Microcosm

by Carl Zimmer

  Our intuitive biology fails us when we try to understand E. coli, and it also fails us when we try to understand ourselves. Like all other living species, humans are the product of evolution. If we weren’t, the entire controversy over biotechnology would not exist in the first place. If human nature were truly distinct, it would be impossible to plug human genes so easily into E. coli or to grow human brain cells in a mouse’s skull. The essence of being human is as much a construction of our minds as the essence of E. coli.

  New research on human evolution makes it impossible to believe that a thing either is or is not a whole human being, as Robert George has claimed. Consider a gene called microcephalin. There are several versions of the gene floating around our species, but one is far more common than the others, found in 70 percent of all people on Earth. Scientists at the University of Chicago decided to trace the history of this version of microcephalin. They found compelling evidence that it entered the human genome long after Homo sapiens had evolved.

  About half a million years ago, our ancestors split off from the ancestors of Neanderthals. The split probably occurred in Africa. Afterward, the ancestors of Neanderthals spread across Europe, while the forerunners of our species stayed behind in Africa. Homo sapiens evolved about 200,000 years ago. It was only after our species emerged that humans evolved full-blown language, abstract thought, the capacity for art, and many of the other qualities that are at the core of what we call human nature.

  About 40,000 years ago, Homo sapiens expanded their range into Europe. And there humans encountered Neanderthals. Neanderthals became extinct about 28,000 years ago, but it appears that before they disappeared they interbred with humans. Most of their genes disappeared over the generations, but at least one survived: their version of microcephalin. It didn’t just survive, in fact—it spread like wildfire. Something about it was strongly favored by natural selection, with the result that it now can be found in the majority of humans alive today. And microcephalin isn’t some minor gene for growing nose hair or coloring toenails. It plays a central role in the development of the brain. Thanks to natural engineering, most humans carry this nonhuman gene, which is involved in building that most human of organs, the brain. By George’s reasoning, most humans are not human.

  Hybridization is not the only way foreign DNA got into our cells. Some 3 billion years ago our single-celled ancestors engulfed oxygen-breathing bacteria, which became the mitochondria on which we depend. And, like E. coli, our genomes have taken in virus upon virus. Scientists have identified more than 98,000 viruses in the human genome, along with the mutant vestiges of 150,000 others. Some have donated their DNA to our own biology, such as the placenta. If we were to strip out all our transgenic DNA, we would become extinct. Some of these viruses inserted copies of themselves after our split from chimpanzees. Some are found in Asians and Europeans but not in Africans, suggesting that they infected the human genome only after some humans emerged from Africa 50,000 years ago. When people acquired this foreign DNA, did they lose their human nature?

  It is awkward to think this way. It feels unnatural. The unnaturalness is in the workings of our minds, however, not in nature. But we will probably get used to it, in the same way we have gotten used to thinking of matter as being made up of subatomic particles. Our repugnance toward breaches in the species barrier and toward the modification of genes is shifting even now. The lack of angry mobs trying to burn down insulin-producing factories to preserve the natural order of things is proof of that.

  This sort of change may well disturb a critic like Leon Kass. In 1997, he testified before Congress in favor of a ban on human cloning, declaring, “In a world whose once-given natural boundaries are blurred by technological change and whose moral boundaries are seemingly up for grabs, it is, I believe, much more difficult than it once was to make persuasive the still compelling case against human cloning. As Raskolnikov put it, ‘Man gets used to everything, the beast!’”

  There’s a contradiction here. On the one hand, our wisdom of repugnance is supposed to be a deeply anchored, reliable guide to what is fundamentally right and wrong—not what happens to be right and wrong this afternoon. On the other hand, Kass is angry that this sort of repugnance can disappear as times change. It’s hard to see how he can have it both ways.

