Lynn Margulis was a forceful 29-year-old adjunct assistant professor from Chicago, divorced and raising two kids, when she brought new attention and credibility to a very strange old idea about the shape of the tree of life. She made her case, in March 1967, with a long paper published in the Journal of Theoretical Biology and titled “On the Origin of Mitosing Cells.” This radical, startling, and ambitious article—previously rejected by more than a dozen journals—proposed to rewrite two billion years of evolutionary history. It laid out an array of evidence supporting the odd conjecture that living ghosts of other life-forms exist and perform functions inside our very own cells. Adopting an earlier term, Margulis called that idea endosymbiosis.

It was the first recognized version of horizontal gene transfer. In these cases, rare but consequential, whole genomes of living organisms—not just individual genes or small clusters—had gone sideways and been captured within other organisms.

The phrase “mitosing cells” in the paper’s title is another way of saying eukaryotic cells, the ones with nuclei and other complex internal structures, the ones that compose all animals and plants and fungi. But the key word in Margulis’s title was “origin.”

“This paper presents a theory,” she wrote—a theory proposing that “the eukaryotic cell is the result of the evolution of ancient symbioses.” Single-celled creatures had entered into other single-celled creatures, like food within stomachs, or like infections within hosts, and by happenstance and overlapping interests, at least a few such pairings had achieved lasting compatibility.

Eventually they became more than partners. The internalized microbes, she argued, had evolved into organelles—working components of a new, composite whole, like the liver or spleen inside a human—with fancy names and distinct functions: mitochondria, chloroplasts, centrioles. They were functional elements of a single new being. A new kind of cell.

The scientific consensus at first, and for some years afterward, was that this smart, knowledgeable, insistent, and charming young woman was in thrall of a loony idea. But eventually the emerging science of molecular phylogenetics confirmed most of her theory of endosymbiosis (mitochondria and chloroplasts as captured bacteria, yes). Margulis became eminent, though never conventional.

As new evidence of horizontal gene transfer continued to accumulate during the 1990s, she and other biologists started questioning the belief that the evolutionary pattern is a tree. “It’s not,” Margulis told a reporter in 2011. “The evolutionary pattern is a web—the branches fuse.”

She was right: the tree of life is not perfectly tree-shaped. There’s something spooky and unnatural about any tree whose limbs grow together, sometimes, rather than always branching apart.

Two years after Margulis published her first provocative paper, challenging the total separation of the prokaryote kingdom (bacteria, lacking nuclei) and the eukaryote kingdom (all other cellular life, including animals and plants), another contrarian scientist embarked on an equally bold quest—to “unravel the course of events” leading to the origin of the simplest cells. His name was Carl Woese. He was an obscure microbiologist at the University of Illinois. In 1969, he confided in a letter to Francis Crick that he hoped to extend the understanding of evolution “backward in time by a billion years or so,” by “using the cell’s ‘internal fossil record’ ” as contained in DNA and RNA. Some years later, Woese’s work would trigger the revolution in molecular phylogenetics and lead to a drastic redrawing of the tree of life, from its roots to its crown.

By 1976, Woese and his team were doing RNA “fingerprinting” of various life forms, including methanogens—microbes that generate swamp gas in muddy wetlands and similar gas in the bellies of cows. Certain bits of structural RNA are built into all life, and the biologists sequenced those pieces, fragment by fragment, and then compared the collections of fragments between one creature and another.

Methanogens were hard to grow in a laboratory, since oxygen poisoned them, but Woese’s collaborators managed it. Under a microscope, these methanogens looked like bacteria. For centuries, they had been considered bacteria. But as Woese examined the fingerprints, he found anomalies. A certain pair of small fragments, common to all bacteria, were missing. Other sequences looked eukaryotic, suggesting a completely distinct form of life: a yeast, a protozoan, what? And still others were just weird.

What was this RNA? Woese wondered, and what manner of organism did it represent? It couldn’t be from a prokaryote. It wasn’t eukaryotic. It wasn’t from Mars, because it contained too many familiar stretches of RNA code.

“Then it dawned on me,” he later wrote. There was “something out there”—out there in the teeming ecosystems of planet Earth, he meant—other than prokaryotes and eukaryotes. A third form of life, separate. A third kingdom. In their seminal 1977 paper on the discovery, published in the Proceedings of the National Academy of Sciences (PNAS), Woese and his postdoc and coauthor, George Fox, gave their kingdom a tentative name: archaebacteria.

The name was misleading, a wrong choice, and would later be changed. It suggested ancient bacteria. By 1990, Woese and other scientists recognized that these creatures weren’t bacterial precursors nor ancient bacterial forms. Bacteria weren’t even their nearest kin. Some evidence had emerged, in fact, that archaea were more closely related to eukaryotes—more closely related to us—than to bacteria. So Woese and two other scientists wrote another paper for PNAS, proposing that there should be three major divisions of life, higher in rank than kingdoms, and those divisions should be domains, which would henceforth be known as the Bacteria, the Eukarya, and the Archaea. The word archaebacteria should now disappear, the authors argued. So should the word prokaryote. Prokaryotes didn’t exist as a phylogenetic category—it was a false unit—because Archaea and Bacteria stood so utterly distinct from each other.

And, of course, there was a tree. It was drawn in straight, simple lines, but it was rich and provocative nonetheless. This diagram asserted what Woese’s RNA fingerprint data showed: that we humans, and all other animals, all plants, all fungi, all eukaryotes, have arisen from an ancestral lineage that was unknown to science before 1977. It was the last of the great classical trees: authoritative, profound, completely new to science, and correct to some degree. But it entirely missed what was coming next.

What came next was an exploding awareness of the role played by horizontal gene transfer in this whole story. That explosion occurred during the 1990s but had deep precedents. The first recognition by science that any such thing might be possible dates to work published in 1928 by an Englishman named Fred Griffith. No one at the time, not even Griffith himself, saw the implications of what he had found.

As a medical officer at the London Pathological Laboratory of Britain’s Ministry of Health, Griffith studied what’s now known as Streptococcus pneumoniae, a dangerous bug that could cause severe, often fatal, pneumonia. During the 1918–19 influenza pandemic, this kind of pneumonia took hold as a secondary infection in many patients and probably killed more millions of people than the flu virus itself.

Griffith’s work, which was pragmatically medical, involved identifying the different types of the streptococcus—there were four—in different patients and parts of the country. He got his data by examining sputum coughed from the lungs of the ill. In 1923, he discovered something important: that each of the four types of the bacterium existed in two different forms—one that was ferociously virulent, one that was mild. Sometimes the virulent form might transmogrify into the mild form, he noticed. He didn’t know why.

His second discovery was far more puzzling: Under certain experimental circumstances, the mild form of, say, Type II bacteria could change into the virulent form of, say, Type I. What? It seemed as though the streptococcus had morphed into a different species.