Two years ago a New Scientist headline announced the “world’s first baby born with new ‘3 parent’ technique.” Whereas an embryo is usually produced by one sperm and one egg, this technique uses genetic material from three separate people. First performed by a New York fertility clinic in Mexico to evade US legal restrictions, the procedure has now been replicated several times. A clinic in Ukraine started offering a similar procedure in late 2016 (albeit on shaky ethical and medical grounds), while regulatory authorities in the United Kingdom approved its use for two women earlier this year.
The cases in the UK and Mexico each involve a woman who carries a rare disease of her mitochondria, the cellular structures that produce energy in our cells. Mitochondria have their own DNA and can harbor their own genetic diseases. These are passed on solely through the maternal line—mitochondria are transmitted down by eggs but not sperm. One approach to blocking transmission of these illnesses involves inserting the DNA-filled nucleus from the egg of the woman into a donor egg full of healthy mitochondria but stripped of its own nucleus. Fertilize that hybrid egg with a sperm, and presto! A child could be born nine months later with DNA from three people and without a catastrophic mitochondrial disorder.
This result could be a blessing—but the science behind it sounds confusing. Isn’t DNA supposed to be our sacred blueprint, wound up in chromosomes and locked up safely in the nucleus of our cells? What are these mitochondrial creatures doing with their own DNA, replicating within our cells and bequeathing diseases to our offspring? If they seem like invaders, it’s because they once were. Mitochondria, it turns out, were originally bacteria; their free-wheeling existence came to an end one day deep in evolutionary history when they entered another single-celled organism and started a new life inside. That receiving cell was the ancestor of all animals, plants, fungi, and protists. The origin of the mitochondria is reflected in the basic shape of its DNA: It is looped in a simple circle, just like a bacteria’s, unlike the linear chromosomes found in our nuclei.
Children conceived with a third person’s mitochondria are, it follows, the offspring of three parents, but the third parent is, in at least some sense, the descendant of an ancient bacteria. After those bacteria took up residence in our common ancestor, they proceeded to swap genetic material with the nucleus, further blurring the boundaries between host and invader, self and other over the eons.
This is not what we think of as Darwinian evolution, the transmission of genes and traits down the family line. DNA, it turns out, can also be passed laterally, between individuals, including those of different species. This discovery represented a tectonic shift in our understanding of nature, a story that David Quammen tells wonderfully in his exhaustively researched book, Tangled Tree: A Radical New History of Life. Crisscrossing the country to interview scientists and visit labs, Quammen provides a vivid portrait of the scientific process, and of the quarrelsome, quirky, (in one instance) evil, and brilliant scientists behind it. We may like to think of DNA as the neat bequest of our parents, the fusion of two unique, circumscribed human lineages. Yet it is—and we are—something more: short strands within a vast interwoven genetic web, stretching back to the earth’s earliest days, linking all living things.
Quammen’s story starts with Charles Darwin, who—well before publishing On the Origin of Species—jotted down a historic sentiment in a notebook: “organized beings represent a tree.” Although it was a long-established concept (it had precursors in both the bible and Aristotle), Darwin’s version “was a thunderous assertion, abstract but eloquent.” His Tree of Life suggested a common ancestor at the tree’s trunk and ever-dividing branches leading from it to new species. It became the standard pictorial representation of evolution until, as Quammen notes, “a small group of scientists would discover: oops, no, it’s wrong.”
One important strand in this story was the discovery of endosymbiosis: the fact that mitochondria—together with chloroplasts, the structures in plant cells that convert sunlight into food—were once bacteria that started a new life within our cellular forefathers. One of the theory’s earliest and most influential proponents, as Quammen tells it, was a nefarious Russian scientist named Constantin Sergeyevich Merezhkowsky. Merezhkowsky fled from the Crimea in 1898, likely because he was a child molester, and wound up in California, where he studied a single-celled alga that performed photosynthesis (while writing some bizarre science fiction on the side). His work led him to embrace the (unproven) hypothesis that chloroplasts in the algae were, in fact, ancient invaders. He would commit suicide in 1921 in a hotel room in Geneva, but his theory lived on, in obscurity.
It was revived decades later by a prominent, controversial scientist named Lynn Margulis. In 1970, Margulis published a book, Origin of Eukaryotic Cells, that expounded a modern version of endosymbiosis. Some saw her theory as brilliant, while others, Quammen writes, “thought she was nuts.” She was ultimately proven right, by another scientist, Fred Doolittle, in Nova Scotia. He and his collaborators analyzed an ancient cellular structure called the ribosome (responsible for building all the cell’s proteins) to prove that both chloroplasts and mitochondria were indeed “foreign” species. They, in turn, relied on techniques innovated by the main character of the book, the complicated, conservative, and grudge-bearing Carl Woese of the University of Illinois.
Woese was a scientist who helped radically redraw the “Tree of Life” like perhaps no other in the twentieth century. Among other things, he and colleagues “discovered” that there was an entirely new type of life known as the “archaea.” Even Woese, however, was mostly left behind by the next big paradigm shift—the discovery of “horizontal gene transfer.”
Horizontal gene transfer gives us new ways of understanding many phenomena. One is the rise of antibiotic-resistant bacteria. When treating a serious infection, physicians will typically send a sample—whether of pus, phlegm, urine, or blood—to the laboratory. Within a couple of days, a report comes back, with the name of the bacteria and a list of what can be used to kill it. Next to each antibiotic on the list will be one of three letters: S (“sensitive”), I (“intermediate”), or R (“resistant”). Depending on the bacteria, there may be mostly S’s, but sometimes a glance at the report produces a queasy sensation. Perhaps there are very few S’s; maybe, there is none.
Darwinian evolution, of course, can explain the rise of antibiotic-resistant bugs. It happens like this. A colony of bacteria gets doused in a deadly antibiotic. Amidst the die off, one bacterium has a lucky mutation that, say, lets it manufacture a molecule that can pump the antibiotic safely out of its cytoplasm into the surrounding slime. That lucky guy thrives and divides and replaces its massacred brethren, and gives rise to a new and nastier colony impervious to the antibiotic. Or as Darwin cheerfully put it On the Origin of Species, “the vigorous, the healthy, and the happy survive and multiply.”
So far so good, for the bacteria
anyway. But unfortunately for us (and unknown to Darwin), bacteria possess
another means to acquire antibiotic resistance without having to sit around
waiting for the next lucky mutation: They can swap genes the way we share
recipes. When one bacterium rolls up close to another—not necessarily even of
the same species—it can share a chromosome containing a slew of genes with,
say, an enzyme that can smash penicillin into pieces.
Horizontal gene transfer is much more than a way for bacteria to share antibiotic resistance genes; it happens throughout nature and in the history of living things. We are all, for instance, partially viruses in a sense: Eight percent of the human genome arrived to us from the outside, from retroviruses, as Quammen notes. Various studies suggest that many of our genes were acquired, horizontally, from bacteria. Life, in other words, is not just a history of divergence, of the sprouting of new forms from a solid trunk. Sometimes, life converges. From this perspective, those three-parent children are no more unusual than you are or I am.
Ultimately The Tree of Life is merely a metaphor, but I think a pleasant one: It connects us to the lineage of all living things, all the way back to the bag of chemicals—or maybe the single molecule—that one day coalesced in the primordial muck. Yet like all metaphors, the “tree” falls short of reality. For in biology, all boundaries are blurred: between species, sometimes even between individual organisms, and probably between the living and the non-living.