Antibiotics & Agriculture part 5: Stokstad's Genie

When  Robert Stokstad discovered antibiotic growth promoters, he was operating in industrial farming's nascent era. In the 1920's, farmers realised that with the right levels of vitamin supplements, they could raise chickens indoors safely cocooned from the outside environment. But this innovation came with some costs, as chicks born in this environment had poor survival, and didn't grow as fast as they did in the wild.
Stokstad's discovery of growth promoters was like a wish come true. Just by adding a low dose antibiotics, we could help more chicks survive into adulthood, and allow them to grow to full size whilst saving money feeding them. But, just like in any morality tale, wishes can come with consequences.
It turns out that the wholesale saturation of the industrial farming environment with antibiotics provided the perfect incubator for antibiotic resistance.

There have been a number of dangerous outbreaks of antibiotic resistant pathogens which can be traced directly to their usage in the agricultural industry. Salmonella, E.coli and even some strains of Staphylococcus aureus  have acquired resistance to antibiotics from farms.
Even more disturbing is that agricultural antibiotic usage has increased the numbers of resistance genes in the overall environment. These genes have been proven to transfer between different bacterial species. Even if the bacteria they reside in are themselves not a threat to human health, these genes can be transferred to pathogens that are threats.

The mounting evidence of this threat prompted some countries to act.
In 1984, after hearing reports that consumer confidence in meat safety was dropping, due to the antibiotic resistance threat, Swedish farmers requested a ban on all growth promoters. They were the first country to implement a ban, but they were not the last.
If you wanted to show the pitfalls of banning agricultural growth promoters, you can find no better example than that of the Netherlands. In these cases, the ban came into force before the farmers could improve infection control practices. As a result, they were beset by outbreaks of bacterial disease that required the use of more therapeutic antibiotics. In the Netherlands, this meant that there was no net change in the amount of antibiotics sold to the agricultural industry.
Sweden was not immune to this effect. Whilst the initial results of the ban showed promising reductions in antibiotic use, it was also characterised by increases in disease outbreaks on farms. The appetite for therapeutic antibiotics increased in direct response to these outbreaks, until it eventually rose to pre-ban levels.

When Denmark embarked on a similar plan to ban antibiotic growth promoters, they did so with an eye on the experiences of previous nations. With this system, they managed to reduce antibiotic use by around 90%. Somehow their ban managed to reduce infections without changing the welfare of their animals, and still managed to keep the Danish pig industry competitively priced.

So why did the Danish experience differ so much from the experiences of other nations ?

When they implemented the ban, they also ensured there was a comprehensive monitoring system in place to send out the alarm if new antibiotic resistant bacteria were produced, and a way of regulating the doses of therapeutic antibiotics given by veterinarians. They didn't ban all of their growth promoters at once. They first rolled back the use of avoparcin in 1995, then followed it with a ban on virginiamycin in 1998, and then finally a ban on all growth promoters in 2000. This gave the farmers the time to change the way they did farming to compensate for the loss of these growth promoters.

In preparation for the ban, Danish farms implemented basic infection controls. The routine disinfection of workers clothes, the workers themselves and their vehicles is now standard in many countries, to prevent the transfer of diseases between farms. Veterinary vigilance became watch words, with herds regularly inspected to ensure that outbreaks were caught and dealt with as early as possible.

The authorities also madee sure that every part of their system was committed to the reduction of antibiotic use. Veterinarians were prevented from directly selling antibiotics to farmers, they could only issue prescriptions, removing a potential conflict of interest. The numbers of antibiotic prescriptions given to specific herds was carefully monitored. Farms that were consuming high levels antibiotics could be spotted more easily under this system, and given the appropriate support.

Denmark also brought in new laws which changed the way that their pigs were raised and weaned. They recognised that a lot of their infection problems could be traced to their piglets being weaned too early and forced into an infection riddled world without the protective antibodies in their mother's milk, and immune systems not fully able to deal with the infection riddled world into which they were being exposed.

