A radical career move by Craig Venter is illustrative. Having grown up as a surfer on the California coast, in 2003 he returned to the sea to decompress from leading the massive effort to sequence the human genome. Venter took his sailboat, Sorcerer II, to the supposedly barren Sargasso Sea, collected samples of the water, and sent them back to his lab to be analyzed, using the shotgun sequence method he had developed for the human genome. In an April 2004 paper in Science, Venter’s team reported that a barrel of Sargasso Sea water contained 1.2 million genes new to science (doubling the previous number), indicating 1,800 new “species” of bacteria and archaea. In functional terms, an astonishing 800 of the new genes were used for sensing or harvesting sunlight. Only 200 such genes had been discovered in all of life before that. On one sailboat trip, Venter had gone from being the world’s leading geneticist to one of its leading field biologists, using the same equipment for both pursuits. To the annoyance of his rivals and critics, he carried on merrily sailing around the world, making new discoveries the whole way. As he reported, “Some 85 percent of the sequences in species are unique every 200 miles. So, instead of the ocean being a giant homogeneous soup, it’s actually millions and millions of microenvironments, dynamically changing.”
In his talks, Venter makes microbial ubiquity graphic:In one milliliter (one fifth of a teaspoon) of seawater, there’s a million bacteria and 10 million viruses. In the air in this room— we’ve been doing the air genome project—all of you just during the course of this hour will be breathing in at least 10,000 different bacteria, and maybe 100,000 viruses. . . . So you’re actually exchanging DNA with your neighbors without even doing it intentionally right now. . . . This is the world of biology that we live in, that we don’t see, where evolution takes place on a minute-to-minute basis. . . . The air that we breathe comes from these organisms. The future of the planet rests with these organisms. . . . If you don’t like bacteria, you’re on the wrong planet. This is the planet of the bacteria.
Indeed, microbes make up 80 percent of Earth’s total biomass, says famed microbial taxonomist Carl Woese. Of all ocean life, 95 percent requires a 1000x microscope to see. Bacteria have been found living in profusion a mile below the bottom of the seafloor, possibly as old as the sediment around them—111 million years.
Look closer to home. Ninety percent of you isn’t you—only a tenth of the cells in your body are human; the rest are microbes. We are a portable swamp. One program of the emerging worldwide Global Metagenomics Initiative is called the International Human Microbiome Consortium, which is busy shotgun-sequencing all of the microbial communities that share our bodily life. We humans have 18,000 distinct genes; our microbes have 3 million. We are one species; they are diverse—a thousand species in our digestive tract (a twenty-one-foot-long bioreactor running on 100 trillion microbes), another thousand in our mouth, five hundred on our skin, another five hundred in those of us with a vagina. “It is inescapable,” says the Metagenomics book, “that we are superorganisms composed of both microbial and human parts.”
What is the actual wet weight of microbes we carry around with us? Bacterial cells are much smaller than human cells—like a honeybee versus a cat, as they say. The textbook Microbial Inhabitants of Humans (2004) estimates the total at nearly three pounds, about the weight of our brain.
• Every few minutes, every one of the microbes in your body (and the ocean, and the soil, and the air) is defying precaution and the sacred, playing God, performing an act illegal in Europe—swapping genes around in the endless search for competitive or collaborative advantage. Profligate, totally careless genetic engineering has been standard practice for 3.5 billion years. Lynn Margulis describes the process with characteristic pith in What Is Sex? (1998), a book she cowrote with her son Dorion Sagan:Genetic engineers have borrowed, not invented, gene shuffling. . . . Bacteria are not really individuals so much as part of a single global superorganism, responding to changed environmental conditions not by speciating but by excreting and incorporating useful genes from their well-endowed neighbors and then rampantly multiplying. . . .
