microcosm: E. coli and the New Science of Life

“Superb…quietly revolutionary.” — Anthony Doerr, author of All the Light We Cannot See

What is life? Can we make it from scratch? Are there rules that all living things must obey? Can there be life without death? Biologists today are seeking answers to these fundamental questions about life. Few people know that many of those answers may reside in a species of bacteria that live in our guts: E. coli.

In this startlingly original biography of a germ, Carl Zimmer traces E. coli‘s pivotal role in the history of biology, from the discovery of DNA to the latest advances in biotechnology. Zimmer describes the remarkably sophisticated strategies E. coli uses to stay alive, from practicing chemical warfare to building microbial cities. He reveals the many surprising and alarming parallels between E. coli‘s life and our own. Zimmer describes the profound insights E. coli has offered about evolution, by changing in real time and by revealing billions of years of history encoded in its genome. E. coli is also the most engineered species on Earth, and as scientists retool this microbe to produce life-saving drugs and clean fuel, they are discovering just how far the definition of life can be stretched.

Microcosm is the first full story of the one species on Earth scientists know best. It is also the story of life itself, of its rules, its mysteries, and its future.

What People Are Saying

Anthony Doerr in The Boston Globe
“Superb…quietly revolutionary.”

The Guardian
“This is a thought-provoking book that wrenches us from our human-centred perspective and gives us a guide to life through the chemical-sensing molecules of a species that was here long before we were, and which will certainly outlive us.”

The Times of London
[Zimmer] “comes up with turns of phrase and images that are deep delights. The ways in which the structure of the cell depends on the tempo of different molecular processes give it a “geography of rhythms”; the building of a flagellum, which takes longer than the bacterium’s replication, is like building a medieval cathedral, in that “a new microbe inherits a partially built tail and passes it on, still unfinished, to its descendants”. (Another flagellar delight is the way in which Zimmer shows that, far from being a structure that could not evolve stepwise, as proponents of intelligent design would have you believe, this complex corkscrew actually reveals its evolved status clearly down at the molecular and genetic level.) Perhaps the phrase that will resonate with me longest, though, is the one he uses to frame the discussion of E. coli as a workhorse of biotechnology and a proving ground for the more ambitious redesigns of life – “playing nature” – so much richer in its implications than the tediously Faustian “playing God”. If you want to get a clearer idea of the sort of nature that science can now play with, this is the book for you.”

Science
“A popular science book on E. coli may not sound like the most interesting read. However, Microcosm is just that. The next time you hear of an outbreak of nasty E. coli on the news, spare a thought for this minute creature, which has arguably helped advance humanity far further than any other organism. Not only has it inhabited human guts for as long as we have existed, it has benefited almost all areas of the biosciences, from genetic engineering to evolutionary theory. To really understand life, it seems we must pay close attention to this bug’s life.”

New York Times Book Review
“From Victorian England to contemporary America, creationists have often denied that we are related to other primates. But the hard truth of our genealogy does even greater damage to human pride. We are cousins of every living thing, including the billions of E. coli bacteria in our intestines. This kinship may not be flattering, but it is useful. By studying these tiny creatures, we learn about other organisms, including ourselves. As the French biologist Jacques Monod once said, “What is true for E. coli is true for the elephant.”

“Carl Zimmer effectively applies this principle in his engrossing new book, “Microcosm,” relating the study of these microbes to larger developments in biology and thoughtfully discussing the social implications of science.”

Forbes
“In biology, “what is true for E. coli is true for the elephant,” a maxim that has held for more than a century of experimentation on the common gut bacterium, leading to breakthroughs in fields ranging from immunology to genetics. As science journalist Carl Zimmer writes in his informative and entertaining biography of biologists’ favorite microbe, E. coli is a living “philosopher’s stone.” E. coli‘s simplicity is its most valued attribute, allowing scientists to systematically track its metabolism and the basic functions of all but 600 of its 4,288 genes. Yet, for the mountain of data that has been painstakingly collected, there is something equally marvelous about an organism that can perform every essential function of life without nervous system or nucleus, negotiating its needs for food, habitat and even occasional sex with its celebrated spinning flagella. Creationists have taken the flagellum’s astonishing micromechanics as proof of intelligent design. But today, scientists are shedding new light on the evolutionary arc of that wondrous little machine. Their findings should speak volumes about the elephant..”

The Independent
“One of the things that makes humans different is our curiosity to poke around in the innards of other creatures. When they first got acquainted with zillions of microscopic bacteria, scientists thought their own innards pretty uninteresting. They were dead wrong.

