WWIV: Nuking Our Microbes

Most history books teach our species-centric view of life, so we grow up believing that our species is pretty deft at mayhem, carnage, and death. But for all of history, at least until we got proficient at making hydrogen bombs, it turns out we were rank amateurs.1 By far the overwhelming causes of death in wars and conflicts haven’t been bullets, bombs, steel, arrows, rocks, or fire. They were bacteria, viruses, and parasites.2 Infections killed far more soldiers and civilians than did any general’s strategic acumen or dictator’s deranged decrees.3

The military’s emphasis on order, spit and polish, short hair, digging latrines, and quarantines isn’t coincidental or merely aesthetic. It comes from a millennial history of dirt and infectious diseases overwhelming and wiping out troops and civilians. One of the reasons it was so easy for a few Spaniards, Brits, and French to conquer vast tracts of land and millions of people is that up to 90 percent of the First Peoples (peoples indigenous to any given geographic area) may have been decimated by smallpox, leptospirosis, yellow fever, and plague brought in by early explorers.4

During the Crimean War, 2,755 UK soldiers were killed in action. Wounds ended a further 2,019 soldiers’ lives. And disease wiped out 16,323.5 In the U.S. Civil War twice as many Union soldiers died of infections as from Confederate attacks.6 It is only in the last seven decades of world history that we’ve radically tipped the mortality balance away from pathogens and in our favor, a true example of unnatural selection. In a real and quantifiable way this required winning the four greatest global wars humans have ever fought—not against one another, but against our microscopic foes.

Micro-WWI: Vaccines. The power of vaccines is extraordinary; they are a weapon that turns the tables on many of the microbes that formerly practiced a whole lot of “natural selection” on us and fundamentally shaped human civilizations. In modern times, as almost all humans are exposed to weaker diseases or to artificial compounds that can stimulate their immune systems, we are driving whole classes of microbes toward unnatural extinction. For example, as late as 1988, polio was crippling more than 200,000 people in the most populous nation on Earth, India. In 2009, Indians suffered half of the world’s total cases of polio. On March 27, 2014, India was declared polio-free. Wild polio now only survives in Nigeria, Afghanistan, and Pakistan.7

Polio is not the only victim of our deliberate selection. If you were born after 1972, you simply never acquired the round scar on your arm or inner thigh that was common and prevalent in your parents and grandparents; you were never vaccinated against smallpox. Thus, one of the deadliest and most prevalent of all diseases became a historical footnote.8 Vaccines, along with clean water, may just be the cheapest and most effective thing humans have done to reduce infant mortality.

Micro-WWII: Antiseptics. It’s hard to overstate the success of this second Great War on microbes. Before Joseph Lister’s sterilization methods became standard operating procedure, going into a hospital, even for minor surgery, frequently meant a death sentence. Compound fractures, which led to immediate amputation and often to subsequent massive infection, had a death toll of about 68 percent.9 A 1915 Science magazine article describes pre-Lister hospitals as “reeking with pus and emptied by death. After operating, when the roll was called reporting a mortality of 40, 50, 75, 90, and 100 percent . . . Now we have hospitals of immaculate whiteness and the roll call reveals few mortalities exceeding 10 percent, most having fallen to 5 percent.” Despite accumulating evidence, many of the most prominent surgeons of the day continued to doubt the existence of “microbes”; these doubters’ wards remained death chambers for decades. But eventually even the stupid understood. Now you’re very unlikely to hear what was once a common phrase: “She died of hospital gangrene.”10

Micro-WWIII: Antibiotics. We no longer see the waves of epidemics that were once common and incredibly deadly; bubonic plague alone killed about 25 million people, or one-third of Europeans, in the mid-fourteenth century.11 The antibiotic miracle launched just as the real World War II began to turn in favor of the Allies, when bacterial infections remained an opponent far deadlier than any opposing army.12 Discovered by accident in a poorly protected lab petri dish, a “mold juice” (aka penicillin) that was so effective at controlling and killing bacterial colonies suddenly emerged as a “miracle cure” for human infections. By the end of WWII the balance of power in the war on bacteria was beginning to tip as well. Suddenly you could stop syphilis, gonorrhea, septicemia, infections that had been felling armies. Consider how radical and how recent this change is: The first U.S. civilian ever treated with antibiotics, in March 1942, died in a New Haven hospital in 1999.13

