The investigators followed Levin’s E. coli for almost a year. They found that the ecology of his gut was hectic, eclectic, and tumultuous. Strains of E. coli kept appearing and disappearing. In the course of the experiment, the microbiologists identified a total of fifty-three different strains, all but two of which went rapidly extinct. These strains of bacteria were apparently colonizing Levin like birds in the Galápagos. The strains were flying in on the food he ate and on every touch from his wife, their two children, their dog and cat, a group that a commentator in Nature dubbed “the Levin Archipelago.”
In these bacterial cells the DNA is not locked away in a walled nucleus. Instead it floats free in a long necklace of DNA, a circle of about ten thousand genes. Other smaller necklaces float about within the cell too, rings of DNA called plasmids. A typical E. coli individual holds two or three plasmids. Dozens of these plasmids can move among different species of bacteria like secret battle codes, written in Darwin’s invisible ink. Some of their genes can actually jump from the plasmid and insert themselves into the main necklace, or eject themselves completely from the cell and enter another bacterial cell, like letters without envelopes. When bacteria are under stress—for instance, when their human host takes an antibiotic—the cells use their jumping genes to pass resistance genes back and forth at a great rate.
“We did a study,” Levin says. “How fast can evolution proceed in a human? My wife took ampicillin. I took erythromycin. Within a few days, we were both dominated by resistant bacteria. Not only was tetracycline resistance coming up, but also streptomycin, kanamycin, carbenicillin—our bacteria were going from almost nothing to multiple resistance in an amazingly short amount of time.
“If you did it in a test tube you wouldn’t be surprised. But to take a couple of pills and see it happen inside you is really kind of awesome. It gives you an eery feeling: when we talk about natural selection, we’re not talking about eons here. It’s not just dead dinosaurs.”
Resistance is now rising in gonorrhea, streptococcus, tuberculosis, salmonella. In the United States, the incidence of the bacterium Neisseria gonorrhoeae with resistance to penicillin more than tripled between the years 1988 and 1990. In 1990 an outbreak of fatal dysentery struck Burundi, and the microbes were resistant to every single oral antibiotic in the country.
Local resistance movements like these can get carried around the world and plunge millions of people into epidemics. In principle this is nothing new. Measles traveled the caravan routes of the Roman Empire from A.D. 165 to A.D. 180. Smallpox followed the same routes in A.D. 251 to 266, and one in three people along the caravan routes died. But today the caravan routes are mostly airborne, and Concordes are faster than camels. A new virus or bacterium can circle the earth in a matter of days.
“In 1941, 10,000 units of penicillin administered four times a day for four days cured patients of pneumococcal pneumonia,” writes the physician Harold Neu of Columbia University. Today a patient could receive twenty-four million units of penicillin a day and still die of the disease. “Bacteria are cleverer than men.”
Not long ago, reading the headlines in a front-page newspaper story about drug resistance, a molecular evolutionist stopped at the word inordinately. The headline said that bacteria in some hospitals are “inordinately” resistant to penicillin. “Well,” he said, “they’re not inordinately resistant to it. They’re completely resistant to it. There might as well not be penicillin there.”
“Considering the shortness of the time span, the number of mechanistically different countermoves that bacteria have invented against antibacterial agents is amazing,” writes Alexander Tomasz of Rockefeller University. These cells have evolved an appalling arsenal of weapons against penicillin and its large family of antibiotics. They have evolved anti-antibiotic enzymes to match every antibiotic that is being thrown at them. All these chemical weapons and counterweapons, says Tomasz, “match one another as defensive and offensive weapons match in classical warfare: shield against the arrow, bazooka against the tank.” There are now drugs designed to attack the bacteria’s resistance to antibiotics: anti-anti-antibiotics. And much of this high-technology war has evolved in the lifetime of doctors now in practice. “The amazing degree of variation” in some kinds of resistance, writes Tomasz, suggests that these resistance traits are “continuing to evolve under our very eyes.”
