The Winds of War

Though the discovery of antibiotics went largely unnoticed, World War II changed everything. By 1945 Fleming’s penicillin was in full production as were many of the antibiotics pioneered by Waksman.  In fact, a large supply of penicillin was a prerequisite for the D-Day invasions of Normandy. At a time of great national pride the production of antibiotics was delegated to the War Department. A memo was sent to the manufacturers of antibiotics in 1943^[16]:

"You are urged to impress upon every worker in your plant that penicillin produced today will be saving the life of someone in a few days or curing the disease of someone now incapacitated. Put up slogans in your plant! Place notices in pay envelopes! Create an enthusiasm for the job down to the lowest worker in your plant."

For obvious reasons, the War Board wasn’t looking to probiotics in 1940. The general public was relatively healthy and of what use was yogurt in fighting Nazis?  Antibiotics helped turn the face of warfare where even a flesh wound meant possible death.  Now soldiers could be returned to battle much quicker and prophylactic doses of antibiotics prevented wasted time from the imminent infections and protected against germ warfare. Predictably, probiotics received scant attention until many decades later when the tide had turned and the enemy was within us.  Widespread use of antibiotics after WWII helped create a nation who had become fat, lazy, and unhealthy enough to fight off a cold (much less a terror like the Third Reich).

Microbes are incredibly intelligent for having no brain, maybe it’s their extremely fast turnover and propensity to “learn” from past generations that are measured in minutes and hours versus years and decades as we must endure.  When microbes sense their end is near, they quickly devise ways to allow their progeny to survive.  We know so little about how they actually do this, and possibly it would behoove us to study these mechanisms a bit more when we tinker with microbes. Microbes have a tactic they readily employ, gene transfer.  When a microbe develops a new gene, such as one for antibiotics resistance, it shares that new gene with the microbes having a similar genetic profile.  This makes a strong case that antibiotic resistant isn’t so much dependant on ancestors as it is neighbors.^[17]

Decades after our deep dependence on antibiotics began it became apparent that we never harnessed the power of the antibiotic at all, but instead unleashed a storm more powerful and far reaching than all the World Wars combined. In the U.S. alone, 23,000 victims of antibiotic-induced colitis and C. difficile diarrhea pass away annually as a result of broad-spectrum antibiotics and their consequences.^{[18] [19] [20]} Thousands of others suffer silently, undergoing surgery after surgery to cut out diseased parts of the colon and living disrupted lives.

Just as humans have developed peaceful means to deal with each other, maybe we should have chosen more peaceful means to deal with the microbes that control so much of our lives.  It’s easy to see microbes as war-loving life forms, but they didn’t spend their billions of years in constant warfare, but rather in peaceful coexistence developing discrete mechanisms to control their environment.

From “ANTIBIOTIC RESISTANCE AND THE FUTURE OF ANTIBIOTICS” an essay by Julian Davies, Ph.D. University of British Columbia:^[15]

The microbial world is immense in number and diversity; specific details are subject to debate, but estimates indicate that there are between 10,000 to 50,000 taxa per gram in different soil types, while the bacterial density may be as large as 109 total bacteria per gram of soil. These are communities, not isolated organisms! In many environments, in the human intestinal tract for example, a small number of dominant phyla may constitute as much as 90 percent of the total population. Are these populations in constant conflict (the “war metaphor”), or do they undergo flux and coexist as controlled communities? It seems most logical that the latter is true, in which case some form of signaling process would be required to modulate the mixed populations under differing conditions. We believe that the signaling is primarily chemical, involving a variety of naturally occurring, low-molecular-weight compounds; after all, this is the predominant form of signaling in higher organisms. Of course, other forms of interactions, such as electrical connections between bacteria, are not excluded; the latter notion is supported by the demonstration of nanowires linking bacterial cells in biofilms. 

It’s easy for us to assume that microbes are at constant battle, and it makes us believe that the best way to deal with microbes is with brute force.  The truer scenario, however, is that microbes would be better dealt with in a peaceful manner.  The human propensity to wage war with each other has been a driving force behind the need for better, faster, and more antibiotics, consequences be damned.

Special thanks to Dr. Grace Liu, PHARMD, from Animal Pharm for contributions to this article.

[15] Davies, Julian. "4 Antibiotic Resistance: Origins and Countermeasures."

[16] "Alexander Fleming Discovery and Development of Penicillin ..." 2013. 1 May. 2014 <https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html>

[17] Martins, A. "Suppl 1: Mechanisms of Resistance in Bacteria: An ..." 2013. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613773/>

[18] "Antibiotic Resistance Threats in the United States, 2013 report." 2013. 4 May. 2014 <http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf>

[19] Dallal, Ramsey M et al. "Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications." Annals of surgery 235.3 (2002): 363.

[20] Muto, Carlene A et al. "A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use." Infection Control and Hospital Epidemiology 26.3 (2005): 273-280.