When Denmark put its ban in place, it did so with the knowledge that a massive full spectrum ban on antibiotic growth promoters could potentially harm its precious pork industry. When they drew up plans to ban antibiotic growth promoters, they paid attention to the science. They thought carefully about the consequences of the ban, and how they could best compensate for these effects using the best science available. Then they brought in the ban slowly, allowing farmers and veterinarians time to adapt to the new system, and ensured that the incentives presented by this new system were geared to limiting further usage of antibiotics.

In 2006, a broad ban on all antibiotic growth promoters was implemented across the European Union in response to mounting public pressure. Countries across the EU are now for better or for worse have to adapt their farming strategies to compensate for the loss of antibiotic growth promoters.
There are signs that the ban is working. The numbers of antibiotic resistance genes in the environment are decreasing.

But let's not pop the champagne corks just yet. There are a few problems with these bans that require further inspection.
In the initial stages of all the bans, outbreaks of bacterial disease often occur more frequently. In some scenarios, Veterinarians can be reticent in prescribing more antibiotics to treat these diseases, leaving the animals to suffer longer, and exposing them to greater risk of death. Improvements to infection control and animal husbandry only go so far in preventing outbreaks of disease. The situation in some countries is so bad that banning agricultural antibiotics actually increases the numbers of therapeutic antibiotics being used. The levels of antibiotics in some cases reaches the levels seen before the ban.
Every time an antibiotic is used, be it in animals, or in humans, has a chance of increase the numbers of resistant strains in the population. Taking this viewpoint, you may say that some of these bans have no effect at all. But you would be ignoring a crucial detail.
 In his Nobel prize speech, Fleming himself gave a warning about how mass underdosing could trigger the creation of antibiotic resistant strains, yet within ten years underdosing became standard practice within the agricultural industry.
It is crucial that we make sure that antibiotics are always used responsibly. The key reason why banning antibiotic growth promoters was that it was one demonstrable case in which antibiotics were used irresponsibly.

The other key problem with these bans is that no one knows the extent to which it will affect human health. It should prevent new strains of antibiotic resistant bacteria evolving on farms, such as livestock associated MRSA, or antibiotic resistant Enterococci.
However, expecting these bans to eliminate all antibiotic resistance is to unfairly place all of the blame on farming and agriculture for our current situation. The primary environment in which antibiotic resistant bacteria most commonly evolve, and where they are at their most dangerous, is found in hospitals. Any antibiotic resistance genes which have already made the jump into this environment are here to stay. Regulating antibiotic use in hospitals is difficult, because that is where we, as humans, need them the most. As much as we may worry about how the price of meat may be affected, if we cannot accept that relatively minor sacrifice, we will not be able to accept the changes and the costs needed to eradicate antibiotic resistance from our healthcare systems.

 The genie of antibiotic resistance is out of the bottle, but it wasn't just Robert Stokstad who had a hand in releasing it. We may sneer at growth promoters because they are the worst example of how we have squandered antibiotics. We may lament at how some faceless evil within the agri-business made the calculation that our future is worth trading for cheaper meat today. But we all had a hand in shaking the genie out of its bottle. We still have a hand in determining our own future. Even those of us who currently live in Europe may soon be inundated with american meat raised antibiotic growth promoters if certain trade agreements are successful. They will once again be faced with the same choice facing everyone else in the world, the choice between a full stomach today or better health tomorrow.

References

The WHO's internal evaluation on the termination of antimicrobial growth promoters in Denmark
http://www.who.int/gfn/en/Expertsreportgrowthpromoterdenmark.pdf

Danish Pig production in a European Context
http://www.lf.dk/~/media/lf/Aktuelt/Publikationer/Svinekod/LFEUBenchUK110318.ashx

Cogliani C., Goossens H. & Greko C. (2011). Restricting Antimicrobial Use in Food Animals: Lessons from Europe, Microbe, 6 (6) 274-279. DOI: