Microcosm (10 page)

In February and March 1982, 25 people in Medford, Oregon, developed cramps and bloody diarrhea. Doctors identified a strain of
E. coli
in some of the patients that had never been seen before. Three months later the same strain caused an outbreak in Traverse City, Michigan. The source of the bacteria proved to be undercooked hamburgers that the victims had eaten at McDonald’s restaurants. A pattern had emerged, and now scientists began to hunt for
E. coli
O157:H7 in samples of bacteria taken from patients in earlier years. Out of 3,000
E. coli
strains collected from American patients in previous years, 1 proved to be O157:H7. It came from a woman in California in 1975. Searches in Great Britain and Canada turned up 7 more cases, but none before 1975.

O157:H7 slipped back into obscurity for a decade. It emerged again in the mid-1990s in a series of outbreaks across the world. In 1993, an outbreak spread in undercooked restaurant hamburgers in Washington State sickened 732 people. Four of them died. Scientists found that cows, sheep, and other livestock can carry O157:H7 in their intestines without getting sick. An estimated 28 percent of cows in the United States carry O157:H7. It can move from animal to human through bad butchering. If a cow’s colon is nicked during slaughter, the bacteria can get mixed into the meat. As meat from many cows gets blended together,
E. coli
O157:H7 can spread through tons of beef. Most of the bacteria are killed off by cooking. But a single crumb of raw beef can carry enough
E. coli
O157:H7 to start a dangerous infection.

Vegetarians are not safe either. Cows shed
E. coli
O157:H7 in their manure, and once on the ground the microbe can survive for months. On farms the bacteria can spread from manure to crops, possibly carried by slugs and earthworms or ferried by irrigation. In 1997, radish sprouts tainted with O157:H7 sickened 12,000 people in Japan, killing 3. Today in the United States the vegetable-growing business is almost as industrialized as the beef business, with a few massive companies supplying produce across much of the country. They are also extending the reach of
E. coli
O157:H7. In September 2006, contaminated spinach from a single farm made people sick across the country, striking 205 people in twenty-six states. Three months later, it was lettuce distributed to Taco Bell restaurants in five states, striking 71 people.

When
E. coli
O157:H7 first passes the lips of one of its human victims, it does not seem much different from a harmless strain. Only after it has drifted through the stomach and reached the large intestine does it begin to show its true colors.
E. coli
O157:H7 has an unusual ability to eavesdrop on us. The cells of the human intestines produce hormones, and the microbe has receptors that can grab them. The hormones tell the bacteria that it’s time to prepare to make us sick. They build themselves flagella and swim, scanning the molecules floating by for signals released by their fellow
E. coli
O157:H7. They follow the signals and gather together. Once they’ve formed a large enough army, they begin constructing their weapons.

Their most potent weapon is a syringe they use to pierce intestinal cells and inject a cocktail of molecules. The molecules reprogram the cells. The skeleton-like fibers that give the cells structure begin sliding over one another. A pedestal-like cup rises from the top of each cell, giving
E. coli
O157:H7 a place to rest. The cells begin to leak, and the bacteria feed on the passing debris. Along with diarrhea comes bleeding, and
E. coli
O157:H7 snatches up the iron in the blood with siderophores.

It’s at about this point, about three days after ingesting
E. coli
O157:H7, that people start to feel awful. They develop violent diarrhea, which begins to turn bloody. The cramps can feel like knife stabs. Most people infected with
E. coli
O157:H7 can recover within a few days. But for every twenty people who get infected, one or two have much worse in store. Their
E. coli
O157:H7 releases a new kind of toxin. This one invades cells and attacks their ribosomes, the factories that build proteins. The cells die and burst open. The toxins move from the intestines into the surrounding blood vessels and spread to the rest of the body. They trigger blood clots and seizures. They shut down entire organs, particularly the kidneys. For some the toxin is fatal. Even for the lucky ones, recovery can take years. Some will need dialysis for the rest of their lives. Children may suffer brain damage and have to learn how to read again.

E. coli
O157:H7 gets a lot of press because it can create sudden epidemics in industrialized countries, but it is just one of many dangerous strains that can make us sick in many ways.
Shigella,
for example, does not rest on a pedestal the way
E. coli
O157:H7 does. It wanders. Once it reaches the intestines, it releases molecules that loosen the junctions between the cells that make up the gut wall and slips through one of the gaps. The breach draws the attention of nearby immune cells, which crawl after the microbe. But
Shigella
does nothing to camouflage itself. On the contrary, it goes out of its way to produce molecules that provoke a strong attack.

