Imagine that an alien penetrated the roof of this building, materializing from a scintillating beam of blue to train a cell gun on you. He, she, or it pulls the trigger. “You” begin to dematerialize. The beam annihilates every human cell in your body. Still, your form, like the recognizable smile of the Cheshire Cat, would persist:
What would remain would be a ghostly image, the skin outlined by a shimmer of bacteria, fungi, round worms, pinworms and various other microbial inhabitants. The gut would appear as a densely packed tube of anaerobic and aerobic bacteria, yeasts, and other microorganisms. Could one look in more detail, viruses of hundreds of kinds would be apparent throughout all tissues. We are far from unique. Any animal or plant would prove to be a similar seething zoo of microbes.4
Life deals in such mixed cultures. It has been working with crowds for billions of years. Most of the DNA of the trillions and trillions of cells in our bodies is not “ours” but belongs to cohabiting bacteria.
Great fleas have little fleas upon their backs to bite ’em,
And little fleas have lesser fleas, and so ad infinitum.
And the great fleas themselves, in turn, have greater fleas to go on;
While these again have greater still, and greater still, and so on.
—Augustus de Morgan, after Jonathan Swift
HYPERSEX AND FRENEMIES
Ten percent of our dry weight is bacteria, but there are ten of “their” cells in our body for every one of “ours,” and we cannot make vitamins K or B12 without them. The maverick Russian geochemist Vladimir Vernadsky thought of life as an impure, colloidal form of water. What we call “human” is also impure, laced with germs. We have met the frenemy, and it is us.
But before leaving this point of the pointillist composition that is our Being made of beings, please notice that even those cells that do not swarm in our guts, on our skin, coming and going, invading pathogenically or aiding probiotically—please notice that even these very central animal cells, the differentiated masses of lung, skin, brain, pancreas, placental, and other would be strictly human tissues that belong to our body proper—even they are infiltrated, adulterated, and packed with Lilliputian others. The mitochondria, for example, that reproduce in your muscles when you work out come from bacteria.
We come messily from a motley. Indeed, we literally come from messmates and morphed diseases, organisms that ate and did not digest one another, and organisms that infected one another and killed each other and formed biochemical truces and merged. About forty genes are shared exclusively by humans and bacteria, suggesting they have been incorporated specifically into our genome.5 Our guts are packed with bacteria whose aggregate microbiogenome has about 150 times more genes than “we” do, 3.3 million to our 23,000.6 But they, though they come and go more easily than the rest of us, changing our mood and food, are also us. The immune system itself seems to be an evolved metasystem, a convoluted go-between, marshaling regulation and inflammation, and making sure that our animal cells and the rest of us—our bacteria and archaea—take it easy on each other.7
Hypersex is a provisional name for the commingling of organisms that meet, eat, engulf, invade, trade genes, acquire genomes, and sometimes permanently merge.8 Life displays mad hospitality. The Korean biologist Kwang Jeon of the University of Tennessee received in the 1970s a batch of amoebas infected with a deadly bacterial strain. Most died. In a set of careful experiments after culturing the survivor amoebas for several generations, he found that the survivors, with fewer bacteria per cell, could no longer live without their infection. Deprived of their new friends and former enemies, the nuclei would not function without micro-injections of bacteria into the cytoplasm. The sickness had become the cure; the pathogens had become organelles; the last had become the first.
Had Jeon, who was a Christian, witnessed speciation in the laboratory? It seems so. But it was not gradual, as neo-Darwinism predicts. It was near-instantaneous, the result not of mutations accumulating in a lineage but of transformative parasitism.
SYMBIOGENETICS
Peculiar behavior, you say? Not really. Considering that life has been growing on Earth for some 3.8 billion years, it is not surprising that life has grown into itself, eaten itself, and merged with itself. Crowd control has long been an issue. Radical solutions have long been the norm. In 2006 researchers at Texas A&M University and the University of Glasgow Veterinary School in Scotland reported in the Proceedings of the National Academy of Sciences that endogenous retroviruses called enJSRVs are essential for attachment of the placenta and therefore pregnancy in sheep. We are as pure as the driven slush.
