On November 22nd, 2011 Lynn Margulis died. Last week Carl Woese died. In their deaths, we lost two of the most radical visionaries of a generations, of several generations really. Last week I posted an updated section from my book, Every Living Thing, about the work of Woese. This week I’ve uploaded the companion story about Lynn Margulis. Though they disagreed with each other, the fates of these two researchers and the truths they revealed were, in many ways, linked. 

The only real valuable thing is intuition.—”Einstein

When I was an undergraduate, two theories were held up for ridicule, to show how farfetched scientific theories can get. One was the theory of continental drift and the other was the symbiotic theory of the origin of the cell.” –William Culberson, professor of Botany at Duke University.

In the summer of 1912, not far from their house in the French Pyrenees, three boys found a cave. They were experienced at exploring; it occupied their free hours, and so they decided to go in. As they did, they came to a small cliff that they climbed until they reached a wide cave gallery. Within the gallery, they found a passage that left the cave like a chimney. The chimney tunnel extended further in its narrowness than they might have hoped. The reasonable response would have been to turn back, yet they pressed deeper. Their shoulders and chests grew so tight that at times it was difficult to breathe. They climbed until they arrived at a place where stalactites blocked their progress. Again, they might have stopped, but they were boys and they could see something on the other side, some further chamber, and so they chipped at one of the pillars and then made their way through. As the anthropologist Lawrence Robbins wrote of what happened next, “they slipped into the unknown, entering a part of the cave that was last seen by humans in he Ice Age.” The tunnel opened into an enormous gallery. The boys were sweaty, exhilarated, and happy to have come through intact. Soon they were speechless, beyond excitement. They could not see well, but in the sweep of their light they found the claw marks of cave bears, bones of large animals, and then footprints that they would later learn were more than 10,000 years old. Then, further down the cave, they saw what was to be their biggest discovery, four, upright clay bison, each the size of a small dog and more than 15,000 years old, pointed as though ready to charge. The boys stood silent. Eventually they hugged, climbed back up through the tunnel, and told the world.

This is how we imagine science. We climb through a hole into a new chamber of the world, laugh, weep, and then the New York Times calls. What the biologist Lynn Margulis would come to believe she had discovered was not unlike a cave full of art. It was a set of signs written within a cell’s walls. She read them and understood. She came out of the cave and announced her finding. Then things departed from the script. No one believed her.

Lynn Margulis was born in a working class neighborhood on the South Side of Chicago where she used to “romp along the connected rooftops and fire escapes of Chicago’s second city of garages.” From an early age, she saw the world from a different, more rarified, perspective. The oldest of four sisters, she grew up tough and responsible. She also grew up, photos and friends combine to attest, beautiful and brilliant. In 1952, at age 14, she went to college at the University of Chicago. It was there that she would find science and, on the stairwell of Eckhart Hall, the boy who would become her first husband. In just a few years, she would begin to pursue science and raise a family. Things from then on would happen quickly. She graduated from the University of Chicago and enrolled in a master’s degree program at the University of Wisconsin where she began her studies while pregnant. She slept through classes as she nourished both ideas and her first son. She was a woman working in what was still a “man’s field.” Her world was filled with hurdles that, without slowing down, she leapt.

Mid‐way through her master’s degree, Margulis looked at amoebas through the microscope for the first time. Margulis had been taught to trust little beyond her own observations, whether those be observations of old, ignored books or, in this case, cells. As she observed these particular cells she was struck by their tiny organs (technically “organelles”). She looked into the amoebas and found important details. Here was the mitochondria, the cell’s powerhouse; in among the other organs of the cell, the nucleus, the cell’s brain; the vacuoles, the cells’ garbage piles. In plant cells, there were chloroplasts, the machinery that harnesses all of the sunlight that we ultimately eat. On the cells’ surface were the beating flagella, the waggling, legs and arms. Under the microscope she found for herself the simple structures responsible for life, the blocks out of which we are all made. Lynn Margulis had not yet discovered anything. She had seen the tunnels and caves of the cell and in them, signs of other chambers, and in them new discoveries. The cells’ organs had been studied for centuries. The shape of these structures and aspects of their function was thought to be relatively well‐known by the time Margulis began to work. Less considered was the origin of these structures, how from something simpler they evolved.

