Outbreaks of multidrug-resistant bacteria and mycobacteria have also resulted from amplification directly by medical personnel,44 syringe or devise reuse,45 device packaging,46 septic catheters or IV lines,47 septic surgical procedures, often involving contaminated implants of heart pacemakers, valves, limbs, joints, or other devices,48 and respiratory assistance equipment.49 In some cases an entire room—its walls, tables, beds—could be so thoroughly saturated with microbes that the physical setting itself served as an amplifier.50
When hospital-based amplification events occurred with enough frequency, they could lead to endemic nosocomial infection. In such cases the hospitals simply came to accept that newly emergent microbes, for example, drug-resistant bacteria, were permanent features of their environment, and the microbes frequently found their way into the general community. Such was the case for hepatitis B,51 vancomycin-resistant enterococci, 52 respiratory syncytial virus,53 MRSA (methicillin-resistant staphylococci),54 MR S. pneumoniae and S. epidermis,55 fluoroquinolone-resistant Serratia and P. aeruginosa, and a host of aminoglycosides-resistant bacterial species.56
In addition, the use of air conditioning or recirculation devices in otherwise airtight facilities has served to amplify airborne infections. Whether the setting was an airplane, nursing home, prison, or office building, the scenario was always the same: constant recirculation of the same air afforded small numbers of microbes enhanced opportunities to infect human beings. Examples include influenza,57 tuberculosis,58 Legionnaires’ Disease, 59 measles, and influenza.
Research into microbial ecology would help identify more amplifiers, as well as measures that could be taken to mitigate their effects. At Yale, Robert Shope was in 1993 trying to develop ways to spot zoonotic events along the frontiers of Homo sapiens encroachment upon rain forest areas. Harking back to his earlier years studying JunÃn and Oropouche in South America, Shope headed a team of scientists that was studying human residents of small islands in the Amazon River near Belém. Busily carving out farmland from the rain forest, they were being monitored by Shope’s group for evidence of novel viruses in their bloodstreams.
Carol Jenkins of the Papua New Guinea Institute of Medical Research headed up a similar effort in that country, following the health of people living in four comparable villages, two of which were employed in large-scale logging and deforestation efforts. Jenkins hoped to witness the emergence of newly recognized microbes or disease trends among the villagers most actively engaged in logging the previously pristine tropical forests.60
Stanford University’s Gary Schoolnick came up with another novel approach to monitoring disease emergence in Mexico. He set up a modest molecular epidemiology laboratory along the Mexico-Guatemala border and trained local residents how to spot unusual diarrhea cases and collect stool samples. The community straddled the Pan American Highway, the primary artery connecting North and South America. Every year millions of people journey from the remote regions of the Southern Hemisphere up the highway to jobs in the north. They carry their microbes with them—microbes Schoolnick hopes to spot as they make their way to the California and Texas borders.
In the microbe magnets—the world’s urban centers—research is needed to determine which aspects of city life most amplify microbial spread. For example, how strong is the correlation between rising rat populations and disease? When, in 1992–93, New York City had a 70 percent jump in reported incidents of rats biting humans, was that a harbinger of coming disease? When city budget cuts led to radical reductions in rodent control programs, and rollbacks in garbage collection left steady supplies of would-be food lying about sidewalks protected only by plastic bags, could a surge in the rat population have been anticipated? Would a surge in disease follow? If New York City already had more than seven million rats in 1992, what was the threshold for a public health crisis? Ten million? Twenty million?61 Just how remote is the possibility that Yersinia pestis could acquire broad powers of antibiotic resistance, making the plague untreatable?
The same questions could be asked about unclean sewage, nonchlorinated drinking water supplies, the role of air pollution in enhancing human lung susceptibility to disease, the role of open water containers in promoting mosquito population growth, failures in urban vaccination programs, over-crowded housing, homelessness, and a plethora of other factors that affect—inversely—the quality of life for Homo sapiens and microbes.
In 1991 Zambia became the first country to undergo a hopeful revolution. With the flick of a switch the University of Zambia Medical Library was on-line via satellite ground station to data bases in medical libraries in the United States and Canada. By the middle of 1993 eleven developing countries were connected to medical data bases in the wealthy world and to each other, via SatelLife. It was expected that six more developing countries would be on-line by the close of 1994.62
The SatelLife movement was the brainchild of Nobel Peace Prize winner Dr. Bernard Lown. Having led the International Physicians for the Prevention of Nuclear War, Lown had developed a vast network of medical associates all over the world. And he recognized how desperately isolated physicians and scientists were in developing countries. A firm believer that “information is power,†Lown worked closely with Russian, Japanese, and Canadian colleagues to develop SatelLife. The Russian government launched a satellite for the program, the NEC Corporation of Japan provided the necessary equipment, and the International Development Research Centre of Canada came up with the funds.
For the first time, physicians in developing countries could consult colleagues in neighboring nations or medical libraries and data banks to help solve puzzling cases and alert one another to disease outbreaks.
