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Matt met Terence at the hotel about 5:00. He was a tall, rather stooped man in his mid-forties, thin though with the beginnings of a paunch. He was dressed in the modern European fashion in a dark rather severely-tailored suit that made him look more like an executive than a scientist. And indeed Mercy had told Matt that Terence had, against his will, been forced ever deeper into the management end of business and away from the research he loved. He looked rather weary and harassed.
"Sorry it took so long to get here, Matt," he said as they shook hands. "Several cases of this horrible disease have been diagnosed over the last few days in Amsterdam. They put the passengers through some pretty extensive screening to prove we hadn't been exposed to anyone infected before they allowed us on the plane. . . ."
Fortunately Terence was not one to waste time over small talk, so over cocktails Matt asked him the question that had been increasingly goading him. . .
“What do you know about this Chou’s Disease?” Matt asked. “Is it going to turn into a worldwide epidemic before it’s finally crushed?”
Terence sipped at his drink thoughtfully. “It’s very hard to say. Even though I’m a biochemist I don’t work in the pharmaceutical field and that has become such a closed discipline it’s hard to tell what’s going on there.”
“Why is that? I understand that this bug is some kind of bacteria. The medical field has been able to control bacteria for a long time haven’t they? Why is this one so hard to control?”
Terence shook his head bleakly.
“It’s the most deadly one ever to appear. Let’s pray it can soon be contained but I’m a long way from feeling secure about that.”
Matt felt his stomach clench. He had hoped Terence would tell him that his fears of the afternoon were groundless.
“As far as controlling bacteria goes,” continued Terence, “we’re not as clearly in control as most people suppose.”
“What do you mean? I thought people only died of bacterial infections in third world countries.”
“That’s the common belief, but we humans have been locked in battle with bacteria throughout all of our time on earth and they’re not about to give in so easy.
“Think of our relationship with bacteria as an arms race. Arms races are common in nature. Predators and prey are always trying to counter each other’s advantages. Prey becomes faster, develops armor or coloration that matches its surroundings or learns to live in large groups to evade predators. The predator develops larger fangs or claws or more acute senses or becomes faster or learns to hunt in groups. Some arms races are less recognizable. Which doesn’t mean they are less important or deadly. The one going on between mankind and bacteria has lasted for ages beyond memory, from a time well before we became human beings. For most of that time we didn’t recognize it as such because bacteria were invisible to us.
“You must understand that bacteria are the oldest known type of life on earth. They live anywhere that is wet: in the water, in the air, in melting ice and snow, in boiling deep-sea thermal vents. The ground is saturated with them. You know that characteristic ‘earthy’ smell you get when you turn over the sod?” Terence chuckled. “No, you wouldn’t. You’re too much the urban boy to ever have experienced that smell. But if you ever do, you’re actually smelling bacteria. The point is that every place in the earth’s ecosystem that has organic material and a little dampness is swarming with bacteria.
“It loves unprotected food. This was one of the first battlegrounds on which we met bacteria that we prevailed – sometimes. Early man boiled, salted, smoked, pickled and froze his food to protect it. He mummified his dead. He didn’t know he was fighting a foe so small that two hundred thousand of them could live on a period at the end of a sentence; he thought that spoiling food was a natural phenomenon like gravity and thunderstorms and rainbows.
“He didn’t know that the same organisms dwelt on and inside his body. By the trillions. In fact a human being is host to around a hundred trillion bacteria. Lumped together they’d weigh about a pound. They include E. coli, staphylococcus, streptococcus, micrococcus, corynebacteria – lots of others. They invade a baby’s body within moments of birth and live on and inside it until death. Then other types of bacteria take over to recycle the body.”
“Recycle, yes,” said Matt, signaling for another round. “I’d never thought of it like that." Sounds like a pretty dangerous crowd to live with.”
“They usually don’t do us much harm. In fact, they’re mostly beneficial to our metabolism and other processes. Moreover, they protect us from invasion by more hostile bacteria. Inadvertently, of course. They ward off outsiders for purely selfish reasons; they’re protecting our body’s nutrients for their own uses.