In the early days of cell biology, there were more vague notions than facts. One of those vague notions was that there might be DNA outside of the nucleus in the cytoplasm, the jellylike fluid of the cell in which the organelles float. While Margulis was a master’s student at the University of Wisconsin, she and one of her professors, Hans Ris, had talked about the implications of the DNA in the cytoplasm. No one knew why DNA should be in the cytoplasm nor for sure that it was there at all, and yet the mere possibility was as intriguing as a secret passage in a cave. Margulis and Ris did not yet have enough observations to require explanation, and yet they wondered what those they did have might mean. Margulis’s discussions with Ris were interesting enough that she wanted to study cytoplasmic DNA for her PhD thesis at the University of California, Berkeley. Studying a potentially nonexistent thing for a PhD project is generally frowned upon (note the lack of funding for Bigfoot research). Her advisors objected but she persisted, a persistence for which she found herself soon, she thought, rewarded. A year later, in 1961, Margulis found what she thought to be evidence of DNA in the chloroplasts of Euglena, a green protist. Margulis presented the results the same year at the meetings of the Society of Protozoologists. The findings were still preliminary but merited mention on a list of the presentations from the meetings of “more than routine significance.” The Euglena results were a narrow opening into the story of cells, and so Margulis started to try to move some rocks at the cave entrance in order that she might break trough.

The results of Margulis’s Euglena experiments suggested the presence of DNA in the chloroplasts within cytoplasm, but were not proof positive. Then in 1963, three years after Margulis had begun her PhD thesis, Hans Ris and W. S. Plaut (her former advisor at Wisconsin) discovered DNA in chloroplasts of Chlamydamonas. In a picture in their published paper, the stained DNA appear as three white round patches against the darker background of the cell. Like all round shapes on a dark background, the patches look like planets or stars. The big white spot of the nucleus’s DNA is at the center, and on either side, as though orbiting, are two smaller forms, the chloroplasts each white with the density of DNA. At that time, there was no accepted explanation for why DNA would be in the chloroplast or more generally anywhere outside of the nucleus. Ris and Plaut, however, noted that the DNA in the chloroplast bore some coarse resemblance to the DNA in some bacteria. Ris and Plaut went on to notice other similarities between chloroplasts and bacteria in general and with blue/green algae more specifically. The chloroplast, like blue‐green algae, has a double membrane that surrounds it, a kind of wall within the bigger wall of the cell. Both contain a similarly organized photosynthetic apparatus through which light is converted to food. Both contain ribosomes. The question then became whether such similarities were more than coincidence and if so to what to attribute them. Ris and Plaut had an idea. They argued that perhaps these similarities were no coincidence. Perhaps, as a marginalized Russian scientist (to whom we will return) had suggested sixty years prior, and as Margulis had raised as a possibility at the Protozoology meeting, chloroplasts are blue green algae that were incorporated into another cell and were living in a symbiosis. Plant cells and the cells of other green eukaryotes (such as Euglena and Chlamydamonas) were actually composed, they were arguing, of two species. Ris and Plaut concluded the article by noting that with the demonstration of the similarities between chloroplasts and “free living organisms, endosymbiosis must again be considered seriously as a possible evolutionary step in the origin of complex cells systems,” like plants or even humans.