  We can be overwhelmed by our emotional reactions to scientific advances. In some cases, we eventually recognize that we were probably right—or wrong—to have those feelings. In other cases, our perception of essences triggers feelings of disgust when those essences seem to be corrupted. That disgust may be triggered by E. coli carrying human genes, or in vitro fertilization, or a person receiving a heart valve from a pig. But as we come to recognize the benefits or risks of those developments, as we see the world not coming to a Pandora’s-box end, our sense of disgust fades.

  We don’t become Dostoyevskian beasts along the way, though. With the advent of organ transplants, we did not slide down a slippery slope into a world in which paraplegics have their livers yanked out against their will. There are certainly new choices to make—to allow the sale of organs or not, for example—but we continue to make them seriously.

  Chimeras and various sorts of genetic engineering will become more common, but they will not, I suspect, produce a moral meltdown. For one thing, a lot of the most startling nightmare scenarios we hear about today have little basis in science. Mice with human neurons will not cry out, “Help me, help me!” There is much more to being human than possessing a peanut-sized clump of neurons. Yet we may decide that engineering such a mouse is cruel to the animal itself. (Repugnance at cruelty toward animals is actually a new sort of disgust many people have acquired, rather than lost, over the past 200 years.) And some chimeras will probably be banned because the challenges they pose to our moral treatment of humans and animals don’t justify the procedure.

  I suspect—or at least I hope—that as we make these decisions, we will come to a deeper understanding of what it means to be human: not as an inviolable essence but as a complex cloud of genes, traits, environmental influences, and cultural forces. If we do gain this wisdom, it may turn out to be the most important gift E. coli has given us.

  Eleven

  N EQUALS 1

  I AM STANDING IN MY YARD on a winter night, looking up at a few bright stars asserting themselves against a gibbous moon. I hold up a petri dish of E. coli against the sky. The moonlight shines through the leafless maples into the agar. It gives the colonies a cool, cloudy glow. They look like worlds and stars. I have reached the final question about E. coli, a twist on Monod’s old boast. Is everything that is true for E. coli true for an alien?

  One night in October 1957, Joshua Lederberg looked up at the stars as well. He was in Australia, where he was spending a sabbatical. Lederberg was only thirty-two at the time, but he had more than a decade of research behind him, for which he would win a Nobel Prize the following year. He had done most of that work on E. coli. He had discovered that the microbe had sex, and he had used its sex life to draw some of the first maps of its genes. He and his wife had confirmed that genes mutate spontaneously, helping to bring Darwin into the molecular age. They had discovered viruses that could merge into their E. coli hosts. Thanks in large part to Lederberg, E. coli was becoming the standard tool for studying the molecular basis of life, and other scientists were beginning to use it to translate the genetic code.

  Now Lederberg was restless. He had come to Australia, to the University of Melbourne, to study the immune system. White blood cells learn to recognize bacteria and other parasites, but they don’t use ordinary genes to encode those lessons. No one at the time knew what language they used. Lederberg would return to the United States recharged, but white blood cells would not be his obsession. Instead, it would be space.

  On that night in the Australian spring, Lederberg had gazed up at a moving point of light. It was not a star or even a meteorite but a steel ball hurled into space by humans. Lederberg had a hunch that
the Soviet Union’s launch of the first Sputnik satellite was going to change the world.

  Lederberg saw in space travel a new frontier for molecular biology. He and other molecular biologists were in the midst of discovering just how uniform life on Earth actually is. E. coli and elephants both encode genes with DNA, both use RNA to carry that information to ribosomes, and both use the same genetic code to translate it into proteins. The uniformity of life was a staggering discovery, Lederberg later wrote, “but its domain has been limited to the thin shell of our own planet, to the way in which one spark of life has illuminated one speck in the cosmos.” Only by going to other worlds would scientists be able to learn whether a similar kind of life had emerged beyond Earth.