“On the other hand, we must never forget that bacteria date from a primeval time before multi-cellular life by aeons. Which is why they’re utterly alien compared to multi-cellular organisms. And no bacteria, not even those we carry around all our life, are our allies. They are vast in number, they’re relentless and they’re our profoundly unsympathetic foes.
“Most of our time on earth, mostly without knowing it, we’ve fought this running battle with these invisible beasties. Scourges like epidemics and high infant mortality rates were accepted as ordinary occurrences. Most families with five children could expect three to die and childbirth was a high-risk event for the mother. People who ate spoiled food or cut themselves would have a good chance of dying. Right up through the nineteenth century cities with dense populations and lousy sanitation facilities were laid waste by water borne plagues like dysentery and cholera. Tuberculosis and influenza were major killers. Medical procedures, even ones that came to be routine in the twentieth century, were considered extremely risky because fatal infection was a good possibility.
“At the beginning of the twentieth century four of the top ten killers of people in the United States were bacterial. Tuberculosis and pneumonia held the top two positions, gastroenteritis caused by various species of bacteria was further down the list and diphtheria was in tenth place. Other bacterial terrors were common: gonorrhea, meningitis, septicemia, dysentery, typhoid fever, whooping cough. I could go on and on.”
“But,” protested Matt, “all that changed some time in the early nineteen hundreds. Penicillin was discovered first, I think, then the other miracle drugs. We won after all didn’t we?”
“Bravo, Matt. You’re right about the first part. Sir Alexander Fleming discovered penicillin in 1928. The sulfonamides followed in the mid-thirties. Antibiotics didn’t come into general use, though, until the 1940s and 50s but when it did our counterattack was catastrophic to bacteria. We leaped ahead in the arms race. The countless millennia that they’d spent slaughtering us reversed overnight. Now the bacteria suffered decimation. By the beginning of the twenty-first century all the bacterial culprits had disappeared from the dreaded top ten (though pneumonia was still number twelve). They were replaced by afflictions like cancer, stroke, heart disease, accidents, homicide and suicide.”
Matt smiled briefly. “The last few reasons for death give a commentary on the times.”
“Indeed. We can’t blame those deaths on any natural enemy outside our species. But as far as our once-invisible enemy was concerned, the medical profession was now armed with a huge and varied arsenal. Some antibiotics broke cell walls open; some choked off the protein nutrients they needed to live; some poisoned or smashed bacteria’s control center, its DNA. Victory was swift and decisive. There seemed no reason to think that it would not last forever. Pharmaceutical companies grew richer than ever. Marketing and producing antibiotics became one of the world’s most lucrative businesses.
“Not only did people benefit. Livestock on antibiotics put on pounds quickly, were more apt to stay healthy and produce cheaper meat. Concerned health authorities began to protest giving antibiotics to animals, but drug companies and agricultural businesses ignored them, continued to manufacture and feed antibiotics to cattle, pigs, sheep, chickens and all the others.”
“So you’re saying,” Matt said, “that reasoning beings had proven once and for all that mindless globs of unicellular life were no match for clever primates. So isn’t this Chou’s thing just another batch of the same non-sentient sludge?”
Terence raised a cautionary finger. “Remember when I said that bacteria had been on earth for aeons before any of our multi-celled ancestors appeared? Maybe those billions of years of evolution have given them an edge in the arms rate. Maybe the arrogant primates underestimated their tenacity, their adaptability. Maybe we’re about to find out the power of this edge.”
Matt frowned. “You’ve built this seemingly foolproof case for mankind’s wisdom prevailing over critters dumber than pond scum. Now you mysteriously hint that they might have a few tricks up their, uh, figurative sleeves.”
“Perhaps. Specialists have known for a long time, at least since the 1940s or ‘50s, that bacteria mutated in response to selection pressure just like other living things. They also knew they were quite prolific. In a nutrient-rich soup they could multiply through mitosis every twenty minutes or so. It didn’t seem likely, though, that they’d be able to resist one of the new virulent (to bacteria) antibiotics. And the ability to withstand two or more antibiotics simultaneously appeared impossible indeed. The days of bacterial onslaught were over, they believed.