‘In this satisfying piece of popular science, Carl Zimmer shows how almost the whole of biology can be unfolded from a tiny, rod-shaped organism first found in soiled nappies a bit over a century ago. Escherichia coli – named after the intrepid nappy-scraper Theodor Escherich – is a normally innocuous dweller in the human gut, and many other places it can get a living. But this minute wonder can sense its surroundings, swim around, and co-operate with its bacterial siblings. It has a kind of sex, on occasion, responds to its environment, is shaped by its history, and tries to fight off attacks from bigger bacteria and much smaller viruses.

‘As Zimmer relates, E. coli is more than a convenient emblem of life’s ingenuity. It has been the focus of work in a thousand labs, and given up innumerable secrets about the inner workings of the cell. Thanks to E. coli, we know how genes work, how they are regulated, and how their switches and modulators form subtle networks. The beast has given insight into evolution, behaviour and even ecology. Layer by layer, Zimmer shows how the intricate details of a bacterium relate to problems all organisms face.

‘His book comes from the US, so has to spend a while debunking creationism’s dumber younger brother, intelligent design. This is apt because E. coli‘s cunningly assembled flagellum is a prime exhibit in the creationists’ case: that life is equipped with machines which they cannot believe arose by chance. As usual, look properly and you find lots of intermediate forms, all doing something useful – if not propelling their host along. The flagellum, like antibiotic resistance, undoubtedly evolved.

‘There follows an excursion into the history and politics of genetic engineering, which may not hold the attention of all those gripped by the unpacking of the bacterium’s bag of tricks. There are intriguing scientists there, some beautiful experiments, and medical and industrial developments with high stakes. But the real star of the show remains a tiny, versatile organism which is happily dining off your last meal as you read this..”

Publisher’s Weekly
“Written in elegant, even poetic prose, Zimmer’s well-crafted exploration should be required reading for all well-educated readers.”

Steven Johnson author of The Ghost Map and Mind Wide Open
“Carl Zimmer may be my favorite science writer around today (others seem to agree), so I’m excited to report that his new book Microcosm: E. coli and the New Science of Life hit the shelves yesterday. I had the opportunity to read it in manuscript form, and it’s really an exceptional book — what Carl calls an “(un)natural history of E. coli” — the world’s most famous microbe. Having just published a book that partially starred a bacterium myself, I know how hard it is to make a book about microbial life engaging to human readers, but Carl pulls it off brilliantly here — it’s creepy, mind-twisting, and delightful all at the same time. It’s the kind of book that literally expands your perspective on the world — it helps you see how this alternative universe of tiny life forms is bound up crucially in our own day-to-day experience..”

Sean B. Carroll author of Endless Forms Most Beautiful and The Making of the Fittest
“Microcosm could well be entitled Fantastic Voyage. Carl Zimmer, one of our most talented and respected science writers, guides us on a memorable journey into the invisible, but amazing world within and around a tiny bacterium. He reveals a life or death battle every bit as dramatic as that on the Serengeti and one that offers profound insights into how life is made and evolves. Microcosm expands our sense of wonder by illuminating a microscopic universe few could imagine, and instills a great sense of pride in the great achievements of the scientists who have discovered and mastered its workings.”

Excerpt

ONE: SIGNATURE

I gaze out a window, a clear, puck-shaped box in my hand. Life fills my view: fescue and clover spreading out across the yard, rose of Sharon holding out leaves to catch sunlight and flowers to lure bumblebees. An orange cat lurks under a lilac bush, gazing up at an oblivious goldfinch. Snowy egrets and seagulls fly overhead. Stinkhorns and toadstools rudely surprise. All of these things have something in common with one another, something not found in rocks or rivers, in tugboats or thumbtacks. They live.

The fact that they live may be obvious, but what it means for them to be alive is not. How do all of the molecules in a snowy egret work together to keep it alive? That’s a good question, made all the better by the fact that scientists have decoded only a few snips of snowy egret DNA. Most other species on Earth are equally mysterious. We don’t even know all that much about ourselves. We can now read the entire human genome, all 3.5 billion base pairs of DNA in which the recipe for Homo sapiens is written. Within this genetic tome, scientists have identified about 18,000 genes, each of which encodes proteins that build our bodies. And yet scientists have no idea what a third of those genes are for and only a faint understanding of most of the others. Our ignorance actually reaches far beyond protein-coding genes. They take up only about 2 percent of the human genome. The other 98 percent of our DNA is a barely explored wilderness.