The immune cells chase after
Shigella
and devour it. But instead of killing
Shigella,
the immune cells are killed by their prey.
Shigella
releases molecules that trigger the immune cells to commit suicide and burst open. The dying immune cells draw the attention of living ones, but they are equally helpless to stop
Shigella.
In fact, they only make it easier for more
Shigella
to invade, by opening up more gaps in the intestinal wall as they push their way in.

Having fended off the immune system,
Shigella
chooses a cell in the intestinal wall to invade. It builds itself a syringe very much like the one made by
E. coli
O157:H7 and pierces a cell. The molecules it injects do not cause the cell to form a pedestal but, rather, cause it to open a passageway through which
Shigella
can slither. Once inside, it takes control of the cell’s skeleton. It moves forward by causing one of the cell’s fibers to grow from its back end while it hacks apart the fibers that cross its path. Once
Shigella
has finished feasting on the cell, it pushes its way out through the membrane and invades a neighbor. The dying cell summons more immune cells to the infection, and they open up more gaps through which more
Shigella
invade.

How is it that
E. coli
can be so many different things? We tend to assume that a species is made up of individuals that all share the same essence. In the ways
Shigella
and
E. coli
O157:H7 act, they seem like completely different species from the harmless K-12. Yet a comparison of their DNA shows otherwise.

If you should find yourself scrubbing your hands outside a livestock tent, stop for a minute and look around. Consider the chickens on display, showing off their chandeliers of feathers. Observe the rabbits burdened with ears too big to lift, the enormous pigs obediently following humans on leashes. Think of their less ridiculous cousins: the jungle fowl, the jackrabbit, the wild boar. These animals demonstrate that there are no fixed essences in life. One of the most important rules of life is that it changes. Boars become pigs, and harmless
E. coli
become killers. It just so happens that
E. coli
is one of the best guides to how life evolves—over days, decades, and billions of years. It vindicates Charles Darwin’s central insights, yet it also reveals how much more bizarre and more fascinating evolution can be than Darwin ever anticipated.

Five

EVERFLUX

THAWING OUT THE ANCESTORS

         
IN A CORNER OF A LABORATORY
at Michigan State University, a table rocks in a precise circle. On top of the orbital shaker are a dozen flasks filled with broth. The liquid swirls without ever breaking a ripple. Each flask contains millions of
E. coli.
They are tended by a biologist named Richard Lenski and his team of technicians and students. Lenski’s experiment looks like countless other experiments that are taking place around the world, but there is one important difference. A typical experiment with
E. coli
may last only a few hours. A team of scientists might use that time to run the bacteria through a maze or rear them without oxygen to see which genes they switch on and off. Once the scientists get enough data to see a pattern, they write up the results and dump the bacteria. But the experiment in Richard Lenski’s lab began in 1988, and forty thousand generations later it’s still going.

Lenski launched the experiment with a single
E. coli.
He placed it on a sterile petri dish and let it divide into identical clones. These clones then became the founders of twelve separate—but genetically identical—lines. Lenski put each line into its own small flask. Instead of the endless feast of sugar that
E. coli
normally enjoys in laboratories, Lenski put his microbes on starvation rations. The bacteria ran out of their glucose by the afternoon. The following morning, Lenski transferred 1 percent of the surviving
E. coli
to a new flask with a fresh supply of sugar.

Periodically Lenski and his students drew some bacteria from each flask and stored them in a freezer. The bacteria’s descendants went on multiplying daily. From time to time, Lenski has thawed out some of the early ancestors. He allows them to recover from their freeze, start eating again, and begin reproducing. And then he has compared them with their descendants. In the process, Lenski has discovered something significant: the bacteria are not what they once were. They are twice as big as their ancestors. They reproduce 70 percent faster. They’ve also become picky about the food they eat. If they’re fed any sugar other than glucose, they grow more slowly than their ancestors. And some of them now mutate at a far higher rate than before. The descendants, in other words, have evolved into something measurably different from their ancestors.

In
The Origin of Species,
Charles Darwin wrote that “natural selection will always act with extreme slowness, I fully admit.” With
E. coli,
Lenski has done something Darwin never dared dream of: he has observed evolution in his own time.