“But there were two characteristics of bacteria no one really understood: just how versatile their response to changing conditions was and how profoundly different they were from multi-cellular beings, a point I keep harping on.
“Take the make-up of their cells in comparison to ours. In eukaryotic cells, like those in our bodies, the DNA is neatly packaged in the cell nucleus. Bacteria’s much more ancient prokaryotic cells don’t have nuclei. Their DNA is a tangled unorganized double helix floating in their cytoplasm. The cytoplasm is that rich stew of salts, sugars, vitamins, proteins and fats inside a cell.
“One characteristic of bacteria that make them so utterly and profoundly different from our, eukaryotic, form of life is the way they handle DNA. They can extract it from the environment to use or they can let snippets of their own DNA escape through their cell walls. Sometimes strands of foreign DNA enter a cell and set up self-replicating shops in its cytoplasm. Some segments of DNA can independently replicate themselves and reinsert the copy into a new position within the chromosome. Their most amazing characteristic, though, is that they can place the copy not only in the same chromosome but also in another chromosome.
“These self-replicating bits of DNA wander the bacterial ecosystem. Sometimes they get sucked into a bacterium host, sometimes they’re spat out. Bacteria aren’t discriminating in their ingestion. To them whatever they take in – a neighbor’s DNA or that of another species, virus DNA, or food – is as welcome as their own DNA. They can gobble up foreign DNA as if it were food and use it as DNA. A wanderer inside the host can snip some data off a chromosome with its genetic scissors or slip some data into the chromosome. If the resulting mutation doesn’t work and the cell dies, so what? The millions of other clone sisters in the neighborhood can fill in.”
“Yeah,” said Matt. “Cloning every twenty minutes speeds up Darwinian evolution pretty dramatically. But how does the weird way bacteria’s manipulates DNA help it defend itself against antibiotics?”
“Well, its program of sharing DNA, enormous quantities of it, continued of course even after their ecosystems were invaded by these massive doses of antibiotics. They shared among their own species and with others, delivered between individuals in the usual manner. Sometimes they ingested DNA from the remains of burst cells – remember that they can take in genetic material as food but make it work like data. Sometimes a virus would randomly take in bits of loose DNA and inject it into a bacterium.
“In the meantime the antibiotics kept attacking. They don’t distinguish between different types of bacteria. When a person takes an antibiotic for one type of infection the antibiotic doesn’t seek out just the bacteria responsible for it. It attacks every one of the hundred trillion in the body. The vast majority of the virulent bacteria in the body are destroyed but a very few survive. These few have the genetic information that kept them alive and that’ll let them make it through the next antibiotic onslaught, but guess what else they do with it?”
Understanding struck Matt. “They trade DNA with other bacteria, of their own species and others. And they squirt some into the ecosystem where it’s picked up by other bugs, which helps all these others survive the next antibiotic attack.”
“Exactly. This is bacteria’s secret weapon, one early specialists never suspected: the ability to disseminate genetic information within a bacterium’s own species as well as others.
“Bacteria surprised them in another way. Its defense system turns out to be as sophisticated as the attack force of the antibiotics. They developed defensive enzymes in the slimy cloud that surrounds them. They grew tougher and thicker cell walls that were less likely to absorb drugs. Some bacteria lost some of their vulnerable porin. Those are the porelike structures that suck in and expel the nutritious filth they live in. Some stored enzymes just inside the cell wall to chew up and digest the drugs that did get in. Other enzymes cracked or chemically smothered antibiotics. Among the pump-factories the cell uses to take material in or chuck it out, new pumps evolved specifically to grab antibiotics and spit them out of the cell. To counter protein-destroying antibiotics, some bacteria changed the way they produced protein to close up sabotage sites and others produced so much excess protein that ten or fifty times the amount of drug was needed to kill the cell. Some even developed immunity proteins that latched on to antibiotics in such a way that turned them into harmless inert lumps.