In 1963, with exciting discoveries seemingly close at hand, Margulis left, with her husband and son, for her husband’s new job in Massachusetts. She had not yet finished her PhD and was working with a difficult PhD advisor who “graduated almost no one.” She did not file her PhD for another two years and, in the meantime and afterward, was working a part time job at Brandeis University to pay the bills. She and her husband would soon divorce and she would find herself taking care of her two sons largely on her own while working a short‐term job. These were not good circumstances for developing theory, but Margulis was captivated by her work. She wanted badly to continue working on the ideas of endosymbiosis. She would soon propose a new vision of the entire history of life, through the lens of endosymbiosis. The term endosymbiosis (endo for inside) referred to the presence of one symbiotic partner (here the chloroplast) inside the other cell itself, living in a symbiotic relationship. At that time, the living world was divided into four kingdoms. Three of the kingdoms, the animals, the plants, and the protists were eukaryotes. Eukaryotes possess a nucleus and organelles (tiny organs) cloaked in membranes. Of the three eukaryote kingdoms, the plants differed in containing an addition organelle—chloroplasts for harnessing light. The fourth kingdom, and the only kingdom of prokaryotes, was that of the bacteria. The bacteria lacked a nucleus, organelles (such as the mitochondria and chloroplasts) with membranes, and true cilia and flagella. The bacteria were, in general, far simpler cells and so, as is often the case with simpler organisms, believed

to be primitive, perhaps not unlike the first cells. An evolutionary story that united these four kingdoms had to explain both their differences and their similarities. If one assumed the Monera were the primitive ancestors, one then needed to ttained a nucleus, mitochondrian and flagella and cilia. For plants, there was then the additional question of the origin of the chloroplast. There were few obvious intermediate life forms, few steps preserved in the fossil record. To many, the problem seemed intractable. Margulis was moving toward a theory that would explain not just the DNA in chloroplasts, but the relationships among the four kingdoms of life. She had worked for her thesis on the autonomy of chloroplasts in Euglena, but that work had offered her a window into a broader theory. It was a theory based on simple Leeuwenhoek‐like observations coupled with reading the work of earlier, relatively ignored scientists with similar ideas. As she worked at Brandeis, her ideas began to crystallize. They would lead her to a conclusion that seemed, to her, almost inevitable. She began to believe not only that the chloroplasts in plant cells were bacteria, but also that the mitochondria in all eukaryote cells were bacteria, and then even that the cilia and flagella (and later also the centrioles that hold the chromosomes in place during cell division), were ancient bacteria. All of these parts of eukaryotic cells, Margulis was to argue, arose through symbioses, events in which one cell engulfed another and then the two cells, one inside, one surrounding, took advantage of each others’ respective life skills. Margulis was casting the entire history of the evolution of eukaryotic life in the context of symbiosis. Our lives, the lives of all animals and plants, were thus fused lives, chimera composed of multiple species. As Margulis would later put it, “any living being larger than a bacterium is a superorganism,” a collective that evolved through the bodily fusion of two or more earlier cells. It was a revolutionary set of ideas. We were, she argued, inhabited by multitudes without which we would die, without which we did not exist at all. Margulis began to think of humans and all other animals as neither animal nor bacteria but instead something in between. There are incentives to positing outrageous theories as a graduate student, or shortly thereafter—fame, name recognition, controversy. Those incentives balance a huge body of disincentives. In young scientists, big truths and practicality do battle. They must. Practicality would suggest that for a young scientist with children and little job security, a revolutionary theory is a) likely to be wrong, b) unlikely to be believed even if it is right and c) likely to get you ostracized by your peers, denied tenure and a job as wait staff.