LAMARCK ON THE BEACH

I live close to the Long Island Sound, and from time to time my wife and I take our girls down to the water. The girls throw rocks and gather seaweed. On some days we are joined by nervous sandpipers. They skitter across the beach, stopping to jab their beaks into the mud before skittering off again on their pencil legs.

Two centuries ago, on a beach on the other side of the Atlantic, a French naturalist watched wading birds as well, and he wondered how they had come to be. Jean-Baptiste Lamarck concluded that they had gradually changed over generations to adapt to their environment. They had evolved. In 1801, he described the evolution of wading birds this way:

One may perceive that the bird of the shore, which does not at all like to swim, and which however, needs to draw near to the water to find its prey, will be continually exposed to sinking in the mud. Wishing to avoid immersing its body in the liquid, it acquires the habit of stretching and elongating its legs. The result of this for the generations of these birds that continue to live in this manner is that the individuals will find themselves elevated as on stilts, on long naked legs.

“Wishing” is only a crude translation of what Lamarck had in mind. He pictured a “subtle fluid” coursing through birds and all other living things, animating them and controlling their growth and movements. This subtle fluid was influenced by the habits the animals acquired as they explored the world. As a giraffe stretched for a leaf on a tree, the subtle fluid coursed into its neck. As more and more fluid traveled through it, the neck grew longer. Likewise, a wading bird stretched its legs to extract itself from the mud. It grew longer legs. Giraffes and wading birds alike could pass their altered bodies to their offspring.

Lamarck did not believe he was terribly original on this point. “The law of nature by which new individuals receive all that has been acquired in organization during the lifetime of their parents is so true, so striking, so much attested by the facts, that there is no observer who has been unable to convince himself of its reality,” he wrote.

And yet as common as that perception may have been, today Lamarck alone is linked to it. That’s because he described this change more provocatively than anyone else before him, making it part of an ambitious theory to explain the evolution of all of life’s diversity. Life, Lamarck argued, was forced to change by an inherent drive from simplicity to complexity. That drive has turned microbes into animals and plants. And at each stage of the rise of complexity, species have also acquired traits they need for their particular environment and have passed them down to their offspring.

Lamarck died in 1829, poor, blind, and scorned for his theory. But he raised questions that naturalists could not shake off: how to explain the fossil record, for example, and the distribution of similar species around the world. Thirty years after Lamarck’s death, Charles Darwin offered his own explanation. He argued for evolution, but he dismissed Lamarck’s inexorable drive from simplicity to complexity. Darwin instead argued that life evolved primarily by natural selection.

Each generation of a species contains a vast range of variations. In the case of shorebirds, some individuals have long legs and some have short ones. Some of those variations allow individuals to survive and reproduce more successfully than others. They pass down their traits to their offspring, and generation after generation their traits become more and more common. Over millions of years, natural selection can produce a wide range of bodies. In birds, for example, feet might evolve into the striking talons of eagles, the webbed flippers of ducks, and the slender poles that keep sandpipers from sinking into the mud. Natural selection acts only on the legs the birds are born with, not on any changes the birds might experience during their life.

By the late 1800s most biologists recognized the reality of evolution, but they were divided as to how life evolves. Many accepted natural selection, but others preferred something along the lines of Lamarck. The German biologist August Weismann wanted Lamarck banished from biology. He made his case by rearing mice and cutting off their tails along the way. Over many generations, the mice never grew shorter tails as a result. Neo-Lamarckians dismissed Weismann’s experiments as meaningless. The animals had not needed shorter tails, they argued, so they never produced them. The neo-Lamarckians doubted the power of natural selection, claiming that the fossil record revealed long-term trends in the history of life that short-term natural selection could not produce.

The followers of Darwin and Lamarck clashed for decades. Uncertainty kept the fights going, because scientists could not get a close look at the chemistry behind heredity. They needed an organism they could observe reproducing and acquiring an adaptation generation by generation. What they needed, it turned out, was
E. coli.

SLOT MACHINES AND VELVET STAMPS

One night in 1942 in Bloomington, Indiana, an Italian refugee sat in a country club, teasing a friend at a slot machine.