“Once genetic knowledge like this is spread it’s here to stay. Bacteria aren’t mortal in the human sense. If they aren’t destroyed they just divide and double every twenty minutes, carrying the resistant DNA forward indefinitely. Even if they change through mutation and natural selection after several billion generations, some of the original strains remain in the genome. And too, bacteria can remain dormant as spores for centuries. When conditions turn favorable again, they come alive all of a sudden and go about their business as if they hadn’t even paused.”
Matt thought all this over for a moment “So the arms race continued after the advent of the antibiotics. We just didn’t notice it because it seemed like we had won.”
“The slaughter of the bacteria by the antibiotics did just the opposite of stopping the arms race. It speeded it up. Bacteria fought back and with a vengeance. It seemed to the average person that we had won but the specialists knew better. Remember, they had known for a long time that bacteria respond to pressures of selection just like all living things.”
“The late twentieth and especially the twenty-first century were vastly different from previous times. Bacterial strains traveled the world at the speed of air travel. At the rate of a hundred trillion bacteria per human host, mingling and exchanging resistant DNA as never before.
“The new, more virulent strains of superbugs began to evolve as early as the 1990s but they were isolated and destroyed for awhile. Further into the new century epidemics began to increase but as long as they affected only the Third World it was easy for the industrialized nations to write their causes off to conditions there: crowding due to overpopulation, unhygienic conditions and so on.
“By the beginning of the twenty-first century it became clear that superbugs were becoming a problem in the developed world too. Medical specialists grew concerned about controlling them. The health agencies remained indifferent though and the medical profession’s proclivity for secrecy obscured the problem. Hospitals weren’t required to disclose infection rates so most didn’t, just as doctors didn’t have to inform patients of risk or exposure to hospital germs.
“And of course the drug companies remained complacent. They continued making their fortunes by maintaining the status quo. By now they well knew how fast resistant species of bacteria could evolve. A hundred million dollars in antibiotic research could be thrown away in a blink by the emergence of a new superbug.”
Matt scowled as the ice in his forgotten drink turned to water. “So we’ve been losing this war for decades and nobody is concerned enough to fight back.”
“A few of us are concerned. I have colleagues that are trying to rally the health industry. But most specialists don’t worry even if epidemics are ignored until they reach disastrous levels. They don’t believe there’ll be an apocalyptic collapse. When the crisis reaches that level they think that maybe medical researchers will be shocked out of their complacency, resume the arms race and win it.”
“But supposing it’s too late,” said Matt. “Suppose bacteria have all developed defensive mutations too sophisticated to overcome?”
“That’s a possibility. Bacteriologists might not be able to find a new drug to withstand highly evolved bacteria for long. In that case there would be a long descent, decades, maybe even a century, back into a pre-antibiotic era a lot like the nineteenth century. Back to high mortality rates for infants and mothers, back to worldwide epidemics, quarantines, tubercular sanitariums. Medical practice would take a drastic step backward. The high-tech surgical procedures that developed during the twenty-first century would be too risky to use except under the direst emergencies. Expense would soar because prevention of infection would be so difficult. There would be no more transplants of cloned organs to replace damaged ones except as a last resort, no prosthetic implants.
“This would still not mean an apocalyptic end to society though. To the first few generations these developments would seem terrifying, disastrous, but it would not mean the human race was being brought to an end by lethal worldwide epidemics. It would only mean returning to life like it had always been between man and bacteria, except for the less than two centuries of our antibiotic supremacy.”
“You’re not reassuring me, Terence. What if some superbug has developed a strain of DNA more resistant than any previous one, one virulent enough to kill us all before we have time to develop a new super-antibiotic?”
Terence sat there for a moment stirring his own watery drink. “I suppose that’s possible, Matt. I pray that it isn’t. One thing is true : People may be distracted from the arms race by other matters of importance in their lives, or because most of them aren’t even aware of it. But not bacteria. They’re single-minded, inexorable, and they never give up. If they added yet another secret weapon to their arsenal, a new disease, it’s quite likely that we would be taken completely by surprise. Could we recover in time to fight and win? I don’t know.”
Neither was very hungry then. They eschewed Terence’s favored steakhouse for a light meal in the hotel’s cocktail lounge and Matt left soon thereafter.