Margulis would call these events symbiogenesis, where the genesis refers to the origin of a new species or kind of life through the merger of two or more existing species.With those odds, one has to love a young scientist who decides to go forth with a crazy theory, even if it is wrong. Even wrong ideas, in youth, can be beautiful. Lynn Margulis’s idea was beautiful and maybe even right and so she went forth. She published her first paper on what would soon be called the Serial Endosymbiosis Theory (SET) in 1967. The paper, entitled “Origin of Mitosing Cells” was a pared down version of what was soon to develop into a much broader argument. It would be followed by a slightly bolder paper entitled, “Evolutionary Criteria in Thallophytes: A Radical Alternative,” in which Margulis laid out her theory in more detail. To many, it would seem that the radical alternative was not the theory but rather Margulis. In 1969, divorced from her first husband, while still working on what amounted to a part‐time job at Brandeis University in Massachusetts and pregnant with her daughter Jennifer, Lynn Margulis was at home for long periods. In her telling, this home stay offered the advantage of many hours of uninterrupted thoughts. Those thoughts in turn led to a more expanded version of her ideas on mitochondria and chloroplasts, and ultimately ideas about life itself. The more Margulis looked, the more it seemed that the world was decomposing into parts, each with a separate history. Her body and her daughter’s body were not single things; they were separate but linked in a kind of symbiosis. Each of their bodies on its own was also a kind of community or maybe even a commune, lives with disparate interests and separate histories, commingling for years to achieve their separate goals. Well into her pregnancy, it seemed as if at the heart of life there were symbioses. For two centuries, male biologists had emphasized the role of struggle, competition, and war in evolution. Lynn Margulis was offering a very different view. The ideas flowed. She wrote an entire book and then more. There were hundreds and hundreds of pages of thoughts. When she entered college, Lynn had wanted to be a writer of fiction. Here she found herself instead writing a story of life so new that many thought it was fiction. She wrote quickly to meet a deadline a publisher had given her. She paid for drawings for the book herself. She eventually pared back the manuscript, culled it into a reasonable‐length book and, half‐sure of greatness in these ideas, sent the book to New York, to the academic press with whom, during the process of writing at nights, she obtained a contract but no advance. She was alternately thrilled and worried. For whole days, worry would win out. Then she would write some more and think again that she was right, that she had for the first time in history seen clearly the history of life. The publisher did not write back, not for months. Finally, there was word, a rejection letter. It offered no explanation and was unsigned. Lynn would later learn that other scientists’ critiques of the manuscript had been so harsh that the publisher cancelled the project. The critiques had been so harsh that the publisher had initially not even bothered to let her know. Her first paper on endosymbiosis, finally published in 1967, had also been rejected, in that case twenty times en route to publication. She may have known by then that hers was to be a battle uphill, but what she could not have yet known was that it was a very long hill. Lynn’s daughter was born. Her own symbioses became more complex. Her two sons were getting older. Her ex‐husband, was contributing almost nothing to childcare. This was not a time to pursue wild ideas. It was a time for stable projects that would produce publishable work and grant funds. It was a time to convince her new department head at Boston University, where she was by then employed, that she deserved her job. But this was not Lynn Margulis’s way. It never would be. She worked even harder on the manuscript, refined her ideas and stayed up later and later to rewrite and reconsider. She had plenty of time to water down her new theory. Instead, she again made it bolder.

Lynn Margulis came to the conclusion that key organs of eukaryote cells (mitochondria, chloroplasts, and flagella, cilia and centrioles) were ancient bacteria, engulfed by another cell, based on several pieces of evidence. As already mentioned, it had recently been discovered that mitochondria and chloroplasts had DNA (most of “our” DNA is in our cells’ nuclei). Other biologists had suggested mitochondria and chloroplasts “looked like” bacteria. Margulis found such similarities compelling. The evidence for cilia and flagella was more preliminary. Cilia, flagella, and centrioles are all composed of an array of fibers called microtubules, arranged in a pattern very similar to fiber inside a certain kind of bacteria, spirochetes. Finally, symbiotic microbes living in relationships such as this, were very common elsewhere, in the cells of insects, in amoeba, and green ciliates, etc… To Margulis, the grand theory was thus simple; the history of life’s most important events was a series of mergers.