Imagine that in a coffee house you brush up against a guy with green hair. In so doing, you acquire that part of his genetic code, along with perhaps a few more novel items. Not only can you now transmit the gene for green hair to your children, but you yourself leave the coffee shop with green hair. Bacteria indulge in this sort of casual quick-gene acquisition all the time. Imagine you are a blue-eyed person (perhaps with newly acquired green hair) who, in a swimming pool, gulps the more common gene for brown eyes. Towelling off, you pick up genes from sunflowers and pigeons. Soon the brown-eyed you is sprouting petals and flying—eventually reproducing into gliding brown-eyed, green-haired quintuplets. This fantasy is mundane reality in the world of bacteria. . . .
Unlike usually useless random mutations, batches of genes taken wholesale from another organism have already proven their mettle. The difference is similar to that between a misprint, which almost always makes a text worse, and an appropriate quote, which serves a purpose.
(That statement appearing here is an example of itself. In quoting Margulis, I engineered a working section of her text into mine. The mutation approach would have yielded nnnonssens xq4 mztWw.)
Gene transmission comes in five forms—two of them “vertical” and familiar to us, three “horizontal” and seemingly exotic but far more common. Vertical gene transfer is sexual or asexual—offspring inherit their genomes directly from two parents via sexual recombination (as we do) or asexually from one parent via splitting, budding, spores, or unfertilized eggs. The genes travel only down through the generations, hence the term vertical. With horizontal gene transfer, “genes can move along a bewildering variety of routes between genomes: sliding through bridges between cellular membranes, hitchhiking inside viruses, or even getting sucked up from the environment as naked fragments,” reports an article in Science. (Those three means of intergenomic travel are referred to as conjugation, transduction, and transformation.)
Microbes do four of the five forms of gene transfer, everything but sex. By current estimates, 80 percent of the genes in microbes traveled horizontally at some point in their past. Some genes are more mobile than others. Carl Woese describes the most mobile as “cosmopolitan genes” or “life-style genes.” They can provide fast local adaptivity. Lots of genes, though, don’t “take.” They show up in a genome and hang around as useless baggage until they’re gradually selected out.
A shocking revelation of recent research is that horizontally transferred genes “can pass between organisms that are not even of the same species, genus, sub-kingdom or kingdom of life form.” (That from the online encyclopedia Citizendium.) Working chunks of DNA have been detected moving naturally between rice and millet. Parasitic plants and fungi swap genes spontaneously with their hosts. Snake DNA has turned up in gerbils. Craig Venter’s lab found that inside the fruit fly’s genome is the entire genome of a common parasitic bacteria called Wolbachia, and 28 of the 1,206 bacterial genes are doing something useful for the fly. That would be like finding a complete flea genome inside ours, with mysterious functions.
Speaking of us, new discoveries about viruses indicate that “taken together, virus-like genes represent a staggering 90 percent of the human genome,” says a report in New Scientist. Most of the genes are baggage, but some turn out to have been behind such crucial evolutionary innovations as the mammalian placenta and the development of the immune system. Suspicion is growing that gene-swapping through viruses is the dominant engine of evolution. Basically free-floating gene packets a hundredth the size of bacteria, viruses come in a hundred million varieties and overwhelmingly outnumber everything else. “The rate at which viruses shuffle DNA around,” says the New Scientist article, “suggests that life is capable of acquiring fresh new material out of the blue, and also of making dramatic leaps in the time it takes to catch a cold.” The report adds, “It is looking more and more as though the biosphere is an int
erconnected network of continuously circulated genes—a pangenome.”
It’s a transgenic world.
• Thanks to horizontal gene transfer, microbes have developed astounding skills. Tiny as they are, microbes can learn. (E. coli anticipate and prepare for the sequence of environments they face in our intestines during digestion.) Microbes do complex quorum sensing, both within species and between species—they are in that sense multicellular. (In order to coordinate group benefits such as biofilm structure and toxin release, they signal each other through chemical autoinducers.) They make rain on purpose. (Some bacteria have a surface protein that binds water molecules into raindrops and snow; when they get stuck in the air, this characteristic gets them back down to the ground. The total of such behavior is Gaian, a global feedback between life and the atmosphere.) They can survive for hundreds of millions of years inside rock and ice. (Microbiologist Russell Vreeland, who revived bacteria that had been trapped inside salt crystals for 250 million years, postulates that geology “acts as a gene bank for microbes.” Glaciers have been described as “gene popsicles.”)