Unnaturally selecting non-pathogenic microbes is essential, but it can also generate blowback. Initially cultured in bedpans and rough vats, penicillin was rare and expensive. Very few harmful microorganisms had been exposed to the substance before, and when they did encounter it almost all died. Seeing how the antibiotics were so effective, we quickly learned to scale production and began to use the substance with abandon. However in thus carpet-bombing microbial communities, we began to discover a few isolated instances of antibiotic resistance. Then, unlike what had happened with antiseptics and vaccines, three disasters occurred almost simultaneously.

Think about the typical ads you see for antibacterial soaps, mouthwashes, and cleaners. Generally they advertise that if you use them regularly, they will kill 99 percent of all bacteria. And they do. But the few bacteria left behind are tough survivors. They are resistant to that particular antibiotic or antibacterial agent and, because so many of their brethren and competitors have been wiped out, the survivors have space, food, and light—a perfect environment in which to spread and colonize. So they reproduce, fast. Places that are constantly scrubbed, disinfected, and sanitized are particularly vulnerable; humans inadvertently turned hospitals, cruise ships, spotless kitchens, and professional sports locker rooms into evolutionary accelerators for some very bad bugs, which is why you hear more and more about friends or relatives getting “hospital-acquired infections.”14

To our peril, we also began to realize that microbial genes are very promiscuous; they hop from place to place. So after a few deadly bugs adapted to their newly toxic human environment, resistance began to increase rapidly across many species of pathogens. And because they reproduce so fast and share resistant genes, Darwin’s evolutionary time scale was seriously compressed. It became a brutal race between miracle cures and resistant pathogens.

The third disaster was overuse. Sometimes humanity’s combined greed and stupidity knows few bounds.15 Initially, doctors used antibiotics when there was little choice, because a raging infection could and did kill within hours and there was no other option. Eventually we got lazy. We overprescribed. We quit finishing our prescribed doses. We began to use antibiotics not just for ourselves and our crying kids, but for animals of all sorts. We even sprayed fruit trees, filling whole environments and generating resistance on a massive scale.

Eventually, entire classes of antibiotics were overwhelmed by brutally competitive bugs. Scientists scoured the globe, digging up dirt from remote regions to find new naturally occurring antibiotics that had not yet been applied in a medical context. Even this, which led to semisynthetic compounds, was not enough. They too were overused and lost effectiveness. As a result, in the United States alone, more than 2 million people suffer an antibiotic-resistant disease every year. A really conservative estimate of the direct death toll, every year in the United States alone, exceeds 23,000. To put this number in context, it’s almost twice the number of HIV/AIDS deaths.16

More than half of the babies born vaginally today in the United States acquire microbes at birth with tetracycline-resistant genes from their mothers.17 Micro-WWIII is far from over. A survey of 2,039 U.S. hospitals in 2009–10 found that 20 percent of hospital-associated infections (HAIs) involved multidrug-resistant organisms.18 Only in December 2013 did the United States begin to put some mild, voluntary guidelines in place to phase out indiscriminate use of antibiotics in animals, to be gradually implemented over three years.19 The situation in many less-developed countries is far worse: Inexpensive antibiotics are available over the counter to anyone for any reason, leading to a terrifying rise in multidrug-resistant bacterial infections, particularly in regions such as Asia.

When engaging in these three major wars against microbes, humanity did not just dip a toe into the microbial environment to cure life-threatening conditions in a few sick people; we engaged in massive environmental engineering and unnatural selection. The assumption that we could so fundamentally alter the environment and evolution of microbes that have coexisted and coevolved with us for millennia without suffering any consequences is an interesting one. Clearly we have seen incredible benefits in terms of overall human mortality by declaring wars on microbes, but we must also ask, as we nonrandomly attempt to napalm the bugs that live on, within, and near us, what might be the results of these actions? We best consider this sooner rather than later because we are just beginning to launch another major offensive. . . .

Micro-WWIV: Antivirals. There are more viruses on Earth, by a factor of 100 million, than there are stars in the universe.20 And they mutate and multiply faster than any other organism. While we have significantly tamed our bacterial environment, it’s only within the past decade or two that we have systematically started to understand and attack complex viral pathogens as well.21 The AIDS epidemic significantly accelerated our entry into this broad and complex conflict. In times past, when someone would come down with a virus, such as the flu, the doctor would say, “Antibiotics are useless; get some rest until you feel better.” But when thousands and thousands of people began to die from AIDS, huge protests led to massive funding, reduced regulatory constraints, and a clear focus on killing HIV.

Like antibiotics, the initial strategy worked. We fought HIV to a standstill, monitoring, controlling, and reducing viral loads. Someday we may be able to eliminate the virus altogether. And we are taking on more and more viruses, including hepatitis, Ebola, and flu.

But as we continue to carry out WWIV against viruses and as we hijack/domesticate/co-opt a whole new microenvironment, we might reflect on what we learned from WWIII and the overuse of antibiotics. First and foremost lesson? It works. Far more humans are alive today and have descendants because we keep performing unnatural selection on the bacterial environment in favor of “survival of the unfit.” But there can be blowback, in the form of some resistance. And viruses mutate hyper-fast, which is why we need to redesign flu vaccines each year, and even then the new vaccine sometimes doesn’t work. This is why we use three or four medicines at the same time to attack the rapidly mutating HIV. It also implies that were viruses to acquire broad immunity to combination therapies, they could come back with a vengeance.

We know little about viruses, and they are so varied and complex that current antivirals only work on a narrow set of pathogens. We will likely go after SARS, MRSA, bird flu, and swine flu on a case-by-case, medicine-by-medicine basis. Broad-spectrum antivirals are under development but remain a ways away, which is a bad thing for patients with certain exotic and rare diseases but may not be horrible from an evolutionary perspective.

We may need to learn a whole lot more about what we are unnaturally selecting on a macro scale before we seriously go after the 1031 viruses that live on Earth. And should we begin using broad-spectrum antivirals, we might wish to remember that our gut contains tenfold more viruses than bacteria, and we are virtually ignorant about what species they are and what roles they play in our health and wellness.22

As we seriously begin to tinker with viral ecologies, we might want to ask three questions: (1) Are we also killing a lot of useful and symbiotic viruses? (2) What are the functions of these viruses? (3) How do we prevent engendering superviruses? Even today, after investing a whole lot of research and money, scientists discuss individual viruses, but they rarely discuss the virome—the way our whole virus population interacts with our bodies and cells every day. The numbers are completely overwhelming; we have about a hundredfold more viruses living on us and in us than we have total human cells. If we remain in the Dark Ages in terms of understanding our symbiosis with viruses, especially the benevolent viruses living in our bodies, our allies could become casualties of our new drug war.23

Billions of people are alive because we have fought and largely won major wars against microbes. But sometimes it’s best to reflect on just how different and unnatural this state of affairs is. The natural norm for humans and animals was to be perpetually covered with dirt and coevolving with microbes. It is humans, not the environment, that redesigned, reformulated, and restructured entire microbial ecologies to suit our current needs. So as we reach for the Lysol, Clorox, Listerine, Dial, Secret, Mr. Clean, or Spic and Span . . . or when you get a scrape and run for the Bacitracin, Neosporin, Mercurochrome, alcohol, or iodine . . . you are unnaturally selecting your microbial environment.

The benefits of doing this can be enormous, but there can also be consequences to overindulging. No one’s arguing that antiseptics, vaccines, antibiotics, or antivirals are a bad thing, or that we shouldn’t have them. What we have achieved with their help is extraordinary. But there are sometimes consequences to such large-scale bioengineering. Restaurants and custodial businesses are particularly prone to severe antibiotic-resistant infections.24 Washing your hands more than twenty times a day makes you 2.8 times likelier to contract dermatitis.25 A general explosion of allergies and resistance may be just one more symptom of how fast we are redefining and redesigning our interactions and relationships with the microbial world. And as far as our species is concerned, our microbial and viral ecology are just as much a part of who we are as our cells. When we unnaturally select microbes, we are driving our own evolution.