Yet this was not the traditional story, the Darwinian story, of competition and evolution by slow, accumulated, change. The story, she would argue, began with a low‐oxygen world. In that world, the first photosynthetic bacteria produced oxygen. With time, other bacteria evolved to use oxygen in respiration. A single cell, already possessing a nucleus but not yet the machinery (a mitochondrian) for using oxygen, then engulfed one of those respiring bacteria, which would become the mitochondrian.lxxiv The two species were more successful together than apart, and so the relationship continued. One individual of that new, combined species then engulfed a photosynthetic bacteria, a cyanobacteria, and became capable not only of respiration but also of photosynthesis. From that second event would descend, ultimately, the plants. Somewhere along the line, another bacterium, perhaps a coil‐shaped spirochete, had also been engulfed, which formed the cilia and flagella and perhaps even the centrioles52 within eukaryotic cells. It was this last event that helped shape the functioning of the nucleus, of cell division and even of cell mobiThese steps were the major events in the evolution of life. All the rest was icing. In each case, the bacteria that had been consumed began to lose some of those features now unnecessary inside its host. The host, in turn, did the same. It began to rely on the cell it had incompletely consumed to turn food energy into usable energy. Soon, without its guest the host could not survive, and without its host neither could the guest. From those three original events, every protist, plant and animal and more generally every eukaryote would descend. It was, as Margulis saw it, our defining series of moments. It took a large body of accumulated evidence for Margulis to finalize her ideas of serial endosymbiosis. Yet, as often seems the case with big discoveries, other researchers had come to similar ideas with less evidence. They had been speculating even more wildly with even fewer facts. The stories of these scientists, had Margulis cared to look, were often not very promising models for hat she would continue to face.

In the late 1800s, lichens had been hypothesized to be not one, but multiple organisms. They were speculated (as we now know to be the case) to be a symbiosis between an algae and a fungus. The theory was controversial, but also exciting. If lichens were really the combined result of multiple interacting species, perhaps such arrangements were common in nature. It would not take long for a few wild scientists (there are always a few) to suggest as much. The Russian scientist Konstantin S. Merezhkovsky argued in 1909 that the pale green chloroplasts in plant cells evolved from bacteria ingested by plant ancestors.lxxv To Merezhkovsky, if lichens were composed of multiple creatures, then why not trees? The green of forests was not plant matter at all, Merezhovsky would contend, but instead the ancient cyanobacteria held up by trees in every leaf, like so many guests standing in the windows of a house, candles in their hands. These were the torches that lit life. Bacteria, hitching a ride and providing some sugar in return. To the bacteria in plant cells we might owe everything, he speculated. Merezhovksy’s idea, expressed as a footnote to his broader work, had initially spurred Ris and then through Ris, Margulis’s thinking on chloroplasts. In Russia, Merezhkovsky was largely alone in his theorylxxvi. Similar ideas had emerged elsewhere, however. Ivan Wallin was born in 1883 was born in Stanton, Ohio, to Swedish parents. He would make his way to a professorship position at the University of Colorado, Boulder where, among other things, he taught anatomy. There, in the name of education, he stood students before a cadaver and asked them questions. When they were wrong, he whacked them (the students, not the cadaver) in the chest. The students, right or wrong, whacked or not, then helped Wallin build his cabin, not far from Boulder. In the cabin, Wallin took the students’ money in poker and drank. Wallin did much of his research in a shed behind the University of Colorado, Boulder’s classrooms or in the cabin his students built. It was in these makeshift facilities that, in looking into cells, he discovered ‐‐ he thought ‐‐ that mitochondria were still bacteria capable of life on their own. He went so far as to claim that he could grow mitochondria outside of the cell in which they were found (a claim which Margulis would also, at least initially, offer). Wallin, like Merezhkovsky, put forth ideas very similar to those that Margulis would later advocate. The ideas were less refined, but Wallin and Merezhkovsky were working in earlier times, when our understanding of the workings of cells was also less refined. No one believed Wallin. He was criticized so harshly that he eventually quit research at the age of 40. Many thousands of miles away Merezhkovsky was also marginalized and then forgotten. In thinking about the likes of Wallin, Merezhovksy, and later Margulis, Richard Klein and Arthur Cronquist, two scientists at the New York Botanical Garden, would call the idea that chloroplasts were symbionts, a bad penny that “has been circulating for a long time.lxxvii”Clearly, the implication was that Margulis ought to drop the dirty, hand‐me‐down. Instead, Margulis, with the insights of new research on the workings of cells and the structure of DNA, would build on Wallin and Merezhovsky. If she were right, her role could be to construct a broader theory and gain acceptance for it, much in the way that Galileo brought Copernicus’s revolution to the world. Galileo had nearly lost his head. Margulis bent hers down and harged. She was, as she would later say in an interview, “not afraid of anything.