The refugee was named Salvador Luria. He had trained as a doctor in Turin, but when he discovered viruses and bacteria he abandoned his medical career for research. During World War II he fled Italy for Paris, where he joined the scientists at the Pasteur Institute studying
E. coli
and its viruses. As the Germans closed in on Paris, Luria fled again, this time to New York. In the United States he met his hero, Max Delbrück, and the two began to work together. The scientists explored the life cycles of viruses as the viruses slipped in and out of
E. coli.
They collaborated with scientists working with the newly invented electron microscope to spy on the creatures as they invaded their hosts. And for several years, Luria and Delbrück puzzled over how
E. coli
recovers from the plagues visited on it by scientists.

In a typical experiment, researchers would add viruses to a dish full of bacteria, and the bacteria would completely disappear from view. But the viruses did not kill them all. After a few hours the survivors would produce visible colonies once more. The bacteria in the new colonies were all resistant; if the scientists moved them into fresh petri dishes and exposed them to the same viruses, their offspring would resist infection, too.

This sort of behavior in bacteria turned a lot of microbiologists into neo-Lamarckians.
E. coli
seemed to respond to viruses the same way shorebirds responded to mud. The challenge had caused them to acquire resistance, which they could then pass on to their descendants. Other experiments seemed to fit this pattern as well. When scientists switched
E. coli’
s diet from glucose to lactose, it began to produce the enzyme necessary for feeding on lactose, as did its descendants. And one other factor also made many microbiologists into neo-Lamarckians: there was little evidence that bacteria had genes. As far as many microbiologists could tell, a microbe such as
E. coli
was nothing but a bag of enzymes and other molecules that could react to changes in its environment.

But some microbiologists thought otherwise. They argued that bacteria did have genes, and that, like the genes of animals, these could mutate spontaneously. In some cases, a mutation might, through pure luck, give a microbe an advantage, such as resistance to a virus. According to this rival explanation,
E. coli
followed Darwin’s rules, not Lamarck’s.

No one had put the alternatives to a good test, and Luria and Delbrück spent months puzzling over how they might do so. They had failed to come up with an experiment by 1942, when they parted ways after Luria accepted a job at Indiana University, “a place I had never heard of,” he wrote later. Not long afterward Luria found himself in Bloomington sitting next to a colleague who was playing a slot machine. The professor was losing, and when Luria teased him he stalked off.

“Right then I began giving some thought to the actual numerology of slot machines,” Luria wrote in his autobiography.

The slot machine the professor was playing was programmed to deliver only a few big jackpots. It might have been built differently. It might have provided the same small chance of paying out a jackpot on every pull of the arm. In that case the jackpot would have given out many more prizes, but much smaller ones. Suddenly Luria realized he had figured out how to run an experiment on
E. coli’
s resistance that could test Darwin’s theory versus Lamarck’s.

The next day Luria began rearing flasks of
E. coli.
Each flask started out with just a few hundred microbes. Since resistant
E. coli
are extremely rare—about one in a million—the founders of each flask were all almost certainly vulnerable. Any resistance to viruses would appear in the flask only after its population began to grow.

After the
E. coli
populations had grown for a while, Luria took some bacteria from each one and spread them on petri dishes laced with viruses. He waited for epidemics to strike, and then for resistant
E. coli
colonies to emerge.

According to Lamarck, living things acquire new traits as they face new challenges, then pass these traits down to their offspring. If Luria’s
E. coli
obeyed Lamarck, the bacteria would acquire resistance
after
Luria exposed them to viruses. That would mean that once Luria had inoculated his virus-laden dishes, every microbe had the same small chance of evolving resistance. Luria ought then to have discovered a few resistant colonies in every dish. The experiment would have resembled a slot machine that pays out a lot of small wins.

If
E. coli
obeyed Darwin, on the other hand, the experiment would play out like a slot machine with a few big wins. According to Darwin’s followers,
E. coli
has a rare random chance of mutating every time it divides regardless of what it is experiencing. In other words, the bacteria in Luria’s experiment might have acquired resistance to viruses while they were growing in the flasks, long
before
Luria exposed them to the viruses. That head start would have produced a very different result for the experiment. If a mutation had emerged early on in one of the colonies, the mutant would have had a lot of time to produce offspring. When Luria took some of the bacteria from such a colony and placed them in a petri dish with viruses, a fair number of them would already be resistant. They would grow into many new colonies in the dish.