The Conscious Cell LYNN MARGULIS Department of Geosciences, University of Massachusetts, Amherst, Massachusetts 01003-5820, USA ABSTRACT: The evolutionary antecedent of the nervous system is “microbial consciousness.” In my description of the origin of the eukaryotic cell via bacte- rial cell merger, the components fused via symbiogenesis are already “con- scious” entities. I have reconstructed an aspect of the origin of the neurotubule system by a hypothesis that can be directly tested. The idea is that the system of microtubules that became neurotubules has as its origin once-independent eubacteria of a very specific kind. Nothing, I claim, has ever been lost without a trace in evolution. The remains of the evolutionary process, the sequence that occurred that produced Cajal’s neuron and other cells, live today. By study of obscure protists that we take to be extant decendants of steps in the evolution of cells, we reconstruct the past directly from living organisms. Even remnants of “microbial mind” can be inferred from behaviors of thriving microorgan- isms. All of the eukaryotes, not just lichens or an animal’s neurons, are prod- ucts of symbiogenesis among formerly free-living bacteria, some highly motile. Eukaryotes have evolved by the inheritance of acquired genomes; they have gained all their new features by ingesting and not digesting whole bacterial cells with complete genomes. KEYWORDS: Borrelia; Karyomastigonts; Mixotricha; Nuclear origins; Spirosymplokos; Evolutionary novelties; Minimal cell; Symbiosis Almost one hundred years ago, Ramón y Cajal in his Historia de Vacaciones wrote1: It is certain that science, internally rebellious, seemingly against fate, has invented the microscope with the aim of surprising such small enemies. Yet this already represents an intellectual gain by the microbe. This microscope, this toy—still imperfect because of limitations of its resolving power—from it escape millions of infinitesimal lives; ul- tramicroscopical bacteria have their bacteria, the impalpable dust of myriad lives dis- persed in the air, the water and on the land, the imperceptible intracellular colonies, a kind of symbiotic federation that only now begin to dawn as if they were risky conjec- tures in the minds of some audacious wise men. One day perhaps it will be legal to track the morphology and customs of such diminutive and ultramicroscopic beings that bor- der on the void even though they are so much larger than molecular constructions. And thus, in all, science can never deplete the domains of life. The invisible, infinitely more important than the visible, infinitely delicate and still unknown, will surround us al- ways. Each age will have its inaccessible enemies because the steed of progress gal- lops, spurred only by the heel of death.1 What is the “statue interior,” the “statue inside” that François Jacob2 alludes to in his autobiography, The Statue Within? What is “the invisible infinitely more impor- tant than the visible”? (FIG. 1). This is what I plan to discuss in this paper. Address for correspondence: Morrill Science Center, University of Massachusetts, Amherst, Massachusetts 01003-5820. 55 56 ANNALS NEW YORK ACADEMY OF SCIENCES FIGURE 1. Top: statue of Ramón y Cajal (by sculptor Mariano Benlliure, 1924). Bot- tom: close-up of three Nobel prize winners—Murray Gell-Mann, François Jacob, and Gerald Edelman [left to right]—at the base of the statue. MARGULIS: THE CONSCIOUS CELL 57 Illustrious predecessors to my commentary, as well as to the nervous system, abound. The illustrious predecessor to the nervous system is “microbial conscious- ness.” When I describe the origin of the eukaryotic cell via bacterial cell merger, I emphasize that the components that fused in symbiogenesis are already “conscious” entities. I speak within the evolutionary context developed for us by one of my illus- trious predecessor scientists: Professor Harold J. Morowitz.3 I present an aspect of the origin of the neurotubule system by a hypothesis that can be directly tested. The idea is that the system of microtubules that became neurotubules has as its origin once-independent eubacteria of a very specific kind. In our films I show live beings that help us comprehend how evolution has proceeded since the beginning.4 Noth- ing, I claim, has ever been lost without a trace in evolution. The remains of the evo- lutionary process, the sequence that occurred that produced Cajal’s neuron and other cells, persist today. By study of what thrives now we can reconstruct the past directly from living organisms, even “microbial mind.”5 SYMBIOSIS AND THE EVOLUTION OF EUKARYOTIC CELLS The protein synthetic system, the cytoplasm of your favorite cell, the neuron, as the cytoplasm of all eukaryotic cells, we claim is archaebacterial in origin. We pos- tulate that the protein synthetic system of eukaryotic cells mainly derives from a type of archaebacterium called Thermoplasma. The undulipodium, that is, the