Like bacteria, viruses “R” us: They have moved into our genomes. Viral structural proteins have been “hijacked” and integrated into mammal reproductive tissues, immune systems, and brains. Some retroviruses disable receptors that lead to infection by other retroviruses. There is no racial, let alone genetic, purity in life. At bottom we are part virus, the offspring not just of our parents but of promiscuous pieces of DNA and RNA. The road to humanity is paved with genetic indiscretions and transgressions, no less than sheep would not be sheep without their acquired enJSRV.
The symbiosis expert Margaret McFall-Ngai asked a roomful of doctors what it meant for our marine ancestors to be surrounded by all those germs—about a hundred million cells per liter. They had no answer, but she told them: She has proposed that the immune system evolved not to eliminate pathogens but to select for symbionts in the microbe-packed waters of our metazoan ancestors.9 The immune system in its origin may thus be more like an employment agency, recruiting desired species, than like a national security state, recognizing and refusing entry to guard the fake purity of the Self.
Today it is widely recognized that the cells of animals were once a wild party of two if not three ancient beings: the oxygen-poisoned archaeon host, the oxygen-using bacteria that became mitochondria, and perhaps wildly squirming spirochetes, which abound in anaerobic environments. These wrigglers often penetrate their fellows, which have no immune systems. They feed at the edges, becoming snaky motors propelling their brethren, or take up residence inside them, wiggling happily ever after.
According to my mother, who’s been right before,10 ancient bacterial symbioses gave our ancestors the intracellular motility abilities we see in mitosis and in the growth of undulating appendages. The creation of new symbioses by mergers on a crowded planet is called symbiogenesis. And we might call all aspects of its study “symbiogenetics”—the science of normative symbioses, the word commanding respect because of its apparent coinage from genetics; in fact, I derived it directly from symbiogenesis, though the connotation is a good one. Although this type of evolution sounds bizarre—a monstrous breach of Platonic etiquette in favor of polymorphous perversity—it is now confirmed by genetic evidence, taught in textbooks. It is a fact, or what the French philosopher of science Bruno Latour and the Belgian physicist-turned-philosopher Isabelle Stengers, not putting too fine a point on it, would call a factish. Nonetheless, although symbiogenesis—the evolution of new species by symbiosis—is now recognized, it is still treated as marginal, applicable to our remote ancestors but not relevant to present-day core evolutionary processes.
This is debatable. We are crisscrossed and cohabited by stranger beings, intimate visitors who affect our behavior, appreciate our warmth, and are in no rush to leave. Like all visible life-forms, we are composites. Near unconditional hospitality is necessary when we consider the sick factish that most of the human genome may be viral DNA.11 Lactating women transfer their six hundred species of bacteria to their babies, as well as oligosaccharides their babies cannot digest but that feed certain bacteria. Bruce Sterling writes science fiction about humans engineered not to have any bacteria, but experiments with real mice deprived of their bacteria developed abnormal levels of immune system cells called invariant natural killer T cells that turned on their hosts, causing higher levels of inflammation, asthma, and inflammatory bowel disease. Although we are
not mice, human studies show that early exposure to antibiotics is associated with asthma. The idea that we need to be pure and free of microbes to be healthy is as medically misguided as eugenicist dreams of triumph through racial homogeneity. Hundreds of species of fungi live in mammal guts despite or because of our immune systems. Indeed, scientists found that immune cells produce dectin-1, a protein that feeds skin fungi of mice; when they engineered the mice not to produce it, the mice experienced tissue damage from excess inflammation. It appears that our immune systems are designed not just to get rid of dangerous strangers but to entice needed others. No notion so disrupts the Pasteurian meme of health through biotic purity as the interest recently generated in fecal transplants, which have been declared safe in treating overgrowth of Clostridium dificile in patients needing to restore gut biota devastated from antibiotics, and are being investigated for the treatment of obesity. Another new medical approach is to develop skin creams that feed beneficial bacteria, warding off pathogens like Staphylococcus aureus.12
Of course these are medical avenues developing within a disease industrial complex that has long been in an emergency mode and makes its money from treatments. But symbiotic partnerships have the possibility not just to restore health but to improve it and alter us, to evolve us into new forms. I can envision future people with harmless luminous patches of bacteria, like tattoos but glowing in the dark, perhaps responding to mood or flashing like fireflies.
