COMING PLAGUE, RECONSIDERED G. EMILY GHODS-ESFAHANI 09 these events. Overuse of DDT, coupled with a revolution in agricultural economics, turned farmlands that were previously alive with diverse plant and insect life into monocultured breeding grounds for the blight of malaria. As plant diversity declined under the plow of farmers cultivating only cash crops, the biodiversity of insects was reduced to pestilential imbalance. With dwindling competition due to these agricultural practices and the use of DDT, the surviving insects overwhelmed farm land, feeding on the cash crops planted to alleviate rampant privation and malnutrition. Disastrously, farmers responded by increasing the use of DDT; resistant mosquitoes survived the spraying, while their natural competitors died off. Resistance to antibiotics only amplied the malaria crisis. Between 1980 and 1986, the sensitivity of malaria to chloroquine decreased by ten-fold each year, a total decrease of 1,000,000 fold. Approximately three-fourths of all malaria victims would become resistant to most malarial drugs, and a growing black market for anti- malaria drugs fostered improper use of the antibiotics, compounding the problem of resistance. Each time an antibiotic drug is used to eliminate a target micro-organism, it creates a selective regime that reduces the relative tness of non-resistant organisms, and increases the relative tness of resistant organisms. If, in such conditions, an organism arises (through random mutation) that can resist the antibiotic, it has substantial tness advantages over its competitors and proliferates. The gene for resistance consequently spreads through the population. Today, this has occurred to such a degree that some pathogens now thrive on bleach and other disinfectants used in hospitals, so that, in many instances, hospital rooms have become Petri dishes for infectious microbes. In the four species of the protozoan genus Plasmodium which cause malaria in humans, the gene for resistance codes for the synthesis of a membrane- spanning protein that pumps harmful chemicals out of the In 1994, Pulitzer Prize-winning reporter Laurie Garrett conceived a book whose foresight seems stunning today. With the growing threat of avian u, the global failure to contain pandemic AIDS, and the rapid emergence of multi-drug-resistant (MDR) forms of many known pathogens, Garretts The Coming Plague remains a topical and essential read for those interested in microbial ecology and public health. By the twentieth centurys end, MDR forms of gonorrhea, tuberculosis, Staphylococcus aureus (Staph), Streptococcus, inuenza, herpes and HIV emerged hand in hand with the potential triple threat of airborne cancer-causing viruses, airborne AIDS and, most recently, airborne avian u. Biology teaches us that such variations in organisms are due to random mutations, and that selective forces act on these mutations to make them more or less frequent in a population. Garrett claims that the selective regime which encourages the proliferation of mutant organisms like MDR pathogens has been shaped by social causes; society has selected these mutant pathogens through poor public health policies and a vast eco-biological imbalance perpetuated by humanitys desire to dominate the planet. Beginning her analysis with the percolating can- do optimism that characterized post-WWII America, Garrett chronicles the unpredictability of emerging infectious diseases, and public healths failure in the face of most major outbreaks. With the discovery of penicillin, the eradication of smallpox, and a nascent campaign to eliminate malaria, scientists declared that humanity could close the book on infectious diseases. Not even a decade later, public health ofcials would have to grapple with one of their greatest failureswhich Garrett chronicles with grim precision. In 1958, an international crusade began with the aim of eradicating a pathogen that beleaguered Southeast Asia, India, and Africa - malaria. The chosen solution was DDT, an insecticide to kill the mosquitoes that carried the parasite. Almost instantaneously, however, mosquito populations resistant to DDT emerged. At the same time, chloroquine-resistant strains of malaria surfaced. Sobering consequences followed hard upon The Coming Plague: Newly Emerging Diseases in a World Out of Balance Laurie Garrett 768 pages. Penguin (Non-Classics) Image courtesy of Tim Shen DARTMOUTH UNDERGRADUATE JOURNAL OF SCIENCE 42 protozoan cells. As a mosquito inserts its proboscis into an MDR malaria-stricken human being, it introduces that strain of malaria into its abdomen. Once in the mosquito abdomen, lateral gene transfer allows resistant parasites to donate plasmids (segments of DNA) that contain resistant gene factors to parasites that lack these factors. Four decades after being optimistically set on wiping malaria off the face of the Earth, the World Health Organization (WHO) declared that no effective strategy for malarial control existed. But Garrett chillingly conveys that malaria would not be WHOs only public health catastrophe. In 1990, WHO declared that all infections of the upper respiratory tract should be assumed to be bacterial, and therefore treated with antibiotics. The ineffectiveness of this policy lies in the signicant detail that most infections of the upper respiratory tractwith the notable exception of Streptococcus pneumoniae are viral. Antibiotics have no effect on viruses; they are exclusively meant to treat bacterial infections. To Garrett, WHOs scorched-earth policy of antibiotic misuse has had consequences that far exceed those of the patient not being relieved of their original ailment, because when antibiotics are improperly prescribed, they result in resistant forms of bacteria. Perhaps as a consequence of antibiotic use and misuse, some Staphylococcus bacteria are so advanced in plasmid exchange that they have evolved membrane spanning proteins that scan passing DNA, looking for useful genes that encode resistance factors. When found, the protein pulls those factors into the bacterium to incorporate the plasmid into the bacterias own DNA. As the microbes outwitted their hosts, it became increasingly clear that public health ofcials needed a strategy, or at least an organization, to localize an effective response in the face of endemics, epidemics, and pandemics. Experts in the eld of public health and microbiology, so called disease cowboys like D. A. Henderson and Joe McCormick, conducted microbe search and destroy missions while they worked to round- up the necessary strategies. When asked if WHO was equipped to handle any emergency in public health, Henderson retorted, by the time WHO realized there was an AIDS epidemic, it already existed on four continents. Thats WHO preparedness and emergency response for you. The sorry state of WHOs 34 multi-national labs, established to detect outbreaks of viral diseases and immediately report them to WHO headquarters in Geneva, also speak to WHOs readiness for public health disasters. Only one half of these labs can diagnose yellow fever, and none have the equipment necessary to detect hemorrhagic fevers such as Ebola, Lassa, Marburg, or Machupoall of which have reemerged in Africa and South America, at intervals unpredictable even for experts in tropical medicine. The obvious next choice for emergency response would be the U.S. Center for Disease Control (CDC). Yet, as it turns out, there is no protocol by which federal or state agencies report outbreaks to the CDC, delaying or eliminating the possibility of suppression at the onset of an epidemic. As a result, the incidence of AIDS in the U.S. is underreported by a conservative estimate of 20%. To Garrett, the solution to these crises in public health does not lie in trusting that microbes will promptly roll over and die in response to eradication efforts, unaided by that process that affords their exibility: evolution. Public healths response to epidemics only amplies the epidemic by iatrogenic meansin other words, induced by the very activities conceived to combat them: the healthcare system. And so, with Harvard economist Dick Levins, Garrett sadly concludes that humans are utterly incapable of embracing complexity. With this indictment and our neglect of the microbescoupled with the growing pandemic of HIV and other viruseswe have provided hundreds upon thousands of microbes with walking test tubes in which to test their mutations. And so humanity must brace itself for the coming plague. Gonorrhea viewed by uorescent microscopy. The bacteria are labeled with uorescent antibodies. Image courtesy of CDC. Tuberculosis bacteria viewed under 1000X magnication and stained with acid-fast Ziehl-Neelsen stain. Image courtesy of CDC and Dr. George P. Kubica SPRING 2006 43