As we begin 2021 we are perhaps acutely aware of the susceptibility that we as humans have in the face of infection. The COVID 19 Crisis has taught us that we are at the mercy of microbial infection and that we are continually challenged to combat this element in the quest for our survival as individuals but also as a species.
Global Pandemics are part of our history. They have challenged us throughout the ages from the Justinian Plague of the 4th Centure, to the Black Death in the 14th Century, malaria, smallpox, Spanish Flu and even the HIV epidemic of the 1980’s have all been viral and bacterial infections that have wreaked havoc on our populations and threatened our survival. The nature of viruses and the way in which we have combatted them has constantly evolved.
Perhaps our greatest scientific achievement in this battle has been the development of vaccines and antibiotics, combating bacterias and viruses to prevent them from taking hold of our system. Since their implementation in teh early parts of the 20th Century, our life expectancy has almost doubled. More importantly our mortality rates have decreased from 1 in 2 children dying before the age of 5yo. Our developed vaccines and antibiotics have been our go to for disease for 100 years, killing diseases like pneumonia and Urinary Tract Infections, Malaria etc. But our greatest weapon has for the past 50 years been slowly getting weaker and less effective. Antibiotics are now losing the power to combat infections and we are now scrambling to find a better way to deal with our old foes of bacteria and viruses.
How Did This Happen?
Over time, trends have developed where bacteria develop resistance to drugs. They adapt. Thus they mutate to resistant forms - this is the way bacteria work. Bacteria are the oldest and most abundant organisms on the planet. Single celled creatures that evade and detect and block chemicals that are a threat to it. Genetically they swap DNA and and arm each other against threats to their existence. This includes white blood cells, vaccines and antibiotics. Bacterias can conjugate and spread genetic information - much like a highly efficient spy ring, they communicate and pass on information as to how to behave and how to combat resistance when it arises.
Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London first discovered Penicillin in 1928. It was our very first antibiotic but by the 1950s bacteria had already become resistant to penicillin and were adapting to it’s attack. By the 1980s our fountain of medicines that have been used to combat infections had slowed to a trickle with the effective increase of resistance to new drugs creating issues for scientists to continually come up with new medications that would combat these new resistant strains of viruses and bacteria. We have almost been undone by our own reliance on this single greatest weapon against microbial infection. The more antibiotics we have introduced into the equation, the more adept viruses and bacteria have become at forming their own defence against our attacks.
Over Prescription has been the big issue. We have relied so heavily on Antibiotics in the past that we have in a way, given our opponents too much information too quickly. We have allowed them to see all our cards straight up and as such, Viruses and Bacteria have developed efficient counter measures to our attacks. Prof Victor Nizet Vice Chair of Basic Research at the Department of Pediatrics at the University of California San Diego claims that up to a third of Antibiotics that have been prescribed have been deemed unnecessary and this has led to an increase in resistance levels at an alarming rate. Any time Antibitotics are exposed to bacteria, all those bacteria have the chance to develop resistance. So by exposing bacteria to a wide array of our catalogue of antibiotics, we have created highly adaptive strains of bacteria.
For the last 10 years we have been warned of the Antibiotic Apocalypse by the medical science community. The high advancement of antibiotic resistant strains of bacteria have been outstripping our efforts to combat them. Even the father of Penicillin Sir Alexander Fleming, warned of the over reliance on Antibiotics in 1946. “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism,” The result of this predicament is that we not only face new viruses and clever bacterias, but the resurgence of old ones that we are not able to treat with our usual weapon of antibiotics. Bianca Nogrady cited in 2016 on the BBC World Changing Ideas in Medicine website that we are seeing alarming rates of infection of a new resistant Tuberculosis strain taking hold in India, China, Papua New Guinea and Russia. Escherichia coli a type of gastroentiritis has been on the rise in the US with resistance to antibiotics. Even Gonorrhea has started to become resistant to normal antibiotic application and is beginning to become difficult to treat with our usual medications.
Antibiotic use is still increasing with predictions of consumption increasing by 200% in the coming decade according to Professor Nizet with 700,000 people dying each year from Antibiotic Resistant infections. This figure could climb to 300mil by 2050 on current trajectory guidelines unless measures are taken to curtail reliance on medications for even the slightest of symptoms. The call from Nogrady is that we should only be administering Antibiotics for the most essential of purposes. Ear infections urinary tract infections and wanton application of medication for the mildest of flu and upper respiratory tract infections are no longer considered essential conditions for antibiotic administration. As well as this the premise that one must ‘always finish a course of antibiotics’ is also being challenged. We have for far too longed considered them the magic bullet for all our small conditions and minor symptoms.
There is also a call to reduce our reliance on Antibiotics used in food production. Agricultural use of medication has been widespread not only for infection control in animals but also for growth promotion. The ABC reported that Avoparcin, a glyco-peptide, is used in Australia as a growth promotant in pigs, chickens and feedlot cattle. Human transfer of antibiotic resistance in animals has been noted by the World Health Organisation in 1997 and then again in Australia by the JETACAR Committee in 1998. It happens via the direct contact with animals, consumption of meat, drinking of contaminated water or the transfer of genes between animal and human bacteria. This increases our exposure to Antibiotics via food consumption and/or water use.
Since the 1990s multi drug resistant bacteria have been on the rise. More people have been presenting with untreatable infections. Science has been looking at different ways to fight infection side by side with antibiotics and vaccines. The future is working on drugs that neutralise bacteria rather than kill them.
Also to increase our immune function and the ability of our WBC to track and destroy bacteria.
One of the areas of research being re-investigated are Bacteriophages. These viruses were first discussed in the early part of the 20th century with Frederick Twort, an English physician making early discoveries in 1915 about a new virus that could potentially attack bacteria. These findings were quickly confirmed and validated by Felix De Herelle a French Canadian physicist in 1917 and dubbed a new development in microbiology that would go on to be one of the most significant advances in biological entities. These phages are now being re-investigated as a way to fight infections as an alternative to Antibioitics. 2016 saw Australian scientists at the CSIRO investigating ways of exploiting phages to hunt down certain types of bacteria and kill them. “Phage therapy is very appealing because you are exploiting an interaction between the bacteria and their natural predators.” says Dr Carola Venturini of the Westmead Institute’s Centre for Infectious Disease and Microbiology. Alongside Professor John Iredell of the Centre for Infectious Disease and Microbiology at the Sydney Medical School, this avenue of recruiting particular viruses to attack bacteria is seen as our best alternative defence to superbugs.
Phages can’t kill human cells. They won't harm any of your human cells except for the bacterial cells that they're meant to kill. Phage therapy has fewer side effects than Antibiotics although their reach of target is less broad than Antibiotics. This narrow Host Range is one of the challenges of Phage research and trying to target viruses that can deal with a number of host target bacteria. University of California San Diego have started developing phages as a way to control several bacterias. In 2016 Tom Patterson PhD became one of the most americans to be successfully treated using bacteriaphage therapy at UC San Diego Health and in 2018 the Centre for Innovative Phage Applications and Therapeutics IPATH has been established with encouraging results.
Antibiotics are still being produced and researched and used, but their voracity is waning and we are running out of support for more and more new antibiotics. These medications are not viewed as profitable any more by the pharmaceutical industry as by the time new medications are rolled out, they have a short shelf life 0f 2 years before the bacteria adapt and they are rendered in effective. So money is drying up for research into Antibiotics. In short we are having to investigate new ways of genetic manipulation (such as that discovered in HIV research of the gene CCR5) as well as bacteriophages and alternative methods to win our battle over microbial infections. It’s a battle that we must win as we face an age of new super bugs and new and adaptive bacterial foes.