  Lederberg worried that this awesome opportunity would be ruined if the United States and the Soviet Union ended up in a heedless race into space. In their rush to plant a flag on the moon or Mars, they might contaminate other worlds with microbes from Earth. When Lederberg returned to the United States, he began to lobby the newly formed National Aeronautics and Space Administration to treat outer space like a petri dish, to be kept free of contamination.

  He quickly organized meetings at which scientists debated the potential risks of space travel. Unless special precautions were taken, they agreed, a visit to another planet would inevitably leave bacteria there. An astronaut would be “a teeming reservoir of microbial contamination,” as Lederberg wrote. Unmanned probes might pick up millions of bacteria from their human engineers, which they could carry to another world.

  A 1959 panel of scientists tried to imagine what would happen if a single E. coli arrived on a planet devoid of life but rich in organic carbon. “The common bacterium Escherichia coli has a mass of 10-12 grams and a minimum fission interval of 30 minutes,” they wrote. “At this rate it would take 66 hours for the progeny of one bacterium to reach the mass of the Earth. The example illustrates that a biological explosion could completely destroy the remains of prebiological synthesis.”

  Lederberg’s efforts ultimately led to an agreement between the United States and the Soviet Union on standards for sterilizing spacecraft. Yet Lederberg became famous not for his worries about contaminating other planets but for his worries about the return trip. If life did exist on other worlds, a spacecraft coming back to Earth might accidentally carry some of it home. Alien microbes might wreak havoc on our planet. They might cause a global plague or trigger a famine by attacking crops.

  “The fate of mankind could be at stake,” Lederberg warned. Soon reporters were describing the dire warnings of the Nobel Prize–winning biologist, using headlines such as “Invasion from Mars? Microbes!” A version of Lederberg even ended up in the 1971 science-fiction movie The Andromeda Strain: the intrepid biologist desperately trying to find a cure for a virus from outer space.

  For all his worries, however, Lederberg did not want to seal off the sky. At NASA’s invitation, he set up a laboratory at Stanford University to begin building a device that could detect signs of life on another planet. In some ways the work was mundane. Lederberg and his colleagues tinkered with conveyor belts and mass spectrometers. But they also faced a profound question, less scientific than philosophical: How can you search for life you’ve never seen? The question, Lederberg decided, required a new branch of biology all its own. He dubbed it exobiology, the biology of life beyond Earth.

  The goal of exobiology was to discover whether life has begun more than once in the universe and whether it has taken more than one form. Does life have to use DNA? Does it have to build its cells from protein? Is there something about these molecules that suits them to life, something no other combination of atoms can possibly have? “These questions might be answered in two ways,” Lederberg wrote. “Presumptuous man might mimic primitive life by imitating Nature, furnishing substitute compounds. More humbly, he might ask Nature the outcome of its own experiments at life, as they might be manifest on other globes in the solar system.”

  Looking for unearthly forms of life would be difficult because scientists could not predict what they might find. Lederberg felt content starting off with a more conventional search. “We can defer our concern for such exotic biological systems until we have got full value from our searches for the more familiar,” he wrote.

  NASA agreed. The agency would search for the familiar, and it would search for it on Mars. Mars was just enough like Earth to offer some hope of harboring life. In 1965, Mariner 4 became the first probe to send back detailed pictures of the surface of Mars. It revealed a bleak landscape, pocked with craters and devoid of forests and other signs of life. If life did exist on Mars, it probably just consisted of microbes. NASA used the pictures from Mariner 4 and later probes to design a mission to land a probe on the surface of Mars. On July 20, 1976, nineteen years after Lederberg watched the first satellite rise from Earth, Viking 1 became the first probe to land on another planet.

  Sadly, the mission was generally agreed to be a bust. Viking 1 found no signs of organisms that could convert carbon dioxide to organic carbon. Some kinds of terrestrial life, such as E. coli, consume organic carbon and release carbon dioxide as waste, but Viking found no trace of this metabolism either. One last experiment remained, a final court of appeals. Viking scooped up soil, heated it up to liberate molecules, and then fired them down a tube, where they could be measured. The probe could detect no organic carbon in the Martian soil whatsoever. This result was devastating, because life has created huge amounts of organic carbon on Earth, not just in the bodies of living things but in the waste they leave behind.