As with pesticides, investigators are now tracking the evolution of antibiotic resistance at the level of DNA. The core of anti-tuberculosis regimens is a drug known as isoniazid. Recently investigators looked at strains of Mycobacterium tuberculosis isolated from two patients. They found that in each strain, the bacteria had dropped from its chromosome a gene called katG, which codes for the production of two enzymes, catalase and peroxidase. In the laboratory the investigators isolated a strain of bacteria that lacked this gene. The strain produced very little of these two enzymes, and was resistant to isoniazid. Into this strain, the investigators inserted the missing gene katG. Instantly the strain started manufacturing the two enzymes, but it was now killed by isoniazid.
Apparently the cells had paid a price to defend themselves from the drug. They had made an evolutionary trade-off, giving up part of their own adaptive equipment for the sake of survival. The bacillus got rid of an Achilles’ heel by evolving a heel-less foot.
Each year about eight million people are colonized by this adaptable bacillus, Mycobacterium tuberculosis. About one in three people on the planet already carry it, and each of them has about one chance in ten of developing the symptoms. In the developing world the disease accounts for almost 7 percent of all deaths. In the United States in the 1980s tuberculosis had been in retreat for a century. Doctors and the directors of public health programs thought of it as a defeated disease. They looked away. Between 1985 and 1992 tuberculosis increased in incidence by nearly 20 percent. The number of cases among children born in the United States under the age of five rose 30 percent just between the years 1987 and 1990. As two physicians observe in a review of the disease and its resurgence, “The principal risk behavior for acquiring TB infection is breathing.”
PHYSICIANS CAN WATCH the human immune system attack invaders, and they can watch the bacteria and viruses dodge and twist. F. MacFarlane Burnet, who won the Nobel Prize for his work in immunology, called this “evolution made visible.” Teams of investigators are now watching the evolution of AIDS in the living bodies of individual patients. Intensive studies of this kind have been conducted in England, the United States, and Africa. Viruses are the first organisms on the planet whose genetic sequences have been read and published from beginning to end. The complete nucleotide sequence of one strain of the AIDS virus HIV-I is 9,749 base pairs long. But this sequence does not stand still, because the virus has no proofreaders. When investigators take a series of samples from an individual patient they see rapid evolution. Individual letters in the sequence change, clusters of letters change, whole chunks of DNA disappear while other chunks insert themselves in new places along the strand. A human body with AIDS is like an entire Galápagos archipelago: it harbors an increasingly diverse group of viruses after the first one has invaded it. The first virus particle to invade evolves into a swarm of variant strains.
In the AIDS virus the gene known as env is the one that evolves fastest. Env codes for the envelope of the virus, which is what the human immune system tries to grasp and destroy. The env gene changes about a million times faster than the normal mutation rate of its host, the human body. In this way, according to present thinking, it keeps eluding the grasp of the immune system. In a sense, the weapon of the virus is variation itself.
The influenza virus also evolves rapidly. The sequence of the human flu virus changes at a rate of more than two letters a year. It can evolve even faster if it happens to meet up with a virus that infects horses, pigs, or seagulls. Very often the strains meet when they both happen to infect the body of the same pig. There they not only give the pig the flu; they also swap gen
es. They hybridize, and the new virus is sometimes changed enough to evade the attacks of the human immune system and sweep the world.
So far, despite all our plagues, we have been lucky. In principle, a random mutation or a hybridization event could someday create a virus that combines the airborne, infectious qualities of flu and the deadly, long-latency, slow-killing qualities of AIDS. It hasn’t happened yet, but there is nothing in Darwin’s process to prevent it, and the larger the pool of human beings on the planet, the more viruses are jumping in. “Our only real competition for domination of the planet remains the viruses,” the microbiologist Joshua Lederberg once said. “The survival of humanity,” he added, “is not preordained.”
Resistance movements can spring up and overwhelm us even within the lines of our own cells. A cell that turns cancerous is a cell that has escaped the molecular restraints that keep most of our cells from multiplying out of control. When doctors hit a colony of these cells with drugs, radiation, or heat, a few of the cells may resist the attack.