The byplay between microbes and humans has always been intimate. They use us to provide food; we use them to ferment food. We cull them with antibiotics; they cull us with disease. Bacteria are the major remaining form of life that threatens us—via tetanus, typhoid fever, diphtheria, syphilis, cholera, leprosy, and tuberculosis, according to the Wikipedia entry on bacteria—and they attack our crops with “leaf spot, fire blights and wilts in plants as well as Johne’s disease, mastitis, salmonella and anthrax in farm animals.” But we’ve employed them for thousands of years in the making of “fermented foods such as cheese, pickles, soy sauce, sauerkraut, vinegar, wine, and yoghurt.”
Scientists in search of ways to convert the inert cellulose of plants into usable energy are studying the miraculous bioreactor in the hindgut of termites. The complex microbial community there can turn a sheet of printer paper into a half gallon of hydrogen gas. Nothing else can do that. Steven Chu, the U.S. Secretary of Energy, has said, “Either we’ll genetically engineer the microorganisms from termite guts to produce more energy from biomass than they need, or we’ll adapt the chemistry within the microorganisms to process the biomass ourselves.”
Craig Venter is awed by the existence of microbes “that can withstand millions of rads of radiation. Their genetic code gets blown into hundreds of little pieces. They can be totally desiccated. But you drop them in water and within 12 to 24 hours they reconstruct their chromosomes exactly as they were before, and they start replicating again.” In that context, he says, “the idea of panspermia, that organisms can travel through space and land in an environment such as Earth and start replicating, is not far out at all. You could potentially view evolution as a 6- to 8-billion-year event, not a 3- to 4-billion-year event, if life can travel around the universe.”
That’s the power of horizontal gene transfer. Life at its most creative is transgenic. No wonder human ingenuity wants to continue expanding on microbial ingenuity, proceeding from yogurt to the drug artemisinin for malaria, from wine to jet fuel.
As a biology student, I was taught to sneer at Jean-Baptiste Lamarck, whose eighteenth-century theory of evolution was based on the idea of the inheritance of acquired characters. The giraffe’s neck, he proposed, got long by a parent stretching for high leaves and then passing that trait on to the calves. Such simple-mindedness, we were told, was corrected by Charles Darwin, who substituted natural selection among random inherited variations as the mechanism of evolution. Darwin’s theory was based on the artificial selection that breeders practice—classic vertical gene transfer. The more we study horizontal gene transfer these days, the more Lamarckian it looks. Convenient traits are acquired all the damn time in direct response to the environment, just as Lamarck proposed.
This has led Carl Woese to propose that a “Darwinian transition” occurred a couple of billion years ago when various organisms began protecting their own gene lines jealously, biasing toward vertical and away from horizontal gene transfer. This was the beginning of what we call species, one generation of identical jellyfish or chipmunks after another. “Species formed,” says Woese, “when organisms stopped treating genes from other organisms with equal importance to their own genes.”
Riffing on Woese, Freeman Dyson says:Some cells decided it was advantageous to keep their intellectual property private. . . . Each invention only benefited the species that invented it. Everybody else had to compete separately. Evolution then went much slower for a couple of billion years. That’s what I call the Darwinian interlude. Since humans came along, that has changed again. Now we’re back in an epoch when genes can be horizontally transferred.
• All biologists are genomicists now, and the pace of molecular biology is accelerating at a rate beyond even what we’ve experienced with information technology. The lead chronicler of biotech, researcher Rob Carlson, keeps updating what are called the Carlson curves. They chart how much faster than Moore’s law we’re developing techniques to sequence and synthesize DNA—to read and write genetic code. (Moore’s law states that computer capability doubles every two years.) Thanks to its accelerating technology, the medical biotech industry is growing by 15 to 20 percent a year, and agricultural biotech by 10 percent a year.