So when multidrug-resistant gonorrhea surfaced in Mozambique in April 1993, Dr. Prassad Modcoicar sat before a computer and typed this message: “I would like to know if there are any published studies or current ongoing research about the efficacy of the antibiotic kanamycin in the treatment of acute gonorrhea in men.â€
Modcoicar’s message was carried by a ground-based satellite uplink to the SatelLife’s orbiting satellite, which bounced his query back to satellite dishes in fifteen nations. In Lusaka, Zambia, Dr. M. R. Shunkutu saw the message and immediately transmitted to Modcoicar the results of a kanamycin study Subhash Hira had done in Lusaka in 1985. Before SatelLife went into operation, Modcoicar would have been obliged to either write letters to physicians in Europe and North America and wait interminable amounts of time for the results or simply experiment on his patients.
With SatelLife, Modcoicar instantly accomplished two tasks: he notified colleagues that he was seeing an outbreak of drug-resistant gonorrhea, and he found a solution for treatment of his patients. With plans to expand SatelLife into Asia and South America, the cheap, nongovernmental doctor-to-doctor service offered the real possibility of revolutionizing disease treatment and surveillance in the developing world. In the future, the kinds of satellite connections offered by SatelLife might also be used to relay information to public health planners all over the world that would allow them to be proactive—to anticipate potential disease outbreaks. For example, El Niño-type climate shifts often begin in one part of the planet and then spread in a predictable pattern. The events are known to be responsible for ecological changes that heighten risks for emergences of cholera, malaria, nearly all arboviral diseases, and most diarrheal diseases, particularly in poorer countries. Advance climate warnings could go out by satellite, delivered in real time and designed specifically to alert physicians of coming changes that might be relevant to vector or microbe activity.63
Genetic data bases, such as the vast GenBank at Los Alamos National Laboratory in New Mexico or GenInfo at the U.S. National Library of Medicine, might also prove invaluable to scientists in developing countries. As PCR technology becomes more widely available, researchers working in poor countries could be able to screen viruses and bacteri
a found in their patients and compare the strains to ones already archived in genetic data banks. If such technology were widely available, the result could be an avalanche of information on emerging strains of drug-resistant microbes, more virulent HIVs, even apparently new microbes.
At Harvard Medical School, Thomas O’Brien is trying to compile an international computerized data bank of genetic sequences for plasmids, transposons, phages, and resistance factors. Enhanced satellite communications systems that function independently from the frequently unreliable telephone systems of developing countries—as is the case with SatelLife —could allow for far more rapid monitoring, or at least reporting, of drug-resistance microbial activities worldwide.
Of course, such sophisticated systems are useless if no one acts on relayed information, or if there is no real primary medical system in a country. Without trained personnel and a functioning public health system it is almost inconceivable that anyone in a poor nation, or for that matter a poorly funded provincial department inside a rich nation, would be able to make use of GenBank or any such data base.
But no one in the belt-tightening world of the 1990s seemed much interested in contributing dollars, marks, or yen to the development of primary health infrastructures in countries like Armenia, Romania, Albania, Burma, or the Dominican Republic. The scale of the problem seemed too great, the payoff for donors too modest.
For every infectious disease, the preferred, easier option was vaccination. And by 1990 an estimated 70 percent of the world’s children had been vaccinated against diphtheria, measles, pertussis, polio, tetanus, and tuberculosis. An estimated 130 million children were vaccinated every year in the developing world at a cost of about $1.5 billion.64
But experts were extremely dubious about the likelihood of expanding the vaccine market, developing new products, or using a newly developed vaccine in the midst of an emerging disease crisis. The phenomenal vaccination achievements of Merieux and the Brazilian government during the 1974 meningococcal bacteria epidemic may never be repeated. The reasons are numerous; they all boil down to money.
Pharmaceutical companies saw no profits in making vaccines intended for use by poor people—who would pay for the products? AIDS was revealing the tremendous hurdles involved in tackling new microbes through immunization. The Swine Flu fiasco left the future of government-sponsored mass vaccination in doubt for reasons of litigation. Further, U.S. courts paid huge awards to alleged victims of contaminated vaccines.
By 1990 more than half of all vaccine manufacturers had pulled out of the business, and though biotechnology was pointing the way to exciting new possibilities for vaccine design, enthusiasm was less than lukewarm in corporate circles.65
“Serious deficiencies are extant,†D. A. Henderson said. “Vaccine production for many vaccines is nowhere what is needed and resources for vaccine purchases are diminishing; vaccine quality control for locally produced vaccines is negligible to nonexistent; and surveillance, the foundation of disease control, remains seriously deficient and for many diseases, totally desert.â€66
Ultimately, humanity will have to change its perspective on its place in Earth’s ecology if the species hopes to stave off or survive the next plague. Rapid globalization of human niches requires that human beings everywhere on the planet go beyond viewing their neighborhoods, provinces, countries, or hemispheres as the sum total of their personal ecospheres. Microbes, and their vectors, recognize none of the artificial boundaries erected by human beings. Theirs is the world of natural limitations: temperature, pH, ultraviolet light, the presence of vulnerable hosts, and mobile vectors.
