Book Review: Microcosm

Carl Zimmer uses E. coli as telescope on life

In February 1982, physicians in Medford, Oregon encountered an unknown pathogen that waged a sort of intelligent biochemical warfare against our bodies. After being ingested, the rod-shaped bacteria—small enough to fit 500 of them side-by-side across the diameter of a single period in twelve-point font—were able to monitor their surroundings for human hormones to determine where they were inside their victims. When they received the signal that they had reached the intestines, the rods sprouted tails that operated as proton-powered outboard motors, swam towards one another, and constructed their nano-weapons: syringes small enough to pierce human cells and deliver injections of treacherous chemical instructions.

The affected cells responded to the injections like mind-controlled doppelgangers. Their membranes deformed into landing pads, making it easier for their rod-shaped masters to sup on them as their internal fluids and molecules started to leak. In some cases, the rods also released toxins that spread through the rest of the victims’ bodies, tinkering with cells from the inside and causing them to explode.

This particular pathogen, known as serotype O157:H7 of the bacteria Escherichia coli, or E. coli 157 for short (the variety behind the spinach and beef food-poisoning scares of 2006 and 2007), is one of the many strains chronicled in science journalist Carl Zimmer’s latest book, Microcosm: E. coli and the New Science of Life (Pantheon Books). (The most recent American tomato/jalapeƱo scare is due to Salmonella, a distinct, but closely-related bacteria that split off from E. coli back when dinosaurs were still walking the earth.)

It may seem like devoting an entire book to one family of single-celled organisms is a bad idea. It’s an election year, after all, and with two wars, a tanking economy, and a warming planet to deal with, bacteria may seem distracting. But Zimmer is no ordinary science writer: he hosts a Web site where he posts photos of science tattoos, writes one of the best and longest running science blogs on the Web, and, in 2001, wrote a book that made parasites seem fascinating, elegant, and frightening all at once.

E. coli itself is a fascinating species. Its manifestations comprise the killers Shigella and O157:H7, as well as innocuous laboratory varieties like K-12 (“[S]o harmless that scientists make no efforts to protect themselves from it; instead, they have to protect it from fungi and bacteria.”), among many other strains. E. coli can build microscopic weapons and wage war, and yet without the beneficial strains living in our gut we might not be able to survive. When scientists started experimenting with genetic engineering, it was E. coli they worked with. And as futurists and computer scientists look for a link between life as we know it and artificial networks like the Internet, it is in the natural functioning of E. coli that they see something of a bridge.

Zimmer covers a lot of ground in Microcosm, and the book runs in chronological order, from E. coli’s discovery by the German pediatrician Theodor Escherich in 1885, right up to the current debate about biotechnology and the ethical implications of engineering “chimeras” like animals with partially human organs.

What’s great about Zimmer’s approach is that he takes the time to introduce the reader to the scientists and experiments that changed our understanding of E. coli and biology in general. Early on, he sets the tone of the book with a narrative account of one of the more seminal studies in the bacteria’s history—the one that showed that a single bacterium could actually swap genes rather than just clone its own through asexual cell division. It’s the story of a young student named Joshua Lederberg and two mutant strains of E. coli:

Lederberg started work at Yale in 1946. He selected a mutant strain that could make neither the amino acid methionine nor biotin, a B vitamin. The other strain he picked couldn’t make the amino acids threonine and proline. Lederberg put the bacteria in a broth he stocked with all four compounds so that the mutant microbes could grow and multiply. They mingled in the broth for a few weeks, with plenty of opportunity for hypothetical sex.

Lederberg drew out the samples of the bacteria and put them on fresh petri dishes. Now he withheld the four nutrients they could not make themselves: threonine, proline, methionine, and biotin. Neither of the original mutants strains could grow in the dishes. If their descendents were simply copies of their ancestors, Lederberg reasoned, they would stop growing as well.

But after weeks of frustration—of ruined plates, of dead colonies—Lederberg finally saw E. coli spreading across his dishes. A few microbes had acquired the ability to make all four amino acids. Lederberg concluded that their ancestors must have combined their genes in something akin to sex. And in their sex they proved they carried genes.

