Antibiotics: Keeping the “Magic” in the “Magic Bullet” – Part I

Thursday, April 12th, 2012 | No Comments

One subject that keeps popping up during the many conversations I have is the use of antibiotics in agriculture. Given the insidious implications of the overuse of antibiotics, I thought I’d look into it.

Introduction

Death from infectious disease is the biggest killer we have ever known or will ever know. At the end of the 19th Century, the average human lifespan was less than 50 years. Living conditions were poor and the chances of catching an infectious disease were high. Once infected, the tools available to fight the infection, if there were any, were either crude, non-specific, marginally effective, or had, like Arsenic for example, horrendous or even lethal side effects.

In the early years of the 20th Century, improved living conditions and social infrastructure dramatically reduced the risk of catching infectious diseases, yet even so, the tools available to treat these diseases had changed little. Then in the mid 1930’s the release of the sulphonamides (sulphur drugs) heralded a new era in the treatment of common communicable diseases like pneumonia and bacterial meningitis. No one could have known that less than 10 years later, a completely new class of drug would appear that would make even the sulphur drugs appear old-fashioned. Yet this is precisely what happened when penicillin, the first true antibiotic arrived.

In the years since, numerous other antibiotics have been discovered and released onto the market. Of all the medical advances made since the beginning of the 20th Century, antibiotics have unquestionably had the greatest impact on human health. In fact, many reading this article would not be alive today were it not for these remarkable drugs.

What is an antibiotic?

An antibiotic is exactly what its name suggests: An anti – biotic, a substance that, at low doses, either inhibits the growth of or kills a living organism. By this definition, petrol would be an excellent antibiotic but not a particularly useful one. For an antibiotic to have any practical use in a clinical setting to treat a bacterial infection in an animal or human, then the ability to kill alone is not enough. It must be both selective and specific in how it kills, so it can eliminate the invading bacteria without being toxic to the infected host. The selectivity comes through the antibiotics ability to block or interfere with a biological process, enzyme pathway or system that is essential to the growth or survival of the bacteria but that is not essential or present in the host. This selectivity is what separates the antibiotics from all the anti-bacterial treatments that came before and why they are often referred to as “magic bullets”, because they selectively target the biochemistry of the bacteria without affecting the host.

Never taunt a wizard

If you have access to powerful magic, you use it whenever possible and antibiotics rapidly revolutionised the treatment of infectious disease. They are now an indispensable part of modern medicine. The challenge is to keep them that way.

The danger of having such a powerful tool is that you tend to overuse it. This is certainly true for antibiotics. Over the years, we have become increasingly lazy and begun to rely on antibiotics, using them in inappropriate circumstances, rather than reserving them for when they are really needed. In the clinic, patients either ask for, or are prescribed antibiotics as a precaution or for viral infections, where they are of no benefit (antibiotics do not work on viruses). Meanwhile on the farm, huge quantities of antibiotics are included in stock feed for healthy animals. We have become disrespectful of the wizard and his magic.

Antibiotics are our most powerful weapon in the war against bacteria. Despite their tiny size, bacteria are resourceful adversaries and as any General will tell you, it is very dangerous to under-estimate an enemy. Within a few years of its release, penicillin-resistant bacteria began to appear. The enemy was fighting back. Since then, resistant strains have appeared for the other antibiotics in our arsenal. In recent years, things have changed however. We are now seeing the appearance of “Superbugs”, bacteria that have become resistant to not just one but many of the commonly used antibiotics. The old enemy is developing some very powerful weapons of its own.

So how did this happen and do we really need to worry? There is considerable evidence to suggest we have a problem, a potentially very big problem…

How big is the problem?

Australian antibiotic use in farming, medicine and veterinary medicine is high. From 1992 to 1997, Australia used over 700,000 kg of antibiotics each year, around 400,000 kg of which, or 56 %, went into stock feed to prevent diseases in intensively raised animals or as a growth promoter1. This means that for every man, woman and child in Australia over 20 grams of antibiotics are used for agricultural purposes per year! While that’s a lot, other counties are even worse. The average for the USA is over 27 grams per person per year. For now, let’s concentrate on the agricultural uses of antibiotics.