Out of nowhere has come a whole new field called synthetic biology. Wikipedia describes it in application terms:Engineers view biology as a technology. Synthetic Biology includes the broad redefinition and expansion of biotechnology, with the ultimate goals of being able to design and build engineered biological systems that process information, manipulate chemicals, fabricate materials and structures, produce energy, provide food, and maintain and enhance human health and our environment.
The idea is to “play Nature,” to reverse-engineer the tangled genetic code of eons and “refactor” it—write fresh genetic code that is manageable, that actually does have intelligent design instead of the infinity of moronic kludges and patches that timeless evolution confers. George Church, a leading molecular geneticist at Harvard, says that biology is at last becoming “an engineering discipline, with interchangeable parts, hierarchical design, interoperable systems, specification sheets—stuff that only an engineer could love.” Rob Carlson reports that the minimalist approach to genome design is paying off: “Most synthetic DNA constructs are usually composed of just a few genes, with cutting edge designs topping out at about 15 genes. Amyris Biotechnologies is using genetic circuits of this size in modified microbes to process sugar into useful compounds, including malaria drugs, jet fuel, diesel, and gasoline analogues.”
In 2008 Craig Venter told an audience in San Francisco how his team took the chromosome from one kind of bacteria, implanted it into another kind, and got it to “boot up” there, totally converting the invaded organism. “This is true identity theft at the ultimate level,” he said, and marveled: “This software builds its own hardware.”
The Stanford bioengineer Drew Endy likes to ask his audiences if they think it would be possible “to reprogram E. coli to smell like wintergreen while growing but like bananas while resting.” If it were possible, what would it take—five students, four months, maybe $25,000? No, in reality it took one hobbyist one day and less than $1,000 to reprogram E. coli to put on an aroma show. In 2001 Endy joined Tom Knight at MIT to start the BioBricks Foundation, which supplies raw materials and tools for creating and adjusting genomes. Undergraduates and hobbyists show off their genetic creations at an annual iGEM (International Genetically Engineered Machine) jamboree. The 2007 iGEM competition attracted 576 participants in fifty-four teams from nineteen countries. Projects included, to quote a report in Slate: self-flavoring and self-coloring yoghurt bacteria; bacteria that mimic the behavior and properties of red blood cells; “infector detector” organisms that indicate the presence of antibioticresistant microbes; a virus that could potentially be used to find and kill breast cancer cells; a living two-cell mercury-detection-and-rem
oval crew for water filtration; and microbes that change color in a pattern meant to mimic fans doing the wave at a Mexican soccer match.
By the next year, 2008, jamboree participants had more than doubled to twelve hundred, in eighty-four teams from twenty-one countries.
Freeman Dyson finds in such jamborees a direct descendent of the annual flower breeders’ show in Philadelphia and reptile breeders’ show in San Diego, where competitors proudly show off new roses, orchids, lizards, and snakes they’ve created. “I predict,” he says, “that the domestication of biotechnology will dominate our lives during the next fifty years at least as much as the domestication of computers has dominated our lives during the previous fifty years.” Dyson is confident that once biotech is freed from the grip of large corporations, it will no longer seem alien or controversial: “In the era of Open Source biology, the magic of genes will be available to anyone with the skill and imagination to use it.”
• The few environmentalists who are paying attention seem unsure whether to join the “synbio” party, ban it, or keep ignoring it. In 2007 Jim Thomas, from the anti-GE group ETC, wrote a survey of synthetic biology titled “Extreme Genetic Engineering.” It is well researched, fair, inclusive, and only moderately alarmist. It does conclude: “In keeping with the Precautionary Principle, ETC Group asserts that—at a minimum—there must be an immediate ban on environmental release of de novo synthetic organisms until wide societal debate and strong governance are in place.” That might have worked if biotech had stayed within a few large corporations under regulatory oversight, but those days are gone. “Every day,” notes Roger Brent of the Molecular Sciences Institute, “in thousands of labs worldwide, genes, mRNAs and proteins, isolated from cells or organisms, are conveyed as bits (via the Internet) or as self-replicating molecules (via Federal Express), and reintroduced into other cells or used to engineer new organisms.”
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