Only a few species on the entire planet are exceptions to this rule. The biggest exception lives in the plastic box in my hand. The box-a petri dish-looks lifeless compared with the biological riot outside my window. A few beads of water cling to the underside of the lid. On the bottom is a layer of agar, a firm gray goo made from dead algae and infused with sugar and other compounds. On top of the agar lies a trail of pale gold spots, a pointillistic flourish. Each of those spots is made up of millions of bacteria. They belong to a species that scientists have studied intensely for a century, that they understand better than almost any other species on the planet. I’ve made this species my guide-an oracle that can speak of the difference between life and lifeless matter, of the rules that govern all living things-bacteria, snowy egret, and curious human. I turn over the dish. On the bottom is a piece of tape labeled “E. coli K-12 (P1 strain).”

I got my dish of Escherichia coli on a visit to Osborne Memorial Laboratories, a fortress of a building on the campus of Yale University. On the third floor is a laboratory filled with nose-turning incubators and murky flasks. A graduate student named Nadia Morales put on purple gloves and set two petri dishes on a lab bench. One was sterile, and the other contained a cloudy mush rich with E. coli. She picked up a loop-a curled wire on a plastic handle-and stuck it in the flame of a Bunsen burner. The loop glowed orange. She moved it away from the flame, and after it cooled down she dipped it into the mush. Opening the empty dish, she smeared a dollop across the sterile agar as if she were signing it. Morales snapped the lid on the second dish and taped it shut.

“You’ll probably start seeing colonies tomorrow,” she said, handing it to me. “In a few days it will get stinky.”

It was as if Morales had given me the philosopher’s stone. The lifeless agar in my petri dish began to rage with new chemistry. Old molecules snapped apart and were forged together into new ones. Oxygen molecules disappeared from the air in the dish, and carbon dioxide and beads of water were created. Life had taken hold. If I had microscopes for eyes, I could have watched the hundreds of E. coli Morales had given me as they wandered, fed, and grew. Each one is shaped like a microscopic submarine, enshrouded by fatty, sugary membranes. It trails propeller-like tails that spin hundreds of times a second. It is packed with tens of millions of molecules, jostling and cooperating to make the microbe grow. Once it grows long enough, it splits cleanly in two. Splitting again and again, it gives rise to a miniature dynasty. When these dynasties grow large enough, they become visible as golden spots. And together the spots reveal the path of Morales’s living signature.

E. coli may seem like an odd choice as a guide to life if the only place you’ve heard about it is in news reports of food poisoning. There are certainly some deadly strains in its ranks. But most E. coli are harmless. Billions of them live peacefully in my intestines, billions more in yours, and many others in just about every warm-blooded animal on Earth. They live in rivers and lakes, forests and backyards. And they also live in thousands of laboratories, nurtured in yeasty flasks and smeared across petri dishes.

In the early twentieth century, scientists began to study harmless strains of E. coli to understand the nature of life. Some of them marched to Stockholm in the late 1900s to pick up Nobel Prizes for their work. Later generations of scientists probed even further into E. coli‘s existence, carefully studying most of its 4,000-odd genes and discovering more rules to life. In E. coli, we can begin to see how genes must work together to sustain life, how life can defy the universe’s penchant for disorder and chaos. As a single-celled microbe, E. coli may not seem to have much in common with a complicated species like our own. But scientists keep finding more parallels between its life and ours. Like us, E. coli must live alongside other members of its species, in cooperation, conflict, and conversation. And like us, E. coli is the product of evolution. Scientists can now observe E. coli as it evolves, mutation by mutation. And in E. coli, scientists can see an ancient history we also share, a history that includes the origin of complex features in cells, the common ancestor of all living things, a world before DNA. E. coli can not only tell us about our own deep history but can also reveal things about the evolutionary pressures that shape some of the most important features of our existence today, from altruism to death.

Through E. coli we can see the history of life, and we can see its future as well. In the 1970s, scientists first began to engineer living things, and the things they chose were E. coli. Today they are manipulating E. coli in even more drastic ways, stretching the boundaries of what we call life. With the knowledge gained from E. coli, genetic engineers now transform corn, pigs, and fish. It may not be long before they set to work on humans. E. coli led the way.

I hold the petri dish up to the window. I can see the trees and flowers through its agar gauze. Each spot of the golden signature refracts their image. I look at life through a lens made of E. coli.