Some partnerships are fantastic. Luminous bacteria cram together to provide various marine animals with organs to light their way; deep-sea anglerfish females even use their shiny bacteria lights as lures to catch other fish. Luminescent bacteria, of the species Vibrio fischeri, provide the bobtailed squid, Euprymna scolopes, a nocturnal animal that feeds in the moonlight, so-called counterillumination: it projects light downward from its light organ, so it doesn’t show up as a tasty morsel outlined in silhouette for hungry predatory fish below.
Nestled within the chromosomes of some parasitic wasps lie bacteria. Multiple insect species transform because of Wolbachia bacteria. The genus is nearly ubiquitous in insect tissues. Too big to fit within the sperm of insects, infective Wolbachia can confer parthenogenesis on insect populations, that is, transform a population with two genders into one that is all females, this of course to the advantage of the “selfish” bacteria, as the sperm bottleneck impedes their propagation. By disabling the gender-bending bacteria, antibiotics can make separate species of jewel wasps interbreed again. More bizarre than the space aliens we imagine abducting and toying with us on their saucers, these gender-changing bacteria bring in suites of genes for metabolic and reproductive features as they establish symbioses, often permanent, in arthropods.
WEIRD DALLIANCES AND UNEXPECTED SPECIATIONS
In an unexpected textbook example of speciation, the Columbia University geneticist Theodosius Dobzhansky selected fruit flies for their ability to withstand heat and cold. Dobzhansky found that after two years the heat-adapted flies could no longer successfully fertilize cold-living ones. The two separated populations of Drosophila paulistorium now conformed to the traditional zoological definition of new animal species. They had been reproductively and geographically isolated, and were now only able to breed with their own kind.
However, Wolfgang Miller of the University of Vienna Medical School, Austria, later found that the “cold-fertile fly population” had retained a symbiont widely distributed in certain tissues, whereas the “hot-fertile flies” had been “cured” of the symbiont. In fact, Dobzhansky’s flies evolved as a result of the presence or absence of “mycoplasma,” now recognized to be in the aforementioned genus of Wolbachia. In other words, the presence or absence of a bacterium, not neo-Darwinism’s much-vaunted but still theoretical gradual accumulation of random genetic variations, correlated with what is, besides the Jeon experiments, perhaps the only real-time observed example of a speciation event.
Humanity’s discovery of and battle with pathogenic microbial strains has misled us to think that microbes are generally extraneous to our bodies and health. But increasingly scientists are realizing that we have, we in part are, an adaptive microbiome, the endogenous collection of often “smart” microbes that is not only negatively connected to sickness but positively correlated to warding off obesity, asthma, allergies, and other maladies. Tel Aviv University’s Eugene Rosenberg found that Drosophila pseudoobscura fruit flies would mate only with others on the same diet; antibiotics removed their dietary pickiness, leading to promiscuity and suggesting that possession of specific gut microbes can be like membership in a special club, leading to selective mating and ultimately speciation. And it is likely not just insects. Our symbiotic bacteria are connected to digestion, sense of smell, immunity, and other aspects of physiology. Prokaryotes are part of the hologenome; they are not just hangers-on but genetic actors.13
Such are the new facts—factishes—of life. As genes are not selves, the notion of the selfish gene remains a trope. Selves are materially recursive beings with sentience, and the minimum self seems to be a cell. Because life is an open thermodynamic system, as well as an open informational one, genomic transfer is rampant.
Leaflike green slugs (recently shown to manufacture chlorophyll themselves)14 and underwater snails with rows of green plastids feeding them show how plants and animals can merge. Convoluta roscoffensis does not eat but burrows under the sand of the beaches of Brittany out of harm’s way when the surf pounds (or a research scientist stomps his wading boots); when the danger passes, the animated algae, the green worms, then reemerge into the sunlight. The “planimal” is fed by the green building of its body, the living architecture that it gardens and which feeds it from within.