So how did the industry get so large? Easy question. We wanted cheaper foodstuffs and the use of antibiotics brought production costs down. The farmers were simply responding to the rules of supply and demand that we created!

It is also important to understand that the antibiotics in stock feed are being given to animals that aren’t sick! They are there either to prevent disease in intensively raised animals or as “digestive enhancers” or “growth promoters”. The reasoning being that the antibiotics improve the functioning of the gastrointestinal tract, make for more efficient digestion and uptake of feed and therefore better feed conversion efficiencies. So the animals put on weight more rapidly, from less feed, in a shorter time and so can be brought to market faster and cheaper, keeping production costs down.

But that’s good isn’t it? Quicker to market from less food and at lower cost?

Before I go on, please keep in the back of your mind that up to 75 % of the antibiotics that go into an animal as stock feed come out the other end unchanged and go back into the environment where they create a selection pressure for the formation or persistence of more antibiotic resistant bacteria within the population… But I’m getting ahead of myself…

What goes up must come down

As with most things, there is a trade off and feeding antibiotics in massive quantities to healthy animals so they get to market quicker and cheaper is no exception. In this case the trade offs are potentially very serious indeed.

So why are people worried and should they worry? There are three main concerns.

  1. The use of antibiotics as growth promoters in agriculture will increase the likelihood of antibiotic resistance developing, specifically to the antibiotics used to treat human diseases;
  2. Antibiotic resistant bacteria will contaminate the foods we eat;
  3. Antibiotic resistance genes from bacteria contaminating our food will transfer to the bacteria in the human gut or to bacteria capable of causing human disease.

There is a massive amount of literature arguing the various sides in this debate, for and against. I will discuss none of it. I take this seemingly arrogant stand for one simple reason: The evidence is irrelevant to the debate. Yes, you did read that correctly. A scientist saying that evidence is irrelevant to a debate. Why?

That nature abhors a vacuum may be an old cliché but it is still true. Create an ecological niche or exclude organisms from a place they once occupied and they will either adapt to reclaim their former territory or new organisms better suited to that environment will move in to take their place. That’s what nature does. That’s what nature has always done. And that’s what nature will continue to do. If you want proof, just ask yourself how often you have to weed the garden. It’s called natural selection.

So why do we need data to prove what we already know must happen. Why do we need data to prove the inevitable?

So let us ask the above three questions:

  1. Will the use of antibiotics increase the likelihood of antibiotic resistance developing? Of course it will. Living things adapt to change.
  2. If antibiotic use in agriculture increases the number of antibiotic resistant bacteria present, will those antibiotic resistant bacteria find their way onto our foods? Of course they will. Thousands of people get sick from contaminated food every day.
  3. If these antibiotic resistant bacteria find their way into the human gut, are they likely to transfer the genes for antibiotic resistance to the bacteria in our gut or bacteria capable of causing human disease? Of course they will. Bacteria are always collecting or exchanging pieces of genetic information. That’s how they adapt to change to ensure their survival.

Indeed, there is overwhelming scientific evidence to support these statements1,2,3,4. Nevertheless, we concluded that the non-therapeutic use of antibiotics in agriculture wasn’t a good idea without doing a single study, reviewing a single piece of scientific evidence or consulting a single expert. Why? Because using common sense and a basic understanding of the fundamental principles by which all living systems work, we could see that it was a bad idea and doomed to failure from the start.

Have you ever noticed when there is a spirited debate about an issue that the arguments often skirt the issue itself? Instead of dealing with the fundamental questions or principles, the focus of the debate is on the “evidence” or “data”, or lack of it and its myriad interpretations. Unless these discussions take place within the larger context, there is the danger that the fundamental questions get forgotten, confused or lost in the detail of data and so the “solution” eventually proposed does little or nothing to deal with the issue it was supposed to address. Doubtless, you can think of numerous examples of this from your own experience. If you can’t, look at any day’s copy of the newspaper for inspiration.