The scenes that Lynn envisioned in our early history, of fusing cells, were not unlike the meeting of continents. The continents fused to create something novel, a supercontinent (akin to her superorganism). In the model of the continents, there was also a model of discovery that might have seemed similar to Lynn, had she noticed. In the 1950s, 500 years after Anton Kirchner had initially suggested that the continents moved about like plates, Alfred Wegener reframed the same hypothesis. Wegener had more evidence than did his predecessor. He could match up the places where coal was found and suggest that those were the areas of ancient forests. He could match up related species on opposite sides of the sea. He could compare the rocks of Morocco and their ancient kin in Connecticut. He saw patterns that seemed to imply that pieces of the Earth’s crust that were long considered joined had once been separate, just as pieces of our cells might have once lived free. As late as 1970 (the year Margulis was made Associate Professor at the University of Boston), not all reasonable scientists believed in plate tectonics. There were patterns, but no sense of what shoved the continents together or pushed them apart. Scientists would believe the theory only when Wegener’s advocacy combined with a more mechanistic theory of the underlying process. When deep‐sea rifts were discovered, the process became apparent. Where continents were pushed together, mountains formed or the crust melted. Where they pulled apart, the Earth was hot with the splitting of rock. Earlier scientists had suggested that mitochondria and chloroplasts were endosymbionts. Margulis believed that she had elaborated the mechanisms by which those endosymbioses evolved. But what Lynn Margulis ultimately needed, if she was to be believed by more than a few other scientists, were more details of the process of how endosymbiosis arose. She needed the cellular equivalent of magma, evidence of the collision. She needed concrete evidence because what she was proposing was more revolutionary than the idea that the continents, long fixed, moved. She was proposing that our bodies were made of multiple bodies, that something as deep as our identity was divided along ancient lines. Margulis’s book on her new theory was finally published in 1971. It was greeted by unceremoniouscriticism, even hate mail. One of the more supportive reviewers wrote, “Readers will find this book sprawling, stimulating, irritating and challenging but they will have difficulty ignoring it.” Her ideas were too bold and widely ranging. She garnered a few supporters, but, it seemed, precious few. She went ahead on the strength of her convictions. Evolution was meant to be frugal and consistent. Her hypotheses were complex and idiosyncratic. They were not testable. Her critics would argue against her ideas, in forum after forum, but she, like her book, could not be ignored.

Slowly, she would gather something of a following, nothing universal and unanimous, but enough to keep her going. By 1970, a review article by Peter Raven,53 then at Stanford University, suggested that her Serial Endosymbiosis Theory was widely believed and that the critics were louder than their numbers. Despite whatever support Margulis had, the fights continued and so did Margulis. Margulis was, with her ideas, stubborn. Richard Dawkins, one of the living granddaddies of evolution, has framed Lynn’s stubbornness negatively. “She would not change her mind,” even, he would go on to imply, when the evidence was overwhelming (Dawkins in saying this was, of course, quick to highlight his own willingness to listen). Others saw her stubbornness as a necessary reality, what one must have when one is right and everyone else disagrees. Scientists are supposed to listen. They are supposed to constantly consider and reconsider their ideas. They are supposed to respond to criticism. Yet criticism will come regardless of whether one is right or wrong. Lynn Margulis had to listen well enough to be bent by the tide when she was wrong, but not so limply that she would bend even when she was right. Scientists before her had advocated the symbiotic origin of mitochondria and chloroplasts. They had both bent to the tide. She would not.

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