“With cancer, when you are in chemotherapy, you get resistance,” says Bruce Levin. “You are seeing the very same problem in yourself.” Most of the cells of a tumor are typically killed by the first doses of chemicals, but those that survive can proliferate. “The rapidly growing cells—it behooves them to avoid being killed,” says Levin. “It’s no different from putting streptomycin into a bacterial culture. Talk about evolution in action! You’re seeing evolution at home. Of course, that’s the last thing on your mind.”
ALL THIS IS a simple corollary to Darwinian law. Wherever we aim at a species point-blank, for whatever reason, we drive its evolution, often in the opposite direction from what we ourselves desire. The law holds, whatever our reason for shooting at a species, and whether the species is submicroscopic or gigantic.
In the late 1970s and early 1980s, between 10 percent and 20 percent of all the elephants in the wild were being killed each year. At that rate wild elephants would have gone extinct by the end of the century. This was an intense selection event.
For poachers, elephants with big tusks were prime targets. Elephants with small tusks were more likely to be passed over, and those with no tusks were not shot. In effect, though no one realized it at the time, African elephants in places where poaching was rife were under enormous selection pressure for tusklessness. And in fact, elephant watchers in the most heavily poached areas began noticing more and more tuskless elephants in the wild. Andrew Dobson, an ecologist at Princeton, has compiled graphs of this trend, tracing the evolution of tusklessness in five African wildlife preserves, Amboseli, Mikumi, Tsavo East, Tsavo West, and Queen Elizabeth. In Amboseli, where the elephants are relatively safe, the proportion of tuskless female elephants is small, just a few percent. But in Mikumi, a park where the elephants are heavily poached, tusklessness is rising. The longer each generation lives the fewer tusks the elephants carry. Among females aged five through ten, about 10 percent are tuskless; among females aged thirty to thirty-five, about 50 percent are tuskless.
Male elephants use their tusks to fight one another over females. When most males are tusked, a male without them is like a knight without a lance. But where fewer and fewer males sport tusks, the untusked male has a fighting chance of getting a harem and passing on his tuskless genes. He is more and more fit. These are evolutionary changes, and no matter what happens in the future, the balance of genes will work itself out for many generations and many centuries—if elephants live that long.
This same sort of evolutionary change is also taking place in the world’s seas. Most sport fishermen and commercial fisheries follow a basic rule: keep the big ones and throw back the little ones. That too is an evolutionary pressure. A net is a powerful agent of Darwinian selection. In one recent laboratory demonstration, investigators raised water fleas in aquarium tanks. Every four days they sieved the tanks with fine-meshed nets. In one set of tanks they threw back the little fleas and killed the big ones. In another set of tanks, they threw back the big fleas and killed the little ones. They kept this up for generations of water fleas, and they saw a dramatic evolutionary response. In the tanks where they culled the small fleas, the fleas began growing faster and delaying the age of first reproduction. Fleas that put all their energy and resources into growing fast had the best chance to escape the net. They saved the act of reproduction (which is expensive in terms of time and resources, even for a flea) until they were older, bigger, and safer.
But in the tanks where the big fleas were killed, evolution ran the opposite course. There the water fleas grew slowly and began reproducing when they were still small. For those fleas it was the one that stayed small longest that lived longest and passed on the most genes.
John Endler has seen the same kind of evolutionary responses among his guppies, both in the wild and in the laboratory. Some guppy eaters like their guppies big, and some like them small, and they too drive the evolution of their prey. The changes are predictable and rapid; they take about fifty guppy generations.
In the worlds oceans, Norwegian cod, chinook salmon, Atlantic salmon, red snapper, and red porgy are getting smaller, very likely through the selection pressures of the net. Fishermen are not happy with the trend toward small fish, any more than elephant poachers are pleased with the trend toward tusklessness. But both resistance movements are direct results of Darwinian law.
“WORKING LATE?” asks one of the lab assistants.
