
Sir Alexander Fleming, along with the biochemist Sir Ernst Chain, won the Nobel
Prize in physiology. Following this, new antibiotics such as tetracycline have been
discovered and this new field of medicine has grown to a market worth $44.68
billioni. Antibiotics are now one of the most common prescribed drugs and
usually the most common not-needed prescribed drug with 80% of antibiotics
being prescribed unnecessarily in American hospitals ii.
The end of antibiotics and a bleak future
Despite, antibiotics providing an effective treatment, 700,000 people still die
each year due to antimicrobial infections that have no treatments available iii.
Why? Because of a phenomena known as to antimicrobial resistance. You see,
bacteria, just like human cells, can undergo random mutations. These mutations
can be non-beneficial e.g. destroying the cell, or beneficial e.g. antibiotic
resistant. If by chance they do become resistant, they can quickly share their
new super power to other cells. First, bacterial cells multiply extremely quickly.
Bacterial cells have been known to grow from one cell to thousands in only a few

hours. The cell can share its resistant gene with daughter cells and thus, creating
a whole culture of antibiotic resistant cells. Secondly, bacterial cells can share
genetic information quickly. These two factors can create, very quickly, a whole
strain of antibiotic resistant bacterial culture. Figure 1 shows the extreme pace at
which newly found antibiotics can become useless. This has forced many
pharmaceutical companies to stop producing new antibiotics, as they no longer
become economically sustainable.

Figure 1 credit of U.S. Department of Health and Services (CDC): Antibiotic Resistance Threats in the United States, 2013

This would only continue to get worse until we, as a society, are be sent back
into the times of Albert Alexander when only a slight cut can potentially kill us.
Operations and surgeries would be just too dangerous to do. Premature babies
are more likely to die, diseases such as pneumonia would return to its 3:10 death
ratio and even pregnancy can kill. In-fact, it is estimated that a sixth of our
population would die without antibioticsiv. Is this the way humans become
extinct?
New hope
Maybe not. There have been many new areas of research that scientists have
been looking into to try and treat bacterial infections. Even though many new
alternatives have been thought up, none of them have so far been as promising
as phage therapy.
Phage therapy is the use of bacterias natural killer; the bacteriophage. These
viruses were first discovered in 1917 by Flix d'Hrelle. D'Hrelle was the first
person to see the clinical potential for this to be used as a valid treatment for
bacterial infections. However, with the discovery of antibiotics, phage therapy

clinical use was dismissed in the western world. Although dismissed by the
western world, the eastern countries such as Stalins Soviet Union, carried on
looking into the potential use of this natural treatment. Soon enough it became a
valid therapy for bacterial infections with 1000s of people being treated
privately all over the world. Today, more than five countries have phage therapy
clinics all able to treat many chronic diseases such as Methicillin-resistant
Staphylococcus aureus (MRSA) with high succession rates.

What they do
Bacteriophages are tiny viruses that only attack bacterial cells. Each one kill
specific bacterial cells in their own unique way however, the majority of
bacteriophages invade the cells by using a kind of needle which breaks into the
bacterias cell wall. It then injects its genetic information by flattening its head.
This information is then replicated inside the bacteria by the bacterias
ribosomes, forming another bacteriophage. This process then continues until
lysis (bacterias cell wall splitting open) occurs. Bacteriophages can take around
10 minutes to lyse one cell and after a day can replicate into billions. After this,
the bacteria are then rendered useless and can no longer produce toxins to harm
the human body or replicate to spread infection. The Bacteriophages would not
infect and destroy normal healthy like antibiotics do thus, preventing infections
like C.difficile which is the cause of 14,000 deaths in the USA each year v. They
are readily available and there are practically thousands of strains which makes
production of them easier and cheaper than antibiotics. Furthermore, it takes
around ten years to produce an antibiotic that can be sold on the market but only
days to find a bacteriophage that is suitable to treat an infection There are also
no side-effects to the bacteriophages unlike antibiotics which can cause
intestinal disorders and secondary infections.
Limitations for this though are that they are not very efficient killers. They take a
lot longer than some antibiotics to work and sometimes dont kill all the cells
making a return of the infection quite possible. Only one strain of bacteriophage
can kill one bacteria which means a lot of trial and error is needed in discovering
which strain is the right one to treat a particular bacterial infection. Furthermore,
bacteriophages lyse bacterial cells which can release deadly toxins into the
human bloodstream.

Bacteriophage structure. Credit of M.

Wurtz, Biocentre of the University of
Basel, Switzerland

Hopefully, a new future

Antimicrobial-resistance is now becoming an ever glooming problem. Not only
costing economies trillions of USD but also causing millions of premature deaths.
Thankfully many governments have realised the possible threat of this and have
promised to resolve some of the problems. Countries like the USA whom, in
September 2014, promised to reduce infections by 2020 by cutting the number
of needless antibiotics given to patients by the use of education and the United
Kingdom whom have promised to work with many scientists and biotechnological
companies to try and find new treatments for antimicrobial resistance.
Hopefully, in the future, we could live in a world where there are no concerns
with cuts and bruises. A world where surgery is safe and childbirth is at its lowest
rates of death. A life where bacteria can no longer harm us. I am positive that
this future life is at risk, if we do not seek alternatives to the very short-term
treatment of antibiotics. Not only are antibiotics logistically hard to produce,
economically not worthwhile but they are also the cause of some serious
diseases. The matter of fact is, not only are bacteria becoming immune to our
treatments but so are other microorganisms; all equally posing a threat to
human life. Hopefully, in the new future we continue to win this microbial war.
References

i Antibiotic Market - Global Industry Size, Share, Trends, Analysis and Forecast 2012 2018 by Transparency Market
Research

ii PCAST report 2014

iii
Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations; 2014

iv
The true cost of antimicrobial resistance: The BMJ, 2013

v
U.S. Department of Health and Services (CDC): Antibiotic Resistance Threats in the United States, 2013