It seems unlikely that any cosmic deity arranged for the partners that are C. roscoffensis to come together, but they did, partly of their own accord, and they probably would have looked odd anyway on Noah’s Ark.
Identifiable new behaviors, combined skills and physiologies, and even multigenome personalities also affect us. Human gut microbiota are not simply hangers-on but influence the timing of maturation of our intestinal cells, our internal nutrient supplies and distribution, our blood vessel growth, our immune systems, and the levels of cholesterol and other lipids in our blood.15 They also—partly because of the presence of neurons in the mammalian intestinal tract, and the communication between gut and brain—influence human mood. Lab work with Campylobacter jejuni shows that this bacterium increases anxiety in mice, whereas the soil bacterium Mycobacterium vaccae inside them cheers them up. In people it has been suggested that yogurt with live cultures, for example with bifidobacteria, improves our sense of well-being.
TOXO
Toxoplasma gondii is a protist notorious for infecting pregnant mothers who may contract it from kitty litter. From the mother Toxoplasma moves to the fetus, often devouring it and leading to a miscarriage. Toxoplasma gondii sexually reproduces in bodies of members of the Felidae family, notably house cats. But mice, usually afraid of cats, lose their fear when their brains become infected with Toxoplasma. Also, and curiously, they become sexually attracted to feline urine.
Toxoplasma also infects large numbers of humans. Even though a possessor of Toxo may not know it’s there, he or she can be affected by it. Toxoplasma infection in men correlates with enhanced risk taking and jealousy. An index of the risk-taking behavior is provided by the fact that males in car and motorcycle accidents are more likely to test Toxoplasma-positive.16 Toxo-men are more likely to be unfriendly, unsociable, and withdrawn. Even if bereft of obvious symptoms, men who carry Toxoplasma are less likely, relative to controls, to be found attractive to women.
Women are another story. Women with Toxoplasma are more likely to be judged outgoing, friendly, and conscientious—and promiscuous. There is, of course, the complication of the stereotype of the woman who lives alone with all the cats. The caricature of such a woman is not of someone outgoing. Perhaps Toxo’s effects alter with age.
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However confounding, Toxo’s effects seem real. Toxoplasma makes enzymes (tyrosine hydroxylase, phenylalanine hydroxylase) that alter brain levels of the neurotransmitter dopamine. Dopamine is a neurotransmitter involved in attention, sociability, and sleep. Cocaine and amphetamines work in large part by blocking the reuptake of dopamine in the brain. Dysfunctional dopamine regulation is theorized to be linked to schizophrenia, and several antipsychotic drugs target dopamine receptors. Up to one-third of the world population is thought to be infected with Toxo, with an estimated infection rate of almost 90 percent in France—a result perhaps of their love of rare beef, steak tartare or saignant, “bleeding.” More alarmingly still, the Czech scientist Jaroslav Flegr found via MRI scans that twelve of forty-four schizophrenia patients showed significant shrinkage of the cerebral cortex, but that the reduction in gray matter of the schizophrenics was almost completely correlated with those who tested positive for T. gondii.17 Toxo, accounting for a range of effects and affects from increased sexual attractiveness and feelings of well-being to full-on mental dysfunction, appears to be a facultative part of our more-than-human hologenome.
We have other “inner aliens.” Candida albicans is the yeast fungus that causes vaginal infections and perlèche, a cracking at the corners of the lips. It thrives on easily digestible sugars and carbohydrates such as those found in beer, wine, cracker crumbs, and confections. It was perhaps spread among the wine-drinking revelers of Provence, troubadours who sang and jested, and who may have used makeup as a way to cover cracked lips that literally hurt when they smiled.18
Spirochetes are a stranger case still. Disease species cause Lyme disease and syphilis, and also other conditions. Spirochetes can go into hiding and form “round bodies,” becoming virtually undetectable in cells. Friedrich Nietzsche and others are thought to have been infected by syphilis, whose “tertiary stage” is sometimes marked by a strange clarity of expression and artistic genius as well as madness.
Cosmic Apprentice: Dispatches from the Edges of Science Page 3