microtubular system in its [9(2)+2] array, the shaft called the axoneme, evolved from motile eubacteria close to the genus Spirocheta. The simplified equation, by hypothesis, is Thermoplasma (archaebacteria) + Spiro- cheta (eubacteria) = the first protist. This motile, nucleated cell, the first protist, re- sembled mastigotes like extant Mastigamoeba or Trichomonas. The first merger occurred in the absence of oxygen, prior to acquisition of mitochondria. The earliest microbes, both bacteria and protists, were already greatly sensitive to their environ- ment. The earliest protists bore, in their cells, the karyomastigont. The organelle sys- tem, the karyomastigont, is found in many extant protists. The karyomastigont comprises a nucleus and a nucleus connector or rhizoplast that links the nucleus to centrioles and axonemes. The karyomastigont, in our opinion,6 preceded the unat- tached nucleus. The nucleus as a double membrane-bounded sphere in the cytoplasm originated when it was severed from the karyomastigont. This scheme posits that spirochete plus thermoplasma generated basal new eukaryotes: protists with karyo- mastigonts. When the karyomastigont was cut, the nucleus, an organelle that from the beginning represented DNA from two different sources (archaebacterial and eu- bacterial), was released. From protists evolved the cells of all animals, plants and those of all other familiar eukaryotic organisms.6,7 The timeline has been given to us by the geochronologists: four eons. The origin of life is still a big question mark. The units by which we represent the ancient his- tory are tens of millions of years (FIG. 2). The fossil record of the marine animals begins with the “Cambrian explosion” 541 millions years ago. The Mesozoic age of reptiles began 225 mya. The age of mammals, the Cenozoic, occupies the last portion, 65–0 mya. People are not even visible on this scale. We count in thousands of millions of years. The entire “Precam- 58 ANNALS NEW YORK ACADEMY OF SCIENCES brian,” the long period prior to any animal or plant, is the age of bacteria and proto- ctists. The eukaryote fossil record begins about 2,000 million years ago. The first hard-shelled marine animals appeared at 541 million years ago. This dates the evo- lution of hard parts. Brains appear later, but consciousness, awareness of the sur- rounding environment, starts with the beginning of life itself, which is the point of this paper. The origin of life is represented in FIGURE 2 as a question mark. The earliest cells generated the two great groups of bacteria: the one to which Thermoplasma belongs (archaebacteria) and the one to which the spirochetes belong (eubacteria). The pro- cess of symbiogenesis in the evolution of nucleated cells began about 2,000 mya. The emergent property of the symbiont fusion was the origin of all larger forms of life. We concentrate here on only one of the many, many evolutionary transitions in the origin of ourselves: we mammals who talk too much. Let us review the very earliest life forms from the point of view of their chemistry. This simplified diagram is based completely on the analysis that Morowitz made some 25 years ago: the minimal cell (FIG. 3).3 The minimal cell must be surrounded by a membrane of its own making. In today’s world, on Earth at least, the cell makes its own genetic material, DNA. Of course it synthesizes messenger RNA coded off that DNA, as well as transfer RNAs, and the rest of ribosomal RNAs to make the ri- bosomal system that synthesizes more proteins that make more DNA. All cells re- quire sources of carbon, nitrogen, oxygen, hydrogen, phosphorus, and sulfur. A source of energy too is required by all life. Life’s energy system is always visible light or chemical (inorganic or organic chemical) only. No other known sources of energy for cells exist besides photo- and chemical. All of life’s chemical transforma- tion occurs in a watery matrix. The minimal system, at least on Earth today, dia- FIGURE 2. History of life on geological time scale (by Kathryn Delisle). MARGULIS: THE CONSCIOUS CELL 59 grammed in FIGURE 3, suggests that any organelle that began as a free-living microbe at first contained FIGURE 3’s entire complement of features. In cells of green hydra, for example, the green animal’s gastrodermal cell is clear- ly a product of symbiogenesis: the cnidarian animal and the alga. But three genomes occur in the Chlorella, the green algal cell: nucleocytoplasm, chloroplast, mitochon- drion. At least two coexist in the hydra cell: nucleocytoplasm and mitochondrion. Thus the single digestive system cell of the animal is a composite of at least five ge- nomes. The point is that all eukaryotic cells, including the neuron, all are products of more than a single genome with more than one single ancestor. All are complex, all are heterogenomic with multiple ancestors. All eukaryotes, all nucleated organ- isms, are composed of cells that are products of symbiogenetic mergers.