“As usual,” Taylor says. He is wearing two days’ worth of black stubble, a scruffy black turtleneck, and a slightly disreputable shade of gray in his face.
“I don’t know why you bother to keep an apartment,” says the assistant. “You’re always here. You might as well just string up a hammock.”
“Might as well,” he says.
It is past midnight, and Taylor is grinding away, but the moths are evolving much faster than he can keep up with them. They are growing more and more resistant in Australia, and also in the United States, mostly west of Alabama. Apparently there is more than one gene involved in their resistance movement. The sodium channel may be only the beginning of the story.
Meanwhile most cotton farmers are still spraying pesticides routinely, often before any pests show up, a practice known as “insurance spraying” or “spray and pray.” So the selection pressures on Heliothis and the other pests in the cotton fields, including the notorious boll weevil, continue to be intense, and the pests keep evolving more and more resistance. As more and more developing countries turn from DDT to pyrethroids, they are likely to provoke precisely the same evolutionary events, the same evolution of kdr and the same control failure.
The chances of success of each new pesticide under development keep dropping, and the costs of development keep rising. One expert wonders whether we have already selected in pests the genes they need to evolve resistance “to practically any toxicant that may be used against them. The answer,” he adds, fatalistically, “will be provided in time by the pests themselves.”
Before human beings had heaped up a mountain of pesticides in the 1940s, when we were still in the foothills of this evolutionary adventure, farmers in the United States were losing about 7 percent of their crops to insects. During the blitz of the 1970s and 1980s the insects did not lose any ground. Instead they nearly doubled their share, to 13 percent. “Indeed,” note the ecologists Robert May and Andrew Dobson, “the fraction of all crops lost to pests in the United States today has changed little from that in medieval Europe, where it was said that of every three grains grown, one was lost to pests … leaving one for next year’s seed and one to eat.”
May and Dobson believe this global evolutionary disaster “may help to show that evolution is not some scholarly abstraction, but rather is a reality that has undermined, and will continue to undermine, any control program that fails to take account of evolutionary processes.”
Meanwhile, the ten least-wanted microbes in the world today, from enterobacteria to streptococcus, are
now resistant to almost everything we can throw at them. Drug companies are bringing out only a few new drugs against them each year, a process that costs about $200 million per drug, and each new drug often takes as much as seven years to bring to market. Harold Neu of Columbia says it is now critical for doctors, patients, and drug companies to avoid all unnecessary use of antibiotics, for humans or animals, “because this selective pressure has been what has brought us to this crisis.”
What we don’t understand on either front is that the more pressure we put on our pests, the more we cause them to evolve around the pressure. The pressure is evolutionary pressure; what we fail to understand is evolution itself. Evolution is not just the Galápagos and not just out there beyond the windowpane buffeting the robin and the oak. Evolution is a very near thing. To us it is a terrible irony. Precisely where we wish to control the environment most tightly and possess it most completely we are powerless to do so, besieged and beleaguered by resistance movements that seem to spring up faster the more we lop them off, like the heads of Hydra. The harder we fight these resistance movements, the harder and faster they evolve before our eyes—precisely because it is our effort at control that is driving their evolution. What we call control is to them merely a change in the environment, just another change in an endless series of changes—and they are superbly placed and designed to keep up with such changes. As long as we keep up the pressure indiscriminately they will continue to rise in plagues against us, like the frogs that came up on the land of Egypt, or the dust of the earth that became lice throughout all the land of Egypt.
“RIGHT,” TAYLOR SAYS, in the voice of midnight, as he lifts another moth from its crater of ice and holds it up with his tweezers. “Hey, what’s your trick?”
He drops it in the bottom of a clear plastic vial. It looks out of place lying there, surrounded by the whirling centrifuges and chirping Geiger counters of the laboratory, like an African mask on the wall of a sleek modern art gallery. Taylor fusses with his preparations. “It’s very—hmmmm—tedious,” he mutters. He picks up a glass rod, to grind a bit of the moth in the bottom of the vial.
The Beak of the Finch Page 31