  “That’s the ball game,” said Gerald Soffen, the Viking project scientist. “No organics on Mars. No life on Mars.”

  It appeared that the surface of Mars was far harsher than scientists had reckoned. Ultraviolet light and highly reactive chemicals such as hydrogen peroxide quickly destroyed any organic carbon. The chances of life on Mars seemed low or nil. Lederberg was more optimistic than some of his colleagues, but not by much. It was possible that life on Mars existed only in a few oases, perhaps around hot springs bubbling up from the interior of the planet. But if there was life on Mars, it was far more retiring than the boisterous, all-consuming life on Earth. “We can no longer be confident that no matter where you look you will find life,” Lederberg told reporters.

  Viking’s failure was no reason to stop looking for life, Lederberg and others believed. They urged NASA to put together a “son of Viking”—a new probe that could take a new set of instruments to Mars. But NASA was more interested in astronauts, those teeming reservoirs of E. coli. As support for exobiology faded, Lederberg returned to other pressing issues in biology, such as the emergence of new diseases and the threat of biological warfare. His days of professional stargazing were over.

  Twenty years later, NASA’s interest in extraterrestrial life grew again. A meteorite from Mars bore strange markings that some scientists suggested were fossils of microbes. The Galileo probe passed by Europa, a moon of Jupiter, and captured images of the ice covering its surface. Perhaps life was lurking underneath. The search for life—now called astrobiology—found new support from NASA, which founded the NASA Astrobiology Institute in 1998.

  Today many astrobiologists search for extreme places on Earth where life manages to survive. E. coli is a rugged creature, but scientists have found many other organisms that live in places where it would quickly die: acid-drenched mine shafts, oxygen-free swamp bottoms, the depths of glaciers, superheated water shooting out of hydrothermal vents, the spaces inside crystals of salt. Planets and moons with similar environments might be suitable homes for life.

  But as weird as some new species may be, they all share E. coli’s fundamental features. They are membranes wrapped around proteins and DNA. They need sources of carbon and energy in order to grow. And they need liquid water as a medium in which their chemistry can take place. If some of these rugged microbes were carried to an underground hydrothermal system on Mars or perhaps slipped beneath th
e icy crust of Europa, they might be able to eke out an existence.

  Yet scientists are also keenly aware that life on Earth may not be the rule for life in the universe. Our own tinkering with life has made that clear. Expanding E. coli’s genetic code does not kill it, so there’s no reason to think that life on other planets couldn’t use other amino acids to build its proteins. All life on Earth uses the four-letter language of bases to encode information in its genes. But scientists have been able to engineer E. coli with man-made bases—in other words, adding new letters to its alphabet. Synthetic biology blurs into astrobiology.

  Life might not even need DNA. Some experiments have suggested that other molecules can take on the same structure, with a backbone carrying information-bearing compounds. They might even be able to replicate themselves accurately. Scientists have even speculated that life may be able to exist without liquid water. Another liquid, such as liquid methane, might serve as its matrix.

  No matter what extraterrestrial life might be made of, our discovery of it would change how we think about life in general. It would finally give scientists more than one planet’s worth of life with which to search for the rules of existence. Scientists would probably start studying alien life at its lowest levels, trying to determine how it stores genetic information. But some of the most interesting comparisons would come later. Living things on Earth have more in common than DNA. E. coli and elephants alike can survive in a changing world thanks to the robust wiring of their genetic circuits. Natural selection shapes their life spans and drives their complex social life, filled with sacrifice and deception. Barriers slice life up into individual organisms, but viruses weave them together in a genetic matrix. Alien life would let us see just how universal these features are.