In the microbial world warfare is a constant. The survival of most organisms necessitates the demise of others. Yeasts secrete antibiotics to ward off attacking bacteria. Viruses invade the bacteria and commandeer their genetic machinery to viral advantage.
A glimpse into the microbial world, aided by powers of exponential magnification, reveals a frantic, angry place, a colorless, high-speed pushing and shoving match that makes the lunch-hour sidewalk traffic of Tokyo seem positively poky. If microbes had elbows, one imagines they would forever be jabbing neighbors in an endless battle for biological turf.
Yet there are times of extraordinary collectivity in the microbial world, when the elbowing yields to combating a shared enemy. Swapping genes to counter an antibiotic threat or secreting a beneficial chemical inside a useful host to allow continued parasitic comfort is illustrative of this microscopic coincidence.
An individual microbe’s world—its ecological milieu—is limited only by the organism’s mobility and its ability to tolerate various ranges of temperature, sunlight, oxygen, acidity or alkalinity, and other factors in its soupy existence. Wherever there may be an ideal soup for a microbe, it will eagerly take hold, immediately joining in the local microbial pushing-and-shoving. Whether transported to fresh soup by its own micro motor and flagellae or with the external assistance of wind, human intercourse, flea, or an iota of dust makes little difference provided the soup in which the organism lands is minimally hostile and maximally comfortable.
The planet is nothing but a crazy quilt of micro soups scattered all over its 196,938,800-square-mile surface.
We, as individuals, can’t see them, or sense their presence in any useful manner. The most sophisticated of their species have the ability to outwit or manipulate the one microbial sensing system Homo sapiens possess: our immune systems. By sheer force of numbers they overwhelm us. And they are evolving far more rapidly than Homo sapiens, adapting to changes in their environments by mutating, undergoing high-speed natural selection, or drawing plasmids and transposons from the vast mobile genetic lending library in their environments.
Further, every microscopic pathogen is a parasite that survives by feeding off a higher organism. The parasites are themselves victims of parasitism. Like a Russian wooden doll-within-a-doll, the intestinal worm is infected with bacteria, which are infected with tiny phage viruses. The whale has a gut full of algae, which are infected with Vibrio cholerae. Each microparasite is another rivet in the Global Village airplane. Interlocked in sublimely complicated networks of webbed systems, they constantly adapt and change. Every individual alteration can change an entire system; each systemic shift can propel an interlaced network in a radical new direction.
In this fluid complexity human beings stomp about with swagger, elbowing their way without concern into one ecosphere after another. The human race seems equally complacent about blazing a path into a rain forest with bulldozers and arson or using an antibiotic “scorched earth†policy to chase unwanted microbes across the duodenum. In both macro- and microecology, human beings appear, as Harvard’s Dick Levins put it, “utterly incapable of embracing complexity.â€
Only by appreciating the fine nuances in their ecologies can human beings hope to understand how their actions, on the macro level, affect their micro competitors and predators.
Time is short.
As the Homo sapiens population swells, surging past the 6 billion mark at the millennium, the opportunities for pathogenic microbes multiply. If, as some have predicted, 100 million of those people might then be infected with HIV, the microbes will have an enormous pool of walking immune-deficient petri dishes in which to thrive, swap genes, and undergo endless evolutionary experiments.
“We are in an eternal competition. We have beaten out virtually every other species to the point where we may now talk about protecting our former predators,†Joshua Lederberg told a 1994 Manhattan gathering of investment bankers.67 “But we’re not alone at the top of the food chain.â€
Our microbe predators are adapting, changing, evolving, he warned. “And any more rapid change would be at the cost of human devastation.â€
The human world was a very optimistic place on September 12, 1978, when the nations’ representatives signed the Declaration of Alma At
a. By the year 2000 all of humanity was supposed to be immunized against most infectious diseases, basic health care was to be available to every man, woman, and child regardless of their economic class, race, religion, or place of birth.
But as the world approaches the millennium, it seems, from the microbes’ point of view, as if the entire planet, occupied by nearly 6 billion mostly impoverished Homo sapiens, is like the city of Rome in 5 B.C.
“The world really is just one village. Our tolerance of disease in any place in the world is at our own peril,†Lederberg said. “Are we better off today than we were a century ago? In most respects, we’re worse off. We have been neglectful of the microbes, and that is a recurring theme that is coming back to haunt us.â€
In the end, it seems that American journalist I. F. Stone was right when he said, “Either we learn to live together or we die together.â€
While the human race battles itself, fighting over ever more crowded turf and scarcer resources, the advantage moves to the microbes’ court. They are our predators and they will be victorious if we, Homo sapiens, do not learn how to live in a rational global village that affords the microbes few opportunities.
It’s either that or we brace ourselves for the coming plague.
Afterword
In the summer of 1993, Ron MacKenzie, now comfortably retired in a southern California desert community, was watching the evening news on television. A brief story caught his attention. It concerned shifts from agricultural production to growing coca plants for cocaine in various regions of Latin America, and MacKenzie recognized the place depicted. It was his beloved San JoaquÃn, Bolivia.
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