An outbreak of E. coli isn't usually the stuff of feel-good stories. Feel-bad is more like it—or even feel-organ-failure. But recent E. coli outbreaks can offer us a bit of solace. We live in the anxious age of synthetic biology, when scientists can reconstruct entire genomes from raw chemicals, and when we all fret that someone is going to use this new technology to create a monster bug and unleash a man-made plague. According to one government report, "The effects of some of these engineered biological agents could be worse than any disease known to man." But a close look at recent outbreaks of E. coli—and a closer look at the bacteria themselves—may help us to put aside our fears for the moment. Engineering plagues is harder than it looks.
In 2006, a pair of major E. coli outbreaks swept across the country. One was carried on spinach, the other on lettuce. The spinach outbreak caused 204 illnesses and three deaths. The lettuce outbreak made 71 people sick. In both outbreaks, many people had to be rushed to the hospital. Some got away with just bloody diarrhea. In other cases, the bacteria released toxins into the bloodstream that caused kidneys and other organs to shut down.
The same strain was behind both cases as well as most other recent outbreaks of E. coli. It's known as E. coli O157:H7, named for some of the molecules on its surface. It emerged in the 1980s as a nasty pathogen found mostly in tainted hamburger meat. It lives comfortably (and harmlessly) in cows and other mammals, but if it gets into a human host, it sometimes wreaks havoc. When animals shed the bacteria in their manure, the pathogen can make its way onto crops, and in recent years it has contaminated not just hamburger meat, spinach, and lettuce but apples and bean sprouts. In addition to the occasional major outbreak, it causes a steady stream of illnesses—about 75,000 a year in the United States—that attract less attention.
Scientists noticed that the most recent outbreaks were particularly brutal. The bug from 2006 sent three to four times more people than expected to the hospital. Typically, only 4 percent of people who get infected with E. coli O157:H7 suffer the worst form of the disease, in which toxins are released into the bloodstream. As many as 15 percent did in 2006.
This worrisome trend led a team of scientists based at Michigan State University to take a look at the DNA of the bacteria. The researchers compared bacteria from recent outbreaks with hundreds of others samples and published the results last Monday. The scientists drew an evolutionary tree based on the differences in the bacteria's genes. One branch of the tree—the one that caused the spinach and lettuce outbreaks in 2006—is significantly more likely to make people sick than the others. And they found that this lineage has been exploding in recent years. In 2002, it accounted for 10 percent of the E. coli cases recorded in Michigan. In 2006, it accounted for 46 percent.
To figure out what makes this new strain so vicious, the scientists selected a microbe from the 2006 spinach outbreak and sequenced its entire genome. They discovered that it is not a minor variation on the basic E. coli O157:H7 plan. It is a major overhaul. Hundreds of its genes can't be found in other strains. It has lost hundreds of others. And many of the genes it shares with its close relatives have mutated.
The scientists concluded that at some point in the not-too-distant past, this strain of E. coli O157:H7 evolved rapidly into a far meaner pathogen than its ancestors. Natural selection altered its genes quickly, thanks to the ability bacteria have to reproduce in as little time as 20 minutes. Speeding up their evolution even further was their ability to take in DNA from other microbes, even from species that are only distantly related. The genomes of bacteria are being continually rejiggered into new combinations of genes. Some bacteria become better at capturing sunlight, others at resisting antibiotics. And, in the case of the spinach strain of E. coli O157:H7, the introduction of viral DNA has made them far nastier.
It is chilling to think just how quickly a new, more dangerous form of E. coli has emerged—and it's tempting to think that its quick arrival bodes ill for synthetic biology. After all, if it just takes a few years for a dangerous strain to evolve in the wild, just think how easy it will be for people to build them in the lab.
In fact, the spinach outbreak teaches a very different lesson. The Michigan State scientists have no idea what is making the new strain so mean. It's a straightforward task to identify the hundreds of new genes in its genome, but the researchers can't say precisely what all those new genes are doing. The same goes for the hundreds of missing genes as well as for the other genes tweaked and fine-tuned by natural selection.
This sort of ignorance is par for the course in the world of microbes. And if a new strain of an intensely studied species is so mysterious, it's hard to believe that bioterrorists could just type out a new plague on their keyboards. Our deep ignorance also raises some doubts about how far synthetic biologists can go with the good applications of the science. In the most ambitious projects, scientists have inserted only a few genes. They've had some spectacular successes, such as making E. coli produce jet fuel and precursors to malaria medicine. But the notion that we might add hundreds of genes to bacteria to do something useful, like turn microbes into solar power generators, may be hubris for a long time to come.
Inventors don't always design their inventions from scratch, though. Perhaps someone could create a new pathogen simply by mimicking nature: combining different sets of genes, mutating a few of them, and using trial and error to find ones that worked? Probably not. Nature's lab bench is colossal. Millions of cattle and other animals are carrying around E. coli O157:H7, and an incalculable number of viruses are invading them, trying out new combinations. Many of those combinations turn out to be failures, but natural selection can give rise to a few spectacular successes. Even if a government built a giant lab just for the purpose of stumbling across a new pathogen, it might take centuries or millenniums to hit on something like the spinach strain.
But this ignorance is not cause for much comfort. Even if we don't need to worry about synthetic bacteria just yet, we do need to worry about new pathogens evolving right in our own backyard (or, rather, our own feedlots and factory farms). As things stand, we become vaguely aware of these bacteria only once they've been sickening and killing for years. One way to speed up the search for nature's new bioweapons would be to set up a monitoring network. If public-health workers were equipped with cheap, fast testing devices, E. coli and other microbes might not be able to surprise us so often in the future. And if some evil genius does someday figure out how to unleash a bioweapon, we will have had an excellent rehearsal.
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