This is not a call to abandon rational decision-making based on hard evidence, data and observations. The life we enjoy today is far better than when important social decisions required the obligatory virgin sacrifice or occasional witch burning. Nevertheless, it is equally damaging to be afraid to take important decisions or implement fundamental change without evidence that would stand up in court or a Senate inquiry. Hell lies down this road. Instead, we need a balance in the way we approach decisions, a balance between evidence and applying rational logic in the absence of sufficient evidence or when it may be difficult or even impossible to obtain that evidence. The above discussion on whether the non-therapeutic use of antibiotics in agriculture is a perfect example of this approach. On this matter, we do not need more evidence; we need decisions – and meaningful action to back them up.

So where does that leave us? Natural history; the fossil record; thousands upon thousands of scientific studies and that you have to mow the lawn every two weeks tells us that no power on earth has ever resisted the forces of nature indefinitely and no power on earth ever will. We don’t need any more evidence to tell us this. Any strategy, chemical, technique or practise that defies the forces of nature will ultimately fail, no matter how clever it may appear to be. And you can know this before you start.

If you find the thought depressing that to go against nature will always fail, think for a moment about what else it means. The wonderful upside is that if you work with the forces of nature then nothing on earth can stop you. Now isn’t that a wonderful prospect because that’s exactly what “sustainable” means!

Having answered the fundamental question of whether the non-therapeutic use of antibiotics in agriculture is a good idea, then why do we need the rest of the article? I want to use the next few Newsletters to take a Big Picture view of what antibiotic resistance is, how it occurs and what it really means for our health and the health of future generations. Why? Because I believe antibiotic resistance is one of the biggest challenges we face today and one we must all address together.

Note that to have this discussion it is impossible to separate the overuse or inappropriate use of antibiotics for agriculture from their overuse or inappropriate use in medicine. For as far as bacteria are concerned, a host is a host and it doesn’t care whether the host happens to be a chicken destined for the Sunday roast or a bank clerk you are fattening up for Christmas!

Stay healthy until next time!

In Part II we will look at how antibiotic resistance occurs and what it means.

In Part III we will look at what is being done on the political front to address the issue of antibiotic resistance.


References

(1) Joint Expert Technical Advisory Committee on Antimicrobial Resistance (JETACAR). The use of antibiotics in food-producing animals: antibiotic-resistant bacteria in animals and humans. Canberra: Commonwealth Department of Health and Aged Care and the Commonwealth Department of Agriculture, Fisheries and Forestry; 1999 Sept.
Available on line at:
http://www.health.gov.au/internet/main/publishing.nsf/Content/2A8435C711929352CA256F180057901E/$File/jetacar.pdf
(2) Harwood V. J., Brownell M., Perusek W., Whitlock J. E. Vancomycin-resistant Enterococcus spp. isolated from wastewater and chicken feces in the United States. Appl Environ Microbiol. 67(10): 4930-4933, 2001.
Available on line at:
http://aem.asm.org/cgi/content/full/67/10/4930?view=long&pmid=11571206
(3) Ferber, D. Antibiotic resistance: Superbugs on the Hoof? Science, 288, No. 5467, 792 – 794, 2000.
(4) World Health Organization: Impacts of antimicrobial growth promoter termination in Denmark. The WHO international review panel’s evaluation of the termination of the use of antimicrobial growth promoters in Denmark. 2003.
Available on line at:
http://www.who.int/salmsurv/en/Expertsreportgrowthpromoterdenmark.pdf

The author is grateful to Professor John Turnidge for helpful discussions and critical comments during the preparation of this manuscript.

A foreshortened version of this article was published as: “Antibiotics: Far too much of a good thing” in CleanFood organic, No. 4, Pages 166-175, 2007.