In the years that followed, the discovery would allow scientists to breed E. coli like flies and to probe genes far more intimately than ever before. Twelve years later, at the ancient age of thirty-three, Lederberg would share the Nobel Prize in Medicine with Tatum and Beadle. But in 1946, when he picked up his petri dishes and noticed the spots that appeared to be the sexual colonies he had dreamed of, Lederberg allowed himself just a single word alongside the results in his notebook: “Hooray.”

As Zimmer writes, the discovery that bacteria can trade genes, and that DNA and RNA can code for the same proteins across species, led French biologist Jacques Monod to proclaim, “What is true for E. coli is true for the Elephant.” Zimmer repeats this adage throughout Microcosm because it is the lynchpin for the entire book: that scientists can work within the E. coli model, rather than experimenting directly with more complicated multi-cellular animals like ourselves; that we can often use simple systems as telescopes into how more complicated systems work; that certain rules and concepts in biology and evolution are consistent across species and even domains.

One of the best parts of Microcosm is its discussion of antibiotics and how E. coli and other bacteria can quickly evolve to outwit them. Zimmer explains how some bacteria can even enter a state of hyper-mutation as a result of antimicrobial or antibiotic attack: when E. coli needs it most, it starts messing with its genetic code in order mutate, and evade the attack, faster.

It’s scary material, considering that widespread antibiotic use got started during World War II with penicillin and now, several generations of antibiotics later, it seems like we’re still losing the war against bacterial resistance. By as early as 1948, Zimmer notes, “doctors reported that penicillin was beginning to fail in their Staphylococcus-infected patients.” Yet:

These disturbing discoveries did nothing to halt the rise of antibiotics. Today the world consumes more than ten thousand tons of antibiotics a year. Some of those drugs save lives, but a lot of them are wasted. Two-thirds of all the prescriptions that doctors hand out for antibiotics are useless. Antibiotics can’t kill viruses, for instance. Many farmers today practically drown their animals with antibiotics because the drugs somehow make the animals grow bigger. But the cost of antibiotics is greater than the profit from the extra meat.

It would have been wonderful if Zimmer had decided to include a little more about where those numbers come from and what they mean. Does useless include prescriptions that are not used to completion or are used for a purpose other than what they were prescribed for? More importantly, however, Zimmer does an excellent job describing the process by which bacteria become resistant.

His discussion of Shigella infections in Japan after World War II is fascinating. It was in the late forties that Japanese doctors started to encounter bacteria that were resistant to not just a single antibiotic, but to all of them. It turned out that the Shigella bacteria were able to trade genes through Lederberg’s bacterial sex and through viral infections of the bacteria themselves. These and other strategies are collectively known as horizontal gene transfer, which, Zimmer writes, “allows genes to leapfrog from microbe to microbe across staggering distances. In the jungles of French Guinea, scientists have found antibiotic-resistant E. coli in the guts of Wayampi Indians, who have never taken the drugs.”

Some of the most interesting questions Zimmer raises in the book come from such discussions of the “murky struggles” between parasite and host, and the role of bacteria and viruses in human evolution:

Most viruses simply invade our cells, which produce new viruses that move on to the next host. But some viruses inset their genetic material in a cell’s genome. If they manage to infect a sperm or an egg, these viruses will be passed down from one generation of humans to the next. Over many generations, mutations cause the viruses to lose their ability to escape their host cells. Many lose most of their genes. What remains are instructions for making copies of their DNA and pasting that DNA back on their host’s genome. These genomic parasites now make up about 8 percent of the human genome. Recent research suggests that some of them have been harnessed by their hosts. A number of essential human genes, which help build things as different as antibodies and placentas, evolved from virus genes. Without our resident viruses we would not be able to survive. Once again, what is true for E. coli is true for the elephant: Where do our own viruses stop, and where do we begin?

With descriptions like that, Microcosm excels at making the science of E.coli accessible for lay audiences. Reaching far beyond the food scares of recent years, it is a story of discovery that illuminates a microscopic and alien world and explains how it has helped guide the course of human history. Anybody that picks up a copy will find that Zimmer has produced a book not just about E. coli, but about microbiology and evolution itself.

Russ Juskalian is a contributor to The Observatory and a freelance writer.