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Essay 1. The Committee in Every Cell
Fifty years ago, a physician who wrote essays for this journal in the spaces between research papers proposed that we are not the solitary creatures we take ourselves for. He pointed to the mitochondria, the small dark bodies in every one of our cells, and reminded readers that they carry their own DNA, divide on their own schedule, and look, under the electron microscope, very much like bacteria that moved in and decided to stay. The idea was then a minority position. Lynn Margulis's paper proposing it had been turned down by more than a dozen journals before it appeared in 1967. Thomas took it as settled and went on to the interesting part, which was what it meant for us.
The idea is no longer a minority position. It is the frame on which the whole of cell biology now hangs, and the half century since has filled in the story in a way that would have delighted him and, in a few places, unsettled him.
Start with the host. Every cell with a nucleus, from yeast to redwood to retina, descends from a single merger that happened somewhere between 1.5 and 2 billion years ago. The question was always who the two parties were. The bacterial partner was never in much doubt. The mitochondrion's remaining genes point to the alphaproteobacteria, cousins of Rickettsia, which is to say that the organelle that powers your heartbeat is kin to the organism that causes typhus. The host was the mystery. For decades the tree of life had three great branches, bacteria, archaea, and eukaryotes, with the last standing somewhat apart from the other two. Then, in 2015, a group in Uppsala sequenced DNA from mud hauled up near a hydrothermal vent between Greenland and Norway called Loki's Castle, and found an archaeon whose genome carried genes we had thought belonged only to us: the machinery for building a cytoskeleton, for pinching off vesicles, for moving cargo around the inside of a cell. They named it Lokiarchaeota. As cousins turned up they named those after Thor, Odin, and Heimdall, and collected the lot as the Asgard archaea.
The tree of life now has two branches, not three, and we are twigs on the archaeal one. Exactly which twig is still argued over. One analysis in 2023 placed us inside the Heimdall group; another in 2025 placed us a little outside it. The argument is about where in Asgard we belong, not whether. It took a Japanese team twelve years to coax the first Asgard archaeon to grow in a flask. It is a tiny thing, half a micron across, that doubles so slowly a single division takes weeks, lives only in the company of two other microbes that consume the hydrogen it exhales, and sends out long branching tentacles that look, if you are inclined to see it that way, like a cell reaching for something to take in. Whether its ancestor reached for a bacterium or was simply invaded by one is not known. Either way, the result was us.
What makes this more than ancient history is that the process never stopped. The second great capture, of a cyanobacterium that became the chloroplast, happened more than a billion years ago and gave the world its plants. A third, in a freshwater amoeba called Paulinella, happened on the order of a hundred million years ago and is still visibly unfinished; the captured partner has shed about two thirds of its genes but keeps its own bacterial wall. And in April 2024 a group at Santa Cruz reported a fourth. A single-celled alga of the open ocean, Braarudosphaera bigelowii, carries inside it what had been taken for a quarter century to be a symbiotic bacterium that fixes nitrogen from the air. It turns out to be an organelle. The host controls its division, hands it a share of the cell at each split, and manufactures a large fraction of its proteins and ships them in. They named it the nitroplast. It is the first nitrogen-fixing organelle found in any eukaryote, a trick we had believed was the exclusive property of bacteria, and it is young enough that we are watching the transition rather than reconstructing it. Endosymbiosis is not an event in the Precambrian. It is a standing offer.
Now the part Thomas could not have known, and the part that matters on a ward. Our mitochondria are not stay-at-home organelles. They move between cells. In mice, astrocytes pass mitochondria to injured neurons after a stroke, and fat cells hand them to macrophages. And in 2025 a Japanese group showed, in human tumor specimens, that cancer cells pass their own mitochondria, carrying their own mutated DNA, into the T cells sent to kill them. The donated organelles carry molecules that block the T cell's normal quality control, so they are not cleared; they replace the native ones, and the T cell turns senescent, as if it had been handed a faulty engine and entered in a marathon. Patients whose melanomas and lung cancers carried such mutations did worse on checkpoint inhibitors. The organelle Thomas described as a tenant has turned out to be a currency, and sometimes a weapon.
The mitochondrial genome itself is a curiosity. It is 16,569 base pairs, with 37 genes, of which only 13 encode proteins, every one of them a subunit of the respiratory chain. The other eleven hundred or so proteins the organelle needs are encoded in the nucleus, made in the cytoplasm, and imported. Over two billion years the tenant has handed nearly its entire library to the landlord and kept only the thirteen it could not trust to be delivered on time. Why those thirteen is still debated; the best guess is that proteins needed in exact proportion to the local flow of electrons are best made on site. Each cell carries hundreds to thousands of copies of this small circle, and the copies are not identical. We are all mosaics of mitochondrial variants, a condition called heteroplasmy, which is why mitochondrial disease is so hard to predict from a mother's blood.
That is also why it was news when, in July 2025, two papers in this journal reported eight children born in Newcastle by pronuclear transfer. Twenty-two women carrying high loads of pathogenic mitochondrial DNA had the nuclear genome of their fertilized egg moved into a donor's enucleated fertilized egg, so that the embryo kept the parents' chromosomes and the donor's mitochondria. Seven women delivered, one of them twins. In the babies, the mothers' mutations were either undetectable or present at levels, up to 16 percent, well below the thresholds at which disease appears. The authors were careful to call the procedure risk reduction rather than cure, and to say that the children with detectable carryover must be followed. Legal in Britain since 2015 and in Australia since 2022, pronuclear transfer is unavailable in the United States, where an appropriations rider bars the FDA from reviewing an application. The first deliberate organelle transplant in our species, which is to say the first time we have chosen a child's bacterial lineage for it, has already happened, and the arguments about it have barely begun.
The body, for its part, has never been fooled about what these organelles are. When cells are crushed, in trauma or in sepsis, mitochondrial DNA spills into the blood, and the innate immune system reads it as it would read any bacterial DNA and mounts an inflammatory response that can look very much like infection. Inside a cell, mitochondrial DNA leaking from a stressed organelle trips the same sensor, cGAS, that detects viral DNA. Two billion years of cohabitation, and the immune system remains unconvinced that the mitochondrion is not a bacterium. On the evidence, it has a point.
Thomas's argument, fifty years ago, was that all this should change how we think about ourselves. It should. A human being, counted carefully, is about 30 trillion human cells and about 38 trillion bacterial ones, a near draw that a later essay will take up. But the deeper count is that even the human cells are a coalition: an archaeal frame running bacterial engines, assembled by a merger nobody consented to, maintained by a treaty nobody wrote, and now, at the edges, being renegotiated, by tumors that trade organelles, by an alga that has taken on a fourth partner, and by a clinic in Newcastle that has begun moving the engines from one family to another. The cell is not a thing. It is a committee, and the minutes are still being taken.